Highlights • Ponatinib dose intensity was shown to be associated with rates of adverse events. • Pancreatitis, rash, and cardiac failure were most strongly associated with dose. • Time-to-event ...analyses suggest a lag between changes in dose and event risk. • No association between dose intensity and venous thromboembolic events was evident. • Results support investigating approaches to lower average ponatinib dose intensity
Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the ...skeletal and cardiovascular systems. We conducted a 1‐year prospective, randomized, double‐blind trial in 143 postmenopausal osteoporotic women (mean ± SD age, 68.4 ± 5.0 years) with at least one prevalent vertebral fractures and low bone mineral density (BMD), comparing groups receiving raloxifene at 60 mg/day (RLX60) or 120 mg/day (RLX120) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D. There were no differences among groups in the occurrence of uterine bleeding, thrombophlebitis, breast abnormalities, or increased endometrial thickness (assessed by ultrasonography). As compared with controls, the changes in values over 1 year for RLX60 and RLX120, respectively, were significant for serum bone alkaline phosphatase (−14.9%, −8.87%), serum osteocalcin (−20.7%, −17.0%), and urinary C‐telopeptide fragment of type I collagen/creatinine (−24.9%, −30.8%), markers of bone turnover; for serum total cholesterol (−7.0% for RLX60) and low density lipoprotein cholesterol (LDL) (−11.4% for RLX60) and for the LDL/HDL cholesterol ratio (−13.2%, −8.3%). BMD increased significantly in the total hip (1.66% for RLX60) and ultradistal radius (2.92%, 2.50%). There were nonsignificant trends toward increases over controls in BMD for lumbar spine, total body, and total hip (for RLX120). Using a >15% cutoff definition, raloxifene had no effect on incident fractures, but using a >30% cutoff, there was a dose‐related reduction (p = 0.047). We conclude that raloxifene therapy is well tolerated, reduces serum lipids, and does not stimulate the uterus or breasts. It has beneficial effects on bone, although, under the conditions of this study, these appear to be of a smaller magnitude than have been reported with estrogen therapy.
The poetry of Robert Browning has been the subject of extensive literary criticism since his death in 1889. Two well-known Browning scholars here present the best of Browning criticism, bringing ...together from many sources representative evaluations of the poet and his poetry. The twenty-one essays here have been arranged chronologically so that the reader can follow the development of Browning studies and the fluctuations of his poetic reputation. They express varied points of view and are typical of the critical methods used by the Browning scholars. Included are essays by George Santayana, John J. Chapman, G. K. Chesterton, Paul Elmer More, William C. DeVane, Hoxie N. Fairchild, and Richard D. Altick.
In the introduction Mr. Litzinger and Mr. Knickerbocker review the broad spectrum of Browning criticism. The editors also provide a bibliographic guide to the rapidly growing body of Browning criticism, which supplements and brings up to date previous Browning bibliographies.
This paper describes the operation of the Coherent CAPTAIN-Mills (CCM) detector located at the Los Alamos Neutron Science Center at Los Alamos National Laboratory. CCM is a 10-ton liquid argon ...detector located 20 meters from a high flux neutron/neutrino source and is designed to search for sterile neutrinos (νs’s) and light dark matter (LDM). An engineering run was performed in fall 2019 to study the characteristics of the CCM120 detector by searching for coherent scattering signals consistent with νs’s and LDM resulting from the production and decays of π+ and π0 in the tungsten target. New parameter space in a leptophobic dark matter (DM) model was excluded for DM masses between ~2.0 and 30 MeV. The lessons learned from this run have guided the development and construction of the new CCM200 detector that will begin operations in 2021 and significantly improve on these searches.
We report the first results of a search for leptophobic dark matter (DM) from the Coherent–CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) ...and 17.9 × 1020 protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM’s first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005 + 16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of mVB=mχ = 2.1, DM masses within the range 9 MeV ≲ mχ ≲ 50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM’s upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.
A solution to the MiniBooNE excess invoking rare three-body decays of the charged pions and kaons to new states in the MeV mass scale was recently proposed as a dark-sector explanation. This class of ...solution illuminates the fact that, while the charged pions were focused in the target-mode run, their decay products were isotropically suppressed in the beam-dump-mode run in which no excess was observed. This suggests a new physics solution correlated to the mesonic sector. We investigate an extended set of phenomenological models that can explain the MiniBooNE excess as a dark sector solution, utilizing long-lived particles that might be produced in the three-body decays of the charged mesons and the two-body anomalous decays of the neutral mesons. Over a broad set of interactions with the long-lived particles, we show that these scenarios can be compatible with constraints from LSND, KARMEN, and MicroBooNE, and evaluate the sensitivity of the ongoing and future data taken by the Coherent CAPTAIN Mills experiment to a potential discovery in this parameter space. Published by the American Physical Society 2024
We show results from the Coherent CAPTAIN Mills (CCM) 2019 engineering run which begin to constrain regions of parameter space for axionlike particles (ALPs) produced in electromagnetic particle ...showers in an 800 MeV proton beam dump, and further investigate the sensitivity of ongoing data-taking campaigns for the CCM200 upgraded detector. Based on beam-on background estimates from the engineering run, we make realistic extrapolations for background reduction based on expected shielding improvements, reduced beam width, and analysis-based techniques for background rejection. We obtain reach projections for two classes of signatures; ALPs coupled primarily to photons can be produced in the tungsten target via the Primakoff process, and then produce a gamma-ray signal in the liquid argon CCM detector either via inverse Primakoff scattering or decay to a photon pair. ALPs with significant electron couplings have several additional production mechanisms (Compton scattering, e+e— annihilation, ALP-bremsstrahlung) and detection modes (inverse Compton scattering, external e+e— pair conversion, and decay to e+e—). In some regions, the constraint is marginally better than both astrophysical and terrestrial constraints. With the beginning of a three year run, CCM will be more sensitive to this parameter space by up to an order of magnitude for both ALP-photon and ALP-electron couplings. The CCM experiment will also have sensitivity to well-motivated parameter space of QCD axion models. It is only a recent realization that accelerator-based large volume liquid argon detectors designed for low-energy coherent neutrino and dark matter scattering searches are also ideal for probing ALPs in the unexplored ~ MeV mass scale.
During catastrophic disasters, government leaders must decide how to efficiently and effectively allocate scarce public health and medical resources. The literature about triage decision making at ...the individual patient level is substantial, and the National Response Framework provides guidance about the distribution of responsibilities between federal and state governments. However, little has been written about the decision-making process of federal leaders in disaster situations when resources are not sufficient to meet the needs of several states simultaneously. We offer an ethical framework and logic model for decision making in such circumstances. We adapted medical triage and the federalism principle to the decision-making process for allocating scarce federal public health and medical resources. We believe that the logic model provides a values-based framework that can inform the gestalt during the iterative decision process used by federal leaders as they allocate scarce resources to states during catastrophic disasters.
This paper describes the operation of the Coherent CAPTAIN-Mills (CCM) detector located at the Los Alamos Neutron Science Center at Los Alamos National Laboratory. CCM is a 10-ton liquid argon ...detector located 20 meters from a high flux neutron/neutrino source and is designed to search for sterile neutrinos (νs’s) and light dark matter (LDM). An engineering run was performed in fall 2019 to study the characteristics of the CCM120 detector by searching for coherent scattering signals consistent with νs’s and LDM resulting from the production and decays of π+ and π0 in the tungsten target. New parameter space in a leptophobic dark matter (DM) model was excluded for DM masses between ~2.0 and 30 MeV. The lessons learned from this run have guided the development and construction of the new CCM200 detector that will begin operations in 2021 and significantly improve on these searches.
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