1,147 research outputs found
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REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States.
BackgroundSome trials have found that patients from the United States derive less benefit than patients enrolled outside the United States. This prespecified REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) subgroup analysis was conducted to determine the degree of benefit of icosapent ethyl in the United States.MethodsREDUCE-IT randomized 8179 statin-treated patients with qualifying triglycerides ≥135 and <500 mg/dL and low-density lipoprotein cholesterol >40 and ≤100 mg/dL and a history of atherosclerosis or diabetes mellitus to icosapent ethyl 4 g/d or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite end point was cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. A hierarchy was prespecified for examination of individual and composite end points.ResultsA total of 3146 US patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women and 9.7% were Hispanic. The primary composite end point occurred in 24.7% of placebo-treated patients versus 18.2% of icosapent ethyl-treated patients (hazard ratio [HR], 0.69 [95% CI, 0.59-0.80]; P=0.000001); the key secondary composite end point occurred in 16.6% versus 12.1% (HR, 0.69 [95% CI, 0.57-0.83]; P=0.00008). All prespecified hierarchical end points were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%; HR, 0.66 [95% CI, 0.49-0.90]; P=0.007), myocardial infarction (8.8% to 6.7%; HR, 0.72 [95% CI, 0.56-0.93]; P=0.01), stroke (4.1% to 2.6%; HR, 0.63 [95% CI, 0.43-0.93]; P=0.02), and all-cause mortality (9.8% to 7.2%; HR, 0.70 [95% CI, 0.55-0.90]; P=0.004); for all-cause mortality in the US versus non-US patients, Pinteraction=0.02. Safety and tolerability findings were consistent with the full study cohort.ConclusionsWhereas the non-US subgroup showed significant reductions in the primary and key secondary end points, the US subgroup demonstrated particularly robust risk reductions across a variety of individual and composite end points, including all-cause mortality.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01492361
Orbital Instabilities in a Triaxial Cusp Potential
This paper constructs an analytic form for a triaxial potential that
describes the dynamics of a wide variety of astrophysical systems, including
the inner portions of dark matter halos, the central regions of galactic
bulges, and young embedded star clusters. Specifically, this potential results
from a density profile of the form , where the radial
coordinate is generalized to triaxial form so that . Using the resulting analytic form of the potential, and the
corresponding force laws, we construct orbit solutions and show that a robust
orbit instability exists in these systems. For orbits initially confined to any
of the three principal planes, the motion in the perpendicular direction can be
unstable. We discuss the range of parameter space for which these orbits are
unstable, find the growth rates and saturation levels of the instability, and
develop a set of analytic model equations that elucidate the essential physics
of the instability mechanism. This orbit instability has a large number of
astrophysical implications and applications, including understanding the
formation of dark matter halos, the structure of galactic bulges, the survival
of tidal streams, and the early evolution of embedded star clusters.Comment: 50 pages, accepted for publication in Ap
Proton Motive Force-Dependent Hoechst 33342 Transport by the ABC Transporter LmrA of Lactococcus lactis
The fluorescent compound Hoechst 33342 is a substrate for many multidrug resistance (MDR) transporters and is widely used to characterize their transport activity. We have constructed mutants of the adenosine triphosphate (ATP) binding cassette (ABC)-type MDR transporter LmrA of Lactococcus lactis that are defective in ATP hydrolysis. These mutants and wild-type LmrA exhibited an atypical behavior in the Hoechst 33342 transport assay. In membrane vesicles, Hoechst 33342 transport was shown to be independent of the ATPase activity of LmrA, and it was not inhibited by orthovanadate but sensitive to uncouplers that collapse the proton gradient and to N,N'-dicyclohexylcarbodiimide, an inhibitor of the F0F1-ATPase. In contrast, transport of Hoechst 33342 by the homologous, heterodimeric MDR transporter LmrCD showed a normal ATP dependence and was insensitive to uncouplers of the proton gradient. With intact cells, expression of LmrA resulted in an increased rate of Hoechst 33342 influx while LmrCD caused a decrease in the rate of Hoechst 33342 influx. Cellular toxicity assays using a triple knockout strain, i.e., L. lactis ΔlmrA ΔlmrCD, demonstrate that expression of LmrCD protects cells against the growth inhibitory effects of Hoechst 33342, while in the presence of LmrA, cells are more susceptible to Hoechst 33342. Our data demonstrate that the LmrA-mediated Hoechst 33342 transport in membrane vesicles is influenced by the transmembrane pH gradient due to a pH-dependent partitioning of Hoechst 33342 into the membrane.
The Optical Alignment System of the ATLAS Muon Spectrometer Endcaps
The muon spectrometer of the ATLAS detector at the Large Hadron Collider (LHC) at CERN consists of over a thousand muon precision chambers, arranged in three concentrical cylinders in the barrel region, and in four wheels in each of the two endcaps. The endcap wheels are located between 7m and 22m from the interaction point, and have diameters between 13m and 24m. Muon chambers are equipped with a complex on-line optical alignment system to monitor their positions and deformations during ATLAS data-taking. We describe the layout of the endcap part of the alignment system and the design and calibration of the optical sensors, as well as the various software components. About 1% of the system has been subjected to performance tests in the H8 beam line at CERN, and results of these tests are discussed. The installation and commissioning of the full system in the ATLAS cavern is well underway, and results from approximately half of the system indicate that we will reach the ambitious goal of a 40mu alignment accuracy, required for reconstructing final-state muons at the highest expected energies
Noise Characterization and Filtering in the MicroBooNE Liquid Argon TPC
The low-noise operation of readout electronics in a liquid argon time
projection chamber (LArTPC) is critical to properly extract the distribution of
ionization charge deposited on the wire planes of the TPC, especially for the
induction planes. This paper describes the characteristics and mitigation of
the observed noise in the MicroBooNE detector. The MicroBooNE's single-phase
LArTPC comprises two induction planes and one collection sense wire plane with
a total of 8256 wires. Current induced on each TPC wire is amplified and shaped
by custom low-power, low-noise ASICs immersed in the liquid argon. The
digitization of the signal waveform occurs outside the cryostat. Using data
from the first year of MicroBooNE operations, several excess noise sources in
the TPC were identified and mitigated. The residual equivalent noise charge
(ENC) after noise filtering varies with wire length and is found to be below
400 electrons for the longest wires (4.7 m). The response is consistent with
the cold electronics design expectations and is found to be stable with time
and uniform over the functioning channels. This noise level is significantly
lower than previous experiments utilizing warm front-end electronics.Comment: 36 pages, 20 figure
The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector
The development and operation of Liquid-Argon Time-Projection Chambers for
neutrino physics has created a need for new approaches to pattern recognition
in order to fully exploit the imaging capabilities offered by this technology.
Whereas the human brain can excel at identifying features in the recorded
events, it is a significant challenge to develop an automated, algorithmic
solution. The Pandora Software Development Kit provides functionality to aid
the design and implementation of pattern-recognition algorithms. It promotes
the use of a multi-algorithm approach to pattern recognition, in which
individual algorithms each address a specific task in a particular topology.
Many tens of algorithms then carefully build up a picture of the event and,
together, provide a robust automated pattern-recognition solution. This paper
describes details of the chain of over one hundred Pandora algorithms and tools
used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE
detector. Metrics that assess the current pattern-recognition performance are
presented for simulated MicroBooNE events, using a selection of final-state
event topologies.Comment: Preprint to be submitted to The European Physical Journal
Convolutional Neural Networks Applied to Neutrino Events in a Liquid Argon Time Projection Chamber
We present several studies of convolutional neural networks applied to data
coming from the MicroBooNE detector, a liquid argon time projection chamber
(LArTPC). The algorithms studied include the classification of single particle
images, the localization of single particle and neutrino interactions in an
image, and the detection of a simulated neutrino event overlaid with cosmic ray
backgrounds taken from real detector data. These studies demonstrate the
potential of convolutional neural networks for particle identification or event
detection on simulated neutrino interactions. We also address technical issues
that arise when applying this technique to data from a large LArTPC at or near
ground level
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Calibration of the charge and energy loss per unit length of the MicroBooNE liquid argon time projection chamber using muons and protons
We describe a method used to calibrate the position- and time-dependent response of the MicroBooNE liquid argon time projection chamber anode wires to ionization particle energy loss. The method makes use of crossing cosmic-ray muons to partially correct anode wire signals for multiple effects as a function of time and position, including cross-connected TPC wires, space charge effects, electron attachment to impurities, diffusion, and recombination. The overall energy scale is then determined using fully-contained beam-induced muons originating and stopping in the active region of the detector. Using this method, we obtain an absolute energy scale uncertainty of 2% in data. We use stopping protons to further refine the relation between the measured charge and the energy loss for highly-ionizing particles. This data-driven detector calibration improves both the measurement of total deposited energy and particle identification based on energy loss per unit length as a function of residual range. As an example, the proton selection efficiency is increased by 2% after detector calibration
Ionization Electron Signal Processing in Single Phase LArTPCs II. Data/Simulation Comparison and Performance in MicroBooNE
The single-phase liquid argon time projection chamber (LArTPC) provides a
large amount of detailed information in the form of fine-grained drifted
ionization charge from particle traces. To fully utilize this information, the
deposited charge must be accurately extracted from the raw digitized waveforms
via a robust signal processing chain. Enabled by the ultra-low noise levels
associated with cryogenic electronics in the MicroBooNE detector, the precise
extraction of ionization charge from the induction wire planes in a
single-phase LArTPC is qualitatively demonstrated on MicroBooNE data with event
display images, and quantitatively demonstrated via waveform-level and
track-level metrics. Improved performance of induction plane calorimetry is
demonstrated through the agreement of extracted ionization charge measurements
across different wire planes for various event topologies. In addition to the
comprehensive waveform-level comparison of data and simulation, a calibration
of the cryogenic electronics response is presented and solutions to various
MicroBooNE-specific TPC issues are discussed. This work presents an important
improvement in LArTPC signal processing, the foundation of reconstruction and
therefore physics analyses in MicroBooNE.Comment: 54 pages, 36 figures; the first part of this work can be found at
arXiv:1802.0870
Design and construction of the MicroBooNE Cosmic Ray Tagger system
The MicroBooNE detector utilizes a liquid argon time projection chamber
(LArTPC) with an 85 t active mass to study neutrino interactions along the
Booster Neutrino Beam (BNB) at Fermilab. With a deployment location near ground
level, the detector records many cosmic muon tracks in each beam-related
detector trigger that can be misidentified as signals of interest. To reduce
these cosmogenic backgrounds, we have designed and constructed a TPC-external
Cosmic Ray Tagger (CRT). This sub-system was developed by the Laboratory for
High Energy Physics (LHEP), Albert Einstein center for fundamental physics,
University of Bern. The system utilizes plastic scintillation modules to
provide precise time and position information for TPC-traversing particles.
Successful matching of TPC tracks and CRT data will allow us to reduce
cosmogenic background and better characterize the light collection system and
LArTPC data using cosmic muons. In this paper we describe the design and
installation of the MicroBooNE CRT system and provide an overview of a series
of tests done to verify the proper operation of the system and its components
during installation, commissioning, and physics data-taking
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