282 research outputs found
Testing and preventive maintenance scheduling optimization for aging systems modeled by generalized renewal process
Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses
Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and ample phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. Here, we generate a single-cell epigenomics and transcriptomics census of naïve-to-memory B cell differentiation in a CVID-discordant MZ twin pair. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B-cells mirroring defective cell-cell communication upon activation. These findings are validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naïve-to-memory B-cell transition in CVID and indicate links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, gives insight into future diagnosis and treatments of CVID patients
Use of moxibustion as an auxiliary treatment in wound healing of the snake Eunectes murinus (anaconda): case report
Atmospheric effects on extensive air showers observed with the Surface Detector of the Pierre Auger Observatory
Atmospheric parameters, such as pressure (P), temperature (T) and density,
affect the development of extensive air showers initiated by energetic cosmic
rays. We have studied the impact of atmospheric variations on extensive air
showers by means of the surface detector of the Pierre Auger Observatory. The
rate of events shows a ~10% seasonal modulation and ~2% diurnal one. We find
that the observed behaviour is explained by a model including the effects
associated with the variations of pressure and density. The former affects the
longitudinal development of air showers while the latter influences the Moliere
radius and hence the lateral distribution of the shower particles. The model is
validated with full simulations of extensive air showers using atmospheric
profiles measured at the site of the Pierre Auger Observatory.Comment: 24 pages, 9 figures, accepted for publication in Astroparticle
Physic
Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter
Data collected by the Pierre Auger Observatory through 31 August 2007 showed
evidence for anisotropy in the arrival directions of cosmic rays above the
Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{eV}. The
anisotropy was measured by the fraction of arrival directions that are less
than from the position of an active galactic nucleus within 75 Mpc
(using the V\'eron-Cetty and V\'eron catalog). An updated
measurement of this fraction is reported here using the arrival directions of
cosmic rays recorded above the same energy threshold through 31 December 2009.
The number of arrival directions has increased from 27 to 69, allowing a more
precise measurement. The correlating fraction is , compared
with expected for isotropic cosmic rays. This is down from the early
estimate of . The enlarged set of arrival directions is
examined also in relation to other populations of nearby extragalactic objects:
galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in
hard X-rays by the Swift Burst Alert Telescope. A celestial region around the
position of the radiogalaxy Cen A has the largest excess of arrival directions
relative to isotropic expectations. The 2-point autocorrelation function is
shown for the enlarged set of arrival directions and compared to the isotropic
expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201
The exposure of the hybrid detector of the Pierre Auger Observatory
The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays.
It consists of a surface array to measure secondary particles at ground level
and a fluorescence detector to measure the development of air showers in the
atmosphere above the array. The "hybrid" detection mode combines the
information from the two subsystems. We describe the determination of the
hybrid exposure for events observed by the fluorescence telescopes in
coincidence with at least one water-Cherenkov detector of the surface array. A
detailed knowledge of the time dependence of the detection operations is
crucial for an accurate evaluation of the exposure. We discuss the relevance of
monitoring data collected during operations, such as the status of the
fluorescence detector, background light and atmospheric conditions, that are
used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic
The Fluorescence Detector of the Pierre Auger Observatory
The Pierre Auger Observatory is a hybrid detector for ultra-high energy
cosmic rays. It combines a surface array to measure secondary particles at
ground level together with a fluorescence detector to measure the development
of air showers in the atmosphere above the array. The fluorescence detector
comprises 24 large telescopes specialized for measuring the nitrogen
fluorescence caused by charged particles of cosmic ray air showers. In this
paper we describe the components of the fluorescence detector including its
optical system, the design of the camera, the electronics, and the systems for
relative and absolute calibration. We also discuss the operation and the
monitoring of the detector. Finally, we evaluate the detector performance and
precision of shower reconstructions.Comment: 53 pages. Submitted to Nuclear Instruments and Methods in Physics
Research Section
Advanced functionality for radio analysis in the Offline software framework of the Pierre Auger Observatory
The advent of the Auger Engineering Radio Array (AERA) necessitates the
development of a powerful framework for the analysis of radio measurements of
cosmic ray air showers. As AERA performs "radio-hybrid" measurements of air
shower radio emission in coincidence with the surface particle detectors and
fluorescence telescopes of the Pierre Auger Observatory, the radio analysis
functionality had to be incorporated in the existing hybrid analysis solutions
for fluoresence and surface detector data. This goal has been achieved in a
natural way by extending the existing Auger Offline software framework with
radio functionality. In this article, we lay out the design, highlights and
features of the radio extension implemented in the Auger Offline framework. Its
functionality has achieved a high degree of sophistication and offers advanced
features such as vectorial reconstruction of the electric field, advanced
signal processing algorithms, a transparent and efficient handling of FFTs, a
very detailed simulation of detector effects, and the read-in of multiple data
formats including data from various radio simulation codes. The source code of
this radio functionality can be made available to interested parties on
request.Comment: accepted for publication in NIM A, 13 pages, minor corrections to
author list and references in v
Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory
We present the results of searches for dipolar-type anisotropies in different
energy ranges above eV with the surface detector array of
the Pierre Auger Observatory, reporting on both the phase and the amplitude
measurements of the first harmonic modulation in the right-ascension
distribution. Upper limits on the amplitudes are obtained, which provide the
most stringent bounds at present, being below 2% at 99% for EeV
energies. We also compare our results to those of previous experiments as well
as with some theoretical expectations.Comment: 28 pages, 11 figure
Clinical phenotypes of acute heart failure based on signs and symptoms of perfusion and congestion at emergency department presentation and their relationship with patient management and outcomes
Objective
To compare the clinical characteristics and outcomes of patients with acute heart failure (AHF) according to clinical profiles based on congestion and perfusion determined in the emergency department (ED).
Methods and results
Overall, 11 261 unselected AHF patients from 41 Spanish EDs were classified according to perfusion (normoperfusion = warm; hypoperfusion = cold) and congestion (not = dry; yes = wet). Baseline and decompensation characteristics were recorded as were the main wards to which patients were admitted. The primary outcome was 1-year all-cause mortality; secondary outcomes were need for hospitalisation during the index AHF event, in-hospital all-cause mortality, prolonged hospitalisation, 7-day post-discharge ED revisit for AHF and 30-day post-discharge rehospitalisation for AHF. A total of 8558 patients (76.0%) were warm+ wet, 1929 (17.1%) cold+ wet, 675 (6.0%) warm+ dry, and 99 (0.9%) cold+ dry; hypoperfused (cold) patients were more frequently admitted to intensive care units and geriatrics departments, and warm+ wet patients were discharged home without admission. The four phenotypes differed in most of the baseline and decompensation characteristics. The 1-year mortality was 30.8%, and compared to warm+ dry, the adjusted hazard ratios were significantly increased for cold+ wet (1.660; 95% confidence interval 1.400-1.968) and cold+ dry (1.672; 95% confidence interval 1.189-2.351). Hypoperfused (cold) phenotypes also showed higher rates of index episode hospitalisation and in-hospital mortality, while congestive (wet) phenotypes had a higher risk of prolonged hospitalisation but decreased risk of rehospitalisation. No differences were observed among phenotypes in ED revisit risk.
Conclusions
Bedside clinical evaluation of congestion and perfusion of AHF patients upon ED arrival and classification according to phenotypic profiles proposed by the latest European Society of Cardiology guidelines provide useful complementary information and help to rapidly predict patient outcomes shortly after ED patient arrival
- …