386 research outputs found
Cerebellar Purkinje cells incorporate immunoglobulins and immunotoxins in vitro: implications for human neurological disease and immunotherapeutics
Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis
Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the first group are directed against neuronal cell surface membrane proteins and are exemplified by antibodies directed against the N-methyl-D-aspartate receptor (anti-NMDAR), found in patients with autoimmune encephalitis, and antibodies directed against the leucine-rich glioma-inactivated 1 protein (anti-LGI1), associated with faciobrachial dystonic seizures and limbic encephalitis. Antibodies in this group produce non-lethal neuronal dysfunction, and their associated conditions often respond to treatment. Antibodies in the second group, as exemplified by anti-Yo antibody, found in patients with rapidly progressive cerebellar syndrome, and anti-Hu antibody, associated with encephalomyelitis, react with intracellular neuronal antigens. These antibodies are characteristically found in patients with underlying malignancy, and neurological impairment is the result of neuronal death. Within the last few years, major advances have been made in understanding the pathogenesis of neurological disorders associated with antibodies against neuronal cell surface antigens. In contrast, the events that lead to neuronal death in conditions associated with antibodies directed against intracellular antigens, such as anti-Yo and anti-Hu, remain poorly understood, and the respective roles of antibodies and T lymphocytes in causing neuronal injury have not been defined in an animal model. In this review, we discuss current knowledge of these two groups of antibodies in terms of their discovery, how they arise, the interaction of both types of antibodies with their molecular targets, and the attempts that have been made to reproduce human neuronal injury in tissue culture models and experimental animals. We then discuss the emerging area of autoimmune neuronal injury associated with immune checkpoint inhibitors and the implications of current research for the treatment of affected patients.publishedVersio
AGRICOH: A Consortium of Agricultural Cohorts
AGRICOH is a recently formed consortium of agricultural cohort studies involving 22 cohorts from nine countries in five continents: South Africa (1), Canada (3), Costa Rica (2), USA (6), Republic of Korea (1), New Zealand (2), Denmark (1), France (3) and Norway (3). The aim of AGRICOH, initiated by the US National Cancer Institute (NCI) and coordinated by the International Agency for Research on Cancer (IARC), is to promote and sustain collaboration and pooling of data to investigate the association between a wide range of agricultural exposures and a wide range of health outcomes, with a particular focus on associations that cannot easily be addressed in individual studies because of rare exposures (e.g., use of infrequently applied chemicals) or relatively rare outcomes (e.g., certain types of cancer, neurologic and auto-immune diseases). To facilitate future projects the need for data harmonization of selected variables is required and is underway. Altogether, AGRICOH provides excellent opportunities for studying cancer, respiratory, neurologic, and auto-immune diseases as well as reproductive and allergic disorders, injuries and overall mortality in association with a wide array of exposures, prominent among these the application of pesticides
Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators
BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention.
METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]).
CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks
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
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
Determination of muon momentum in the MicroBooNE LArTPC using an improved model of multiple Coulomb scattering
We discuss a technique for measuring a charged particle's momentum by means
of multiple Coulomb scattering (MCS) in the MicroBooNE liquid argon time
projection chamber (LArTPC). This method does not require the full particle
ionization track to be contained inside of the detector volume as other track
momentum reconstruction methods do (range-based momentum reconstruction and
calorimetric momentum reconstruction). We motivate use of this technique,
describe a tuning of the underlying phenomenological formula, quantify its
performance on fully contained beam-neutrino-induced muon tracks both in
simulation and in data, and quantify its performance on exiting muon tracks in
simulation. Using simulation, we have shown that the standard Highland formula
should be re-tuned specifically for scattering in liquid argon, which
significantly improves the bias and resolution of the momentum measurement.
With the tuned formula, we find agreement between data and simulation for
contained tracks, with a small bias in the momentum reconstruction and with
resolutions that vary as a function of track length, improving from about 10%
for the shortest (one meter long) tracks to 5% for longer (several meter)
tracks. For simulated exiting muons with at least one meter of track contained,
we find a similarly small bias, and a resolution which is less than 15% for
muons with momentum below 2 GeV/c. Above 2 GeV/c, results are given as a first
estimate of the MCS momentum measurement capabilities of MicroBooNE for high
momentum exiting tracks
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
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
Measurement of cosmic-ray reconstruction efficiencies in the MicroBooNE LArTPC using a small external cosmic-ray counter
The MicroBooNE detector is a liquid argon time projection chamber at Fermilab
designed to study short-baseline neutrino oscillations and neutrino-argon
interaction cross-section. Due to its location near the surface, a good
understanding of cosmic muons as a source of backgrounds is of fundamental
importance for the experiment. We present a method of using an external 0.5 m
(L) x 0.5 m (W) muon counter stack, installed above the main detector, to
determine the cosmic-ray reconstruction efficiency in MicroBooNE. Data are
acquired with this external muon counter stack placed in three different
positions, corresponding to cosmic rays intersecting different parts of the
detector. The data reconstruction efficiency of tracks in the detector is found
to be , in good agreement with the Monte Carlo reconstruction
efficiency . This analysis represents
a small-scale demonstration of the method that can be used with future data
coming from a recently installed cosmic-ray tagger system, which will be able
to tag of the cosmic rays passing through the MicroBooNE
detector.Comment: 19 pages, 12 figure
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