72 research outputs found
Acute Opioid Withdrawal Mimicking Postoperative Joint Infection Following anterior cruciate ligament (ACL) Reconstruction: A Case Report.
BACKGROUND A short course of opioid narcotics is often prescribed for postoperative anterior cruciate ligament (ACL) reconstruction pain management. Unfortunately, there is a well-documented incidence of opioid withdrawal syndrome (OWS) following short-term use of these medications. OWS can present with symptoms such as influenza-like illness. It is important to differentiate OWS from infectious illnesses, especially after surgery. CASE REPORT We present a case of OWS in a patient who underwent ACL reconstruction 7 days prior. The patient\u27s OWS symptoms were similar to symptoms of a postoperative infection. The knee was aspirated, and the analysis of the aspirate was not concerning for an infection. The patient\u27s symptoms spontaneously resolved on postoperative day 10. This is the first documented case of OWS mimicking ACL reconstruction joint infection. CONCLUSIONS OWS after surgery may present with symptoms similar to joint infection. It is important to consider OWS as a potential complication after surgery and differentiate it from infection to avoid any further unnecessary invasive treatments for the patient
High specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG positive Ewing sarcoma
Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available
Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory
The Pierre Auger Collaboration has reported evidence for anisotropy in the
distribution of arrival directions of the cosmic rays with energies
eV. These show a correlation with the distribution
of nearby extragalactic objects, including an apparent excess around the
direction of Centaurus A. If the particles responsible for these excesses at
are heavy nuclei with charge , the proton component of the
sources should lead to excesses in the same regions at energies . We here
report the lack of anisotropies in these directions at energies above
(for illustrative values of ). If the anisotropies
above are due to nuclei with charge , and under reasonable
assumptions about the acceleration process, these observations imply stringent
constraints on the allowed proton fraction at the lower energies
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 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
A Universal System for Highly Efficient Cardiac Differentiation of Human Induced Pluripotent Stem Cells That Eliminates Interline Variability
The production of cardiomyocytes from human induced pluripotent stem cells (hiPSC) holds great promise for patient-specific cardiotoxicity drug testing, disease modeling, and cardiac regeneration. However, existing protocols for the differentiation of hiPSC to the cardiac lineage are inefficient and highly variable. We describe a highly efficient system for differentiation of human embryonic stem cells (hESC) and hiPSC to the cardiac lineage. This system eliminated the variability in cardiac differentiation capacity of a variety of human pluripotent stem cells (hPSC), including hiPSC generated from CD34(+) cord blood using non-viral, non-integrating methods.We systematically and rigorously optimized >45 experimental variables to develop a universal cardiac differentiation system that produced contracting human embryoid bodies (hEB) with an improved efficiency of 94.7±2.4% in an accelerated nine days from four hESC and seven hiPSC lines tested, including hiPSC derived from neonatal CD34(+) cord blood and adult fibroblasts using non-integrating episomal plasmids. This cost-effective differentiation method employed forced aggregation hEB formation in a chemically defined medium, along with staged exposure to physiological (5%) oxygen, and optimized concentrations of mesodermal morphogens BMP4 and FGF2, polyvinyl alcohol, serum, and insulin. The contracting hEB derived using these methods were composed of high percentages (64-89%) of cardiac troponin I(+) cells that displayed ultrastructural properties of functional cardiomyocytes and uniform electrophysiological profiles responsive to cardioactive drugs.This efficient and cost-effective universal system for cardiac differentiation of hiPSC allows a potentially unlimited production of functional cardiomyocytes suitable for application to hPSC-based drug development, cardiac disease modeling, and the future generation of clinically-safe nonviral human cardiac cells for regenerative medicine
Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis
Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometricâ=â1.28Eâ09 and 4.10Eâ18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.publishedVersio
Estimation of the burden of varicella in Europe before the introduction of universal childhood immunization
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