942 research outputs found
Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer:a systematic review and meta-analysis
BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause serious immune-related adverse events (irAEs). This study aimed to identify risk factors for all types of irAEs induced by ICIs in patients with non-small-cell lung cancer (NSCLC), by systematic review and meta-analyses. METHODS: A systematic search was performed in Pubmed, Embase and Web of Science by two independent reviewers. Studies were selected that included patients with NSCLC and evaluated characteristics of patients with and without irAEs induced by ICIs. Quality and risk of bias of the selected studies were assessed. Random effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for risk factors of developing all type of irAEs, and separately for pneumonitis, interstitial lung disease and severe irAEs. With the objective of exploring sources of heterogeneity, stratified analyses were performed by quality and region. RESULTS: 25 studies met the inclusion criteria. In total, the data of 6696 patients were pooled. 33 different risk factors for irAEs were reported. irAEs of interest were reported for 1653 (25%) of the patients. Risk factors related to the development of irAEs were: C-reactive protein, neutrophil lymphocyte ratio (NLR), use of PD-1 inhibitor, high PD-L1 expression, an active or former smoking status, ground glass attenuation, and a better treatment response. CONCLUSION: The identified risk factors for the development of these irAEs are mostly related to the alteration of the immune system, proinflammatory states and loss of immunological self-tolerance. Patients identified as having a higher risk for irAEs should be monitored more closely
Non SUSY Unification in Left-Right Models
We explore in a model independent way the possibility of achieving the non
supersymmetric gauge coupling unification within left-right symmetric models,
with the minimal particle content at the left-right mass scale which could be
as low as 1 TeV in a variety of models, and with a unification scale M in the
range GeV GeV.Comment: 18 pages, Latex file, uses epsf style, four figures. Submitted for
publication to Phys. Rev. D on Oct. 13, 199
Quantitative analysis of chromatin interaction changes upon a 4.3 Mb deletion at mouse 4E2
BACKGROUND: Circular chromosome conformation capture (4C) has provided important insights into three dimensional (3D) genome organization and its critical impact on the regulation of gene expression. We developed a new quantitative framework based on polymer physics for the analysis of paired-end sequencing 4C (PE-4Cseq) data. We applied this strategy to the study of chromatin interaction changes upon a 4.3 Mb DNA deletion in mouse region 4E2. RESULTS: A significant number of differentially interacting regions (DIRs) and chromatin compaction changes were detected in the deletion chromosome compared to a wild-type (WT) control. Selected DIRs were validated by 3D DNA FISH experiments, demonstrating the robustness of our pipeline. Interestingly, significant overlaps of DIRs with CTCF/Smc1 binding sites and differentially expressed genes were observed. CONCLUSIONS: Altogether, our PE-4Cseq analysis pipeline provides a comprehensive characterization of DNA deletion effects on chromatin structure and function
The Sensitivity of HAWC to High-Mass Dark Matter Annihilations
The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view
detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in
central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC
will observe gamma rays and cosmic rays with an array of water Cherenkov
detectors. The full HAWC array is scheduled to be operational in Spring 2015.
In this paper, we study the HAWC sensitivity to the gamma-ray signatures of
high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be
sensitive to diverse searches for dark matter annihilation, including
annihilation from extended dark matter sources, the diffuse gamma-ray emission
from dark matter annihilation, and gamma-ray emission from non-luminous dark
matter subhalos. Here we consider the HAWC sensitivity to a subset of these
sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the
Galactic center. We simulate the HAWC response to gamma rays from these sources
in several well-motivated dark matter annihilation channels. If no gamma-ray
excess is observed, we show the limits HAWC can place on the dark matter
cross-section from these sources. In particular, in the case of dark matter
annihilation into gauge bosons, HAWC will be able to detect a narrow range of
dark matter masses to cross-sections below thermal. HAWC should also be
sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The
constraints placed by HAWC on the dark matter cross-section from known sources
should be competitive with current limits in the mass range where HAWC has
similar sensitivity. HAWC can additionally explore higher dark matter masses
than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR
Search for very-high-energy emission from Gamma-ray Bursts using the first 18 months of data from the HAWC Gamma-ray Observatory
The High Altitude Water Cherenkov (HAWC) Gamma-ray Observatory is an
extensive air shower detector operating in central Mexico, which has recently
completed its first two years of full operations. If for a burst like GRB
130427A at a redshift of 0.34 and a high-energy component following a power law
with index -1.66, the high-energy component is extended to higher energies with
no cut-off other than from extragalactic background light attenuation, HAWC
would observe gamma rays with a peak energy of 300 GeV. This paper
reports the results of HAWC observations of 64 gamma-ray bursts (GRBs) detected
by and , including three GRBs that were also
detected by the Large Area Telescope (-LAT). An ON/OFF analysis
method is employed, searching on the time scale given by the observed light
curve at keV-MeV energies and also on extended time scales. For all GRBs and
time scales, no statistically significant excess of counts is found and upper
limits on the number of gamma rays and the gamma-ray flux are calculated. GRB
170206A, the third brightest short GRB detected by the Gamma-ray Burst Monitor
on board the satellite (-GBM) and also
detected by the LAT, occurred very close to zenith. The LAT measurements can
neither exclude the presence of a synchrotron self-Compton (SSC) component nor
constrain its spectrum. Instead, the HAWC upper limits constrain the expected
cut-off in an additional high-energy component to be less than
for reasonable assumptions about the energetics and redshift of the burst.Comment: 19 pages, 6 figures, published in Ap
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