1,160 research outputs found
Convex optimization problem prototyping for image reconstruction in computed tomography with the Chambolle-Pock algorithm
The primal-dual optimization algorithm developed in Chambolle and Pock (CP),
2011 is applied to various convex optimization problems of interest in computed
tomography (CT) image reconstruction. This algorithm allows for rapid
prototyping of optimization problems for the purpose of designing iterative
image reconstruction algorithms for CT. The primal-dual algorithm is briefly
summarized in the article, and its potential for prototyping is demonstrated by
explicitly deriving CP algorithm instances for many optimization problems
relevant to CT. An example application modeling breast CT with low-intensity
X-ray illumination is presented.Comment: Resubmitted to Physics in Medicine and Biology. Text has been
modified according to referee comments, and typos in the equations have been
correcte
Factors associated with ethnical disparity in overall survival for patients with hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is an important cause of cancer-related death worldwide. Ethnical disparity in overall survival has been demonstrated for HCC patients in the United States (U.S.). We aimed to evaluate the contributors to this survival disparity. The SEER database was used to identify HCC patients from 2004 to 2012. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate overall survival by ethnicity and the contributors to ethnical survival disparity. A total of 33 062 patients were included: 15 986 Non-Hispanic Whites, 6535 Hispanic Whites, 4842 African Americans, and 5699 Asians. Compared to Non-Hispanic Whites, African Americans had worse survival (HR, 1.18; 95%CI, 1.14-1.23), while Asians had a better survival (HR, 0.85; 95%CI, 0.82-0.89), and Hispanic Whites had a similar survival (HR, 1.01; 95%CI, 0.97-1.05). Multivariate Cox analysis identified that tumor presentation- and treatment-related factors significantly contributed to the ethnical survival disparity. Especially, tumor size was the most important contributor (HR, 1.11; 95%CI, 1.07-1.16). There is no ethnical survival disparity in patients undergoing liver transplantation and sub-analysis of patients within the Milan criteria for liver transplantation demonstrated no significant survival disparity between African Americans and non-Hispanic Whites in transplantation adjustment analysis (HR, 1.23; 95%CI, 1.11-1.35 in non-adjustment analysis to HR, 1.05; 95%CI, 0.95-1.15 after adjustment). Finally, no important contributor to the superior overall survival in Asians was identified. In conclusion, poor tumor presentation at diagnosis, limited benefit from resection and restricted utilization of liver transplantation are important contributors to poorer survival of African Americans with HCC
Protein Kinase Cδ Suppresses Autophagy to Induce Kidney Cell Apoptosis in Cisplatin Nephrotoxicity
Nephrotoxicity is a major adverse effect in cisplatin chemotherapy, and renoprotective approaches are unavailable. Recent work unveiled a critical role of protein kinase Cδ (PKCδ) in cisplatin nephrotoxicity and further demonstrated that inhibition of PKCδ not only protects kidneys but enhances the chemotherapeutic effect of cisplatin in tumors; however, the underlying mechanisms remain elusive. Here, we show that cisplatin induced rapid activation of autophagy in cultured kidney tubular cells and in the kidneys of injected mice. Cisplatin also induced the phosphorylation of mammalian target of rapamycin (mTOR), p70S6 kinase downstream of mTOR, and serine/threonine-protein kinase ULK1, a component of the autophagy initiating complex. In vitro, pharmacologic inhibition of mTOR, directly or through inhibition of AKT, enhanced autophagy after cisplatin treatment. Notably, in both cells and kidneys, blockade of PKCδ suppressed the cisplatin-induced phosphorylation of AKT, mTOR, p70S6 kinase, and ULK1 resulting in upregulation of autophagy. Furthermore, constitutively active and inactive forms of PKCδ respectively enhanced and suppressed cisplatin-induced apoptosis in cultured cells. In mechanistic studies, we showed coimmunoprecipitation of PKCδ and AKT from lysates of cisplatin-treated cells and direct phosphorylation of AKT at serine-473 by PKCδin vitro Finally, administration of the PKCδ inhibitor rottlerin with cisplatin protected against cisplatin nephrotoxicity in wild-type mice, but not in renal autophagy-deficient mice. Together, these results reveal a pathway consisting of PKCδ, AKT, mTOR, and ULK1 that inhibits autophagy in cisplatin nephrotoxicity. PKCδ mediates cisplatin nephrotoxicity at least in part by suppressing autophagy, and accordingly, PKCδ inhibition protects kidneys by upregulating autophagy
The global epidemiology of hepatitis E virus infection: A systematic review and meta-analysis
Background and aims: Hepatitis E virus (HEV), as an emerging zoonotic pathogen, is a leading cause of acute viral hepatitis worldwide, with a high risk of developing chronic infection in immunocompromised patients. However, the global epidemiology of HEV infection has not been comprehensively assessed. This study aims to map the global prevalence and identify the risk factors of HEV infection by performing a systematic review and meta-analysis. Methods: A systematic searching of articles published in Medline, Embase, Web of science, Cochrane and Google scholar databases till July 2019 was conducted to identify studies with HEV prevalence data. Pooled prevalence among different countries and continents was estimated. HEV IgG seroprevalence of subgroups was compared and risk factors for HEV infection were evaluated using odd ratios (OR). Results: We identified 419 related studies which comprised of 1 519 872 individuals. A total of 1 099 717 participants pooled from 287 studies of general population estimated a global anti-HEV IgG seroprevalence of 12.47% (95% CI 10.42-14.67; I2 = 100%). Notably, the use of ELISA kits from different manufacturers has a substantial impact on the global estimation of anti-HEV IgG seroprevalence. The pooled estimate of anti-HEV IgM seroprevalence based on 98 studies is 1.47% (95% CI 1.14-1.85; I2 = 99%). The overall estimate of HEV viral RNA-positive rate in general population is 0.20% (95% CI 0.15-0.25; I2 = 98%). Consumption of raw meat (P =.0001), exposure to soil (P <.0001), blood transfusion (P =.0138), travelling to endemic areas (P =.0244), contacting with dogs (P =.0416), living in rural areas (P =.0349) and receiving education less than elementary school (P <.0001) were identified as risk factors for anti-HEV IgG positivity. Conclusions: Globally, approximately 939 million corresponding to 1 in 8 individuals have ever experienced HEV infection. 15-110 million individuals have recent or ongoing HEV infection. Our study highlights the substantial burden of HEV infection and calls for increasing routine screening and preventive measures
The evolution of superluminous supernova LSQ14mo and its interacting host galaxy system
We present and analyse an extensive dataset of the superluminous supernova (SLSN) LSQ14mo (z = 0.256), consisting of a multi-colour light curve from-30 d to +70 d in the rest-frame (relative to maximum light) and a series of six spectra from PESSTO covering-7 d to +50 d. This is among the densest spectroscopic coverage, and best-constrained rising light curve, for a fast-declining hydrogen-poor SLSN. The bolometric light curve can be reproduced with a millisecond magnetar model with 4 M⊙ ejecta mass, and the temperature and velocity evolution is also suggestive of a magnetar as the power source. Spectral modelling indicates that the SN ejected 6 M⊙ of CO-rich material with a kinetic energy of 7 × 1051 erg, and suggests a partially thermalised additional source of luminosity between-2 d and +22 d. This may be due to interaction with a shell of material originating from pre-explosion mass loss. We further present a detailed analysis of the host galaxy system of LSQ14mo. PESSTO and GROND imaging show three spatially resolved bright regions, and we used the VLT and FORS2 to obtain a deep (five-hour exposure) spectra of the SN position and the three star-forming regions, which are at a similar redshift. The FORS2 spectrum at + 300 days shows no trace of SN emission lines and we place limits on the strength of [O i] from comparisons with other Ic supernovae. The deep spectra provides a unique chance to investigate spatial variations in the host star-formation activity and metallicity. The specific star-formation rate is similar in all three components,as is the presence of a young stellar population. However, the position of LSQ14mo exhibits a lower metallicity, with 12 + log (O/H) = 8.2 in both the R23 and N2 scales (corresponding to 0.3 Z⊙). We propose that the three bright regions in the host system are interacting, which could induce gas flows triggering star formation in low-metallicity regions. © ESO, 2017
PD-L1, Galectin-9 and CD8+ tumor-infiltrating lymphocytes are associated with survival in hepatocellular carcinoma
Novel systemic treatments for hepatocellular carcinoma (HCC) are strongly needed. Immunotherapy is a promising strategy that can induce specific antitumor immune responses. Understanding the mechanisms of immune resistance by HCC is crucial for development of suitable immunotherapeutics. We used immunohistochemistry on tissue-microarrays to examine the co-expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM and IDO, as well as tumor CD8+ lymphocyte infiltration in HCC, in two independent cohorts of patients. We found that at least some expression in tumor cells was seen in 97% of cases for HVEM, 83% for PD-L1, 79% for Gal-9 and 66% for IDO. In the discovery cohort (n = 94), we found that lack of, or low, tumor expression of PD-L1 (p < 0.001), Galectin-9 (p < 0.001) and HVEM (p < 0.001), and low CD8+TIL count (p = 0.016), were associated with poor HCC-specific survival. PD-L1, Galectin-9 and CD8+TIL count were predictive of HCC-specific survival independent of baseline clinicopathologic characteristics and the combination of these markers was a powerful predictor of HCC-specific survival (HR 0.29; p <0.001). These results were confirmed in the validation cohort (n = 60). We show that low expression levels of PD-L1 and Gal-9 in combination with low CD8+TIL count predict extremely poor HCC-specific survival and it requires a change in two of these parameters to significantly improve prognosis. In conclusion, intra-tumoral expression of these immune inhibiting molecules was observed in the majority of HCC patients. Low expression of PD-L1 and Galectin-9 and low CD8+TIL count are associated with poor HCC-specific survival. Combining immune biomarkers leads to superior predictors of HCC mortality
Gravitational Waves From Known Pulsars: Results From The Initial Detector Era
We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom
Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects
In gravitational-wave detection, special emphasis is put onto searches that
focus on cosmic events detected by other types of astrophysical observatories.
The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical
telescopes and neutrino observatories, provide a trigger time for analyzing
gravitational wave data coincident with the event. In certain cases the
expected frequency range, source energetics, directional and progenitor
information is also available. Beyond allowing the recognition of gravitational
waveforms with amplitudes closer to the noise floor of the detector, these
triggered searches should also lead to rich science results even before the
onset of Advanced LIGO. In this paper we provide a broad review of LIGO's
astrophysically triggered searches and the sources they target
First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data
Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of
continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a
fully coherent search, based on matched filtering, which uses the position and rotational parameters
obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto-
noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch
between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have
been developed, allowing a fully coherent search for gravitational waves from known pulsars over a
fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of
11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial
outliers, further studies show no significant evidence for the presence of a gravitational wave signal.
Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of
the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for
the first time. For an additional 3 targets, the median upper limit across the search bands is below the
spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried
out so far
Swift follow-up observations of candidate gravitational-wave transient events
We present the first multi-wavelength follow-up observations of two candidate
gravitational-wave (GW) transient events recorded by LIGO and Virgo in their
2009-2010 science run. The events were selected with low latency by the network
of GW detectors and their candidate sky locations were observed by the Swift
observatory. Image transient detection was used to analyze the collected
electromagnetic data, which were found to be consistent with background.
Off-line analysis of the GW data alone has also established that the selected
GW events show no evidence of an astrophysical origin; one of them is
consistent with background and the other one was a test, part of a "blind
injection challenge". With this work we demonstrate the feasibility of rapid
follow-ups of GW transients and establish the sensitivity improvement joint
electromagnetic and GW observations could bring. This is a first step toward an
electromagnetic follow-up program in the regime of routine detections with the
advanced GW instruments expected within this decade. In that regime
multi-wavelength observations will play a significant role in completing the
astrophysical identification of GW sources. We present the methods and results
from this first combined analysis and discuss its implications in terms of
sensitivity for the present and future instruments.Comment: Submitted for publication 2012 May 25, accepted 2012 October 25,
published 2012 November 21, in ApJS, 203, 28 (
http://stacks.iop.org/0067-0049/203/28 ); 14 pages, 3 figures, 6 tables;
LIGO-P1100038; Science summary at
http://www.ligo.org/science/Publication-S6LVSwift/index.php ; Public access
area to figures, tables at
https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p110003
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