Genomic analysis of circulating tumor DNA (ctDNA) is increasingly incorporated into the clinical management of patients with advanced cancer. Beyond tumor profiling, ctDNA analysis also can enable ...calculation of circulating tumor fraction (TF), which has previously been found to be prognostic. While most prognostic models in metastatic cancer are tumor type specific and require significant patient-level data, quantification of TF in ctDNA has the potential to serve as a pragmatic, tumor-agnostic prognostic tool.
This study utilized a cohort of patients in a nationwide de-identified clinico-genomic database with metastatic castration-resistant prostate cancer (mCRPC), metastatic breast cancer (mBC), advanced non-small-cell lung cancer (aNSCLC), or metastatic colorectal cancer (mCRC) undergoing liquid biopsy testing as part of routine care. TF was calculated based on single-nucleotide polymorphism aneuploidy across the genome. Clinical, disease, laboratory, and treatment data were captured from the electronic health record. Overall survival (OS) was evaluated by TF level while controlling for relevant covariables.
A total of 1725 patients were included: 198 mCRPC, 402 mBC, 902 aNSCLC, and 223 mCRC. TF ≥10% was highly correlated with OS in univariable analyses for all cancer types: mCRPC hazard ratio (HR) 3.3, 95% confidence interval (CI) 2.04-5.34, P < 0.001, mBC (HR 2.4, 95% CI 1.71-3.37, P < 0.001), aNSCLC (HR 1.68, 95% CI 1.34-2.1, P < 0.001), and mCRC (HR 2.11, 95% CI 1.39-3.2, P < 0.001). Multivariable assessments of TF had similar point estimates and CIs, suggesting a consistent and independent association with survival. Exploratory analysis showed that TF remained consistently prognostic across a wide range of cutpoints.
Plasma ctDNA TF is a pragmatic, independent prognostic biomarker across four advanced cancers with potential to guide clinical conversations around expected treatment outcomes. With further prospective validation, ctDNA TF could be incorporated into care paradigms to enable precision escalation and de-escalation of cancer therapy based on patient-level tumor biology.
•Circulating TF is an independent prognostic factor for most common advanced cancer types in real-world settings.•Prospective interventional validation might enable rational escalation or de-escalation strategies.
Responses of microphytobenthos to light Perkins, R. G.; Underwood, G. J. C.; Brotas, V. ...
Marine ecology. Progress series (Halstenbek),
01/2001, Letnik:
223
Journal Article
Recenzirano
Odprti dostop
The effect of high (ambient) and low (shaded to 50% of ambient) light on microphytobenthic biofilm primary production, vertical migration and allocation of photoassimilated carbon into extracellular ...carbohydrates was investigated over the low tide emersion period at Sarilhos Pequenos on the Tagus estuary, Portugal, in July 2000. Carbon uptake (14C measurements), electron transport (pulse-amplitude modulated PAM-fluorescence) and carbon allocation into extracellular carbohydrate fractions were measured. There was a decrease in the maximum rate of primary production (P
max) (14C) over the emersion period (16 decreasing to 5 mg C m–2h–1at midday and the end of emersion, respectively) that was independent of the incident light and the light history to which the biofilms had been exposed. Primary production (14C) did not correlate with measurements ofin siturelative electron transport rate (rel.ETR), due in part to the light-induced migration of the cells away from the sediment surface during periods of high irradiance (photosynthetic photon flux density PPFD > 1200 mol m–2s–1). Downward migration coincided with the light level at whichP
max(14C) was reached, 750 mol m–2s–1, and with a point of inflexion on the rel.ETR versus PPFD curve. Above this light level rel.ETR was over-estimated due to migration of the cells into a lower light field in the sediment. Shading significantly increased the extracellular polymeric substance (EPS) production rate (from 0.4 to 1.0 mg C m–2h–1in ambient and shaded light, respectively) and percentage allocation of photoassimilates into EPS (from 4 ± 1.0 to 18 ± 3.5% of total production in ambient and shaded light, respectively). In contrast, percentage allocation of photoassimilates to low molecular weight extracellular carbohydrate was higher in the non-shaded treatments (35 ± 4.5% compared with 13 ± 3.8% in ambient and shaded treatments, respectively), probably due to photosynthetic ‘overflow’. In non-shaded biofilms there was little or no increase in the concentration of all extracellular carbohydrate fractions until the last hour before tidal immersion. Results indicate that diel patterns in microphytobenthic primary production are not predictable solely from light data.
This study investigated the potential spread of CTX-M-14 Escherichia coli from a known ESBL E. coli positive farm and risk factors for the presence of CTX-M E. coli on dairy farms. Between November ...2009 and March 2010, 65 farms in North West England and North Wales were visited and animals sampled for E. coli producing CTX-M ESBLs. Seventeen of these were known to have received animals from a known ESBL E. coli positive ‘index’ farm since 2005 (linked farms). The prevalence of CTX-M E. coli in the population of linked farms was 58.8% (10/17; CI95% 32.9–81.6%) and in the randomly selected control population was 35.4% (17/48; CI95% 22.2–50.5%). There was no significant (p>0.05) linkage for the detection of any CTX-M E. coli or specifically a CTX-M-14 E. coli to the index farm. Group 1 (CTX-M-15, CTX-M-55, CTX-M-1, CTX-M-32), group 2 (CTX-M-2) and group 9 (CTX-M-14, CTX-M-14B, CTX-M-27) CTX-M E. coli were identified on the study farms. Molecular analysis revealed that three plasmids from linked farms had similar sizes (95kbp), replicon type (IncK) and backbone genes as that from the index farm. Logistic regression analysis revealed that farms that had used a 3rd or 4th generation cephalosporin (ceftiofur, cefoperazone and cefquinome) in livestock in the last 12months were nearly 4times more likely to have ESBL E. coli present (p=0.037; OR=3.93). There was no significant association between presence of CTX-M E. coli and the use of any 1st or 2nd generation cephalosporins. Several other risk factors for the presence of CTX-M E. coli were identified, such as storage of slurry in a pit, operating an open herd policy and infrequent cleaning of calf feeding equipment.
The Far Ultraviolet Spectroscopic Explorer satellite observes light in the far-ultraviolet spectral region, 905-1187 Å, with a high spectral resolution. The instrument consists of four co-aligned ...prime-focus telescopes and Rowland spectrographs with microchannel plate detectors. Two of the telescope channels use Al:LiF coatings for optimum reflectivity between approximately 1000 and 1187 Å, and the other two channels use SiC coatings for optimized throughput between 905 and 1105 Å. The gratings are holographically ruled to correct largely for astigmatism and to minimize scattered light. The microchannel plate detectors have KBr photocathodes and use photon counting to achieve good quantum efficiency with low background signal. The sensitivity is sufficient to examine reddened lines of sight within the Milky Way and also sufficient to use as active galactic nuclei and QSOs for absorption-line studies of both Milky Way and extragalactic gas clouds. This spectral region contains a number of key scientific diagnostics, including O VI, H I, D I, and the strong electronic transitions of H2 and HD.
Here we report the chemical induction of the twist-bend nematic phase in a nematic mixture of ether-linked liquid crystal dimers by the addition of a dimer with methylene links; all dimers have an ...odd number of groups in the spacer connecting the two mesogenic groups. The twist-bend phase has been identified from its optical texture and x-ray scattering pattern as well as NMR spectroscopy, which demonstrates the phase chirality. Theory predicts that the key macroscopic property required for the stability of this chiral phase formed from achiral molecules is for the bend elastic constant to tend to be negative; in addition the twist elastic constant should be smaller than half the splay elastic constant. To test these important aspects of the prediction we have measured the bend and splay elastic constants in the nematic phase preceding the twist-bend nematic using the classic Frederiks methodology and all three elastic constants employing the dynamic light scattering approach. Our results show that, unlike the splay, the bend elastic constant is small and decreases significantly as the transition to the induced twist-bend nematic phase is approached, but then exhibits unexpected behavior prior to the phase transition.
Abstract
A new analysis of the data set from the Pierre Auger Observatory provides evidence for anisotropy in the arrival directions of ultra-high-energy cosmic rays on an intermediate angular scale, ...which is indicative of excess arrivals from strong, nearby sources. The data consist of 5514 events above
with zenith angles up to 80° recorded before 2017 April 30. Sky models have been created for two distinct populations of extragalactic gamma-ray emitters: active galactic nuclei from the second catalog of hard
Fermi
-LAT sources (2FHL) and starburst galaxies from a sample that was examined with
Fermi
-LAT. Flux-limited samples, which include all types of galaxies from the
Swift
-BAT and 2MASS surveys, have been investigated for comparison. The sky model of cosmic-ray density constructed using each catalog has two free parameters, the fraction of events correlating with astrophysical objects, and an angular scale characterizing the clustering of cosmic rays around extragalactic sources. A maximum-likelihood ratio test is used to evaluate the best values of these parameters and to quantify the strength of each model by contrast with isotropy. It is found that the starburst model fits the data better than the hypothesis of isotropy with a statistical significance of 4.0
σ
, the highest value of the test statistic being for energies above
. The three alternative models are favored against isotropy with 2.7
σ
–3.2
σ
significance. The origin of the indicated deviation from isotropy is examined and prospects for more sensitive future studies are discussed.
Abstract
A workshop on The Next Generation Gamma-Ray Source sponsored by the Office of Nuclear Physics at the Department of Energy, was held November 17-19, 2016 in Bethesda, Maryland. The goals of ...the workshop were to identify basic and applied research opportunities at the frontiers of nuclear physics that would be made possible by the beam capabilities of an advanced laser Compton beam facility. To anchor the scientific vision to realistically achievable beam specifications using proven technologies, the workshop brought together experts in the fields of electron accelerators, lasers, and optics to examine the technical options for achieving the beam specifications required by the most compelling parts of the proposed research programs. An international assembly of participants included current and prospective
γ
-ray beam users, accelerator and light-source physicists, and federal agency program managers. Sessions were organized to foster interactions between the beam users and facility developers, allowing for information sharing and mutual feedback between the two groups. The workshop findings and recommendations are summarized in this whitepaper.
The D0 Run IIb luminosity measurement Casey, B.C.K.; Corcoran, M.; DeVaughan, K. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
01/2013, Letnik:
698
Journal Article
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An assessment of the recorded integrated luminosity is presented for data collected with the D0 detector at the Fermilab Tevatron Collider from June 2006 to September 2011 (Run IIb). In addition, a ...measurement of the effective cross-section for inelastic interactions, also referred to as the luminosity constant, is reported. This measurement incorporates new features that lead to a substantial improvement in the precision of the result. A luminosity constant of σLM=48.3±1.9±0.6mb is obtained, where the first uncertainty is due to the accuracy of the inelastic cross-section used by both CDF and D0, and the second uncertainty is due to D0 sources. The recorded luminosity for the highest ET jet trigger is Lrec=9.2±0.4fb−1, with a relative uncertainty of 4.3%.
ABSTRACT We analyze the distribution of arrival directions of ultra-high-energy cosmic rays recorded at the Pierre Auger Observatory in 10 years of operation. The data set, about three times larger ...than that used in earlier studies, includes arrival directions with zenith angles up to 80°, thus covering from to in declination. After updating the fraction of events correlating with the active galactic nuclei (AGNs) in the Véron-Cetty and Véron catalog, we subject the arrival directions of the data with energies in excess of 40 EeV to different tests for anisotropy. We search for localized excess fluxes, self-clustering of event directions at angular scales up to 30°, and different threshold energies between 40 and 80 EeV. We then look for correlations of cosmic rays with celestial structures both in the Galaxy (the Galactic Center and Galactic Plane) and in the local universe (the Super-Galactic Plane). We also examine their correlation with different populations of nearby extragalactic objects: galaxies in the 2MRS catalog, AGNs detected by Swift-BAT, radio galaxies with jets, and the Centaurus A (Cen A) galaxy. None of the tests show statistically significant evidence of anisotropy. The strongest departures from isotropy (post-trial probability %) are obtained for cosmic rays with EeV in rather large windows around Swift AGNs closer than 130 Mpc and brighter than 1044 erg s−1 (18° radius), and around the direction of Cen A (15° radius).
We present a detailed study of the large-scale anisotropies of cosmic rays with energies above 4 EeV measured using the Pierre Auger Observatory. For the energy bins 4, 8 EeV and E ≥ 8 EeV, the most ...significant signal is a dipolar modulation in R.A. at energies above 8 EeV, as previously reported. In this paper we further scrutinize the highest-energy bin by splitting it into three energy ranges. We find that the amplitude of the dipole increases with energy above 4 EeV. The growth can be fitted with a power law with index β = 0.79 0.19. The directions of the dipoles are consistent with an extragalactic origin of these anisotropies at all the energies considered. Additionally, we have estimated the quadrupolar components of the anisotropy: they are not statistically significant. We discuss the results in the context of the predictions from different models for the distribution of ultrahigh-energy sources and cosmic magnetic fields.
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