Plasma lipoxin A4 and resolvin D1 are not associated with reduced adenoma risk in a randomized trial of aspirin to prevent colon adenomas

Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4 (LXA4) and resolvin D1(RvD1)] with risk for recurrent adenoma. In this pilot study, we used data and biosamples from an adenoma chemoprevention study investigating the effects of aspirin and/or folic acid on the occurrence of colorectal adenomas. In the parent study, 1121 participants with a recent adenoma were randomized to study agents to be taken until the next surveillance colonoscopy about 3 years later. In this pilot study, LXA4 and RvD1 from samples taken near the end of study treatment were measured in a randomly selected sub-set of 200 participants. Commercially available ELISA kits to assay the analytes were validated using a metabololipidomic LC-MS/MS assay. Poisson regression with a robust error variance was used to calculate risk ratios and 95% confidence intervals. Plasma LXA4 and RvD1 were not associated with the risk of adenoma occurrence. LXA4 at the end of study follow-up was 32% (P = 0.01) proportionately higher in women compared to men. A similar non-significant trend toward higher levels among women was observed for RvD1. Our preliminary findings provided no evidence that plasma LXA4 or RvD1 are associated with reduced risk of colorectal adenoma occurrence, but suggest LXA4 may differ among men and women. Future studies focusing on SPM's local effects and levels in the colon are needed

The impact of the rising colorectal cancer incidence in young adults on the optimal age to start screening

BACKGROUND: In 2016, the Microsimulation Screening Analysis-Colon (MISCAN-Colon) model was used to inform the US Preventive Services Task Force colorectal cancer (CRC) screening guidelines. In this study, 1 of 2 microsimulation analyses to inform the update of the American Cancer Society CRC screening guideline, the authors re-evaluated the optimal screening strategies in light of the increase in CRC diagnosed in young adults. METHODS: The authors adjusted the MISCAN-Colon model to reflect the higher CRC incidence in young adults, who were assumed to carry forward escalated disease risk as they age. Life-years gained (LYG; benefit), the number of colonoscopies (COL; burden) and the ratios of incremental burden to benefit (efficiency ratio [ER] = ΔCOL/ΔLYG) were projected for different screening strategies. Strategies differed with respect to test modality, ages to start (40 years, 45 years, and 50 years) and ages to stop (75 years, 80 years, and 85 years) screening, and screening intervals (depending on screening modality). The authors then determined the model-recommended strategies in a similar way as was done for the US Preventive Services Task Force, using ER thresholds in accordance with the previously accepted ER of 39. RESULTS: Because of the higher CRC incidence, model-predicted LYG from screening increased compared with the previous analyses. Consequently, the balance of burden to benefit of screening improved and now 10-yearly colonoscopy screening starting at age 4

Proliferation, apoptosis and their regulatory protein expression in colorectal adenomas and serrated lesions

Background Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epithelial proliferation and apoptosis. Methods We conducted a protein expression analysis using tissue microarrays of 625 colorectal adenomas and 142 serrated lesions to determine potential differences in regulation of epithelial proliferation and apoptosis. We quantitated proliferation with Ki-67; apoptosis with activated caspase-3 (CASP3); up- and down-regulators of proliferation with cyclin D1, p16INK2, and p21Cip1; and apoptosis regulators with BAX, BCL2, and survivin. Linear mixed effects models and circos diagrams were used to determine relationships among expression and lesion characteristics. Results Adenomas had a significantly higher CASP-3 labeling index (LI) than serrated lesions, resulting in a lower net growth ratio (Ki-67 LI/activated CASP-3 LI, p-value<0.0001). Cyclin D1 LI, p16 LI and p21 LI were lower in adenomas compared to serrated lesions, while expression of both BCL2 and BAX were higher (p <0.001). Among adenomas, cyclin D1 LI and p16 LI levels increased with greater villous component, and the highest BAX expression was detected in adenomas larger than 2 cm (both p<0.0001). Right-sided adenomas had higher CASP3 LI than left colorectal adenomas (p = 0.008). Significant differences in cyclin D1 LI, p21 LI and survivin LI were also observed across histopathologic subtypes of serrated lesions. Conclusions Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis

Optimizing colorectal cancer screening by race and sex

BACKGROUND: Colorectal cancer (CRC) risk varies by race and sex. This study, 1 of 2 microsimulation analyses to inform the 2018 American Cancer Society CRC screening guideline, explored the influence of race and sex on optimal CRC screening strategies. METHODS: Two Cancer Intervention and Surveillance Modeling Network microsimulation models, informed by US incidence data, were used to evaluate a variety of screening methods, ages to start and stop, and intervals for 4 demographic subgroups (black and white males and females) under 2 scenarios for the projected lifetime CRC risk for 40-year-olds: 1) assuming that risk had remained stable since the early screening era and 2) assuming that risk had increased proportionally to observed incidence trends under the age of 40 years. Model-based screening recommendations were based on the predicted level of benefit (life-years gained) and burden (required number of colonoscopies), the incremental burden-to-benefit ratio, and the relative efficiency in comparison with strategies with similar burdens. RESULTS: When lifetime CRC risk was assumed to be stable over time, the models differed in the recommended age to start screening for whites (45 vs 50 years) but consistently recommended screening from the age of 45 years for blacks. When CRC risk was assumed to be increased, the models recommended starting at the age of 45 years, regardless of race and sex. Strategies recommended under both scenarios included colonoscopy every 10 or 15 years, annual fecal immunochemical testing, and computed tomographic colonography every 5 years through the age of 75 years. CONCLUSIONS: Microsimulation modeling suggests that CRC screening should be considered from the age of 45 years for blacks and for whites if the lifetime risk has increased proportionally to the incidence for younger adults

Study of Z → llγ decays at √s = 8 TeV with the ATLAS detector

This paper presents a study of Z → llγ decays with the ATLAS detector at the Large Hadron Collider. The analysis uses a proton–proton data sample corresponding to an integrated luminosity of 20.2 fb−1 collected at a centre-ofmass energy √s = 8 TeV. Integrated fiducial cross-sections together with normalised differential fiducial cross-sections, sensitive to the kinematics of final-state QED radiation, are obtained. The results are found to be in agreement with stateof-the-art predictions for final-state QED radiation. First measurements of Z → llγ γ decays are also reported

Search for third-generation vector-like leptons in pp collisions at s√ = 13 TeV with the ATLAS detector

A search for vector-like leptons in multilepton (two, three, or four-or-more electrons plus muons) final states with zero or more hadronic τ-lepton decays is presented. The search is performed using a dataset corresponding to an integrated luminosity of 139 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the LHC. To maximize the separation of signal and background, a machine-learning classifier is used. No excess of events is observed beyond the Standard Model expectation. Using a doublet vector-like lepton model, vector-like leptons coupling to third-generation Standard Model leptons are excluded in the mass range from 130 GeV to 900 GeV at the 95% confidence level, while the highest excluded mass is expected to be 970 GeV

Search for boosted diphoton resonances in the 10 to 70 GeV mass range using 138 fb−1 of 13 TeV pp collisions with the ATLAS detector

A search for diphoton resonances in the mass range between 10 and 70 GeV with the ATLAS experiment at the Large Hadron Collider (LHC) is presented. The analysis is based on pp collision data corresponding to an integrated luminosity of 138 fb−1 at a centre-of-mass energy of 13 TeV recorded from 2015 to 2018. Previous searches for diphoton resonances at the LHC have explored masses down to 65 GeV, finding no evidence of new particles. This search exploits the particular kinematics of events with pairs of closely spaced photons reconstructed in the detector, allowing examination of invariant masses down to 10 GeV. The presented strategy covers a region previously unexplored at hadron colliders because of the experimental challenges of recording low-energy photons and estimating the backgrounds. No significant excess is observed and the reported limits provide the strongest bound on promptly decaying axion-like particles coupling to gluons and photons for masses between 10 and 70 GeV

Evidence for the charge asymmetry in pp → tt¯ production at s√ = 13 TeV with the ATLAS detector

Inclusive and differential measurements of the top–antitop (tt¯) charge asymmetry Att¯C and the leptonic asymmetry Aℓℓ¯C are presented in proton–proton collisions at s√ = 13 TeV recorded by the ATLAS experiment at the CERN Large Hadron Collider. The measurement uses the complete Run 2 dataset, corresponding to an integrated luminosity of 139 fb−1, combines data in the single-lepton and dilepton channels, and employs reconstruction techniques adapted to both the resolved and boosted topologies. A Bayesian unfolding procedure is performed to correct for detector resolution and acceptance effects. The combined inclusive tt¯ charge asymmetry is measured to be Att¯C = 0.0068 ± 0.0015, which differs from zero by 4.7 standard deviations. Differential measurements are performed as a function of the invariant mass, transverse momentum and longitudinal boost of the tt¯ system. Both the inclusive and differential measurements are found to be compatible with the Standard Model predictions, at next-to-next-to-leading order in quantum chromodynamics perturbation theory with next-to-leading-order electroweak corrections. The measurements are interpreted in the framework of the Standard Model effective field theory, placing competitive bounds on several Wilson coefficients

Search for light long-lived neutral particles that decay to collimated pairs of leptons or light hadrons in pp collisions at s√ = 13 TeV with the ATLAS detector

A search for light long-lived neutral particles with masses in the O(MeV–GeV) range is presented. The analysis targets the production of long-lived dark photons in the decay of a Higgs boson produced via gluon–gluon fusion or in association with a W boson. Events that contain displaced collimated Standard Model fermions reconstructed in the calorimeter or muon spectrometer are selected in 139 fb−1 of s√ = 13 TeV pp collision data collected by the ATLAS detector at the LHC. Background estimates for contributions from Standard Model processes and instrumental effects are extracted from data. The observed event yields are consistent with the expected background. Exclusion limits are reported on the production cross-section times branching fraction as a function of the mean proper decay length cτ of the dark photon, or as a function of the dark-photon mass and kinetic mixing parameter that quantifies the coupling between the Standard Model and potential hidden (dark) sectors. A Higgs boson branching fraction above 1% is excluded at 95% CL for a Higgs boson decaying into two dark photons for dark-photon mean proper decay lengths between 10 mm and 250 mm and dark photons with masses between 0.4 GeV and 2 GeV

Measurements of Zγ+jets differential cross sections in pp collisions at s√ = 13 TeV with the ATLAS detector

Differential cross-section measurements of Zγ production in association with hadronic jets are presented, using the full 139 fb−1 dataset of s√ = 13 TeV proton–proton collisions collected by the ATLAS detector during Run 2 of the LHC. Distributions are measured using events in which the Z boson decays leptonically and the photon is usually radiated from an initial-state quark. Measurements are made in both one and two observables, including those sensitive to the hard scattering in the event and others which probe additional soft and collinear radiation. Different Standard Model predictions, from both parton-shower Monte Carlo simulation and fixed-order QCD calculations, are compared with the measurements. In general, good agreement is observed between data and predictions from MATRIX and MiNNLOPS, as well as next-to-leading-order predictions from MADGRAPH5_AMC@NLO and SHERPA