Development and Validation of Hepamet Fibrosis Scoring System-a Simple, Non-invasive Test to Identify Patients With Nonalcoholic Fatty liver Disease With Advanced Fibrosis

BACKGROUND & AIMS: Fibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis. METHODS: We collected data from 2452 patients with NAFLD at medical centers in Italy, France, Cuba, and China. We developed the Hepamet fibrosis scoring system using demographic, anthropometric, and laboratory test data, collected at time of liver biopsy, from a training cohort of patients from Spain (n=768) and validated the system using patients from Cuba (n=344), Italy (n=288), France (n=830), and China (n=232). Hepamet fibrosis score (HFS) were compared with those of previously developed fibrosis scoring systems (the NAFLD fibrosis score [NFS] and FIB-4). The diagnostic accuracy of the Hepamet fibrosis scoring system was assessed based on area under the receiver operating characteristic (AUROC) curve, sensitivity, specificity, diagnostic odds ratio, and positive and negative predictive values and likelihood ratios. RESULTS: Variables used to determine HFS were patient sex, age, homeostatic model assessment score, presence of diabetes, levels of aspartate aminotransferase, and albumin, and platelet counts; these were independently associated with advanced fibrosis. HFS discriminated between patients with and without advanced fibrosis with an AUROC curve value of 0.85 whereas NFS or FIB-4 did so with AUROC values of 0.80 (P=.0001). In the validation set, cut-off HFS of 0.12 and 0.47 identified patients with and without advanced fibrosis with 97.2% specificity, 74% sensitivity, a 92% negative predictive value, a 76.3% positive predictive value, a 13.22 positive likelihood ratio, and a 0.31 negative likelihood ratio. HFS were not affected by patient age, body mass index, hypertransaminasemia, or diabetes. The Hepamet fibrosis scoring system had the greatest net benefit in identifying patients who should undergo liver biopsy analysis and led to significant improvements in reclassification, reducing the number of patients with undetermined results to 20% from 30% for the FIB-4 and NFS systems (P<.05). CONCLUSIONS: Using clinical and laboratory data from patients with NAFLD, we developed and validated the Hepamet fibrosis scoring system, which identified patients with advanced fibrosis with greater accuracy than the FIB-4 and NFS systems. the Hepamet system provides a greater net benefit for the decision-making process to identify patients who should undergo liver biopsy analysis

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study

2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naı¨ve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P¼0.004). There was no interaction between AR and docetaxel status (P¼0.83 for OS, P¼0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; PA (p.L702H) and 520 3

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

Background There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC.Methods We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial).Results In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts.Conclusion Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required.Clinical trial number NCT02288936 (PREMIERE trial)

Search for top-philic heavy resonances in pp collisions at s=13 TeV with the ATLAS detector

A search for the associated production of a heavy resonance with a top-quark or a top-antitop-quark pair, and decaying into a tt¯ pair is presented. The search uses the data recorded by the ATLAS detector in pp collisions at s=13 TeV at the Large Hadron Collider during the years 2015–2018, corresponding to an integrated luminosity of 139 fb-1. Events containing exactly one electron or muon are selected. The two hadronically decaying top quarks from the resonance decay are reconstructed using jets clustered with a large radius parameter of R=1. The invariant mass spectrum of the two top quark candidates is used to search for a resonance signal in the range of 1.0 TeV to 3.2 TeV. The presence of a signal is examined using an approach with minimal model dependence followed by a model-dependent interpretation. No significant excess is observed over the background expectation. Upper limits on the production cross section times branching ratio at 95% confidence level are provided for a heavy Z′ boson based on a simplified model, for Z′ mass between 1.0 TeV and 3.0 TeV. The observed (expected) limits range from 21 (14) fb to 119 (86) fb depending on the choice of model parameters

Search for non-resonant Higgs boson pair production in the 2b+2ℓ+ETmiss final state in pp collisions at s = 13 TeV with the ATLAS detector

A search for non-resonant Higgs boson pair (HH) production is presented, in which one of the Higgs bosons decays to a b-quark pair (bb¯) and the other decays to WW*, ZZ*, or τ+τ−, with in each case a final state with ℓ+ℓ−+ neutrinos (ℓ = e, μ). The analysis targets separately the gluon-gluon fusion and vector boson fusion production modes. Data recorded by the ATLAS detector in proton-proton collisions at a centre-of-mass energy of 13 TeV at the Large Hadron Collider, corresponding to an integrated luminosity of 140 fb−1, are used in this analysis. Events are selected to have exactly two b-tagged jets and two leptons with opposite electric charge and missing transverse momentum in the final state. These events are classified using multivariate analysis algorithms to separate the HH events from other Standard Model processes. No evidence of the signal is found. The observed (expected) upper limit on the cross-section for non-resonant Higgs boson pair production is determined to be 9.7 (16.2) times the Standard Model prediction at 95% confidence level. The Higgs boson self-interaction coupling parameter κλ and the quadrilinear coupling parameter κ2V are each separately constrained by this analysis to be within the ranges [−6.2, 13.3] and [−0.17, 2.4], respectively, at 95% confidence level, when all other parameters are fixed

Search for resonant production of dark quarks in the dijet final state with the ATLAS detector

This paper presents a search for a new Z′ resonance decaying into a pair of dark quarks which hadronise into dark hadrons before promptly decaying back as Standard Model particles. This analysis is based on proton-proton collision data recorded at s = 13 TeV with the ATLAS detector at the Large Hadron Collider between 2015 and 2018, corresponding to an integrated luminosity of 139 fb−1. After selecting events containing large-radius jets with high track multiplicity, the invariant mass distribution of the two highest-transverse-momentum jets is scanned to look for an excess above a data-driven estimate of the Standard Model multijet background. No significant excess of events is observed and the results are thus used to set 95% confidence-level upper limits on the production cross-section times branching ratio of the Z′ to dark quarks as a function of the Z′ mass for various dark-quark scenarios

Searches for lepton-flavour-violating decays of the Higgs boson into eτ and μτ in √s = 13 TeV pp collisions with the ATLAS detector

This paper presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ, performed using data collected with the ATLAS detector at the LHC. The searches are based on a data sample of proton-proton collisions at a centre-of-mass energy s = 13 TeV, corresponding to an integrated luminosity of 138 fb −1. Leptonic (τ → ℓνℓ ντ) and hadronic (τ → hadrons ντ) decays of the τ-lepton are considered. Two background estimation techniques are employed: the MC-template method, based on data-corrected simulation samples, and the Symmetry method, based on exploiting the symmetry between electrons and muons in the Standard Model backgrounds. No significant excess of events is observed and the results are interpreted as upper limits on lepton-flavour-violating branching ratios of the Higgs boson. The observed (expected) upper limits set on the branching ratios at 95% confidence level, B (H → eτ) < 0.20% (0.12%) and B (H → μτ) < 0.18% (0.09%), are obtained with the MC-template method from a simultaneous measurement of potential H → eτ and H → μτ signals. The best-fit branching ratio difference, B (H → μτ) → B (H → eτ), measured with the Symmetry method in the channel where the τ-lepton decays to leptons, is (0.25 ± 0.10)%, compatible with a value of zero within 2.5σ. [Figure not available: see fulltext.]