Effect of aging on esophageal motility in patients with and without GERD

Background/Aims: The impact of aging on esophageal motility is not completely understood. This study aims at assessing 1) whether degeneration of esophageal body motility occurs with age and 2) whether this development is influenced by gastroesophageal reflux disease (GERD)

Effect of aging on esophageal motility in patients with and without GERD

Background/Aims: The impact of aging on esophageal motility is not completely understood. This study aims at assessing 1) whether degeneration of esophageal body motility occurs with age and 2) whether this development is influenced by gastroesophageal reflux disease (GERD)

Regulation of TMPRSS6 by BMP6 and iron in human cells and mice.

Mutations in transmembrane protease, serine 6 (TMPRSS6), encoding matriptase-2, are responsible for the familial anemia disorder iron-refractory iron deficiency anemia (IRIDA). Patients with IRIDA have inappropriately elevated levels of the iron regulatory hormone hepcidin, suggesting that TMPRSS6 is involved in negatively regulating hepcidin expression. Hepcidin is positively regulated by iron via the bone morphogenetic protein (BMP)-SMAD signaling pathway. In this study, we investigated whether BMP6 and iron also regulate TMPRSS6 expression. Here we demonstrate that, in vitro, treatment with BMP6 stimulates TMPRSS6 expression at the mRNA and protein levels and leads to an increase in matriptase-2 activity. Moreover, we identify that inhibitor of DNA binding 1 is the key element of the BMP-SMAD pathway to regulate TMPRSS6 expression in response to BMP6 treatment. Finally, we show that, in mice, Tmprss6 mRNA expression is stimulated by chronic iron treatment or BMP6 injection and is blocked by injection of neutralizing antibody against BMP6. Our results indicate that BMP6 and iron not only induce hepcidin expression but also induce TMPRSS6, a negative regulator of hepcidin expression. Modulation of TMPRSS6 expression could serve as a negative feedback inhibitor to avoid excessive hepcidin increases by iron to help maintain tight homeostatic balance of systemic iron levels

Incidence and survival of patients with oligometastatic esophagogastric cancer: A multicenter cohort study

urpose/objective: This multicenter study assessed the incidence and survival of patients with esophagogastric cancer and oligometastatic disease (OMD) in two tertiary referral cancer centers in The Netherlands and Switzerland. Materials/methods: Between 2010 and 2021, patients with metastatic esophagogastric cancer were identified. Patients with de-novo OMD were included (first-time diagnosis of ≤5 distant metastases on 18F-FDG-PET/CT). Control of the primary tumor was considered in patients who underwent primary tumor resection or definitive chemoradiotherapy without locoregional recurrence. Treatment of OMD was categorized into (1) systemic therapy, (2) local treatment (stereotactic body radiotherapy or metastasectomy), (3) local plus systemic therapy, or (4) best supportive care. The primary outcomes were overall survival (OS) and independent prognostic factors for OS. Independent prognostic factors for OS were analyzed using multivariable Cox proportional hazard models. Results: In total, 830 patients with metastatic esophagogastric cancer were identified of whom 200 patients with de-novo OMD were included (24%). The majority of included patients had esophageal cancer (73%) with adenocarcinoma histology (79%) and metachronous OMD (52%). The primary tumor was controlled in 68%. Treatment of OMD was systemic therapy (25%), local treatment (43%), local plus systemic therapy (13%), or best supportive care (18%). Median follow-up was 14 months (interquartile range: 7-27). Median OS was 16 months (95% CI: 13-21). Improved OS was independently associated with local plus systemic therapy compared with systemic therapy alone (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.25-0.87). Worse OS was independently associated with squamous cell carcinoma (HR 1.70, 95% CI: 1.07-2.74), bone oligometastases (HR 2.44, 95% CI: 1.28-4.68), brain oligometastases (HR 1.98, 95% CI: 1.05-4.69), and two metastatic locations (HR 2.07, 95% CI: 1.04-4.12). Median OS after local plus systemic therapy was 35 months (95% CI: 22-NA) as compared with 13 months (95% CI: 9-21, p < 0.001) after systemic therapy alone for OMD. Conclusion: Patients with metastatic esophagogastric cancer present in 25% with de-novo OMD. Local treatment of OMD plus systemic therapy was independently associated with long-term OS and independently improved OS when compared with systemic therapy alone. Randomized controlled trials are warranted to confirm these results. Keywords: Esophageal neoplasms; Gastric neoplasms; Lymphatic metastasis; Metastasectomy; Neoplasm metastasis; Radiosurgery

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at s√=8 TeV with ATLAS

Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of s√=8 TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9 + 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured