Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Vascular wall injury and inflammation are key pathogenic mechanisms responsible for early testicular degeneration during acute besnoitiosis in bulls

Background: Bovine besnoitiosis, caused by the apicomplexan parasite Besnoitia besnoiti, is a chronic and debilitating cattle disease that notably impairs fertility. Acutely infected bulls may develop respiratory signs and orchitis, and sterility has been reported in chronic infections. However, the pathogenesis of acute disease and its impact on reproductive function remain unknown. Methods: Herein, we studied the microscopic lesions as well as parasite presence and load in the testis (pampiniform plexus, testicular parenchyma and scrotal skin) of seven bulls with an acute B. besnoiti infection. Acute infection was confirmed by serological techniques (IgM seropositive results and IgG seronegative results) and subsequent parasite detection by PCR and histological techniques. Results: The most parasitized tissue was the scrotal skin. Moreover, the presence of tachyzoites, as shown by immunohistochemistry, was associated with vasculitis, and three bulls had already developed juvenile tissue cysts. In all animals, severe endothelial injury was evidenced by marked congestion, thrombosis, necrotizing vasculitis and angiogenesis, among others, in the pampiniform plexus, testicular parenchyma and scrotal skin. Vascular lesions coexisted with lesions characteristic of a chronic infection in the majority of bulls: Hyperkeratosis, acanthosis and a marked diffuse fibroplasia in the dermis of the scrotum. An intense inflammatory infiltrate was also observed in the testicular parenchyma accompanied by different degrees of germline atrophy in the seminiferous tubules with the disappearance of various strata of germ cells in four bulls. Conclusions: This study confirmed that severe acute besnoitiosis leads to early sterility that might be permanent, which is supported by the severe lesions observed. Consequently, we hypothesized that testicular degeneration might be a consequence of (i) thermoregulation failure induced by vascular lesions in pampiniform plexus and scrotal skin lesions; (ii) severe vascular wall injury induced by the inflammatory response in the testis; and (iii) blood-testis barrier damage and alteration of spermatogenesis by immunoresponse.[Figure not available: See fulltext.

Measurement of charged particle spectra in minimum-bias events from proton-proton collisions at root s =13 TeV

Pseudorapidity, transverse momentum, and multiplicity distributions are measured in the pseudorapidity range vertical bar eta vertical bar 0.5 GeV in proton-proton collisions at a center-of-mass energy of root s = 13 TeV. Measurements are presented in three different event categories. The most inclusive of the categories corresponds to an inelastic pp data set, while the other two categories are exclusive subsets of the inelastic sample that are either enhanced or depleted in single diffractive dissociation events. The measurements are compared to predictions from Monte Carlo event generators used to describe high-energy hadronic interactions in collider and cosmic-ray physics.Peer reviewe

Measurement of the CP-violating phase phi_s in the Bs0→^0_\mathrm{s}\to J/ψ ϕ/\psi\, \phi(1020) →μ+μ−\to \mu^+\mu^-K+^+K−^- channel in proton-proton collisions at s=\sqrt{s} = 13 TeV

The CP-violating weak phase ?s and the decay width difference ??s between the light and heavy B0s mass eigenstates are measured with the CMS detector at the LHC in a sample of 48 500 reconstructed B0s? J/I) d (1020) ?11+11? K+K? events. The measurement is based on a data sample corresponding to an integrated luminosity of 96.4 fb?1, collected in proton-proton collisions at ?s = 13 TeV in 2017?2018. To extract the values of ?s and ??s, a time-dependent and flavor-tagged angular analysis of the 11+11?K+K? final state is performed. The analysis employs a dedicated tagging trigger and a novel opposite-side muon flavor tagger based on machine learning techniques. The measurement yields ?s = ?11 ?50 (stat) ? 10 (syst) mrad and ??s = 0.114 ? 0.014 (stat)? 0.007 (syst) ps?1, in agreement with the standard model predictions. When combined with the previous CMS measurement at ?s = 8 TeV, the following values are obtained: ?s = ?21 ? 44 (stat) ? 10 (syst) mrad, ??s = 0.1032 ? 0.0095 (stat) ? 0.0048 (syst) ps?1, a significant improvement over the 8 TeV result. ? 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY licens

Measurement of the C P-violating phase φs in the B0 s → J/ψφ(1020) → μ+μ− K+K− channel in proton-proton collisions at √s = 13 TeV

The C P-violating weak phase φs and the decay width difference s between the light and heavy B0 s mass eigenstates are measured with the CMS detector at the LHC in a sample of 48 500 reconstructed B0 s → J/ψ φ(1020) → μ+μ− K+K− events. The measurement is based on a data sample corresponding to an integrated luminosity of 96.4 fb−1, collected in proton-proton collisions at √s = 13 TeV in 2017–2018. To extract the values of φs and s, a time-dependent and flavor-tagged angular analysis of the μ+μ−K+K− final state is performed. The analysis employs a dedicated tagging trigger and a novel opposite-side muon flavor tagger based on machine learning techniques. The measurement yields φs = −11±50 (stat)±10 (syst) mrad and s = 0.114±0.014 (stat)±0.007 (syst) ps−1, in agreement with the standard model predictions. When combined with the previous CMS measurement at √s = 8 TeV, the following values are obtained: φs = −21 ± 44 (stat) ± 10 (syst) mrad, s = 0.1032 ± 0.0095 (stat) ± 0.0048 (syst) ps−1, a significant improvement over the 8 TeV result

Search for heavy resonances decaying to WW, WZ, or WH boson pairs in a final state consisting of a lepton and a large-radius jet in proton-proton collisions at s =13 TeV

A search for new heavy resonances decaying to pairs of bosons (WW, WZ, or WH) is presented. The analysis uses data from proton-proton collisions collected with the CMS detector at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 137 fb(-1). One of the bosons is required to be a W boson decaying to an electron or muon and a neutrino, while the other boson is required to be reconstructed as a single jet with mass and substructure compatible with a quark pair from a W, Z, or Higgs boson decay. The search is performed in the resonance mass range between 1.0 and 4.5 TeVand includes a specific search for resonances produced via vector boson fusion. The signal is extracted using a twodimensional maximum likelihood fit to the jet mass and the diboson invariant mass distributions. No significant excess is observed above the estimated background. Model-independent upper limits on the production cross sections of spin-0, spin-1, and spin-2 heavy resonances are derived as functions of the resonance mass and are interpreted in the context of bulk radion, heavy vector triplet, and bulk graviton models. The reported bounds are the most stringent to date