404 research outputs found

    Outcomes of Surgical Management of Familial Intrahepatic Cholestasis 1 and Bile Salt Export Protein Deficiencies

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    Progressive familial intrahepatic cholestasis (PFIC) with normal circulating gamma-glutamyl transpeptidase levels can result from mutations in the ATP8B1 gene (encoding familial intrahepatic cholestasis 1 [FIC1] deficiency) or the ABCB11 gene (bile salt export protein [BSEP] deficiency). We investigated the outcomes of partial external biliary diversion, ileal exclusion, and liver transplantation in these two conditions. We conducted a retrospective multicenter study of 42 patients with FIC1 deficiency (FIC1 patients) and 60 patients with BSEP deficiency (BSEP patients) who had undergone one or more surgical procedures (57 diversions, 6 exclusions, and 57 transplants). For surgeries performed prior to transplantation, BSEP patients were divided into two groups, BSEP-common (bearing common missense mutations D482G or E297G, with likely residual function) and BSEP-other. We evaluated clinical and biochemical outcomes in these patients. Overall, diversion improved biochemical parameters, pruritus, and growth, with substantial variation in individual response. BSEP-common or FIC1 patients survived longer after diversion without developing cirrhosis, being listed for or undergoing liver transplantation, or dying, compared to BSEP-other patients. Transplantation resolved cholestasis in all groups. However, FIC1 patients commonly developed hepatic steatosis, diarrhea, and/or pancreatic disease after transplant accompanied by biochemical abnormalities and often had continued poor growth. In BSEP patients with impaired growth, this generally improved after transplantation. Conclusion: Diversion can improve clinical and biochemical status in FIC1 and BSEP deficiencies, but outcomes differ depending on genetic etiology. For many patients, particularly BSEP-other, diversion is not a permanent solution and transplantation is required. Although transplantation resolves cholestasis in patients with FIC1 and BSEP deficiencies, the overall outcome remains unsatisfactory in many FIC1 patients; this is mainly due to extrahepatic manifestations.Peer reviewe

    Observation of the Rare Decay of the η Meson to Four Muons

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    A search for the rare η→Ό+Ό−Ό+Ό− double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb−1. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→Ό+Ό− decay as normalization, the branching fraction B(η→Ό+Ό−Ό+Ό−)=[5.0±0.8(stat)±0.7(syst)±0.7(B2ÎŒ)]×10−9 is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions

    Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

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    A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level

    First measurement of the top quark pair production cross section in proton-proton collisions at s \sqrt{s} = 13.6 TeV

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    The first measurement of the top quark pair (ttÂŻ) production cross section in proton-proton collisions at s√ = 13.6 TeV is presented. Data recorded with the CMS detector at the CERN LHC in Summer 2022, corresponding to an integrated luminosity of 1.21 fb−1, are analyzed. Events are selected with one or two charged leptons (electrons or muons) and additional jets. A maximum likelihood fit is performed in event categories defined by the number and flavors of the leptons, the number of jets, and the number of jets identified as originating from b quarks. An inclusive ttÂŻ production cross section of 881 ± 23 (stat + syst) ± 20 (lumi) pb is measured, in agreement with the standard model prediction of 924+32−40 pb

    Measurements of inclusive and differential cross sections for the Higgs boson production and decay to four-leptons in proton-proton collisions at s \sqrt{s} = 13 TeV

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    Measurements of the inclusive and differential fiducial cross sections for the Higgs boson production in the H → ZZ → 4ℓ (ℓ = e, ÎŒ) decay channel are presented. The results are obtained from the analysis of proton-proton collision data recorded by the CMS experiment at the CERN LHC at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb−1. The measured inclusive fiducial cross section is 2.73 ± 0.26 fb, in agreement with the standard model expectation of 2.86 ± 0.1 fb. Differential cross sections are measured as a function of several kinematic observables sensitive to the Higgs boson production and decay to four leptons. A set of double-differential measurements is also performed, yielding a comprehensive characterization of the four leptons final state. Constraints on the Higgs boson trilinear coupling and on the bottom and charm quark coupling modifiers are derived from its transverse momentum distribution. All results are consistent with theoretical predictions from the standard model

    Search for Scalar Leptoquarks Produced via τ-Lepton-Quark Scattering in pppp Collisions at s=13TeV\sqrt{s}=13 TeV

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    The first search for scalar leptoquarks produced in τ-lepton–quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138  fb−1^{−1}. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength

    Observation of four top quark production in proton-proton collisions at √s = 13 TeV

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    Search for a high-mass dimuon resonance produced in association with b quark jets at s \sqrt{s} = 13 TeV

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    Mutation detection in X-linked disorders: Ornithine carbamoyl transferase deficiency and Pelizaeus-Merzbacher disease

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    This study was carried out to establish methods of mutation detection in the X-linked disorders: ornithine carbamoyl transferase (OCT) deficiency and Pelizaeus-Merzbacher disease (PMD) and to determine the molecular basis of these disorders. Two main approaches were used: single strand conformation polymorphism (SSCP) analysis and cytosine-guanine dinucleotide (CpG) site analysis. SSCP screening of the coding regions of the OCT and proteolipid protein genes in 5 families with late onset OCT deficiency and 14 families with PMD, identified sequence variations in 3 and 4 families respectively. On direct sequencing of the OCT gene 2 novel amino acid substitutions: Ala(176)Thr and Arg(97)Leu were identified and the fourth reported case of Arg(245)Trp. Sequencing of the proteolipid protein gene identified 3 novel changes: Leu(223)Pro, Thr(181)Pro and a G to T change at the -1 position of the 3’ acceptor splice site of exon 4. The fourth PMD family which gave a variant SSCP pattern is currently under analysis by a collaborating group. The second approach was the analysis of 5’CpG3’ dinucleotide sites located within the recognition sequences of the restriction enzymes: TaqI (TCGA), MspI (CCGG) and CfoI (GCGC), using the principal that mutation abolished digestion. Genomic DNA or PCR product of exons containing a restriction enzyme site, from patients with classical or late onset OCT deficiency, was digested and the products were analysed by Southern blotting or by separation on high percentage agarose gels respectively. Two point mutations: Arg(109)Gln and Pro(193)Leu, which removed the TaqI and MspI sites in exons 5 and 7 respectively, were identified
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