774 research outputs found

    Linguistic multi-criteria decision-making model with output variable expressive richness

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    The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.In general, traditional decision-making models are based on methods that perform calculations on quantitative measures. These methods are usually applied to assess possible solutions to a problem, resulting in a ranking of alternatives. However, when it comes to making decisions about qualitative measures –such as service quality–, the quantitative assessment is a bit difficult to interpret. Therefore, taking into account the maturity of the linguistic assessment models, this paper puts forth a new solution proposal. It is a decision-making model that uses linguistic labels –represented with the 2-tuple notation– and a variable expressive richness when providing output results. This solution allows expressing results in a manner closer to the human cognitive system. To achieve this goal, a mechanism has been implemented for measuring the distance among the aggregate ratings, providing the decision-maker with a fast and intuitive answer. The proposal is illustrated with an application example based on the TOPSIS model, using linguistic labels throughout the entire process

    VLTI status update: a decade of operations and beyond

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    We present the latest update of the European Southern Observatory's Very Large Telescope interferometer (VLTI). The operations of VLTI have greatly improved in the past years: reduction of the execution time; better offering of telescopes configurations; improvements on AMBER limiting magnitudes; study of polarization effects and control for single mode fibres; fringe tracking real time data, etc. We present some of these improvements and also quantify the operational improvements using a performance metric. We take the opportunity of the first decade of operations to reflect on the VLTI community which is analyzed quantitatively and qualitatively. Finally, we present briefly the preparatory work for the arrival of the second generation instruments GRAVITY and MATISSE.Comment: 10 pages, 7 figures, Proceedings of the SPIE, 9146-1

    Spanish cohort of VEXAS syndrome : clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism

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    The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms

    Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

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    Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

    Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

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    BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

    Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

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    Observation and branching fraction measurement of the decay Ξb- → Λ0 bπ -

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    Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

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    The decay B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} is studied in proton-proton collisions at a center-of-mass energy of s=13\sqrt{s}=13 TeV using data corresponding to an integrated luminosity of 5 fb−1\mathrm{fb}^{-1} collected by the LHCb experiment. In the Λc+K−\Lambda_{c}^+ K^{-} system, the Ξc(2930)0\Xi_{c}(2930)^{0} state observed at the BaBar and Belle experiments is resolved into two narrower states, Ξc(2923)0\Xi_{c}(2923)^{0} and Ξc(2939)0\Xi_{c}(2939)^{0}, whose masses and widths are measured to be m(Ξc(2923)0)=2924.5±0.4±1.1 MeV,m(Ξc(2939)0)=2938.5±0.9±2.3 MeV,Γ(Ξc(2923)0)=0004.8±0.9±1.5 MeV,Γ(Ξc(2939)0)=0011.0±1.9±7.5 MeV, m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV}, where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt Λc+K−\Lambda_{c}^{+} K^{-} sample. Evidence of a new Ξc(2880)0\Xi_{c}(2880)^{0} state is found with a local significance of 3.8 σ3.8\,\sigma, whose mass and width are measured to be 2881.8±3.1±8.5 MeV2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV} and 12.4±5.3±5.8 MeV12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}, respectively. In addition, evidence of a new decay mode Ξc(2790)0→Λc+K−\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-} is found with a significance of 3.7 σ3.7\,\sigma. The relative branching fraction of B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} with respect to the B−→D+D−K−B^{-} \to D^{+} D^{-} K^{-} decay is measured to be 2.36±0.11±0.22±0.252.36 \pm 0.11 \pm 0.22 \pm 0.25, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

    Test of lepton universality in b→sℓ+ℓ−b \rightarrow s \ell^+ \ell^- decays

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    The first simultaneous test of muon-electron universality using B+→K+ℓ+ℓ−B^{+}\rightarrow K^{+}\ell^{+}\ell^{-} and B0→K∗0ℓ+ℓ−B^{0}\rightarrow K^{*0}\ell^{+}\ell^{-} decays is performed, in two ranges of the dilepton invariant-mass squared, q2q^{2}. The analysis uses beauty mesons produced in proton-proton collisions collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 fb−1\mathrm{fb}^{-1}. Each of the four lepton universality measurements reported is either the first in the given q2q^{2} interval or supersedes previous LHCb measurements. The results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-046.html (LHCb public pages

    First observation of a doubly charged tetraquark and its neutral partner

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    A combined amplitude analysis is performed for the decays B0→D‟0Ds+π−B^0 \rightarrow \overline{D}^0 D^+_s\pi^- and B+→D−Ds+π+B^+\rightarrow D^- D^+_s\pi^+, which are related by isospin symmetry. The analysis is based on data collected by the LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8 and 13 TeV\,\rm{TeV}. The full data sample corresponds to an integrated luminosity of 9 fb−1\,\rm{fb^{-1}}. Two new resonant states with masses of 2.908±0.011±0.020 GeV2.908\pm0.011\pm0.020\,\rm{GeV} and widths of 0.136±0.023±0.011 GeV0.136\pm0.023\pm0.011\,\rm{GeV} are observed, which decay to Ds+π+D^+_s\pi^+ and Ds+π−D^+_s\pi^- respectively. The former state indicates the first observation of a doubly charged open-charm tetraquark state with minimal quark content [csˉudˉ][c\bar{s}u\bar{d}], and the latter state is a neutral tetraquark composed of [csˉuˉd][c\bar{s}\bar{u}d] quarks. Both states are found to have spin-parity 0+0^+, and their resonant parameters are consistent with each other, which suggests that they belong to an isospin triplet.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-026.html (LHCb public pages
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