ANTECIPAÇÃO DE REFERENTES EM DPS COMPLEXOS COM RELATIVAS PREPOSICIONADAS: interação com conhecimento metacognitivo e memória de trabalho

This study examines early mapping of complex DPs in prepositional relative clauses with for/to (‘para’), i.e. attributing the thematic role of beneficiary. The main question is whether the standard variant for this type of relative clauses in Brazilian Portuguese (with preposition) as compared to the non-standard chopped variant (without a preposition) allows for early referent mapping, given the possibility of incremental integration of preceding contextual visual and linguistic information. A picture matching experiment was applied to 41 speakers of the standard variety of BP. Preceding visual and auditory linguistic context was presented in which a character participated in two distinct events (one event presented with a di-transitive verb and another presented with a transitive verb), involving distinct co-participants. We aimed to verify whether the presentation of a standard variant probe question, with the preposition, immediately following the visual and linguistic contextual scenes would benefit early identification of the referent expressed in the complex DP, compared to a non-standard prepositionless (chopped variant) probe question. Accuracy and Reaction Time (RT) with regards to the picture matching task were the dependent variables. We also intended to examine the influence of knowledge of standard grammar as well as verbal working memory on task performance. Participants were asked to try and click on the image matching the probe sentence containing the relative clause as soon as possible. Our results did not reveal any advantage for the use of the standard prepositional relative clause compared to the non-standard version in terms of referent anticipation. However, accuracy of image selection was significantly higher for standard relative clauses. Higher scores in the standard grammar test and the reading span test were positively correlated to RT(s) as well as accuracy (for the non-standard relative clause). Relative clause complexity, possible ambiguity of the non-standard chopped relative clauses and the limited sensitivity of the task in detecting potential early mapping are all factors that seem to affect the results.Este estudo investiga, particularmente, o mapeamento antecipado do referente de um DP complexo, apresentando uma oração relativa preposicionada com para, ou seja, com papel temático de beneficiário. Explora-se a contribuição que o tipo de estratégia relativa utilizada (padrão ou cortadora) pode trazer para a antecipação do referente, dada a possibilidade de integração incremental de informação contextual visual e linguística precedente. Em um experimento de seleção de imagem, aplicado a 41 participantes, falantes cultos de português do Brasil, a ser reportado, apresentaram-se contextos visuais e linguísticos auditivos prévios em que um personagem participa de dois eventos distintos (um evento apresentado com verbo bitransitivo e um evento apresentado com verbo transitivo), envolvendo coparticipantes distintas. Busca-se verificar em que medida o uso, na sentença-teste auditiva, que segue os preâmbulos discursivos e visuais, de uma estratégia padrão da língua, na qual a preposição aparece precedendo o pronome relativo, poderia favorecer a antecipação do referente do DP complexo, em comparação à estratégia cortadora, em que a preposição não está presente. Empregou-se uma tarefa de correspondência sentença-gravura na qual a acurácia e o tempo de resposta foram considerados como variáveis dependentes. Ademais, objetivou-se verificar a influência de conhecimento de norma padrão e de memória de trabalho verbal no desempenho da tarefa. Solicita-se que tentem clicar o mais rápido possível na imagem descrita pela sentença contendo a relativa. Nossos resultados não indicaram uma vantagem do uso da relativa padrão sobre a cortadora para a antecipação do referente do DP complexo. No entanto, a acurácia da seleção da imagem foi significativamente melhor para esse tipo de relativa. Melhor desempenho no teste normativo e no teste de reading span foi associado a TRs mais rápidos e maior acurácia na relativa cortadora. Fatores que parecem influenciar esse quadro são complexidade da estrutura relativa, possível ambiguidade da relativa cortadora e a sensibilidade limitada do teste para flagrar essa possível antecipação

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics

Performance of the ALICE Experiment at the CERN LHC

ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables.ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables.ALICE is the heavy-ion experiment at the CERN Large Hadron Collider. The experiment continuously took data during the first physics campaign of the machine from fall 2009 until early 2013, using proton and lead-ion beams. In this paper we describe the running environment and the data handling procedures, and discuss the performance of the ALICE detectors and analysis methods for various physics observables

Heavy flavour decay muon production at forward rapidity in proton–proton collisions at √s=7 TeV

The production of muons from heavy flavour decays is measured at forward rapidity in proton–proton collisions at √s=7 TeV collected with the ALICE experiment at the LHC. The analysis is carried out on a data sample corresponding to an integrated luminosity Lint=16.5 nb−1. The transverse momentum and rapidity differential production cross sections of muons from heavy flavour decays are measured in the rapidity range 2.5<y<4, over the transverse momentum range 2<pt<12 GeV/c. The results are compared to predictions based on perturbative QCD calculations

Long-range angular correlations of π, K and p in p–Pb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV

Angular correlations between unidentified charged trigger particles and various species of charged associated particles (unidentified particles, pions, kaons, protons and antiprotons) are measured by the ALICE detector in p-Pb collisions at a nucleon--nucleon centre-of-mass energy of 5.02 TeV in the transverse-momentum range 0.3 < $p_T$ < 4 GeV/c. The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range |$\eta_{lab}$| < 0.8. Fourier coefficients are extracted from the long-range correlations projected onto the azimuthal angle difference and studied as a function of $p_T$ and in intervals of event multiplicity. In high-multiplicity events, the second-order coefficient for protons, $v_2^p$, is observed to be smaller than that for pions, $v_2^\pi$, up to about $p_T$ = 2 GeV/c. To reduce correlations due to jets, the per-trigger yield measured in low-multiplicity events is subtracted from that in high-multiplicity events. A two-ridge structure is obtained for all particle species. The Fourier decomposition of this structure shows that the second-order coefficients for pions and kaons are similar. The $v_2^p$ is found to be smaller at low $p_T$ and larger at higher $p_T$ than $v_2^\pi$, with a crossing occurring at about 2 GeV. This is qualitatively similar to the elliptic-flow pattern observed in heavy-ion collisions. A mass ordering effect at low transverse momenta is consistent with expectations from hydrodynamic model calculations assuming a collectively expanding system.Angular correlations between unidentified charged trigger particles and various species of charged associated particles (unidentified particles, pions, kaons, protons and antiprotons) are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV in the transverse-momentum range $0.3 < p_{\rm T} < 4$ GeV/$c$. The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range $|\eta_{\rm lab}|<0.8$. Fourier coefficients are extracted from the long-range correlations projected onto the azimuthal angle difference and studied as a function of $p_{\rm T}$ and in intervals of event multiplicity. In high-multiplicity events, the second-order coefficient for protons, $v_2^p$, is observed to be smaller than that for pions, $v_2^\pi$, up to about $p_{\rm T} = 2$ GeV/$c$. To reduce correlations due to jets, the per-trigger yield measured in low-multiplicity events is subtracted from that in high-multiplicity events. A two-ridge structure is obtained for all particle species. The Fourier decomposition of this structure shows that the second-order coefficients for pions and kaons are similar. The $v_2^p$ is found to be smaller at low $p_{\rm T}$ and larger at higher $p_{\rm T}$ than $v_2^pi$, with a crossing occurring at about 2 GeV. This is qualitatively similar to the elliptic-flow pattern observed in heavy-ion collisions. A mass ordering effect at low transverse momenta is consistent with expectations from hydrodynamic model calculations assuming a collectively expanding system.Angular correlations between unidentified charged trigger particles and various species of charged associated particles (unidentified particles, pions, kaons, protons and antiprotons) are measured by the ALICE detector in p–Pb collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV in the transverse-momentum range 0.3<pT<4 GeV/c . The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range |ηlab|<0.8 . Fourier coefficients are extracted from the long-range correlations projected onto the azimuthal angle difference and studied as a function of pT and in intervals of event multiplicity. In high-multiplicity events, the second-order coefficient for protons, v2p , is observed to be smaller than that for pions, v2π , up to about pT=2 GeV/c . To reduce correlations due to jets, the per-trigger yield measured in low-multiplicity events is subtracted from that in high-multiplicity events. A two-ridge structure is obtained for all particle species. The Fourier decomposition of this structure shows that the second-order coefficients for pions and kaons are similar. The v2p is found to be smaller at low pT and larger at higher pT than v2π , with a crossing occurring at about 2 GeV/c . This is qualitatively similar to the elliptic-flow pattern observed in heavy-ion collisions. A mass ordering effect at low transverse momenta is consistent with expectations from hydrodynamic model calculations assuming a collectively expanding system

K*(892)^0 and PHI(1020) production in Pb-Pb collisions at sqrt(sNN) = 2.76 TeV

The yields of the K*(892) and PHI(1020) resonances are measured in Pb-Pb collisions at sqrt(sNN) = 2.76 TeV through their hadronic decays using the ALICE detector. The measurements are performed in multiple centrality intervals at mid-rapidity (|y|<0.5) in the transverse-momentum ranges 0.3<pt<5 GeV/c for the K*(892)^0 and 0.5<pt<5 GeV/c for the PHI(1020). The yields of K*(892)^0 are suppressed in central Pb-Pb collisions with respect to pp and peripheral Pb-Pb collisions. This suppression is discussed in a scenario in which the K*(892)^0 decays during the evolution of the fireball and the decay products scatter, thus escaping detection through invariant-mass reconstruction. In contrast, the PHI(1020) meson, due to its long lifetime, decays outside the fireball. These particles are also used as probes to study the mechanisms of particle production. The shape of the pt distribution of the PHI(1020) meson, but not its yield, is reproduced fairly well by hydrodynamical models for central Pb-Pb collisions. In central Pb-Pb collisions at low and intermediate pt, the p/PHI(1020) ratio is flat in pt, while the p/pi and PHI(1020)/pi ratios show a pronounced increase and have similar shapes to each other. These results indicate that the shapes of the pt distributions of these particles in central Pb-Pb collisions are determined predominantly by the particle masses and radial flow. Finally, PHI(1020) production in Pb-Pb collisions is enhanced, with respect to the yield in pp collisions and the yield of charged pions, by an amount similar to the Lambda and Xi

Centrality, rapidity and transverse momentum dependence of J/ψJ/\psi suppression in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}}=2.76 TeV

The inclusive J/$\psi$ nuclear modification factor ($R_{AA}$) in Pb-Pb collisions at $\sqrt{s_{NN}}$=2.76TeV has been measured by ALICE as a function of centrality in the $e^+e^-$ decay channel at mid-rapidity |y| < 0.8 and as a function of centrality, transverse momentum and rapidity in the $\mu^+\mu^-$ decay channel at forward-rapidity 2.5 < y < 4.The J/$\psi$ yields measured in Pb-Pb are suppressed compared to those in pp collisions scaled by the number of binary collisions.The $R_{AA}$ integrated over a centrality range corresponding to 90% of the inelastic Pb-Pb cross section is 0.72 +- 0.06 (stat.) +- 0.10 (syst.) at mid-rapidity and 0.57 +- 0.01 (stat.) +- 0.09 (syst.) at forward-rapidity. At low transverse momentum, significantly larger values of $R_{AA}$ are measured at forward-rapidity compared to measurements at lower energy.These features suggest that a contribution to the J/$\psi$ yield originates from charm quarks (re)combination in the deconfined partonic medium.The inclusive J/ψ nuclear modification factor ( RAA ) in Pb–Pb collisions at sNN=2.76 TeV has been measured by ALICE as a function of centrality in the e+e− decay channel at mid-rapidity ( |y|<0.8 ) and as a function of centrality, transverse momentum and rapidity in the μ+μ− decay channel at forward-rapidity ( 2.5<y<4 ). The J/ψ yields measured in Pb–Pb are suppressed compared to those in pp collisions scaled by the number of binary collisions. The RAA integrated over a centrality range corresponding to 90% of the inelastic Pb–Pb cross section is 0.72±0.06(stat.)±0.10(syst.) at mid-rapidity and 0.58±0.01(stat.)±0.09(syst.) at forward-rapidity. At low transverse momentum, significantly larger values of RAA are measured at forward-rapidity compared to measurements at lower energy. These features suggest that a contribution to the J/ψ yield originates from charm quark (re)combination in the deconfined partonic medium.The inclusive $J/\psi$ nuclear modification factor $R_{\rm AA}$ in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$=2.76 TeV has been measured by ALICE as a function of centrality in the e$^+$e$^-$ decay channel at mid-rapidity $|y|<0.8$ and as a function of centrality, transverse momentum and rapidity in the $\mu^{+}\mu^{-}$ decay channel at forward-rapidity $2.5<y<4$.The $J/\psi$ yields measured in Pb-Pb are suppressed compared to those in pp collisions scaled by the number of binary collisions. The $R_{\rm AA}$ integrated over a centrality range corresponding to 90% of the inelastic Pb-Pb cross section is $0.72\pm0.06$ (stat.) $\pm0.10$ (syst.) at mid-rapidity and $0.57 \pm 0.01$ (stat.) $\pm0.09$ (syst.) at forward-rapidity. At low transverse momentum, significantly larger values of $R_{\rm AA}$ are measured at forward-rapidity compared to measurements at lower energy. These features suggest that a contribution to the $J/\psi$ yield originates from charm quarks (re)combination in the deconfined partonic medium