Measurements of neutrino oscillation parameters from the T2K experiment using 3.6×1021 protons on target.

The T2K experiment presents new measurements of neutrino oscillation parameters using 19.7(16.3)×1020 protons on target (POT) in (anti-)neutrino mode at the far detector (FD). Compared to the previous analysis, an additional 4.7×1020 POT neutrino data was collected at the FD. Significant improvements were made to the analysis methodology, with the near-detector analysis introducing new selections and using more than double the data. Additionally, this is the first T2K oscillation analysis to use NA61/SHINE data on a replica of the T2K target to tune the neutrino flux model, and the neutrino interaction model was improved to include new nuclear effects and calculations. Frequentist and Bayesian analyses are presented, including results on sin2θ13 and the impact of priors on the δCP measurement. Both analyses prefer the normal mass ordering and upper octant of sin2θ23 with a nearly maximally CP-violating phase. Assuming the normal ordering and using the constraint on sin2θ13 from reactors, sin2θ23=0.561-0.032+0.021 using Feldman-Cousins corrected intervals, and Δm322=2.494-0.058+0.041×10-3eV2 using constant Δχ2 intervals. The CP-violating phase is constrained to δCP=-1.97-0.70+0.97 using Feldman-Cousins corrected intervals, and δCP=0,π is excluded at more than 90% confidence level. A Jarlskog invariant of zero is excluded at more than 2σ credible level using a flat prior in δCP, and just below 2σ using a flat prior in sinδCP. When the external constraint on sin2θ13 is removed, sin2θ13=28.0-6.5+2.8×10-3, in agreement with measurements from reactor experiments. These results are consistent with previous T2K analyses.

Delayed diagnosis of foreign body aspiration in children.

AIMS: To assess the diagnostic and therapeutic difficulties as well as the long-term complications of prolonged endobronchial foreign body retention. METHOD: Between January 2000 and May 2021, 794 patients with suspected foreign body aspiration (FBA) were hospitalized in our department. A total of 12 patients with a delayed diagnosis of over 1 month were included. FBAs were confirmed by flexible or rigid endoscopy. A retrospective analysis of medical records was performed. RESULTS: Six male patients and six female patients were hospitalized due to prolonged FBA. The average age was 6.90 years (range: 1-13 years). The average duration of the foreign body retention was 2.60 years (2 months to 9 years). A choking event was found in eight cases. Coughing and wheezing were the main symptoms and signs. A misdiagnosis of asthma was made for five patients. Two atypical clinical presentations led to diagnosis of endobronchial foreign body, unilateral pleurisy, and hemoptysis. We report one case of an occult foreign body externalized spontaneously through a pneumo-pleuro-cutaneous fistula. The most common clinical and radiological findings were of pneumonia and atelectasis. Computed tomography showed localized bronchiectasis in three patients. FBAs were removed with a rigid bronchoscope in eight cases. Other extractions were carried out with a flexible endoscope. The foreign bodies were most frequently of vegetable origin, such as seeds and peanuts. A granulation tissue was observed in seven cases. Bronchial stenosis and bronchiectasis are the most common late complications. Only one patient needed a surgical intervention. CONCLUSIONS: FBA should always be considered in the differential diagnosis of chronic or recurrent respiratory diseases, even in the absence of a previous choking event. Clinical and radiological findings should be carefully evaluated for a possible FBA. Delay in diagnosis and treatment of FBA should be avoided in order to prevent complications. Open surgery may be required when lung abscess has occurred.

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors.

Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for the screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified two molecules which show anti-nsp5 activity, both in our cell-based assay and in vitro on purified nsp5 protein, and inhibit SARS-CoV-2 replication in A549-ACE2 cells with EC50 values in the 4-8 µM range. The here described high-throughput-compatible assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors.

Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for high-throughput screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified four molecules, including the broad-spectrum antiviral merimepodib/VX-497, which show anti-nsp5 activity and inhibit SARS-CoV-2 replication in A549-ACE2 cells with IC 50 values in the 4-21 µM range. The here described assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.

Search for Electron Antineutrino Appearance in a Long-Baseline Muon Antineutrino Beam.

Electron antineutrino appearance is measured by the T2K experiment in an accelerator-produced antineutrino beam, using additional neutrino beam operation to constrain parameters of the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) mixing matrix. T2K observes 15 candidate electron antineutrino events with a background expectation of 9.3 events. Including information from the kinematic distribution of observed events, the hypothesis of no electron antineutrino appearance is disfavored with a significance of 2.40σ and no discrepancy between data and PMNS predictions is found. A complementary analysis that introduces an additional free parameter which allows non-PMNS values of electron neutrino and antineutrino appearance also finds no discrepancy between data and PMNS predictions.

Search for CP Violation in Neutrino and Antineutrino Oscillations by the T2K Experiment with 2.2×10

The T2K experiment measures muon neutrino disappearance and electron neutrino appearance in accelerator-produced neutrino and antineutrino beams. With an exposure of 14.7(7.6)×10^{20} protons on target in the neutrino (antineutrino) mode, 89 ν_{e} candidates and seven anti-ν_{e} candidates are observed, while 67.5 and 9.0 are expected for δ_{CP}=0 and normal mass ordering. The obtained 2σ confidence interval for the CP-violating phase, δ_{CP}, does not include the CP-conserving cases (δ_{CP}=0, π). The best-fit values of other parameters are sin^{2}θ_{23}=0.526_{-0.036}^{+0.032} and Δm_{32}^{2}=2.463_{-0.070}^{+0.071}×10^{-3} eV^{2}/c^{4}.

Validation of an analytical method for 1,2,4-triazole in soil using liquid chromatography coupled to electrospray tandem mass spectrometry and monitoring of propiconazole degradation in a batch study.

1,2,4-triazole is one of the most important metabolites resulting from the degradation of a large class of pesticides, the triazole fungicides. These fungicides are widely used on fruits, vegetables and cereals. Two different analytical methods which are quick, cheap and easy to implement were developed and validated to monitor propiconazole and 1,2,4-triazole in soil using LC-MS/MS. The limits of quantification reached were 4.0 µg kg-1 for propiconazole and 1.1 µg kg-1 for 1,2,4-triazole. The recovery range was from 93 to 99% with a relative standard deviation <11.2% and from 83 to 97% with a RSD <7.8% for propiconazole and 1,2,4-triazole respectively. These methods: were used to monitor the degradation of propiconazole and the formation of 1,2,4-triazole in soil in a batch study lasting 28 days.

Combined Analysis of Neutrino and Antineutrino Oscillations at T2K.

T2K reports its first results in the search for CP violation in neutrino oscillations using appearance and disappearance channels for neutrino- and antineutrino-mode beams. The data include all runs from January 2010 to May 2016 and comprise 7.482×10^{20} protons on target in neutrino mode, which yielded in the far detector 32 e-like and 135 µ-like events, and 7.471×10^{20} protons on target in antineutrino mode, which yielded 4 e-like and 66 µ-like events. Reactor measurements of sin^{2}2θ_{13} have been used as an additional constraint. The one-dimensional confidence interval at 90% for the phase δ_{CP} spans the range (-3.13, -0.39) for normal mass ordering. The CP conservation hypothesis (δ_{CP}=0, π) is excluded at 90% C.L.

Measurement of Coherent π

We report the first measurement of the flux-averaged cross section for charged current coherent π^{+} production on carbon for neutrino energies less than 1.5 GeV, and with a restriction on the final state phase space volume in the T2K near detector, ND280. Comparisons are made with predictions from the Rein-Sehgal coherent production model and the model by Alvarez-Ruso et al., the latter representing the first implementation of an instance of the new class of microscopic coherent models in a neutrino interaction Monte Carlo event generator. We observe a clear event excess above background, disagreeing with the null results reported by K2K and SciBooNE in a similar neutrino energy region. The measured flux-averaged cross sections are below those predicted by both the Rein-Sehgal and Alvarez-Ruso et al.

Measurement of Muon Antineutrino Oscillations with an Accelerator-Produced Off-Axis Beam.

T2K reports its first measurements of the parameters governing the disappearance of ν[over ¯]_{µ} in an off-axis beam due to flavor change induced by neutrino oscillations. The quasimonochromatic ν[over ¯]_{µ} beam, produced with a peak energy of 0.6 GeV at J-PARC, is observed at the far detector Super-Kamiokande, 295 km away, where the ν[over ¯]_{µ} survival probability is expected to be minimal. Using a data set corresponding to 4.01×10^{20} protons on target, 34 fully contained µ-like events were observed. The best-fit oscillation parameters are sin^{2}(θ[over ¯]_{23})=0.45 and |Δm[over ¯]_{32}^{2}|=2.51×10^{-3} eV^{2} with 68% confidence intervals of 0.38-0.64 and 2.26-2.80×10^{-3} eV^{2}, respectively. These results are in agreement with existing antineutrino parameter measurements and also with the ν_{µ} disappearance parameters measured by T2K.

Scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDX) and aerosol time-of-flight mass spectrometry (ATOFMS) single particle analysis of metallurgy plant emissions.

The chemical composition of single particles deposited on industrial filters located in three different chimneys of an iron-manganese (Fe-Mn) alloy manufacturing plant have been compared using aerosol time-of-flight mass spectrometry (ATOFMS) and scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDX). Very similar types of particles were observed using both analytical techniques. Calcium-containing particles dominated in the firing area of the sintering unit, Mn and/or Al-bearing particles were observed at the cooling area of the sintering unit, while Mn-containing particles were dominant at the smelting unit. SEM-EDX analysis of particles collected downstream of the industrial filters showed that the composition of the particles emitted from the chimneys is very similar to those collected on the filters. ATOFMS analysis of ore samples was also performed to identify particulate emissions that could be generated by wind erosion and manual activities. Specific particle types have been identified for each emission source (chimneys and ore piles) and can be used as tracers for source apportionment of ambient PM measured in the vicinity of the industrial site.

Measurement of the inclusive electron neutrino charged current cross section on carbon with the T2K near detector.

The T2K off-axis near detector ND280 is used to make the first differential cross-section measurements of electron neutrino charged current interactions at energies ∼1 GeV as a function of electron momentum, electron scattering angle, and four-momentum transfer of the interaction. The total flux-averaged ν(e) charged current cross section on carbon is measured to be ⟨σ⟩(ϕ)=1.11±0.10(stat)±0.18(syst)×10⁻³8 cm²/nucleon. The differential and total cross-section measurements agree with the predictions of two leading neutrino interaction generators, NEUT and GENIE. The NEUT prediction is 1.23×10⁻³8 cm²/nucleon and the GENIE prediction is 1.08×10⁻³8 cm²/nucleon. The total ν(e) charged current cross-section result is also in agreement with data from the Gargamelle experiment.

Precise measurement of the neutrino mixing parameter θ23 from muon neutrino disappearance in an off-axis beam.

New data from the T2K neutrino oscillation experiment produce the most precise measurement of the neutrino mixing parameter θ23. Using an off-axis neutrino beam with a peak energy of 0.6 GeV and a data set corresponding to 6.57×10(20) protons on target, T2K has fit the energy-dependent νµ oscillation probability to determine oscillation parameters. The 68% confidence limit on sin(2)(θ23) is 0.514(-0.056)(+0.055) (0.511±0.055), assuming normal (inverted) mass hierarchy. The best-fit mass-squared splitting for normal hierarchy is Δm32(2)=(2.51±0.10)×10(-3) eV(2)/c(4) (inverted hierarchy: Δm13(2)=(2.48±0.10)×10(-3) eV(2)/c(4)). Adding a model of multinucleon interactions that affect neutrino energy reconstruction is found to produce only small biases in neutrino oscillation parameter extraction at current levels of statistical uncertainty.

Observation of electron neutrino appearance in a muon neutrino beam.

The T2K experiment has observed electron neutrino appearance in a muon neutrino beam produced 295 km from the Super-Kamiokande detector with a peak energy of 0.6 GeV. A total of 28 electron neutrino events were detected with an energy distribution consistent with an appearance signal, corresponding to a significance of 7.3σ when compared to 4.92±0.55 expected background events. In the Pontecorvo-Maki-Nakagawa-Sakata mixing model, the electron neutrino appearance signal depends on several parameters including three mixing angles θ12, θ23, θ13, a mass difference Δm(32)(2) and a CP violating phase δ(CP). In this neutrino oscillation scenario, assuming |Δm(32)(2)|=2.4×10(-3) eV(2), sin(2)θ(23)=0.5, and Δm322>0 (Δm(32)(2)<0), a best-fit value of sin(2)2θ(13)=0.140(-0.032)(+0.038) (0.170(-0.037)(+0.045)) is obtained at δ(CP)=0. When combining the result with the current best knowledge of oscillation parameters including the world average value of θ(13) from reactor experiments, some values of δ(CP) are disfavored at the 90% C.L.

Measurement of neutrino oscillation parameters from muon neutrino disappearance with an off-axis beam.

The T2K Collaboration reports a precision measurement of muon neutrino disappearance with an off-axis neutrino beam with a peak energy of 0.6 GeV. Near detector measurements are used to constrain the neutrino flux and cross section parameters. The Super-Kamiokande far detector, which is 295 km downstream of the neutrino production target, collected data corresponding to 3.01×10(20) protons on target. In the absence of neutrino oscillations, 205±17 (syst) events are expected to be detected while only 58 muon neutrino event candidates are observed. A fit to the neutrino rate and energy spectrum, assuming three neutrino flavors and normal mass hierarchy yields a best-fit mixing angle sin2(θ23)=0.514±0.082 and mass splitting |Δm(32)(2)|=2.44(-0.15)(+0.17)×10(-3) eV2/c4. Our result corresponds to the maximal oscillation disappearance probability.

Indication of electron neutrino appearance from an accelerator-produced off-axis muon neutrino beam.

The T2K experiment observes indications of ν(µ) → ν(e) appearance in data accumulated with 1.43×10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Δm(23)(2)| = 2.4×10(-3) eV(2), sin(2)2θ(23) = 1 and sin(2)2θ(13) = 0, the expected number of such events is 1.5±0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7×10(-3), equivalent to 2.5σ significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2θ(13) < 0.28(0.34) for δ(CP) = 0 and a normal (inverted) hierarchy.

Improved search for nu(mu) --> nu(e) oscillation in a long-baseline accelerator experiment.

We performed an improved search for nu(mu) --> nu(e) oscillation with the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment, using the full data sample of 9.2 x 10(19) protons on target. No evidence for a nu(e) appearance signal was found, and we set bounds on the nu(mu) --> nu(e) oscillation parameters. At Deltam(2)=2.8 x 10(-3) eV(2), the best-fit value of the K2Knu(mu) disappearance analysis, we set an upper limit of sin(2)2theta(mue) < 0.13 at a 90% confidence level.

Search for coherent charged pion production in neutrino-carbon interactions.

We report the result from a search for charged-current coherent pion production induced by muon neutrinos with a mean energy of 1.3 GeV. The data are collected with a fully active scintillator detector in the K2K long-baseline neutrino oscillation experiment. No evidence for coherent pion production is observed, and an upper limit of is set on the cross section ratio of coherent pion production to the total charged-current interaction at 90% confidence level. This is the first experimental limit for coherent charged pion production in the energy region of a few GeV.

Evidence for muon neutrino oscillation in an accelerator-based experiment.

We present results for nu(mu) oscillation in the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment. K2K uses an accelerator-produced nu(mu) beam with a mean energy of 1.3 GeV directed at the Super-Kamiokande detector. We observed the energy-dependent disappearance of nu(mu), which we presume have oscillated to nu(tau). The probability that we would observe these results if there is no neutrino oscillation is 0.0050% (4.0 sigma).