Signatures of Subacute Potentially Catastrophic Illness in the ICU: Model Development and Validation

Objectives: Patients in ICUs are susceptible to subacute potentially catastrophic illnesses such as respiratory failure, sepsis, and hemorrhage that present as severe derangements of vital signs. More subtle physiologic signatures may be present before clinical deterioration, when treatment might be more effective. We performed multivariate statistical analyses of bedside physiologic monitoring data to identify such early subclinical signatures of incipient life-threatening illness. Design: We report a study of model development and validation of a retrospective observational cohort using resampling (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis type 1b internal validation) and a study of model validation using separate data (type 2b internal/external validation). Setting: University of Virginia Health System (Charlottesville), a tertiary-care, academic medical center. Patients: Critically ill patients consecutively admitted between January 2009 and June 2015 to either the neonatal, surgical/trauma/burn, or medical ICUs with available physiologic monitoring data. Interventions: None. Measurements and Main Results: We analyzed 146 patient-years of vital sign and electrocardiography waveform time series from the bedside monitors of 9,232 ICU admissions. Calculations from 30-minute windows of the physiologic monitoring data were made every 15 minutes. Clinicians identified 1,206 episodes of respiratory failure leading to urgent unplanned intubation, sepsis, or hemorrhage leading to multi-unit transfusions from systematic individual chart reviews. Multivariate models to predict events up to 24 hours prior had internally validated C-statistics of 0.61-0.88. In adults, physiologic signatures of respiratory failure and hemorrhage were distinct from each other but externally consistent across ICUs. Sepsis, on the other hand, demonstrated less distinct and inconsistent signatures. Physiologic signatures of all neonatal illnesses were similar. Conclusions: Subacute potentially catastrophic illnesses in three diverse ICU populations have physiologic signatures that are detectable in the hours preceding clinical detection and intervention. Detection of such signatures can draw attention to patients at highest risk, potentially enabling earlier intervention and better outcomes

First measurement of the νμ charged-current cross section on a water target without pions in the final state

This paper reports the first differential measurement of the charged-current interaction cross section of νμ on water with no pions in the final state. This flux-averaged measurement has been made using the T2K experiment\u27s off-axis near detector, and is reported in doubly differential bins of muon momentum and angle. The flux-averaged total cross section in a restricted region of phase space was found to be σ=(0.95±0.08(stat)±0.06(det syst)±0.04(model syst)±0.08(flux))×10-38 cm2/n

Updated T2K measurements of muon neutrino and antineutrino disappearance using 1.5×1021 protons on target

We report measurements by the T2K experiment of the parameters θ23 and Δm322 governing the disappearance of muon neutrinos and antineutrinos in the three-flavor neutrino oscillation model. Utilizing the ability of the experiment to run with either a mainly neutrino or a mainly antineutrino beam, the parameters are measured separately for neutrinos and antineutrinos. Using 7.482×1020 POT in neutrino running mode and 7.471×1020 POT in antineutrino mode, T2K obtained sin2(θ23)=0.51-0.07+0.08 and Δm322=2.53-0.13+0.15×10-3 eV2/c4 for neutrinos, and sin2(θ-23)=0.42-0.07+0.25 and Δm-232=2.55-0.27+0.33×10-3 eV2/c4 for antineutrinos (assuming normal mass ordering). No significant differences between the values of the parameters describing the disappearance of muon neutrinos and antineutrinos were observed

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-μ in an off-axis beam due to flavor change induced by neutrino oscillations. The quasimonochromatic ν-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-μ survival probability is expected to be minimal. Using a data set corresponding to 4.01×1020 protons on target, 34 fully contained μ-like events were observed. The best-fit oscillation parameters are sin2(θ-23)=0.45 and |Δm-322|=2.51×10-3 eV2 with 68% confidence intervals of 0.38-0.64 and 2.26-2.80×10-3 eV2, respectively. These results are in agreement with existing antineutrino parameter measurements and also with the νμ disappearance parameters measured by T2K

Measurement of double-differential muon neutrino charged-current interactions on C8 H8 without pions in the final state using the T2K off-axis beam

We report the measurement of muon neutrino charged-current interactions on carbon without pions in the final state at the T2K beam energy using 5.734×1020 protons on target. For the first time the measurement is reported as a flux-integrated, double-differential cross section in muon kinematic variables (cosθμ, pμ), without correcting for events where a pion is produced and then absorbed by final state interactions. Two analyses are performed with different selections, background evaluations and cross-section extraction methods to demonstrate the robustness of the results against biases due to model-dependent assumptions. The measurements compare favorably with recent models which include nucleon-nucleon correlations but, given the present precision, the measurement does not distinguish among the available models. The data also agree with Monte Carlo simulations which use effective parameters that are tuned to external data to describe the nuclear effects. The total cross section in the full phase space is σ=(0.417±0.047(syst)±0.005(stat))×10-38 cm2 nucleon-1 and the cross section integrated in the region of phase space with largest efficiency and best signal-over-background ratio (cosθμ\u3e0.6 and pμ\u3e200 MeV) is σ=(0.202±0.036(syst)±0.003(stat))×10-38 cm2 nucleon-1

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 7.482×1020 protons on target in neutrino mode, which yielded in the far detector 32 e-like and 135 μ-like events, and 7.471×1020 protons on target in antineutrino mode, which yielded 4 e-like and 66 μ-like events. Reactor measurements of sin22θ13 have been used as an additional constraint. The one-dimensional confidence interval at 90% for the phase δCP spans the range (-3.13, -0.39) for normal mass ordering. The CP conservation hypothesis (δCP=0, π) is excluded at 90% C.L

Measurement of neutrino and antineutrino oscillations by the T2K experiment including a new additional sample of ve interactions at the far detector

The T2K experiment reports an updated analysis of neutrino and antineutrino oscillations in appearance and disappearance channels. Asample of electron neutrino candidates at Super-Kamiokande in which a pion decay has been tagged is added to the four single-ring samples used in previous T2K oscillation analyses. Through combined analyses of these five samples, simultaneous measurements of four oscillation parameters, j?m2 32j, sin2 ?23, sin2 ?13, and dCP and of the mass ordering are made. A set of studies of simulated data indicates that the sensitivity to the oscillation parameters is not limited by neutrino interaction model uncertainty. Multiple oscillation analyses are performed, and frequentist and Bayesian intervals are presented for combinations of the oscillation parameters with and without the inclusion of reactor constraints on sin2 ?13.When combined with reactor measurements, the hypothesis of CP conservation (dCP 0 or p) is excluded at 90% confidence level. The 90% confidence region for dCP is -2.95;-0.44(-1.47;-1.27) for normal (inverted) ordering. The central values and 68% confidence intervals for the other oscillation parameters for normal (inverted) ordering are ?m2 32 2.540.082.510.08 10-3 eV2=c4 and sin2?23 0.55+0.05 -0.09 (0.55+0.05 -0.08 ), compatible with maximal mixing. In the Bayesian analysis, the data weakly prefer normal ordering (Bayes factor 3.7) and the upper octant for sin2 ?23 (Bayes factor 2.4)

First measurement of the muon neutrino charged current single pion production cross section on water with the T2K near detector

The T2K off-axis near detector, ND280, is used to make the first differential cross section measurements of muon neutrino charged current single positive pion production on a water target at energies ∼0.8 GeV. The differential measurements are presented as a function of the muon and pion kinematics, in the restricted phase space defined by pπ+\u3e200 MeV/c, pμ\u3e200 MeV/c, cos(θπ+)\u3e0.3 and cos(θμ)\u3e0.3. The total flux integrated νμ charged current single positive pion production cross section on water in the restricted phase space is measured to be

Measurement of Coherent π+ Production in Low Energy Neutrino-Carbon Scattering

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. models