Multivariate brain-behaviour associations in psychiatric disorders.

Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one brain and one behavioural variable (univariate) or multiple variables against one brain/behaviour feature ('single' multivariate). Recently, large multimodal datasets have propelled a new wave of studies that leverage on 'doubly' multivariate approaches capable of parsing the multifaceted nature of both brain and behaviour simultaneously. Within this movement, canonical correlation analysis (CCA) and partial least squares (PLS) emerge as the most popular techniques. Both seek to capture shared information between brain and behaviour in the form of latent variables. We provide an overview of these methods, review the literature in psychiatric disorders, and discuss the main challenges from a predictive modelling perspective. We identified 39 studies across four diagnostic groups: attention deficit and hyperactive disorder (ADHD, k = 4, N = 569), autism spectrum disorders (ASD, k = 6, N = 1731), major depressive disorder (MDD, k = 5, N = 938), psychosis spectrum disorders (PSD, k = 13, N = 1150) and one transdiagnostic group (TD, k = 11, N = 5731). Most studies (67%) used CCA and focused on the association between either brain morphology, resting-state functional connectivity or fractional anisotropy against symptoms and/or cognition. There were three main findings. First, most diagnoses shared a link between clinical/cognitive symptoms and two brain measures, namely frontal morphology/brain activity and white matter association fibres (tracts between cortical areas in the same hemisphere). Second, typically less investigated behavioural variables in multivariate models such as physical health (e.g., BMI, drug use) and clinical history (e.g., childhood trauma) were identified as important features. Finally, most studies were at risk of bias due to low sample size/feature ratio and/or in-sample testing only. We highlight the importance of carefully mitigating these sources of bias with an exemplar application of CCA.

First Measurement of η Meson Production in Neutrino Interactions on Argon with MicroBooNE.

We present a measurement of η production from neutrino interactions on argon with the MicroBooNE detector. The modeling of resonant neutrino interactions on argon is a critical aspect of the neutrino oscillation physics program being carried out by the DUNE and Short Baseline Neutrino programs. η production in neutrino interactions provides a powerful new probe of resonant interactions, complementary to pion channels, and is particularly suited to the study of higher-order resonances beyond the Δ(1232). We measure a flux-integrated cross section for neutrino-induced η production on argon of 3.22±0.84(stat)±0.86(syst) 10^{-41} cm^{2}/nucleon. By demonstrating the successful reconstruction of the two photons resulting from η production, this analysis enables a novel calibration technique for electromagnetic showers in GeV accelerator neutrino experiments.

Search for Heavy Neutral Leptons in Electron-Positron and Neutral-Pion Final States with the MicroBooNE Detector.

We present the first search for heavy neutral leptons (HNLs) decaying into νe^{+}e^{-} or νπ^{0} final states in a liquid-argon time projection chamber using data collected with the MicroBooNE detector. The data were recorded synchronously with the NuMI neutrino beam from Fermilab's main injector corresponding to a total exposure of 7.01×10^{20} protons on target. We set upper limits at the 90% confidence level on the mixing parameter |U_{µ4}|^{2} in the mass ranges 10≤m_{HNL}≤150 MeV for the νe^{+}e^{-} channel and 150≤m_{HNL}≤245 MeV for the νπ^{0} channel, assuming |U_{e4}|^{2}=|U_{τ4}|^{2}=0. These limits represent the most stringent constraints in the mass range 35

First Double-Differential Measurement of Kinematic Imbalance in Neutrino Interactions with the MicroBooNE Detector.

We report the first measurement of flux-integrated double-differential quasielasticlike neutrino-argon cross sections, which have been made using the Booster Neutrino Beam and the MicroBooNE detector at Fermi National Accelerator Laboratory. The data are presented as a function of kinematic imbalance variables which are sensitive to nuclear ground-state distributions and hadronic reinteraction processes. We find that the measured cross sections in different phase-space regions are sensitive to different nuclear effects. Therefore, they enable the impact of specific nuclear effects on the neutrino-nucleus interaction to be isolated more completely than was possible using previous single-differential cross section measurements. Our results provide precision data to help test and improve neutrino-nucleus interaction models. They further support ongoing neutrino-oscillation studies by establishing phase-space regions where precise reaction modeling has already been achieved.

First Measurement of Quasielastic Λ Baryon Production in Muon Antineutrino Interactions in the MicroBooNE Detector.

We present the first measurement of the cross section of Cabibbo-suppressed Λ baryon production, using data collected with the MicroBooNE detector when exposed to the neutrinos from the main injector beam at the Fermi National Accelerator Laboratory. The data analyzed correspond to 2.2×10^{20} protons on target running in neutrino mode, and 4.9×10^{20} protons on target running in anti-neutrino mode. An automated selection is combined with hand scanning, with the former identifying five candidate Λ production events when the signal was unblinded, consistent with the GENIE prediction of 5.3±1.1 events. Several scanners were employed, selecting between three and five events, compared with a prediction from a blinded Monte Carlo simulation study of 3.7±1.0 events. Restricting the phase space to only include Λ baryons that decay above MicroBooNE's detection thresholds, we obtain a flux averaged cross section of 2.0_{-1.7}^{+2.2}×10^{-40} cm^{2}/Ar, where statistical and systematic uncertainties are combined.

First Constraints on Light Sterile Neutrino Oscillations from Combined Appearance and Disappearance Searches with the MicroBooNE Detector.

We present a search for eV-scale sterile neutrino oscillations in the MicroBooNE liquid argon detector, simultaneously considering all possible appearance and disappearance effects within the 3+1 active-to-sterile neutrino oscillation framework. We analyze the neutrino candidate events for the recent measurements of charged-current ν_{e} and ν_{µ} interactions in the MicroBooNE detector, using data corresponding to an exposure of 6.37×10^{20} protons on target from the Fermilab booster neutrino beam. We observe no evidence of light sterile neutrino oscillations and derive exclusion contours at the 95% confidence level in the plane of the mass-squared splitting Δm_{41}^{2} and the sterile neutrino mixing angles θ_{µe} and θ_{ee}, excluding part of the parameter space allowed by experimental anomalies. Cancellation of ν_{e} appearance and ν_{e} disappearance effects due to the full 3+1 treatment of the analysis leads to a degeneracy when determining the oscillation parameters, which is discussed in this Letter and will be addressed by future analyses.

Search for an Excess of Electron Neutrino Interactions in MicroBooNE Using Multiple Final-State Topologies.

We present a measurement of ν_{e} interactions from the Fermilab Booster Neutrino Beam using the MicroBooNE liquid argon time projection chamber to address the nature of the excess of low energy interactions observed by the MiniBooNE Collaboration. Three independent ν_{e} searches are performed across multiple single electron final states, including an exclusive search for two-body scattering events with a single proton, a semi-inclusive search for pionless events, and a fully inclusive search for events containing all hadronic final states. With differing signal topologies, statistics, backgrounds, reconstruction algorithms, and analysis approaches, the results are found to be either consistent with or modestly lower than the nominal ν_{e} rate expectations from the Booster Neutrino Beam and no excess of ν_{e} events is observed.

First Measurement of Energy-Dependent Inclusive Muon Neutrino Charged-Current Cross Sections on Argon with the MicroBooNE Detector.

We report a measurement of the energy-dependent total charged-current cross section σ(E_{ν}) for inclusive muon neutrinos scattering on argon, as well as measurements of flux-averaged differential cross sections as a function of muon energy and hadronic energy transfer (ν). Data corresponding to 5.3×10^{19} protons on target of exposure were collected using the MicroBooNE liquid argon time projection chamber located in the Fermilab booster neutrino beam with a mean neutrino energy of approximately 0.8 GeV. The mapping between the true neutrino energy E_{ν} and reconstructed neutrino energy E_{ν}^{rec} and between the energy transfer ν and reconstructed hadronic energy E_{had}^{rec} are validated by comparing the data and Monte Carlo (MC) predictions. In particular, the modeling of the missing hadronic energy and its associated uncertainties are verified by a new method that compares the E_{had}^{rec} distributions between data and a MC prediction after constraining the reconstructed muon kinematic distributions, energy, and polar angle to those of data. The success of this validation gives confidence that the missing energy in the MicroBooNE detector is well modeled and underpins first-time measurements of both the total cross section σ(E_{ν}) and the differential cross section dσ/dν on argon.

Search for Neutrino-Induced Neutral-Current Δ Radiative Decay in MicroBooNE and a First Test of the MiniBooNE Low Energy Excess under a Single-Photon Hypothesis.

We report results from a search for neutrino-induced neutral current (NC) resonant Δ(1232) baryon production followed by Δ radiative decay, with a ⟨0.8⟩ GeV neutrino beam. Data corresponding to MicroBooNE's first three years of operations (6.80×10^{20} protons on target) are used to select single-photon events with one or zero protons and without charged leptons in the final state (1γ1p and 1γ0p, respectively). The background is constrained via an in situ high-purity measurement of NC π^{0} events, made possible via dedicated 2γ1p and 2γ0p selections. A total of 16 and 153 events are observed for the 1γ1p and 1γ0p selections, respectively, compared to a constrained background prediction of 20.5±3.65(syst) and 145.1±13.8(syst) events. The data lead to a bound on an anomalous enhancement of the normalization of NC Δ radiative decay of less than 2.3 times the predicted nominal rate for this process at the 90% confidence level (C.L.). The measurement disfavors a candidate photon interpretation of the MiniBooNE low-energy excess as a factor of 3.18 times the nominal NC Δ radiative decay rate at the 94.8% C.L., in favor of the nominal prediction, and represents a greater than 50-fold improvement over the world's best limit on single-photon production in NC interactions in the sub-GeV neutrino energy range.

Search for a Higgs Portal Scalar Decaying to Electron-Positron Pairs in the MicroBooNE Detector.

We present a search for the decays of a neutral scalar boson produced by kaons decaying at rest, in the context of the Higgs portal model, using the MicroBooNE detector. We analyze data triggered in time with the Fermilab NuMI neutrino beam spill, with an exposure of 1.93×10^{20} protons on target. We look for monoenergetic scalars that come from the direction of the NuMI hadron absorber, at a distance of 100 m from the detector, and decay to electron-positron pairs. We observe one candidate event, with a standard model background prediction of 1.9±0.8. We set an upper limit on the scalar-Higgs mixing angle of θ<(3.3-4.6)×10^{-4} at the 95% confidence level for scalar boson masses in the range (100-200) MeV/c^{2}. We exclude, at the 95% confidence level, the remaining model parameters required to explain the central value of a possible excess of K_{L}^{0}→π^{0}νν[over ¯] decays reported by the KOTO collaboration. We also provide a model-independent limit on a new boson X produced in K→πX decays and decaying to e^{+}e^{-}.

First Measurement of Differential Charged Current Quasielasticlike ν_{µ}-Argon Scattering Cross Sections with the MicroBooNE Detector.

We report on the first measurement of flux-integrated single differential cross sections for charged-current (CC) muon neutrino (ν_{µ}) scattering on argon with a muon and a proton in the final state, ^{40}Ar (ν_{µ},µp)X. The measurement was carried out using the Booster Neutrino Beam at Fermi National Accelerator Laboratory and the MicroBooNE liquid argon time projection chamber detector with an exposure of 4.59×10^{19} protons on target. Events are selected to enhance the contribution of CC quasielastic (CCQE) interactions. The data are reported in terms of a total cross section as well as single differential cross sections in final state muon and proton kinematics. We measure the integrated per-nucleus CCQE-like cross section (i.e., for interactions leading to a muon, one proton, and no pions above detection threshold) of (4.93±0.76_{stat}±1.29_{sys})×10^{-38} cm^{2}, in good agreement with theoretical calculations. The single differential cross sections are also in overall good agreement with theoretical predictions, except at very forward muon scattering angles that correspond to low-momentum-transfer events.

Improved Limits on Millicharged Particles Using the ArgoNeuT Experiment at Fermilab.

A search for millicharged particles, a simple extension of the standard model, has been performed with the ArgoNeuT detector exposed to the Neutrinos at the Main Injector beam at Fermilab. The ArgoNeuT liquid argon time projection chamber detector enables a search for millicharged particles through the detection of visible electron recoils. We search for an event signature with two soft hits (MeV-scale energy depositions) aligned with the upstream target. For an exposure of the detector of 1.0×10^{20} protons on target, one candidate event has been observed, compatible with the expected background. This search is sensitive to millicharged particles with charges between 10^{-3}e and 10^{-1}e and with masses in the range from 0.1 to 3 GeV. This measurement provides leading constraints on millicharged particles in this large unexplored parameter space region.

First Measurement of Inclusive Muon Neutrino Charged Current Differential Cross Sections on Argon at E_{ν}∼0.8 GeV with the MicroBooNE Detector.

We report the first measurement of the double-differential and total muon neutrino charged current inclusive cross sections on argon at a mean neutrino energy of 0.8 GeV. Data were collected using the MicroBooNE liquid argon time projection chamber located in the Fermilab Booster neutrino beam and correspond to 1.6×10^{20} protons on target of exposure. The measured differential cross sections are presented as a function of muon momentum, using multiple Coulomb scattering as a momentum measurement technique, and the muon angle with respect to the beam direction. We compare the measured cross sections to multiple neutrino event generators and find better agreement with those containing more complete treatment of quasielastic scattering processes at low Q^{2}. The total flux integrated cross section is measured to be 0.693±0.010(stat)±0.165(syst)×10^{-38} cm^{2}.

The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector.

The development and operation of liquid-argon time-projection chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies.

Pancreatic Lipase Immunoreactivity in Serum of Dogs with Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is a relatively common endocrine disorder in dogs and is routinely associated with concurrent pancreatic injury. OBJECTIVES: The aims of this study were to determine the prevalence of pancreatic injury in dogs with DKA based on measurement of pancreatic lipase immunoreactivity in serum (PLI); compare demographic, clinicopathologic, and ultrasonographic findings in dogs with and without evidence of concurrent pancreatic injury; determine the impact of pancreatic injury on duration of hospitalization and short-term outcome. ANIMALS: One hundred and nineteen dogs with DKA with or without concurrent pancreatic injury. METHODS: Retrospective study. Dogs with DKA were divided into three groups on the basis of PLI results: positive for pancreatic injury (PLIpos ), negative for pancreatic injury (PLIneg ), and not tested (PLIna ). Demographics, clinicopathologic test results, findings on abdominal ultrasonography (AUS), duration of hospitalization, and short-term outcome were compared between the three groups. RESULTS: Based on serum PLI activity, 45 dogs (73%) with DKA had evidence of concurrent pancreatic injury. Median total carbon dioxide was significantly lower in the PLIpos dogs compared to the PLIneg dogs. There was fair agreement (κ = 0.26) between serum PLI activity and AUS. Evidence of pancreatic injury was not associated with significantly longer periods of hospitalization (PLIpos median 6 days, range 4-7 days, PLIneg median 4 days, range 3-6 days) and did not influence short-term outcome (PLIpos failure to survive to discharge 11/45, 24%, PLIneg failure to survive to discharge 2/17, 12%). CLINICAL IMPORTANCE: Concurrent pancreatic injury is common in dogs with DKA, but did not affect prognosis in this population of dogs.

Ductal Plate Malformation in the Liver of Boxer Dogs: Clinical and Histological Features.

Ductal plate malformations (DPMs) represent developmental biliary disorders with a wide phenotypic spectrum. This study characterizes DPM in 30 Boxer dogs. Median age was 1.5 (range, 0.3-10.0) years, with 12 dogs <1 year. Clinical features included increased serum levels of liver enzymes (28), gastrointestinal signs (16), poor body condition (14), abdominal effusion (9), and hepatic encephalopathy (2). Additional malformations included gallbladder atresia (8), atrophied left liver (2), absent quadrate lobe with left-displaced gallbladder (1), portal vasculature atresia (left liver, 1), intrahepatic portosystemic shunt (1), and complex intrahepatic arteriovenous malformation (1). All dogs had portal tracts dimensionally expanded by a moderate-to-severe multiple small bile duct phenotype embedded in abundant extracellular matrix; 80% displayed variable portal-to-portal bridging. Quantitative analysis confirmed significantly increased fibrillar collagen and a 3-fold increased portal tract area relative to 6 Boxer and 10 non-Boxer controls. Biliary phenotype was dominated by tightly formed CK19-positive ductules, typically 10 to 15 µm in diameter, with 3 to >30 profiles per portal tract, reduced luminal apertures, and negative Ki-67 immunoreactivity. CK19-positive biliary epithelium intersected directly with zone 1 hepatocytes as a signature feature when considered with other DPM characteristics. Phenotypic variation included a multiple small bile duct phenotype (all dogs), predominantly thin-walled sacculated ducts (4), well-formed saccular ducts (4), and sacculated segmental, interlobular, and intralobular ducts (Caroli malformation, 2 dogs, one with bridging portal fibrosis). Histologic evidence of portal venous hypoperfusion accompanied increased biliary profiles in every case. We propose that this spectrum of disorders be referred to as DPM with appropriate modifiers to characterize the unique phenotypes.

First measurement of neutrino and antineutrino coherent charged pion production on argon.

We report on the first cross section measurements for charged current coherent pion production by neutrinos and antineutrinos on argon. These measurements are performed using the ArgoNeuT detector exposed to the NuMI beam at Fermilab. The cross sections are measured to be 2.6(-1.0)(+1.2)(stat)(-0.4)(+0.3)(syst)×10(-38) cm(2)/Ar for neutrinos at a mean energy of 9.6 GeV and 5.5(-2.1)(+2.6)(stat)(-0.7)(+0.6)(syst)×10(-39) cm(2)/Ar for antineutrinos at a mean energy of 3.6 GeV.

First measurements of inclusive muon neutrino charged current differential cross sections on argon.

The ArgoNeuT Collaboration presents the first measurements of inclusive muon neutrino charged current differential cross sections on argon. Obtained in the NuMI neutrino beam line at Fermilab, the flux-integrated results are reported in terms of outgoing muon angle and momentum. The data are consistent with the Monte Carlo expectation across the full range of kinematics sampled, 0°<θ(µ)<36° and 0

Search for the standard model Higgs boson in the H→WW→lνq'q decay channel.

We present a search for the standard model Higgs boson (H) in pp collisions at sqrt(s)=1.96 TeV in events containing a charged lepton (ℓ), missing transverse energy, and at least two jets, using 5.4 fb(-1) of integrated luminosity recorded with the D0 detector at the Fermilab Tevatron Collider. This analysis is sensitive primarily to Higgs bosons produced through the fusion of two gluons or two electroweak bosons, with subsequent decay H→WW→ℓνq'q, where ℓ is an electron or muon. The search is also sensitive to contributions from other production channels, such as WH→ℓνbb. In the absence of a signal, we set limits at the 95% C.L. on the cross section for H production σ(pp→H+X) in these final states. For a mass of M(H)=160 GeV, the limit is a factor of 3.9 larger than the cross section in the standard model and consistent with an a priori expected sensitivity of 5.0.

[Effects of modulators of calcium metabolism on mesenteric artery contractions during activation of P2X receptors in guinea-pig].

ATP evokes changes in the vascular tone through the activation of P2X and P2Y purinoceptors. To evaluate relative contribution of Ca2+ entry through the L-type voltage-gated calcium channels and Ca2+ -induced Ca2+ -release (CICR) mechanisms in initiation of vascular smooth muscle contraction induced by P2XRs activation, we have applied P2X receptor agonist -meATP (10 microM) and measured changes in phasic isometric tension of endothelium-denuded mesenteric artery rings in the presence of antagonists IP3Rs (60 mcmol/l APB) or RyRs (100 mcmol/l tetracaine) combined with on-off modulation of the L-type calcium channels by nicardipine (5 microM). We found that activation of P2XRs results in Ca2+ release from SR through both IP3Rs and RyRs. In addition, Ca2+ entry via L-type Ca2+ channels also participates in Ca2+ release from SR presumably through CICR mechanism. However, the phasic contractions in the presence of nicardipine were found to be less sensitive to inhibition of IP3Rs than RyRs (47.1 +/- 9.5% and 22.9 +/- 1.4% comparing to 38.3 +/- 9.6% and 518 +/- 7.8% in control solution for IP3R and RyR inhibition, respectively). This finding suggests that Ca2+ entered the cell through L-type Ca2+ channels, has easier access to IP3Rs than to RyRs. This suggestion is further supported by immunostaining IP3Rs and RyRs. Confocal imaging revealed that sub-PM SR elements are enriched with IP3Rs, while RyRs are predominantly located in the central/perinuclear SR elements.