70 research outputs found

    CYP2D6 genotypes in revolving door patients with bipolar disorders: A case series

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    RATIONALE: In psychiatric disorders, interindividual differences in cytochrome P450 (CYP)2D6 (CYP2D6) enzymatic activity could be responsible of adverse drug reactions (ADRs) and therapeutic failures (TFs) for CYP2D6-metabolized drugs, contributing to the periodical hospital readmissions of the revolving door (RD) condition.PATIENT CONCERNS: We investigated CYP2D6 genotypes in a controlled series of 5 consecutive RD patients with Bipolar Disorder (BD).DIAGNOSES: Psychiatric patients affected by Bipolar Disorder.INTERVENTIONS: We defined TFs as a difference at the Brief Psychiatric Rating Scale score \u394BPRS\u200a<\u200a25% at each 1-week of stable treatment, and ADRs as the onset of extrapyramidal symptoms and/or metabolic impairment with weight gain.OUTCOMES: At 3 months, a mean number of 2.75\u200a\ub1\u200a1.26 ADR and a mean \u394BPRS score of 16.07\u200a\ub1\u200a0.05% were observed. At 6 months of follow-up, compared to the only patient without BD (\u394BPRS\u200a<\u200a32.10%), BD patients (n\u200a=\u200a4) showed TFs (\u394BPRS\u200a<\u200a25%). CYP2D6 genotyping revealed intermediate metabolizer phenotypes for BD patients and an extensive metabolizer phenotype for the patient without BD. In BD patients, the ratio of drugs maintained/discontinued for TFs or ADRs was 1.75 for non-CYP2D6 versus 0.33 for CYP2D6 interacting drugs, while the proportion of ADR:TF was 0:4 versus 6:3.LESSONS: Our findings may suggest that CYP2D6 clinically relevant genotypes may be involved in the unwanted outcomes observed in RD patients with BD

    Identification and reconstruction of low-energy electrons in the ProtoDUNE-SP detector

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    Measurements of electrons from Îœe\nu_e interactions are crucial for the Deep Underground Neutrino Experiment (DUNE) neutrino oscillation program, as well as searches for physics beyond the standard model, supernova neutrino detection, and solar neutrino measurements. This article describes the selection and reconstruction of low-energy (Michel) electrons in the ProtoDUNE-SP detector. ProtoDUNE-SP is one of the prototypes for the DUNE far detector, built and operated at CERN as a charged particle test beam experiment. A sample of low-energy electrons produced by the decay of cosmic muons is selected with a purity of 95%. This sample is used to calibrate the low-energy electron energy scale with two techniques. An electron energy calibration based on a cosmic ray muon sample uses calibration constants derived from measured and simulated cosmic ray muon events. Another calibration technique makes use of the theoretically well-understood Michel electron energy spectrum to convert reconstructed charge to electron energy. In addition, the effects of detector response to low-energy electron energy scale and its resolution including readout electronics threshold effects are quantified. Finally, the relation between the theoretical and reconstructed low-energy electron energy spectrum is derived and the energy resolution is characterized. The low-energy electron selection presented here accounts for about 75% of the total electron deposited energy. After the addition of lost energy using a Monte Carlo simulation, the energy resolution improves from about 40% to 25% at 50~MeV. These results are used to validate the expected capabilities of the DUNE far detector to reconstruct low-energy electrons.Comment: 19 pages, 10 figure

    Impact of cross-section uncertainties on supernova neutrino spectral parameter fitting in the Deep Underground Neutrino Experiment

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    A primary goal of the upcoming Deep Underground Neutrino Experiment (DUNE) is to measure the O(10)\mathcal{O}(10) MeV neutrinos produced by a Galactic core-collapse supernova if one should occur during the lifetime of the experiment. The liquid-argon-based detectors planned for DUNE are expected to be uniquely sensitive to the Îœe\nu_e component of the supernova flux, enabling a wide variety of physics and astrophysics measurements. A key requirement for a correct interpretation of these measurements is a good understanding of the energy-dependent total cross section σ(EÎœ)\sigma(E_\nu) for charged-current Îœe\nu_e absorption on argon. In the context of a simulated extraction of supernova Îœe\nu_e spectral parameters from a toy analysis, we investigate the impact of σ(EÎœ)\sigma(E_\nu) modeling uncertainties on DUNE's supernova neutrino physics sensitivity for the first time. We find that the currently large theoretical uncertainties on σ(EÎœ)\sigma(E_\nu) must be substantially reduced before the Îœe\nu_e flux parameters can be extracted reliably: in the absence of external constraints, a measurement of the integrated neutrino luminosity with less than 10\% bias with DUNE requires σ(EÎœ)\sigma(E_\nu) to be known to about 5%. The neutrino spectral shape parameters can be known to better than 10% for a 20% uncertainty on the cross-section scale, although they will be sensitive to uncertainties on the shape of σ(EÎœ)\sigma(E_\nu). A direct measurement of low-energy Îœe\nu_e-argon scattering would be invaluable for improving the theoretical precision to the needed level.Comment: 25 pages, 21 figure

    Highly-parallelized simulation of a pixelated LArTPC on a GPU

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    The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

    Adolescence, imperceptible boundary between normality and pathology: a literature review

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    A reorganization of the brain occurs in adolescence and it is documented by neuroimaging, neurophysiology and pathology of development. The high levels of neural plasticity allow the intellectual and emotional development during adolescence, a transition period of life full of physical and psychological changes. However, potentially dangerous agents could be the genesis of psychopathology of the adult and mental illness or distress. Adolescence is a crucial phase for the maturation of the brain. Therefore, future research should study how the environment affects and influences the function and the organization of the brain. Teenagers look for new experiences and strong emotions, sometimes endangering their health. Neuroscientific explanations have been proposed for the typical teenagers' behavior. In the postnatal period the highest density of gray matter can be found in the primary sensorimotor cortex, while prefrontal cortex matures later. Subcortical areas of the brain, especially the limbic system and the reward system, develop earlier; therefore, there is an imbalance between the more mature subcortical areas and the less mature prefrontal areas during adolescence. This could explain the typical behavior patterns of this period of life
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