Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs

Fetal alcohol spectrum disorder (FASD) is a leading potentially preventable birth defect. Poor nutrition may contribute to adverse developmental outcomes of prenatal alcohol exposure, and supplementation of essential micronutrients such as choline has shown benefit in rodent models. The sheep model of first-trimester binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Primary outcome measures included volumetrics of the whole brain, cerebellum, and pituitary derived from magnetic resonance imaging (MRI) in 6-month-old lambs, testing the hypothesis that alcohol-exposed lambs would have brain volume reductions that would be ameliorated by maternal choline supplementation. Pregnant sheep were randomly assigned to one of five groups – heavy binge alcohol (HBA; 2.5 g/kg/treatment ethanol), heavy binge alcohol plus choline supplementation (HBC; 2.5 g/kg/treatment ethanol and 10 mg/kg/day choline), saline control (SC), saline control plus choline supplementation (SCC; 10 mg/kg/day choline), and normal control (NC). Ewes were given intravenous alcohol (HBA, HBC; mean peak BACs of ~280 mg/dL) or saline (SC, SCC) on three consecutive days per week from gestation day (GD) 4–41; choline was administered on GD 4–148. MRI scans of lamb brains were performed postnatally on day 182. Lambs from both alcohol groups (with or without choline) showed significant reductions in total brain volume; cerebellar and pituitary volumes were not significantly affected. This is the first report of MRI-derived volumetric brain reductions in a sheep model of FASD following binge-like alcohol exposure during the first trimester. These results also indicate that maternal choline supplementation comparable to doses in human studies fails to prevent brain volume reductions typically induced by first-trimester binge alcohol exposure. Future analyses will assess behavioral outcomes along with regional brain and neurohistological measures

Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester

Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4-41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD

Deep Underground Neutrino Experiment (DUNE) Near Detector Conceptual Design Report

International audienceThe Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation

DUNE Offline Computing Conceptual Design Report

This document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation

DUNE Offline Computing Conceptual Design Report

International audienceThis document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment