CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Soy Niña

Este libro pretende contribuir al reencuentro de la educación con esas finalidades que verdaderamente importan a una niña o un niño: ser feliz, jugar, vivir juntos y (no) aprender. Para ello hemos puesto el arte, nuestras experiencias y el saber acumulado al servicio del disfrute, el cuestionamiento, el análisis crítico y la construcción común de un presente deseable. Un texto colaborativo coordinado por Ignacio Calderón Almendros y realizado por alumnado de Educación y Cambio Social en el Grado en Educación Infantil de la Universidad de Málaga

Guía de estudio núm. 9. Fibras naturales y arte textil en Boyacá y Santander

Un relato conciso y de fácil comprensión sobre los tejedores en los departamentos de Boyacá y Santander y su historia, acompañado de hermosas ilustraciones y fotografías, hacen de la guía de estudio de la exposición gráfica ‘Fibras naturales y arte textil en Boyacá y Santander’ una fuente de conocimiento accesible para los públicos; en especial lo fue para los de Bucaramanga, Tunja, Riohacha y Cúcuta, ciudades donde itineró esta exposición. Gracias a que ilustra los contextos social, económico y cultural del trabajo textil tradicional en este territorio desde la época prehispánica hasta nuestros días, se puede construir un panorama general sobre la industria textil de la lana, el algodón y el fique. De esta manera la guía reseña el largo proceso de mestizaje y desarrollo de esta industria durante la Colonia y buena parte de la República. Igualmente, se refiere al impacto que progresivamente tuvo sobre la producción casera de la región y su desarrollo hacia posibilidades artísticas

Magnetic resonance spectroscopy and imaging on fresh human brain tumor biopsies at microscopic resolution

[EN] The metabolic compn. and concn. knowledge provided by magnetic resonance spectroscopy (MRS) liq. and high-resoln. magic angle spinning spectroscopy (HR-MAS) has a relevant impact in clin. practice during magnetic resonance imaging (MRI) monitoring of human tumors. In addn., the combination of morphol. and chem. information by MRI and MRS has been particularly useful for diagnosis and prognosis of tumor evolution. MRI spatial resoln. reachable in human beings is limited for safety reasons and the demanding necessary conditions are only applicable on exptl. model animals. Nevertheless, MRS and MRI can be performed on human biopsies at high spatial resoln., enough to allow a direct correlation between the chem. information and the histol. features obsd. in such biopsies. Although HR-MAS is nowadays a well-established technique for spectroscopic anal. of tumor biopsies, with this approach just a mean metabolic profile of the whole sample can be obtained and thus the high histol. heterogeneity of some important tumors is mostly neglected. The value of metabolic HR-MAS data strongly depends on a wide statistical anal. and usually the microanatomical rationale for the correlation between histol. and spectroscopy is lost. We present here a different approach for the combined use of MRI and MRS on fresh human brain tumor biopsies with native contrast. This approach has been designed to achieve high spatial (18 × 18 × 50 m) and spectral (0.031 L) resoln. in order to obtain as much spatially detailed morphol. and metabolical information as possible without any previous treatment that can alter the sample. The preservation of native tissue conditions can provide information that can be translated to in vivo studies and addnl. opens the possibility of performing other techniques to obtain complementary information from the same sample.The authors acknowledge the SCSIE-University of Valencia Microscopy Service for the histological preparations. They also acknowledge financial support from the Spanish Government project SAF2007-6547, the Generalitat Valenciana project GVACOMP2009-303, and the E.U.s VI Framework Program via the project "Web accessible MR decision support system for brain tumor diagnosis and prognosis, incorporating in vivo and ex vivo genomic and metabolomic data" (FP6-2002-LSH 503094).Martínez-Bisbal, M.; Martínez-Granados, B.; Rovira, V.; Celda, B.; Esteve, V. (2015). Magnetic resonance spectroscopy and imaging on fresh human brain tumor biopsies at microscopic resolution. Analytical and Bioanalytical Chemistry. 407(22):6771-6780. https://doi.org/10.1007/s00216-015-8847-36771678040722Stadlbauer A, Gruber S, Nimsky C, Fahlbusch R, Hammen T, Buslei R, Tomandl B, Moser E, Ganslandt O (2006) Preoperative grading of gliomas by using metabolite quantification with high-spatial-resolution proton MR spectroscopic imaging. Radiology 238:958Howe FA, Barton SJ, Cudlip SA, Stubbs M, Saunders DE, Murphy M, Wilkins P, Opstad KS, Doyle VL, McLean MA, Bell BA, Griffiths JR (2003) Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med 49:223Castillo M, Kwock L (1999) Clinical applications of proton magnetic resonance spectroscopy in the evaluation of common intracranial tumors. Top Magn Reson Imaging 10:104Howe FA, Opstad KS (2003) 1H MR spectroscopy of brain tumours and masses. 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J Magn Reson Imaging 23:99Lai PH, Weng HH, Chen CY, Hsu SS, Ding S, Ko CW, Fu JH, Liang HL, Chen KH (2008) In vivo differentiation of aerobic brain abscesses and necrotic glioblastomas multiforme using proton MR spectroscopic imaging. AJNR Am J Neuroradiol 29:1511Vuori K, Kankaanranta L, Hakkinen AM, Gaily E, Valanne L, Granstrom ML, Joensuu H, Blomstedt G, Paetau A, Lundbom N (2004) Low-grade gliomas and focal cortical developmental malformations: differentiation with proton MR spectroscopy. Radiology 230:703Di Costanzo A, Scarabino T, Trojsi F, Popolizio T, Catapano D, Giannatempo GM, Bonavita S, Portaluri M, Tosetti M, d’Angelo VA, Salvolini U, Tedeschi G (2008) Proton MR spectroscopy of cerebral gliomas at 3 T: spatial heterogeneity, and tumour grade and extent. Eur Radiol 18:1727Law M, Yang S, Wang H, Babb JS, Johnson G, Cha S, Knopp EA, Zagzag D (2003) Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol 24:1989Catalaa I, Henry R, Dillon WP, Graves EE, McKnight TR, Lu Y, Vigneron DB, Nelson SJ (2006) Perfusion, diffusion and spectroscopy values in newly diagnosed cerebral gliomas. NMR Biomed 19:463Devos A, Lukas L, Suykens JA, Vanhamme L, Tate AR, Howe FA, Majos C, Moreno-Torres A, van der Graaf M, Arus C, Van Huffel S (2004) Classification of brain tumours using short echo time 1H MR spectra. J Magn Reson 170:164Burtscher IM, Skagerberg G, Geijer B, Englund E, Stahlberg F, Holtas S (2000) Proton MR spectroscopy and preoperative diagnostic accuracy: an evaluation of intracranial mass lesions characterized by stereotactic biopsy findings. AJNR Am J Neuroradiol 21:84Ishimaru H, Morikawa M, Iwanaga S, Kaminogo M, Ochi M, Hayashi K (2001) Differentiation between high-grade glioma and metastatic brain tumor using singlevoxel proton MR spectroscopy. Eur Radiol 11:1784Sjobakk TE, Johansen R, Bathen TF, Sonnewald U, Kvistad KA, Lundgren S, Gribbestad IS (2007) Metabolic profiling of human brain metastases using in vivo proton MR spectroscopy at 3T. BMC Cancer 7:141Stadlbauer A, Nimsky C, Buslei R, Pinker K, Gruber S, Hammen T, Buchfelder M, Ganslandt O (2007) Proton magnetic resonance spectroscopic imaging in the border zone of gliomas: correlation of metabolic and histological changes at low tumor infiltration—initial results. Investig Radiol 42:218Law M, Cha S, Knopp EA, Johnson G, Arnett J, Litt AW (2002) High-grade gliomas and solitary metastases: differentiation by using perfusion and proton spectroscopic MR imaging. Radiology 222:715Schlemmer HP, Bachert P, Herfarth KK, Zuna I, Debus J, van Kaick G (2001) Proton MR spectroscopic evaluation of suspicious brain lesions after stereotactic radiotherapy. AJNR Am J Neuroradiol 22:1316Weybright P, Sundgren PC, Maly P, Hassan DG, Nan B, Rohrer S, Junck L (2005) Differentiation between brain tumor recurrence and radiation injury using MR spectroscopy. AJR Am J Roentgenol 185:1471Stadlbauer A, Moser E, Gruber S, Buslei R, Nimsky C, Fahlbusch R, Ganslandt O (2004) Improved delineation of brain tumors: an automated method for segmentation based on pathologic changes of 1H-MRSI metabolites in gliomas. Neuroimage 23:454Dowling C, Bollen AW, Noworolski SM, McDermott MW, Barbaro NM, Day MR, Henry RG, Chang SM, Dillon WP, Nelson SJ, Vigneron DB (2001) Preoperative proton MR spectroscopic imaging of brain tumors: correlation with histopathologic analysis of resection specimens. AJNR Am J Neuroradiol 22:604Benveniste H, Blackband S (2002) MR microscopy and high resolution small animal MRI: applications in neuroscience research. Prog Neurobiol 67:393Benveniste H, Blackband SJ (2006) Translational neuroscience and magneticresonancemicroscopy. Lancet Neurol 5:536Thelwall PE, Shepherd TM, Stanisz GJ, Blackband SJ (2006) Effects of temperature and aldehyde fixation on tissue water diffusion properties, studied in an erythrocyte ghost tissue model. Magn Reson Med 56:282Fatterpekar GM, Naidich TP, Delman BN, Aguinaldo JG, Gultekin SH, Sherwood CC, Hof PR, Drayer BP, Fayad ZA (2002) Cytoarchitecture of the human cerebral cortex: MR microscopy of excised specimens at 9.4 Tesla. AJNR Am J Neuroradiol 23:1313Yushkevich PA, Avants BB, Pluta J, Das S, Minkoff D, Mechanic-Hamilton D, Glynn S, Pickup S, Liu W, Gee JC, Grossman M, Detre JA (2009) A high-resolution computational atlas of the human hippocampus from postmortem magnetic resonance imaging at 9.4 T. Neuroimage 44:385Blackwell ML, Farrar CT, Fischl B, Rosen BR (2009) Target-specific contrast agents for magnetic resonance microscopy. Neuroimage 46:382Shenkar R, Venkatasubramanian PN, Zhao JC, Batjer HH, Wyrwicz AM, Awad IA (2008) Advanced magnetic resonance imaging of cerebral cavernous malformations: part I. High-field imaging of excised human lesions. Neurosurgery 63:782Gonzalez-Segura A, Morales JM, Gonzalez-Darder JM, Cardona-Marsal R, Lopez-Gines C, Cerda-Nicolas M, Monleon D (2011) Magnetic resonance microscopy at 14 Tesla and correlative histopathology of human brain tumor tissue. PLoS One 6, e27442Shepherd TM, Flint JJ, Thelwall PE, Stanisz GJ, Mareci TH, Yachnis AT, Blackband SJ (2009) Postmortem interval alters the water relaxation and diffusion properties of rat nervous tissue—implications for MRI studies of human autopsy samples. Neuroimage 44:820Brazilian Aging Brain Study Group, Grinberg LT, Amaro E Jr, Teipel S, dos Santos DD, Pasqualucci CA, Leite RE, Camargo CR, Goncalves JA, Sanches AG, Santana M, Ferretti RE, Jacob-Filho W, Nitrini R, Heinsen H (2008) Assessment of factors that confound MRI and neuropathological correlation of human postmortem brain tissue. Cell Tissue Bank 9:195Tkac I, Starcuk Z, Choi IY, Gruetter R (1999) In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time. Magn Reson Med 41:649Pfeuffer J, Tkac I, Provencher SW, Gruetter R (1999) Toward an in vivo neurochemical profile: quantification of 18 metabolites in short-echo-time (1) H NMR spectra of the rat brain. J Magn Reson 141:104Pfeuffer J, Tkac I, Choi IY, Merkle H, Ugurbil K, Garwood M, Gruetter R (1999) Localized in vivo 1H NMR detection of neurotransmitter labeling in rat brain during infusion of [1-13C] D-glucose. 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Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial

Background: Additional safe and efficacious vaccines are needed to control the COVID-19 pandemic. We aimed to analyse the efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate. Methods: HERALD is a randomised, observer-blinded, placebo-controlled, phase 2b/3 clinical trial conducted in 47 centres in ten countries in Europe and Latin America. By use of an interactive web response system and stratification by country and age group (18–60 years and ≥61 years), adults with no history of virologically confirmed COVID-19 were randomly assigned (1:1) to receive intramuscularly either two 0·6 mL doses of CVnCoV containing 12 μg of mRNA or two 0·6 mL doses of 0·9% NaCl (placebo) on days 1 and 29. The primary efficacy endpoint was the occurrence of a first episode of virologically confirmed symptomatic COVID-19 of any severity and caused by any strain from 15 days after the second dose. For the primary endpoint, the trial was considered successful if the lower limit of the CI was greater than 30%. Key secondary endpoints were the occurrence of a first episode of virologically confirmed moderate-to-severe COVID-19, severe COVID-19, and COVID-19 of any severity by age group. Primary safety outcomes were solicited local and systemic adverse events within 7 days after each dose and unsolicited adverse events within 28 days after each dose in phase 2b participants, and serious adverse events and adverse events of special interest up to 1 year after the second dose in phase 2b and phase 3 participants. Here, we report data up to June 18, 2021. The study is registered at ClinicalTrials.gov, NCT04652102, and EudraCT, 2020–003998–22, and is ongoing. Findings: Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0–61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7% (95% CI 42·5–86·1; CVnCoV 12 cases in 1735·29 person-years, placebo 37 cases in 1569·87 person-years). In participants aged 18–60 years, vaccine efficacy against symptomatic disease was 52·5% (95% CI 36·2–64·8; CVnCoV 71 cases in 1591·47 person-years, placebo, 136 cases in 1449·23 person-years). Too few cases occurred in participants aged 61 years or older (CVnCoV 12, placebo nine) to allow meaningful assessment of vaccine efficacy. Solicited adverse events, which were mostly systemic, were more common in CVnCoV recipients (1933 [96·5%] of 2003) than in placebo recipients (1344 [67·9%] of 1978), with 542 (27·1%) CVnCoV recipients and 61 (3·1%) placebo recipients reporting grade 3 solicited adverse events. The most frequently reported local reaction after any dose in the CVnCoV group was injection-site pain (1678 [83·6%] of 2007), with 22 grade 3 reactions, and the most frequently reported systematic reactions were fatigue (1603 [80·0%] of 2003) and headache (1541 [76·9%] of 2003). 82 (0·4%) of 19 783 CVnCoV recipients reported 100 serious adverse events and 66 (0·3%) of 19 746 placebo recipients reported 76 serious adverse events. Eight serious adverse events in five CVnCoV recipients and two serious adverse events in two placebo recipients were considered vaccination-related. None of the fatal serious adverse events reported (eight in the CVnCoV group and six in the placebo group) were considered to be related to study vaccination. Adverse events of special interest were reported for 38 (0·2%) participants in the CVnCoV group and 31 (0·2%) participants in the placebo group. These events were considered to be related to the trial vaccine for 14 (<0·1%) participants in the CVnCoV group and for five (<0·1%) participants in the placebo group. Interpretation: CVnCoV was efficacious in the prevention of COVID-19 of any severity and had an acceptable safety profile. Taking into account the changing environment, including the emergence of SARS-CoV-2 variants, and timelines for further development, the decision has been made to cease activities on the CVnCoV candidate and to focus efforts on the development of next-generation vaccine candidates. Funding: German Federal Ministry of Education and Research and CureVac

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. Methods: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. Findings: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p&lt;0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p&lt;0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). Interpretation: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. Funding: None

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume I Introduction to DUNE

International audienceThe preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE's physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume II: DUNE Physics

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay -- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume II of this TDR, DUNE Physics, describes the array of identified scientific opportunities and key goals. Crucially, we also report our best current understanding of the capability of DUNE to realize these goals, along with the detailed arguments and investigations on which this understanding is based. This TDR volume documents the scientific basis underlying the conception and design of the LBNF/DUNE experimental configurations. As a result, the description of DUNE's experimental capabilities constitutes the bulk of the document. Key linkages between requirements for successful execution of the physics program and primary specifications of the experimental configurations are drawn and summarized. This document also serves a wider purpose as a statement on the scientific potential of DUNE as a central component within a global program of frontier theoretical and experimental particle physics research. Thus, the presentation also aims to serve as a resource for the particle physics community at large

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