The DUNE far detector vertical drift technology. Technical design report

DUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe 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 implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

Perturbations hépatiques induites expérimentalement par une concentration sublétale de procymidone (fongicide dicarboximide) chez Brachydanio rerio (Téléostéen, Cyprinidé) : approche histo-cytopathologique

La procymidone[N-(3,5 dichlorophényl)-1,2 diméthylcyclopropane-1,2 dicarboximide] est une molécule utilisée pour ses capacités antifongiques principalement dans la lutte contre Botrytis et Sclerotinia. Elle présente une rémanence de plusieurs semaines dans l'environnement et est donc susceptible de contaminer, après lessivage des sols, les milieux aquatiques et les organismes qui les peuplent. L'analyse des perturbations histo-cytologiques hépatiques induites chez le Cyprinidé Brachydanio rerio par une concentration sublétale (1 mg.l-1) de ce fongicide a été réalisée après 4, 7 et 14 jours de contamination expérimentale. L'éventuelle réversibilité des perturbations induites a été étudiée après 14 jours de contamination suivis de 14 jours de décontamination. Les résultats révèlent des réponses hépatocytaires non spécifiques à l'agression toxique et d'intensité croissante en fonction de la durée de contamination. Il s'agit de réponses adaptatives (déplétion glycogénique, accumulation lipidique, réduction de la surface d'absorption hépatocellular...) et de réponses dégénératives (désorganisation des travées hépatocytaires, lyse du parenchyme dans les régions périvasculaires...). Ces réponses s'accompagnent d'une activation notable de la réponse immunitaire cellulaire non spécifique (augmentation du nombre des macrophages) en relation avec l'accroissement du catabolisme tissulaire hépatique induit. Des perturbations plus originales ont été observées : il s'agit de développements d'une organisation concentrique des travées hépatocytaires et de protrusions cytoplasmiques entre hépatocytes adjacents amenant parfois la membrane plasmique au contact de l'enveloppe nucléaire. Le retour en eau non contaminée provoque la réduction des atteintes hépatiques (réversibilités des perturbations induites) et une forte activation du métabolisme hépatocytaire (hyperdéveloppement du réticulum endoplasmique, accroissement du nombre des mitochondries)

Perturbations hépatiques induites expérimentalement par une concentration sublétale de procymidone (fongicide dicarboximide) chez Brachydanio rerio (Téléostéen, Cyprinidé) : approche histo-cytopathologique

La procymidone[N-(3,5 dichlorophényl)-1,2 diméthylcyclopropane-1,2 dicarboximide] est une molécule utilisée pour ses capacités antifongiques principalement dans la lutte contre Botrytis et Sclerotinia. Elle présente une rémanence de plusieurs semaines dans l'environnement et est donc susceptible de contaminer, après lessivage des sols, les milieux aquatiques et les organismes qui les peuplent. L'analyse des perturbations histo-cytologiques hépatiques induites chez le Cyprinidé Brachydanio rerio par une concentration sublétale (1 mg.l-1) de ce fongicide a été réalisée après 4, 7 et 14 jours de contamination expérimentale. L'éventuelle réversibilité des perturbations induites a été étudiée après 14 jours de contamination suivis de 14 jours de décontamination. Les résultats révèlent des réponses hépatocytaires non spécifiques à l'agression toxique et d'intensité croissante en fonction de la durée de contamination. Il s'agit de réponses adaptatives (déplétion glycogénique, accumulation lipidique, réduction de la surface d'absorption hépatocellular...) et de réponses dégénératives (désorganisation des travées hépatocytaires, lyse du parenchyme dans les régions périvasculaires...). Ces réponses s'accompagnent d'une activation notable de la réponse immunitaire cellulaire non spécifique (augmentation du nombre des macrophages) en relation avec l'accroissement du catabolisme tissulaire hépatique induit. Des perturbations plus originales ont été observées : il s'agit de développements d'une organisation concentrique des travées hépatocytaires et de protrusions cytoplasmiques entre hépatocytes adjacents amenant parfois la membrane plasmique au contact de l'enveloppe nucléaire. Le retour en eau non contaminée provoque la réduction des atteintes hépatiques (réversibilités des perturbations induites) et une forte activation du métabolisme hépatocytaire (hyperdéveloppement du réticulum endoplasmique, accroissement du nombre des mitochondries)

Histopathology to assess the health status of wild fish downstream from pharmaceutical manufacture discharges

Pharmaceutical Active Ingredients (APIs) are frequently detected in surface waters at levels from 1ng/l up to a few µg/l. Several sources of APIs are indentified including effluents from pharmaceutical factories that contain high concentrations of various APIs and are able to disturb the health of aquatic organisms. The aim of present work was to assess adverse effects induced by pharmaceutical factory discharges in wild fish. For this purpose, a multi-organ histopathological approach was performed in liver, gonads, gill, kidney and spleen of fish collected upstream and downstream from four pharmaceutical manufactures. Preliminary results indicated a high level of intersex in gudgeons living downstream from steroid synthesis manufacture that could support disturbance of reproductive function associated to population effects. To complete, these fish exhibited also a set of changes in gill ultra-structure such as epithelial lifting and necrosis, secondary lamellae fusions, erythrocytes stases and mucous cells proliferation that could induce disruption of iono and osmoregulation process. Necrosis was also observed in kidney. Results of histological analysis performed in other investigated sites will be presented here and relationship with industrial production and individual or population adverse effects will be discussed. These first results confirm that chemicals contained in industrial effluents can induce histological adverse effects in wild fish from receiving area. Moreover, this work argues for the implementation of monitoring programs using effect-based monitoring tools such as histopathological approaches

Histopathology to assess the health status of wild fish downstream from pharmaceutical manufacture discharges

Pharmaceutical Active Ingredients (APIs) are frequently detected in surface waters at levels from 1ng/l up to a few µg/l. Several sources of APIs are indentified including effluents from pharmaceutical factories that contain high concentrations of various APIs and are able to disturb the health of aquatic organisms. The aim of present work was to assess adverse effects induced by pharmaceutical factory discharges in wild fish. For this purpose, a multi-organ histopathological approach was performed in liver, gonads, gill, kidney and spleen of fish collected upstream and downstream from four pharmaceutical manufactures. Preliminary results indicated a high level of intersex in gudgeons living downstream from steroid synthesis manufacture that could support disturbance of reproductive function associated to population effects. To complete, these fish exhibited also a set of changes in gill ultra-structure such as epithelial lifting and necrosis, secondary lamellae fusions, erythrocytes stases and mucous cells proliferation that could induce disruption of iono and osmoregulation process. Necrosis was also observed in kidney. Results of histological analysis performed in other investigated sites will be presented here and relationship with industrial production and individual or population adverse effects will be discussed. These first results confirm that chemicals contained in industrial effluents can induce histological adverse effects in wild fish from receiving area. Moreover, this work argues for the implementation of monitoring programs using effect-based monitoring tools such as histopathological approaches

Advantages and limits of using preclinical/clinical data to predict ecotoxicological effects on wild fish : example of azole pharmaceutical compounds

European regulation related to pharmaceuticals and pharmacovigilance require improving environmental risk assessment of these compounds. In this context, identification of biological pathways that could be disrupted in nontargeted aquatic species using qualitative preclinical/clinical data associated to toxicological data appears as a promising approach. Azole drugs is a widely used group of pharmaceutical active ingredients (APIs) characterized by a lack of data related to ecotoxicological effects. The aim of this study was to generate hypothesis about the potential ecotoxicological effects of 'azole'drugs on teleost fish. Numerous studies have reported that imidazoles and triazoles, which are used in antifungal and anti-tumoral therapies respectively, are steroidogenesis disruptors due to their adverse or therapeutic mechanism of action based on inhibition of cytochromes enzymatics complexes. However, other azole APIs such as protons pump inhibitors, carbimazole, triptans, sartans, setrons, allopurinol, aciclovir, zolpidem, theophyllin exhibit various biological activities. Pharmacodynamical data on targeted and adverse effects could allow identifying ecotoxicological effects, 'Drugs Interactions' data and 'Contraindications/Precautions for uses' data may also inform about possible mixture effects and interactions with pathological contexts. Preliminary results, qualitative pharmacological data indicate possible deleterious effects of protons pump inhibitors (benzimidazole compounds) on acid excretion and Na+ uptake in gill via interference with Na+/H+ exchanger localized in gill epithelial pavement cells, especially in hypercapnia/hypoxia contexts. These disruptions may imply deleterious consequences on vital functions as respiration, iono and osmoregulation, excretion. Results obtained for other azole drugs will be presented here and advantages and limits of this approach will be discussed

Phthalate metabolites in the European eel (Anguilla anguilla) from Mediterranean coastal lagoons

International audienceThe levels and fate of phthalate metabolites have been poorly evaluated in fish, despite their potential ecotoxicological impacts. The present study aims to characterize the levels of phthalate metabolites in muscle tissue of yellow eels (Anguilla anguilla) from two coastal Mediterranean lagoons, during three sampling periods. Nine phthalate metabolites were detected in > 70% of the samples. Slightly higher levels of phthalate metabolites were detected in March and June compared to October, suggesting possible seasonal variations in environmental release and/or phthalate metabolization process by eels. The large sample size (N = 117) made it possible to explore correlations between phthalate metabolites' levels and individual parameters, such as body length, age, body condition and hepatic histo-pathologies. Body length and estimated age poorly correlated with phthalate metabolites, suggesting that eels did not accumulate phthalates during growth, contrary to persistent compounds. Eels presented different grades of hepatic fibrosis and lipidosis. A negative correlation was found between the severity of these pathologies in the liver and the sum of phthalate metabolites levels, supporting the hypothesis that eels with damaged liver are less able to metabolize xenobiotics

Cadmium and copper contents in a freshwater fish species (brook trout, Salvelinus fontinalis) from the subantarctic Kerguelen Islands

International audienceThe subantarctic Kerguelen Islands (49 degrees S, 70 degrees E) contain freshwaters among the most isolated in the world from direct human activities. Cadmium and copper concentrations were analyzed in muscle and liver tissues of 57 non-migratory brook trout (Salvelinus fontinalis) inhabiting the Sud River of Kerguelen Islands. The mean cadmium concentration in liver was 1.13 mu g/g dry wt, within the range of levels measured in liver of marine fish from the Southern Ocean. Muscular Cd levels (0.12 mu g/g dry wt) were roughly ten times higher than those measured in Kerguelen's marine fish species. Copper levels were very high in the two organs (62.27 mu g/g dry wt in liver and 3.02 mu g/g dry wt in muscle) compared to those detected in fish from the Southern Ocean. Regarding the seasonal trend, the highest Cu and Cd muscular levels were measured in fish at the end of the austral winter, whereas the highest hepatic levels were observed at the end of the austral summer. Moreover, hepatic cadmium levels were higher in females than in males. These results could be related to brook trout spawning physiological preparations and foraging behavior during the summer period. We provide here the first results about Cu and Cd levels in liver and muscle of a freshwater fish species in an insular subantarctic context. They are in agreement with the high cadmium contamination found in fish of the Southern Ocea

Ecotoxicological consequences of pharmaceutical facility discharges on wild fish : a french case of study

Discharges of wastewater treatment plants receiving effluents from pharmaceutical factories represent a non-negligible source of biologically active chemicals in surface waters able to induce ecological/ecotoxicological effects on wildlife and populations. Recently, ecotoxicological effects on teleost fish and tadpoles exposed to dilutions of Indian bulk drug manufactures effluents have been concluded, suggesting that deleterious biological effects could be induced. Furthermore, an in situ study has demonstrated a high proportion of intersex in gudgeons (Gobio gobio) living downstream from a French bulk drug manufacture discharges which could be explained by the nature of pharmaceutical production. The present work consists of an evaluation of long-term adverse effects induced by another French pharmaceutical manufacture discharges in wild fish (Gasterosteus aculeatus) using a multi biomarker approach. Ecotoxicological analysis includes a semi-quantitative evaluation of histopathological lesions in liver and spleen, an analysis of intersexe frequencies, DNA damages on erythrocytes, and biochemical markers related to biotransformation capabilities (EROD, GST, CYP 3A) and neurotoxicity (AchE). Our results highlights a marked hepatotoxic effects mainly characterized by fibrosis, lipoid degradation, confirmed by inductions of biochemical responses, increased densities of splenic melanomacrophages aggregates, and elevated DNA damages in sticklebacks sampled in receiving waters. This works argues for the implementation of monitoring programs, using effect-based tools, and the need to improve our knowledge about possible ecotoxicological disturbances occurring in specific waters which receiving pharmaceutical facilities discharges. This work was supported by the French Ministry for Ecology and Sustainable Development (MEDDE-Program 181)