43 research outputs found
Faster and safer:Research priorities in water and health
The United Nations’ Sustainable Development Goals initiated in 2016 reiterated the need for safe water and healthy lives across the globe. The tenth anniversary meeting of the International Water and Health Seminar in 2018 brought together experts, students, and practitioners, setting the stage for development of an inclusive and evidence-based research agenda on water and health. Data collection relied on a nominal group technique gathering perceived research priorities as well as underlying drivers and adaptation needs. Under a common driver of public health protection, primary research priorities included the socioeconomy of water, risk assessment and management, and improved monitoring methods and intelligence. Adaptations stemming from these drivers included translating existing knowledge to providing safe and timely services to support the diversity of human water needs. Our findings present a comprehensive agenda of topics at the forefront of water and health research. This information can frame and inform collective efforts of water and health researchers over the coming decades, contributing to improved water services, public health, and socioeconomic outcomes
Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer
Background and aims:
Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC.
Methods:
We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids.
Results:
Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency.
Conclusions:
Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy
Fate in soil of murine Norovirus : used as a surrogate for human norovirus present in wastewater reused in agricultural irrigation
Les eaux usées traitées d'origine domestique présentent généralement une charge non négligeable en virus entériques pathogènes de l'Homme, malgré leur traitement. Afin de pouvoir à terme comparer les risques sanitaires associés à différents modes de gestion de ces eaux usées, nous avons entrepris un travail sur (i) la prévision des quantités de virus entériques excrétés à partir des données épidémiologiques relatives aux gastroentérites aiguës, (ii) le devenir environnemental de ces virus lorsque les eaux usées sont rejetées en rivière, et (iii) le devenir de ces virus lorsqu'ils sont apportées au sol par irrigation. L'étude a porté sur un bassin de collecte des eaux usées de 240 000 habitants à proximité de Clermont-Ferrand, sur les rivières Artière et Allier et la nappe alluviale de l'Allier potentiellement contaminées par les rejets d'eau usée, et sur un sol du périmètre d'irrigation réutilisant ces eaux. Les concentrations en divers virus ont été suivies sur la même période dans les eaux usées brutes et traitées, dans les eaux douces de surface et souterraine. Nous avons proposé une méthode d'estimation du nombre journalier de nouveaux cas de gastroentérites aiguës d'étiologie virale en 2015-2016 à partir de données épidémiologiques et avons combiné ces estimations à un modèle d'excrétion virale pour évaluer les quantités de virus entériques arrivant à la station d'épuration. Le devenir des virus a été modélisé en tenant compte d'un abattement en station d'épuration et de dilutions-mélanges en rivières. Le devenir des virus apportés au sol par les eaux usées traitées réutilisées en irrigation agricole a été étudié sur un sol bien représenté dans le périmètre en utilisant un virus modèle. Ce devenir a été décrit par un modèle combinant transfert, immobilisation réversible et élimination, et en distinguant eau mobile et eau immobile comme virus libres et virus adsorbés sur des colloïdes en suspension. La méthode permettant de passer de l'épidémiologie à une excrétion de virus nous a permis de bien simuler les arrivées de virus à la station d'épuration avec un pic hivernal et l'impact prépondérant des norovirus GII sur les cas de gastroentérites virales. La simulation de l'abattement en station d'épuration et des phénomènes de dilutions-mélanges en rivière permet de simuler correctement la charge virale en aval du rejet d'eaux usées, mais leur devenir ultérieur reste mal caractérisé. Apporté au sol, le virus modèle était progressivement éliminé ou immobilisé de façon irréversible avec un abattement journalier de 0.38 log10. La fraction réversiblement immobilisée pouvait être estimée par une isotherme de Freundlich. L'ajout de Mg2+ a favorisé l'immobilisation du virus comme son adsorption sur des colloïdes dispersés dans l'eau mobile. Alors que les eaux usées stérilisées n'avaient pas d'effet majeur sur l'immobilisation du virus par rapport à une solution artificielle de sol en raison d'effets antagonistes des composés organiques et des cations minéraux, l'eau souterraine riche en Mg2+ favorisait l'immobilisation des virus. Un volet plante réalisé en marge de ce travail a montré l'impact d'irrigations sur les contaminations de surface et après internalisation via les racines. Complétée et améliorée, notre étude pourrait être couplée à une évaluation quantitative des risques viraux.Urban treated wastewaters may be heavily contaminated by human pathogenic enteric viruses that cause acute gastroenteritis, despite their treatment. In order to compare health risks of different wastewater management scenarios, we investigated (i) how to predict virus shedding from epidemiological data on acute gastroenteritis, (ii) the environmental fate of these viruses when wastewaters are discharged into rivers, and (iii) the fate of these viruses when they are brought to the soil by irrigation. Our study focused on a wastewater collection basin of 240,000 inhabitants near Clermont-Ferrand, on the Artière and Allier Rivers and the Allier alluvial groundwater potentially contaminated by wastewater discharges, and on a soil in the irrigation perimeter reusing these wastewaters. Concentrations of various viruses were monitored over the same period in raw and treated wastewaters, as well as in surface and underground freshwaters. We proposed a method based on epidemiological data to estimate the daily number of new cases of acute gastroenteritis of viral etiology in 2015-2016; and we combined these estimates with a viral shedding model to estimate the quantities of enteric viruses arriving at the treatment plant. The fate of viruses has been simulated by taking into account the removal of viruses in the treatment plant and dilution-mixing in rivers. The fate of viruses brought to the soil by treated wastewater reused in agricultural irrigation was studied on a well-represented soil in the perimeter using a surrogate virus. Its fate has been described by a model combining transfer, reversible immobilization and removal; the model distinguished between mobile and immobile waters, as well as between free viruses and viruses adsorbed on colloids in suspension. The method for switching from epidemiology to virus shedding allowed us to accurately simulate virus inflows to the treatment plant, including a winter peak and the prominent role of norovirus GII in viral gastroenteritis cases. The simulation of virus removal in the treatment plant and subsequent dilution-mixing phenomena in rivers allow correctly simulating the viral load in the river downstream of the wastewater discharge, but their subsequent fate remains poorly characterized. When brought to the soil, the surrogate virus was progressively removed or irreversibly immobilized, according to a 0.38 log10 daily removal. The reversibly immobilized fraction could be estimated by a Freundlich isotherm. The addition of Mg2+ favored the immobilization of viruses, as well as their adsorption on colloids dispersed in mobile water. While sterilized wastewater had no major effect on virus immobilization compared to artificial soil solution due to the antagonistic effects of their organic compounds and mineral cations, groundwater rich in Mg2+ favored immobilization of viruses. An additional work, complementary to this PhD, showed the impact of irrigations on vegetable surface and internalized contaminations. After improvement, our study could be coupled with a quantitative viral risks assessment.Key words: enteric virus, sewage, discharge, reuse, irrigation, environmental fate, scenarios, assessment
Devenir des virus entériques de l'homme dans les eaux et les sols : vers une comparaison de scénarios de rejets et de recyclages
Présentée et soutenue publiquement le 14/03/2018Urban treated wastewaters may be heavily contaminated by human pathogenic enteric viruses that cause acute gastroenteritis, despite their treatment. In order to compare health risks of different wastewater management scenarios, we investigated (i) how to predict virus shedding from epidemiological data on acute gastroenteritis, (ii) the environmental fate of these viruses when wastewaters are discharged into rivers, and (iii) the fate of these viruses when they are brought to the soil by irrigation. Our study focused on a wastewater collection basin of 240,000 inhabitants near Clermont-Ferrand, on the Artière and Allier Rivers and the Allier alluvial groundwater potentially contaminated by wastewater discharges, and on a soil in the irrigation perimeter reusing these wastewaters. Concentrations of various viruses were monitored over the same period in raw and treated wastewaters, as well as in surface and underground freshwaters. We proposed a method based on epidemiological data to estimate the daily number of new cases of acute gastroenteritis of viral etiology in 2015-2016; and we combined these estimates with a viral shedding model to estimate the quantities of enteric viruses arriving at the treatment plant. The fate of viruses has been simulated by taking into account the removal of viruses in the treatment plant and dilution-mixing in rivers. The fate of viruses brought to the soil by treated wastewater reused in agricultural irrigation was studied on a well-represented soil in the perimeter using a surrogate virus. Its fate has been described by a model combining transfer, reversible immobilization and removal; the model distinguished between mobile and immobile waters, as well as between free viruses and viruses adsorbed on colloids in suspension. The method for switching from epidemiology to virus shedding allowed us to accurately simulate virus inflows to the treatment plant, including a winter peak and the prominent role of norovirus GII in viral gastroenteritis cases. The simulation of virus removal in the treatment plant and subsequent dilution-mixing phenomena in rivers allow correctly simulating the viral load in the river downstream of the wastewater discharge, but their subsequent fate remains poorly characterized. When brought to the soil, the surrogate virus was progressively removed or irreversibly immobilized, according to a 0.38 log10 daily removal. The reversibly immobilized fraction could be estimated by a Freundlich isotherm. The addition of Mg2+ favored the immobilization of viruses, as well as their adsorption on colloids dispersed in mobile water. While sterilized wastewater had no major effect on virus immobilization compared to artificial soil solution due to the antagonistic effects of their organic compounds and mineral cations, groundwater rich in Mg2+ favored immobilization of viruses. An additional work, complementary to this PhD, showed the impact of irrigations on vegetable surface and internalized contaminations. After improvement, our study could be coupled with a quantitative viral risks assessment.Key words: enteric virus, sewage, discharge, reuse, irrigation, environmental fate, scenarios, assessment,Les eaux usées traitées d'origine domestique présentent généralement une charge non négligeable en virus entériques pathogènes de l'Homme, malgré leur traitement. Afin de pouvoir à terme comparer les risques sanitaires associés à différents modes de gestion de ces eaux usées, nous avons entrepris un travail sur (i) la prévision des quantités de virus entériques excrétés à partir des données épidémiologiques relatives aux gastroentérites aiguës, (ii) le devenir environnemental de ces virus lorsque les eaux usées sont rejetées en rivière, et (iii) le devenir de ces virus lorsqu'ils sont apportées au sol par irrigation. L'étude a porté sur un bassin de collecte des eaux usées de 240 000 habitants à proximité de Clermont-Ferrand, sur les rivières Artière et Allier et la nappe alluviale de l'Allier potentiellement contaminées par les rejets d'eau usée, et sur un sol du périmètre d'irrigation réutilisant ces eaux. Les concentrations en divers virus ont été suivies sur la même période dans les eaux usées brutes et traitées, dans les eaux douces de surface et souterraine. Nous avons proposé une méthode d'estimation du nombre journalier de nouveaux cas de gastroentérites aiguës d'étiologie virale en 2015-2016 à partir de données épidémiologiques et avons combiné ces estimations à un modèle d'excrétion virale pour évaluer les quantités de virus entériques arrivant à la station d'épuration. Le devenir des virus a été modélisé en tenant compte d'un abattement en station d'épuration et de dilutions-mélanges en rivières. Le devenir des virus apportés au sol par les eaux usées traitées réutilisées en irrigation agricole a été étudié sur un sol bien représenté dans le périmètre en utilisant un virus modèle. Ce devenir a été décrit par un modèle combinant transfert, immobilisation réversible et élimination, et en distinguant eau mobile et eau immobile comme virus libres et virus adsorbés sur des colloïdes en suspension. La méthode permettant de passer de l'épidémiologie à une excrétion de virus nous a permis de bien simuler les arrivées de virus à la station d'épuration avec un pic hivernal et l'impact prépondérant des norovirus GII sur les cas de gastroentérites virales. La simulation de l'abattement en station d'épuration et des phénomènes de dilutions-mélanges en rivière permet de simuler correctement la charge virale en aval du rejet d'eaux usées, mais leur devenir ultérieur reste mal caractérisé. Apporté au sol, le virus modèle était progressivement éliminé ou immobilisé de façon irréversible avec un abattement journalier de 0.38 log10. La fraction réversiblement immobilisée pouvait être estimée par une isotherme de Freundlich. L'ajout de Mg2+ a favorisé l'immobilisation du virus comme son adsorption sur des colloïdes dispersés dans l'eau mobile. Alors que les eaux usées stérilisées n'avaient pas d'effet majeur sur l'immobilisation du virus par rapport à une solution artificielle de sol en raison d'effets antagonistes des composés organiques et des cations minéraux, l'eau souterraine riche en Mg2+ favorisait l'immobilisation des virus. Un volet plante réalisé en marge de ce travail a montré l'impact d'irrigations sur les contaminations de surface et après internalisation via les racines. Complétée et améliorée, notre étude pourrait être couplée à une évaluation quantitative des risques viraux
Immobilisation réversible et élimination irréversibles de virus dans des sols ou des mélanges de matériaux constitutifs des sols ; un ensemble de données ouvert accompagné de commentaires brefs sur les grandes tendances.
Immobilization of murine noroviruses in a cultivated phaeozem soil and its reversibility
Immobilization of murine noroviruses in a cultivated phaeozem soil and its reversibility. Environmental Microbiology & Microbial Ecolog
Vomiting symptom of acute gastroenteritis estimated from epidemiological data can help predict river contamination by human pathogenic enteric viruses
International audienceContamination of fresh water bodies by human enteric viruses from wastewater discharge is a well-established phenomenon. Here we propose a model of viral contamination of rivers based on acute gastroenteritis epidemiology and assess how well it can simulate in situ experimental monitoring. Noroviruses, rotaviruses, enteroviruses, adenoviruses and hepatitis A viruses were quantified by molecular methods after water concentration. Water flows were obtained from the Hydro databank and wastewater treatment plant (WWTP) data. Acute gastroenteritis cases based on medical prescriptions were recorded by the French public health agency. We estimated the total number of daily viral acute gastroenteritis cases and modeled virus shedding and fate in WWTPs and rivers. Simulated virus concentrations were compared to the weighted sum of measured concentrations. Seasonal variations in viral acute gastroenteritis were predicted from vomiting occurrence. All viruses except hepatitis A virus were widely detected in wastewaters and river, in concentrations reaching 10+6 genome copies·L-1 for adenoviruses in the Artiere River. We were able to predict virus load in raw wastewater and in the Artiere River. Estimated weighting coefficients showed the high impact of noroviruses GII. This model can thus serve to compare water treatment, discharge and reuse scenarios.Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved
Entomophagy and Public Health: A Review of Microbiological Hazards
International audienceThe world population’s constant increase and the continuous need to ensure food safety and security are among the major challenges to be faced in the next 30 years. In addition, human diet is evolving with a decreased inclusion of proteins from animal sources. In this context, consumption of insects by humans (entomophagy) could be an alternative solution to the intake of protein derived from conventional livestock, due to the lower environmental impact of insect rearing compared to traditional farming. Furthermore, various insect species have promising nutritional profiles regarding both macro and micronutrients. Nowadays, it is recognized that about 2 billion people consume insects at a worldwide scale, with more than 2000 different species to have been reported. Since the beginning of the 2000s, mass rearing of insects for human consumption has been developing all over the world. Nevertheless edible insects are foodstuffs of animal origin and are usually consumed in their entirety, including the digestive tract, meaning that they may contain biological agents with hazardous potential (e.g. bacteria, parasites, viruses, prions, yeasts, molds, mycotoxins, histamine, and antibiotic resistance genes) and they must undergo a thorough analysis. Therefore, establishing the synthesis of the current knowledge on entomophagy and the related biological hazards is the main purpose of this review
Slip rate determined from cosmogenic nuclides on normal-fault facets
International audienceFacets are major topographic features built over several 100 k.y. above active normal faults. Their development integrates cumulative displacements over a longer time frame than many other geomorphological markers, and they are widespread in diverse extensional settings. We have determined the 36Cl cosmogenic nuclide concentration on limestone faceted spurs at four sites in the Central Apennines (Italy), representing variable facet height (100–400 m). The 36Cl concentration profiles show nearly constant values over the height of the facet, suggesting the facet slope has reached a steady-state equilibrium for 36Cl production. We model the 36Cl buildup on a facet based on a gradual exposure of the sample resulting from fault slip and denudation. Data inversion with this forward model yields accurate constraints on fault slip rates over the past 20–200 k.y., which are in agreement with the long-term rate independently determined on some of those faults over the past 1 m.y. 36Cl measurements on faceted spurs can therefore constrain fault slip rate over time spans as long as 200 k.y., a time period presently undersampled in most morphotectonic studies
Newsbrief - evaluating the effectiveness of window/wall interface details in managing rainwater
Dr. Michael A. Lacasse: https://orcid.org/0000-0001-7640-3701Dr. Michael A. Lacasse: https://orcid.org/0000-0001-7640-3701Also available in French: En bref - \ue9valuer l'efficacit\ue9 des d\ue9tails de l'interface fen\ueatre-mur \ue0 contr\uf4ler l'eau de pluiePeer reviewed: NoNRC publication: Ye