Probabilistic risk analysis of groundwater remediation strategies

Heterogeneity of subsurface environments and insufficient site characterization are some of the reasons why decisions about groundwater exploitation and remediation have to be made under uncertainty. A typical decision maker chooses between several alternative remediation strategies by balancing their respective costs with the probability of their success or failure. We conduct a probabilistic risk assessment (PRA) to determine the likelihood of the success of a permeable reactive barrier, one of the leading approaches to groundwater remediation. While PRA is used extensively in many engineering fields, its applications in hydrogeology are scarce. This is because rigorous PRA requires one to quantify structural and parametric uncertainties inherent in predictions of subsurface flow and transport. We demonstrate how PRA can facilitate a comprehensive uncertainty quantification for complex subsurface phenomena by identifying key transport processes contributing to a barrier's failure, each of which is amenable to uncertainty analysis. Probability of failure of a remediation strategy is computed by combining independent and conditional probabilities of failure of each process. Individual probabilities can be evaluated either analytically or numerically or, barring both, can be inferred from expert opinio

Effect of dietary grape pomace on fattening rabbit performance, fatty acid composition, and shelf life of meat

The use of agroindustry by-products in animal diets allows the use of residues that are not fit for human consumption. In this study, it was investigated whether fattening commercial rabbits during 30 days with a non-medicated feed, with 20% addition of grape pomace (GPD), affected production traits and the fatty acid composition, antioxidants properties, and the shelf life of the meat compared to a conventional strategy (CON). Furthermore, it was tested, by chromatographic analysis, whether this alternative diet allowed the transfer of phenolic compounds to the meat. Thirty-six weaned rabbits were allotted to the two treatments. In each treatment, 18 rabbits were fattened in three indoor cages, each housing three males and three female rabbits. No significant differences were found in live weights (p > 0.05), but the feed conversion rate and carcass weight and yield were found to be impaired in the GPD group (p = 0.05). The GPD group had a higher intramuscular fat percentage (2.01 vs. 1.54), improved polyunsaturated/saturated fatty acids ratio (0.75 vs. 0.66), and better atherogenicity (0.71 vs. 0.83) and thrombogenicity (1.14 vs. 1.24) indexes, while the n-6/n-3 ratio was higher (25.4 vs. 20.3). Total volatile basic nitrogen in meat was lower in the GPD group (p = 0.01), suggesting a delayed spoilage. However, no improvements in total phenolic content, antioxidant capacity, reducing power, and lipid oxidation (p > 0.05) were found in the meat. Even though the GPD pellets offered to the animals had several grape-derived phenolic compounds, and higher antioxidant properties compared to the CON diet, none of the phenolic compounds detected in feeds were detected in the meat samples. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

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

Model de relació entre l’atenció primària i comunitària i l’atenció hospitalària ambulatòria

Atenció primària; Atenció hospitalària; PacientAtención primaria; Atención hospitalaria; PacientePrimary care; Hospital care; PatientL’objectiu del present document és definir un model de relació entre l’atenció primària i comunitària i l’atenció hospitalària ambulatòria que doni una resposta resolutiva, equitativa i de qualitat durant tot el procés assistencial. A tal fi es defineix el diagrama del procés assistencial pel qual els metgesa especialistes de medicina de família i comunitària (MFiC) sol·liciten l’atenció, mitjançant l’ordre clínica, dels seus homòlegs d’atenció hospitalària ambulatòria (MAH). A més, s’estableixen un seguit de recomanacions relatives a la relació que s’estableix entre l’MFiC i el MAH a l’hora de contribuir a la millora de la salut de la persona atesa

Model de relació en la derivació de pacients entre l’àmbit d’atenció primària i l’àmbit d'atenció hospitalària ambulatòria

Atenció primària; Atenció hospitalària; PacientAtención primaria; Atención hospitalaria; PacientePrimary care; Hospital care; PatientL’objectiu del present document és definir un model de relació entre l’atenció primària i comunitària i l’atenció hospitalària ambulatòria que doni una resposta resolutiva, equitativa i de qualitat durant tot el procés assistencial. A tal fi es defineix el diagrama del procés assistencial pel qual els metgesa especialistes de medicina de família i comunitària (MFiC) sol·liciten l’atenció, mitjançant l’ordre clínica, dels seus homòlegs d’atenció hospitalària ambulatòria (MAH). A més, s’estableixen un seguit de recomanacions relatives a la relació que s’estableix entre l’MFiC i el MAH a l’hora de contribuir a la millora de la salut de la persona atesa

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

13 páginas,1 figura, 3 tablas, 1 apéndice. Se extraen los autores pertenecientes a The CIBERER network que trabajan en Centros del CSIC del Appendix ACIBER (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.This study has been funded by Instituto de Salud Carlos III (ISCIII) and Spanish Ministry of Science and InnovationPeer reviewe

Respuesta de Sigmodon hispidus (Rodentia: Muridae) a la inoculación experimental con el virus de la estomatitis vesicular serotipo New Jersey

Sigmodon hispidus (cotton rat) was previously found to have antibodies against Vesicular Stomatitis Virus, New Jersey serotype (VSV-NJ) under field conditions in Costa Rica. In order to evaluate their response to the virus and potential role as reservoirs, a total of 30 adult laboratory-raised cotton rats were experimentally inoculated with 107 TCID50/ml VSV-NJ, Greentree strain, as follows: 10 by subcutaneous route (group A), 10 by oral abrasion (group B) and 10 by intranasal route (group C). Two negative control animals were included in each group. Animals developed neutralizing antibody titers ranging between 1:10-1:2560 six days after the inoculation. This species showed an immune response to Vesicular Stomatitis Virus by increasing antibody titers after inoculation, and most individuals maintained their antibody titers over time. However, live virus and replication of the virus in the host could not be demonstrated by virus isolation attempts in tissue culture methods. Hyperactivity was the only clinical sign observed in the subcutaneous and oral abrasion groups. The intranasal group presented dyspnea, depression, and weight loss. In this group, 7 of the inoculated animals died 6 days post inoculation and the last one died on day 37 post inoculation. The necropsy of the animals in this group revealed pneumonia, hyperemia in the intranasal bone, and cerebral and hepatic congestion. Control animals did not show antibody development or clinical signs. After 122 days post-inoculation, case fatality rate was 12.5% in group A, 43% in group B, and 100% in group C.Se encontró previamente que Sigmodon hispidus (rata algodonera) tenía anticuerpos contra el virus de la estomatitis vesicular, serotipo de Nueva Jersey (VSV-NJ) en condiciones de campo en Costa Rica. Para evaluar su respuesta al virus y su potencial papel como reservorio, un total de 30 ratas algodoneras adultas criadas en laboratorio fueron inoculadas experimentalmente con 107 TCID50/ml VSV-NJ, cepa Greentree, de la siguiente manera: 10 por vía subcutánea (grupo A ), 10 por abrasión bucal (grupo B) y 10 por vía intranasal (grupo C). Se incluyeron dos animales de control negativo en cada grupo. Los animales desarrollaron títulos de anticuerpos neutralizantes que oscilaban entre 1:10 y 1:2560 seis días después de la inoculación. Esta especie mostró una respuesta inmune al virus de la estomatitis vesicular al aumentar los títulos de anticuerpos después de la inoculación, y la mayoría de los individuos mantuvieron sus títulos de anticuerpos a lo largo del tiempo. Sin embargo, el virus vivo y la replicación del virus en el huésped no pudieron demostrarse mediante intentos de aislamiento del virus en métodos de cultivo de tejidos. La hiperactividad fue el único signo clínico observado en los grupos de abrasión subcutánea y oral. El grupo intranasal presentó disnea, depresión y pérdida de peso. En este grupo, 7 de los animales inoculados murieron 6 días después de la inoculación y el último murió el día 37 después de la inoculación. La necropsia de los animales de este grupo reveló neumonía, hiperemia en el hueso intranasal y congestión cerebral y hepática. Los animales de control no mostraron desarrollo de anticuerpos ni signos clínicos. Después de 122 días posteriores a la inoculación, la tasa de letalidad fue del 12,5 % en el grupo A, del 43 % en el grupo B y del 100 % en el grupo C.Universidad Nacional, Costa RicaEscuela de Medicina Veterinari

Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer

Altres ajuts: The Australian National Medical Research Council (APP1061551, APP1135928) and the Australian Research Council (DP210102385)Background: RNA modifications are important regulators of transcript activity and an increasingly emerging body of data suggests that the epitranscriptome and its associated enzymes are altered in human tumors. Methods: Combining data mining and conventional experimental procedures, NSUN7 methylation and expression status was assessed in liver cancer cell lines and primary tumors. Loss-of-function and transfection-mediated recovery experiments coupled with RNA bisulfite sequencing and proteomics determined the activity of NSUN7 in downstream targets and drug sensitivity. Results: In this study, the initial screening for genetic and epigenetic defects of 5-methylcytosine RNA methyltransferases in transformed cell lines, identified that the NOL1/NOP2/Sun domain family member 7 (NSUN7) undergoes promoter CpG island hypermethylation-associated with transcriptional silencing in a cancer-specific manner. NSUN7 epigenetic inactivation was common in liver malignant cells and we coupled bisulfite conversion of cellular RNA with next-generation sequencing (bsRNA-seq) to find the RNA targets of this poorly characterized putative RNA methyltransferase. Using knock-out and restoration-of-function models, we observed that the mRNA of the coiled-coil domain containing 9B (CCDC9B) gene required NSUN7-mediated methylation for transcript stability. Most importantly, proteomic analyses determined that CCDC9B loss impaired protein levels of its partner, the MYC-regulator Influenza Virus NS1A Binding Protein (IVNS1ABP), creating sensitivity to bromodomain inhibitors in liver cancer cells exhibiting NSUN7 epigenetic silencing. The DNA methylation-associated loss of NSUN7 was also observed in primary liver tumors where it was associated with poor overall survival. Interestingly, NSUN7 unmethylated status was enriched in the immune active subclass of liver tumors. Conclusion: The 5-methylcytosine RNA methyltransferase NSUN7 undergoes epigenetic inactivation in liver cancer that prevents correct mRNA methylation. Furthermore, NSUN7 DNA methylation-associated silencing is associated with clinical outcome and distinct therapeutic vulnerability

Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer

Abstract Background RNA modifications are important regulators of transcript activity and an increasingly emerging body of data suggests that the epitranscriptome and its associated enzymes are altered in human tumors. Methods Combining data mining and conventional experimental procedures, NSUN7 methylation and expression status was assessed in liver cancer cell lines and primary tumors. Loss-of-function and transfection-mediated recovery experiments coupled with RNA bisulfite sequencing and proteomics determined the activity of NSUN7 in downstream targets and drug sensitivity. Results In this study, the initial screening for genetic and epigenetic defects of 5-methylcytosine RNA methyltransferases in transformed cell lines, identified that the NOL1/NOP2/Sun domain family member 7 (NSUN7) undergoes promoter CpG island hypermethylation-associated with transcriptional silencing in a cancer-specific manner. NSUN7 epigenetic inactivation was common in liver malignant cells and we coupled bisulfite conversion of cellular RNA with next-generation sequencing (bsRNA-seq) to find the RNA targets of this poorly characterized putative RNA methyltransferase. Using knock-out and restoration-of-function models, we observed that the mRNA of the coiled-coil domain containing 9B (CCDC9B) gene required NSUN7-mediated methylation for transcript stability. Most importantly, proteomic analyses determined that CCDC9B loss impaired protein levels of its partner, the MYC-regulator Influenza Virus NS1A Binding Protein (IVNS1ABP), creating sensitivity to bromodomain inhibitors in liver cancer cells exhibiting NSUN7 epigenetic silencing. The DNA methylation-associated loss of NSUN7 was also observed in primary liver tumors where it was associated with poor overall survival. Interestingly, NSUN7 unmethylated status was enriched in the immune active subclass of liver tumors. Conclusion The 5-methylcytosine RNA methyltransferase NSUN7 undergoes epigenetic inactivation in liver cancer that prevents correct mRNA methylation. Furthermore, NSUN7 DNA methylation-associated silencing is associated with clinical outcome and distinct therapeutic vulnerability