Caracterización geoquímica de los sedimentos de la red de drenaje del Rio Garona en la Val d'Aran (Catalunya, España).

A geochemical survey of stream sediments from the Garona River was performed in order to define the main regional lithogeochemical units and, based on this geochemical exploration study, to establish the reference levels of some chemical elements in the upper Garona River basin. The analysis of the lower grainsize fraction (˂180 μm) by HR-ICP-MS of 33 stream sediment samples allowed us establish reference levels for 48 elements. We have also studied the leachates of the sediments to model the environmentally available geochemical fraction. The trace elements with the lowest reference level, ranging between 10 and 50 mg/kg, are Th, Pr, Ga, Y, Ni, Pb, As, Cu, Zr, Li, Cr, Nd, La, and V. Instead, Zn, Rb, Sr, Ce and Ba show concentrations higher than 50 mg/kg. Some enrichments were observed in the streams sediments according to the three main litogeochemical units defined; the Maladeta-Marimanya granitoids (higher concentrations of Y, Th, Pb and U), the metasediments of an extensive area of the basin (enrichments in Pb, Sr and Sn), and the black shales (in Cu, U, Sr, Ni, Zn, V, Sb and Mo) which are present in local areas of the basin.SíPeer Reviewe

Reducing medication errors for adults in hospital settings

Background: Medication errors are preventable events that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional or patient. Medication errors in hospitalised adults may cause harm, additional costs, and even death. Objectives: To determine the effectiveness of interventions to reduce medication errors in adults in hospital settings. Search methods: We searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers on 16 January 2020. Selection criteria: We included randomised controlled trials (RCTs) and interrupted time series (ITS) studies investigating interventions aimed at reducing medication errors in hospitalised adults, compared with usual care or other interventions. Outcome measures included adverse drug events (ADEs), potential ADEs, preventable ADEs, medication errors, mortality, morbidity, length of stay, quality of life and identified/solved discrepancies. We included any hospital setting, such as inpatient care units, outpatient care settings, and accident and emergency departments. Data collection and analysis: We followed the standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care (EPOC) Group. Where necessary, we extracted and reanalysed ITS study data using piecewise linear regression, corrected for autocorrelation and seasonality, where possible. Main results: We included 65 studies: 51 RCTs and 14 ITS studies, involving 110,875 participants. About half of trials gave rise to 'some concerns' for risk of bias during the randomisation process and one-third lacked blinding of outcome assessment. Most ITS studies presented low risk of bias. Most studies came from high-income countries or high-resource settings. Medication reconciliation –the process of comparing a patient's medication orders to the medications that the patient has been taking– was the most common type of intervention studied. Electronic prescribing systems, barcoding for correct administering of medications, organisational changes, feedback on medication errors, education of professionals and improved medication dispensing systems were other interventions studied. Medication reconciliation. Low-certainty evidence suggests that medication reconciliation (MR) versus no-MR may reduce medication errors (odds ratio [OR] 0.55, 95% confidence interval (CI) 0.17 to 1.74; 3 studies; n=379). Compared to no-MR, MR probably reduces ADEs (OR 0.38, 95%CI 0.18 to 0.80; 3 studies, n=1336; moderate-certainty evidence), but has little to no effect on length of stay (mean difference (MD) -0.30 days, 95%CI -1.93 to 1.33 days; 3 studies, n=527) and quality of life (MD -1.51, 95%CI -10.04 to 7.02; 1 study, n=131). Low-certainty evidence suggests that, compared to MR by other professionals, MR by pharmacists may reduce medication errors (OR 0.21, 95%CI 0.09 to 0.48; 8 studies, n=2648) and may increase ADEs (OR 1.34, 95%CI 0.73 to 2.44; 3 studies, n=2873). Compared to MR by other professionals, MR by pharmacists may have little to no effect on length of stay (MD -0.25, 95%CI -1.05 to 0.56; 6 studies, 3983). Moderate-certainty evidence shows that this intervention probably has little to no effect on mortality during hospitalisation (risk ratio (RR) 0.99, 95%CI 0.57 to 1.7; 2 studies, n=1000), and on readmissions at one month (RR 0.93, 95%CI 0.76 to 1.14; 2 studies, n=997); and low-certainty evidence suggests that the intervention may have little to no effect on quality of life (MD 0.00, 95%CI -14.09 to 14.09; 1 study, n=724). Low-certainty evidence suggests that database-assisted MR conducted by pharmacists, versus unassisted MR conducted by pharmacists, may reduce potential ADEs (OR 0.26, 95%CI 0.10 to 0.64; 2 studies, n=3326), and may have no effect on length of stay (MD 1.00, 95%CI -0.17 to 2.17; 1 study, n=311). Low-certainty evidence suggests that MR performed by trained pharmacist technicians, versus pharmacists, may have little to no difference on length of stay (MD -0.30, 95%CI -2.12 to 1.52; 1 study, n=183). However, the CI is compatible with important beneficial and detrimental effects. Low-certainty evidence suggests that MR before admission may increase the identification of discrepancies compared with MR after admission (MD 1.27, 95%CI 0.46 to 2.08; 1 study, n=307). However, the CI is compatible with important beneficial and detrimental effects. Moderate-certainty evidence shows that multimodal interventions probably increase discrepancy resolutions compared to usual care (RR 2.14, 95%CI 1.81 to 2.53; 1 study, n=487). Computerised physician order entry (CPOE)/clinical decision support systems (CDSS). Moderate-certainty evidence shows that CPOE/CDSS probably reduce medication errors compared to paper-based systems (OR 0.74, 95%CI 0.31 to 1.79; 2 studies, n=88). Moderate-certainty evidence shows that, compared with standard CPOE/CDSS, improved CPOE/CDSS probably reduce medication errors (OR 0.85, 95%CI 0.74 to 0.97; 2 studies, n=630). Low-certainty evidence suggests that prioritised alerts provided by CPOE/CDSS may prevent ADEs compared to non-prioritised (inconsequential) alerts (MD 1.98, 95%CI 1.65 to 2.31; 1 study; participant numbers unavailable). Barcode identification of participants/medications. Low-certainty evidence suggests that barcoding may reduce medication errors (OR 0.69, 95%CI 0.59 to 0.79; 2 studies, n=50,545). Reduced working hours. Low-certainty evidence suggests that reduced working hours may reduce serious medication errors (RR 0.83, 95%CI 0.63 to 1.09; 1 study, n=634). However, the CI is compatible with important beneficial and detrimental effects. Feedback on prescribing errors. Low-certainty evidence suggests that feedback on prescribing errors may reduce medication errors (OR 0.47, 95%CI 0.33 to 0.67; 4 studies, n=384). Dispensing system. Low-certainty evidence suggests that dispensing systems in surgical wards may reduce medication errors (OR 0.61, 95%CI 0.47 to 0.79; 2 studies, n=1775). Authors' conclusions: Low- to moderate-certainty evidence suggests that, compared to usual care, medication reconciliation, CPOE/CDSS, barcoding, feedback and dispensing systems in surgical wards may reduce medication errors and ADEs. However, the results are imprecise for some outcomes related to medication reconciliation and CPOE/CDSS. The evidence for other interventions is very uncertain. Powered and methodologically sound studies are needed to address the identified evidence gaps. Innovative, synergistic strategies –including those that involve patients– should also be evaluated.Fil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Fernandez Nievas, Simon E. No especifíca;Fil: Seijo, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Rodriguez, Maria Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Vietto, Valeria. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: García Perdomo, Herney A.. Universidad del Valle; ColombiaFil: Virgilio, Sacha. No especifíca;Fil: Fajreldines, Ana V.. Universidad Austral; ArgentinaFil: Tost, Josep. No especifíca;Fil: Rose, Christopher J.. No especifíca;Fil: Garcia Elorrio, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentin

Primer mamífero Mesozoico de Chile: el registro más austral de un gondwanaterio del Cretácico tardío

Se describe a Magallanodon baikashkenke gen. et. sp. nov., un nuevo mamífero gondwanaterio del Cretácico tardío de la Región de Magallanes, en el sur de Chile (Valle del Río de Las Chinas, Estancia Cerro Guido, norte de Puerto Natales, Provincia de Última Esperanza). Las capas portadoras se ubican entre los niveles del Campaniano tardío-Maastrichtiano temprano de la Formación Dorotea (Cuenca de Magallanes/Austral). Los nuevos restos constituyen el registro más austral de un mamífero gondwanaterio del Mesozoico, como así también el primer mamífero Mesozoico conocido para Chile. El nuevo taxón es comparable en tamaño a las formas hipsodontes Gondwanatherium (Cretácico tardío) y Sudamerica (Paleoceno temprano), pero con molares notoriamente braquidontes soportados por cuatro a cinco raíces. Como en otros gondwanaterios, posee al menos un incisivo superior rodentiforme en la serie superior. Se diagnostica y describe brevemente el nuevo taxón, considerado tentativamente como un ferugliotérido (Ferugliotheriidae). De confirmarse esta asignación, este nuevo taxón representaría el miembro de mayor tamaño para la familia. El patrón oclusal de los molariformes, con el desgaste, se semeja también al de otros gondwanaterios, en particular al de los ferugliotéridos y al del sudamerícido Gondwanatherium, agregando en consecuencia más evidencias en favor de la proximidad filogenética entre ambas familias. Se llevó a cabo un análisis de la microestructura del esmalte del incisivo superior de Magallanodon; como resultado, se encontraron varias similitudes importantes con el patrón existente en Gondwanatherium (Sudamericidae). Se discute la significación de Magallanodon en la adquisición, entre los gondwanaterios, de un patrón molariforme caracterizado por la presencia de lofos transversos. Finalmente, se discute la significación del nuevo hallazgo en el contexto de las biotas australes, incluyendo aquellas de Patagonia y Antártica.We describe Magallanodon baikashkenke gen. et. sp. nov., a new gondwanatherian mammal from the Late Cretaceous of the Magallanes Region in southern Chile (Río de Las Chinas Valley, Estancia Cerro Guido, north of Puerto Natales city, Última Esperanza Province). The mammal-bearing layer is placed within the Late Campanian-Early Maastrichtian levels of the Dorotea Formation (Magallanes/ Austral Basin). The new remains constitute the southernmost record of a Mesozoic gondwanatherian mammal, as well as the first Mesozoic mammal from Chile. This taxon is comparable in size to the hypsodont-toothed Gondwanatherium (Late Cretaceous) and Sudamerica (Early Paleocene) but with noticeably brachyodont molariforms supported by four to five roots. As in other gondwanatherians, it has at least one hypertrophied, rodent-like incisor in the upper jaw. The new taxon is here diagnosed and described, and is regarded as a possible ferugliotheriid (?Ferugliotheriidae). If confirmed, it would represent the largest known taxon for this family. Its molariform occlusal crown pattern, after wear, resembles that of other gondwanatherians, particularly ferugliotheriids and that of the sudamericid Gondwanatherium. This adds new evidence on the phylogenetic proximity of ferugliotheriid and sudamericid gondwanatherians. An analysis of the enamel microstructure of the upper incisor of Magallanodon was performed demonstrating several crucial similarities with the pattern shown by Gondwanatherium (Sudamericidae). We discuss the significance of Magallanodon for understanding the acquisition, within gondwanatherians, of a lophed molariform pattern. Finally, we discuss the significance of the new finding in the context of southern biotas, including those of Patagonia and Antarctica.Fil: Goin, Francisco Javier. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Martinelli, Agustín Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Soto Acuña, Sergio. Universidad de Santiago de Chile. Facultad de Ciencias; ChileFil: Vieytes, Emma Carolina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología de Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Manriquez, Leslie. Universidad de Vale do Rio dos Sinos; BrasilFil: Fernandez, Roy A.. Universidad de Santiago de Chile. Facultad de Ciencias; ChileFil: Pino, Juan Pablo. Instituto Antártico Chileno; ChileFil: Trevisan Cristine. Instituto Antártico Chileno; ChileFil: Kaluza, Jonatan Ezequiel. Universidad de Santiago de Chile. Facultad de Ciencias; Chile. Fundación de Historia Natural Félix de Azara; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reguero, Marcelo Alfredo. Museo Nacional de Historia Natural de Santiago; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Leppe, Marcelo. Instituto Antártico Chileno; ChileFil: Ortiz, Hector. Universidad de Santiago de Chile. Facultad de Ciencias; ChileFil: Rubilar Rogers, David. Museo Nacional de Historia Natural de Santiago; ChileFil: Vargas, Alexander. Universidad de Santiago de Chile. Facultad de Ciencias; Chil

Role of Mitochondrial Complex IV in Age-Dependent Obesity

Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion

Design of a Skipper CCD Focal Plane for the SOAR Integral Field Spectrograph

We present the development of a Skipper Charge-Coupled Device (CCD) focal plane prototype for the SOAR Telescope Integral Field Spectrograph (SIFS). This mosaic focal plane consists of four 6k $\times$ 1k, 15 $\mu$m pixel Skipper CCDs mounted inside a vacuum dewar. We describe the process of packaging the CCDs so that they can be easily tested, transported, and installed in a mosaic focal plane. We characterize the performance of $\sim 650 \mu$m thick, fully-depleted engineering-grade Skipper CCDs in preparation for performing similar characterization tests on science-grade Skipper CCDs which will be thinned to 250$\mu$m and backside processed with an antireflective coating. We achieve a single-sample readout noise of $4.5 e^{-} rms/pix$ for the best performing amplifiers and sub-electron resolution (photon counting capabilities) with readout noise $\sigma \sim 0.16 e^{-} rms/pix$ from 800 measurements of the charge in each pixel. We describe the design and construction of the Skipper CCD focal plane and provide details about the synchronized readout electronics system that will be implemented to simultaneously read 16 amplifiers from the four Skipper CCDs (4-amplifiers per detector). Finally, we outline future plans for laboratory testing, installation, commissioning, and science verification of our Skipper CCD focal plane

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur

Comprehensive Analysis of NRG1 Common and Rare Variants in Hirschsprung Patients

Hirschsprung disease (HSCR, OMIM 142623) is a developmental disorder characterized by the absence of ganglion cells along variable lengths of the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. The RET proto-oncogene is the major gene for HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. Many other genes have been described to be associated with the pathology, as NRG1 gene (8p12), encoding neuregulin 1, which is implicated in the development of the enteric nervous system (ENS), and seems to contribute by both common and rare variants. Here we present the results of a comprehensive analysis of the NRG1 gene in the context of the disease in a series of 207 Spanish HSCR patients, by both mutational screening of its coding sequence and evaluation of 3 common tag SNPs as low penetrance susceptibility factors, finding some potentially damaging variants which we have functionally characterized. All of them were found to be associated with a significant reduction of the normal NRG1 protein levels. The fact that those mutations analyzed alter NRG1 protein would suggest that they would be related with HSCR disease not only in Chinese but also in a Caucasian population, which reinforces the implication of NRG1 gene in this pathology

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors

Longitudinal study of DNA methylation during the first 5 years of life.

Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention