Pulmonary Hypertension with “Normal” Pulmonary Vascular Resistance

Abstracts not available for Perspectives

High velocity infrared thermography and numerical trajectories of solid particles in compressible gas flow

The use of High Velocity Infrared Thermography as a valuable alternative to other existing techniques for the visualization and tracking of solid particles transported by a gas jet has been assessed by considering different situations in terms of problem characteristic numbers (jet Reynolds and Mach numbers and Particle Stokes and gravitational Froude numbers). Particles paths have also been calculated by means of a hybrid Eulerian-Lagrangian technique under the intent to cross-validate the two (experimental and numerical) approaches. The results indicate that such a strategy is robust and sufficiently flexible to be used in relatively wide regions of the space of parameters. Experiments have clearly demonstrated that thermography can properly capture particle dynamics with a level of detail comparable to that provided by simulations. Computations have proved to be valuable on their own by allowing the explorations of regions of the parameters space otherwise out of reach. Different tests have been conducted considering both isolated particles and "swarms". We show that the observed dynamics are induced by the delicate interplay of different effects, including inertial, gravitational and eventually "lift" contributions produced by a non-perfect horizontal orientation of the jet or other uncertainties (such as those due to a non mono-sized set of particles). (C) 2018 Elsevier B.V. All rights reserved

Analysis of unsaturated materials hydration incorporating the effect of thermo-osmotic flow

The geological disposal of a high level radioactive waste relies in a system composed of engineered and geological barriers. The soils and rocks involved in the design of this type of solution are generally initially unsaturated and subject to complex thermal, hydraulic and mechanical (THM) coupled phenomena triggered by the simultaneous heating and hydration of the barrier materials under confined conditions. Mathematical THM formulations are typically used to analyze the behavior and long term performance of the barriers system. These types of formulations generally do not include some coupled processes, for example thermo-osmosis (i.e. the movement of liquid water induced by gradient of temperature), because they are considered not significant when compared against the main or direct processes (e.g., Darcy’s, Fourier’s and Fick’s laws). In this work, the potential effects of thermo-osmotic phenomenon is studied in detail. Typical flow equations are modified to include thermo-osmotic flows and then they are implemented in numerical simulators. Two case studies are analyzed. The first one focuses on a simple and already proposed model to study the behavior of a geological barrier for nuclear waste when subjected to heating and hydration. The other case corresponds to the study of an engineered clay barrier material in the laboratory subjected to hydraulic and thermal gradients similar to the ones expected in real repository conditions. In both cases the analyses with and without thermo-osmotic flows are compared. From these comparisons it is observed that the effect of thermo-osmosis can be quite significant. Thermo-osmotic effects also assisted to explain the apparent low wetting observed in the hydration of a clayey barrier material

Impacto de escenarios de transferencias interregionales en Colombia

En este trabajo se evalúan los efectos económicos de diferentes escenarios de asignación regional empleados en el esquema actual de transferencias interregionales en Colombia, destacando los posibles compromisos entre la eficiencia y la equidad regional. Las simulaciones realizadas en el trabajo, utilizando un modelo de equilibrio general computable interregional, contribuyen al análisis del impacto del crecimiento relacionado con algunos de los objetivos generales que persiguen los gobiernos centrales al asignar transferencias sub-nacionales a los gobiernos locales. En este sentido, se simulan escenarios contra factuales en los que las políticas redistributivas están diseñadas para evaluar los posibles resultados del Producto Bruto Regional. Los resultados muestran que cuando la distribución se lleva a cabo sobre la base del tamaño de la población regional, hay ganancias potenciales en el crecimiento nacional junto con un aumento en las disparidades regionales. Sin embargo, cuando la distribución se lleva a cabo de acuerdo con otros criterios redistributivos, como el número de personas en condición de pobreza o las brechas horizontales de equidad fiscal, existen mejoras potenciales en la desigualdad regional, a pesar de estar acompañadas de efectos negativos del crecimiento. En este sentido, si se prioriza el criterio redistributivo para compensar la reducción del crecimiento, las regiones que enfrentan un aumento neto en las transferencias deben asignar los recursos adicionales para mejorar en términos de Productividad Total de los Factores (PTF), específicamente, priorizando en inversiones que mejoran la PTF en el largo plazo, tales como aquellas en capital humano enfocadas a la educación y la salud.We assess the economic effects of different scenarios of regional allocation of the current interregional transfers’ scheme in Colombia, highlighting potential tradeoffs between regional equity and efficiency. The simulations conducted in this work, using an interregional computable general equilibrium model, contribute to the analysis of the growth impact related to some of the broad objectives that central governments pursue when allocating subnational transfers to local governments. We simulate counterfactual scenarios in which redistributive policies are designed to assess potential Gross Regional Product (GRP) outcomes had they been applied to the Colombian economy. The results show that when the distribution is carried out based on regional population shares, there are potential gains in national growth together with an increase in regional disparities. However, when the distribution is carried out according to other redistributive criteria, such as the number of people impoverished or the horizontal equity gaps, there is a potential improvement in regional inequality despite negative growth effects. In this sense, if we prioritize the redistributive criterion in order to offset the reduction of growth, regions that face a net increase in transfers should allocate the additional resources to improve in terms of Total Factor Productivity (TFP), specifically, in long-term TFP-enhancing investments, such as human capital in the form of education and health outcomes.Enfoque Colombia es un país con amplias desigualdades en el ingreso, en comparación con otras economías. En 2016, el Índice Gini llegó a 0,51, situando al país como uno de los más desiguales del continente, solo superado por Haití. De otro lado, existen notables diferencias económicas regionales dentro del país. Por ejemplo, el PIB per cápita en el departamento de Casanare es diez veces mayor que el de Vaupés. Uno de los mecanismos a través del cual se abordan las desigualdades es mediante la redistribución del ingreso de las regiones más prósperas hacia aquellas donde hay más prevalencia de pobreza. En efecto, las políticas de descentralización han introducido mecanismos para redistribuir los ingresos de los recursos del Gobierno Nacional Central (GNC), pero las desigualdades aún persisten. La pregunta que se aborda en el trabajo ‘Impacto de escenarios de transferencias interregionales en Colombia’ es ¿Cuál sería el mecanismo de distribución de los recursos del Sistema General de Participaciones (SGP) que reduzca esas desigualdades? Contribución En esta investigación se llevó a cabo un análisis de la distribución de los recursos de GNC, evaluando diferentes escenarios contrafactuales. Este constituye el primer esfuerzo por evaluar cuáles serían los efectos de un cambio en la forma como se distribuyen las transferencias recibidas por los entes territoriales a través del Sistema General de Participaciones (SGP). Específicamente, se utilizó un modelo de equilibrio general interregional para simular los efectos que tendría un cambio en el SGP sobre el PIB agregado y sobre el producto bruto regional. Los mecanismos que se evaluaron son tres: (i) un escenario en el que se distribuyen los recursos solo teniendo en cuenta la población, (ii) uno en el que se utiliza el número de personas en condición de pobreza extrema y, por último, (iii) uno que tiene en cuenta los requerimientos para cerrar la brecha existente entre los ingresos potenciales de cada entidad territorial y sus necesidades de gasto. Destacado: Cuando la distribución se lleva a cabo sobre la base del tamaño de la población regional, hay ganancias potenciales en el crecimiento nacional junto con un aumento en las disparidades regionales. Resultados Con base en los supuestos del modelo que se usaron, los resultados evidencian que, si se distribuyen los recursos teniendo en cuenta la población, se aumentan las desigualdades, mientras que, en los otros dos escenarios, estas se reducen. Además, se encuentra que el criterio por el cual se maximiza el crecimiento del ingreso agregado, es el número de habitantes. Por otro lado, cuando la distribución se lleva a cabo de acuerdo con criterios redistributivos, como la cantidad de personas pobres o las brechas de equidad horizontal, no se alcanza el mismo crecimiento del ingreso agregado. Sin embargo, un criterio redistributivo también puede influir positivamente sobre el crecimiento, en especial si los recursos empleados se enfocan en aumentar la productividad de las regiones. Esos incrementos en productividad se pueden lograr si los mayores recursos se invierten en formación de capital humano y en mejoras en la salud de los individuos, en vez de convertirse en fuentes de gastos corrientes

Mutation of a conserved, hydrophobic, cryptic epitope improves manufacturability and immunogenicity of the SARS-CoV-2 RBD

The supply of COVID-19 vaccine doses still lags behind the global demand for first time vaccination and booster doses. Distribution of vaccine doses has been far from equitable across the world given the steep prices and logistical challenges that low- and middle-income countries face. Subunit protein vaccine candidates have now been shown to elicit protective responses against SARS-CoV-2 infection, while providing additional benefits for manufacturing capability and stability requirements compared to many currently approved vaccines. Here we report a second-generation engineered RBD sequence variant with enhanced manufacturability and immunogenicity over the wild-type ancestral RBD and a first-generation engineered variant (RBD-L452K-F490W (RBD-J)). Introducing two additional mutations, S383D and L518D, to a hydrophobic cryptic epitope in the RBD core improved expression titers and biophysical stability compared to RBD-J. These two additional mutations in RBD-S383D-L452K-F490W-L518D (RBD-J6) ablated the interaction of two neutralizing antibodies, CR3022 and EY6A, targeting the class 4 epitope on the RBD core, but the protein is still bound by human convalescent sera. Mice immunized with a Beta sequence variant of RBD-J and RBD-J6 displayed on a virus-like particle were protected against challenges with Alpha and Beta variants of SARS-CoV-2. Sera from mice immunized with three doses of a RBD-J6 β – VLP showed comparable neutralizing activity to several variants of concern compared to two doses of Comirnaty. Please click Download on the upper right corner to see the full abstract

Factores predisponentes a la parvovirosis canina registrados en un hospital de Cuautitlan, México

Canine parvovirus (CPV) was initially described in the Canidae family, but later extended to Ursidae, Procionidae, and Felidae families, among others. Its epidemiology has not been fully described. Nevertheless, climate appears to have a direct influence on the severity of the disease symptomatology. Aim of this study was to analyze the influence of different factors such as age, breed, gender, vaccination status, and climatic variables, by means of analyzing cases of this disease recorded at an veterinary hospital from Cuautitlan (México). For this purpose, clinic histories from 2016 until 2017, were analyzed. Prevalence of 1.86% was determined, being animals under seven months-old those with the highest susceptibility to CPV. In addition, from March to May, the highest number of cases were diagnosed, with peak on April. The environmental temperature explains the higher presentation of cases of parvovirus. Considering these results, it can be concluded that CPV seems to be more frequent during the warmer months, followed by high number of offspring and lower consumption of food.El parvovirus canino (PVC) se restringió inicialmente a infectar a los perros, pero luego seextendió a otras familias como felidae (gatos y otros felinos), procionidae (mapaches, coatíes)y ursidae (osos). A pesar de que su epidemiología no ha sido descrita completamente,el clima parece tener influencia directa en los rangos de presentación. En este trabajo secompararon factores como edad, raza, género, estado vacunal y variables climáticas, conla aparición de la enfermedad en un hospital veterinario de Cuautitlan (México). Mediantela revisión de 3.862 historias clínicas de los años 2016-2017, se encontró una prevalencia de1,86% (72 animales) diagnosticados con PVC, siendo los menores de 7 meses los de mayorsusceptibilidad, especialmente durante los meses de marzo a mayo, con mayor incidencia enabril. La variable aumento de la temperatura ambiental explicó la mayor presentación de laenfermedad, seguida por el sexo hembra, el mayor número de crías, la joven edad y el menorconsumo de alimento

Computational neuroimaging strategies for single patient predictions

AbstractNeuroimaging increasingly exploits machine learning techniques in an attempt to achieve clinically relevant single-subject predictions. An alternative to machine learning, which tries to establish predictive links between features of the observed data and clinical variables, is the deployment of computational models for inferring on the (patho)physiological and cognitive mechanisms that generate behavioural and neuroimaging responses. This paper discusses the rationale behind a computational approach to neuroimaging-based single-subject inference, focusing on its potential for characterising disease mechanisms in individual subjects and mapping these characterisations to clinical predictions. Following an overview of two main approaches – Bayesian model selection and generative embedding – which can link computational models to individual predictions, we review how these methods accommodate heterogeneity in psychiatric and neurological spectrum disorders, help avoid erroneous interpretations of neuroimaging data, and establish a link between a mechanistic, model-based approach and the statistical perspectives afforded by machine learning

Force-Sensitive Autoinhibition of the von Willebrand Factor ls Mediated by Interdomain Interactions

Von Willebrand factor (VWF) plays a central role in hemostasis. Triggered by shear-stress, it adheres to platelets at sites of vascular injury. Inactivation of VWF has been associated to the shielding of its adhesion sites and proteolytic cleavage. However, the molecular nature of this shielding and its coupling to cleavage under shear-forces in flowing blood remain unknown. In this study, we describe, to our knowledge, a new force-sensory mechanism for VWF-platelet binding, which addresses these questions, based on a combination of molecular dynamics (MD) simulations, atomic force microscopy (AFM), and microfluidic experiments. Our MD simulations demonstrate that the VWF A2 domain targets a specific region at the VWF A1 domain, corresponding to the binding site of the platelet glycoprotein Ibα (GPIbα) receptor, thereby causing its blockage. This implies autoinhibition of the VWF for the binding of platelets mediated by the A1-A2 protein-protein interaction. During force-probe MD simulations, a stretching force dissociated the A1A2 complex, thereby unblocking the GPIbα binding site. Dissociation was found to be coupled to the unfolding of the A2 domain, with dissociation predominantly occurring before exposure of the cleavage site in A2, an observation that is supported by our AFM experiments. This suggests that the A2 domain prevents platelet binding in a force-dependent manner, ensuring that VWF initiates hemostasis before inactivation by proteolytic cleavage. Microfluidic experiments with an A2-deletion VWF mutant resulted in increased platelet binding, corroborating the key autoinhibitory role of the A2 domain within VWF multimers. Overall, autoinhibition of VWF mediated by force-dependent interdomain interactions offers the molecular basis for the shear-sensitive growth of VWF-platelet aggregates, and might be similarly involved in shear-induced VWF self-aggregation and other force-sensing functions in hemostasis

Soil microbial community response to corrinoids is shaped by a natural reservoir of vitamin B12

Soil microbial communities perform critical ecosystem services through the collective metabolic activities of numerous individual organisms. Most microbes use corrinoids, a structurally diverse family of cofactors related to vitamin B12. Corrinoid structure influences the growth of individual microbes, yet how these growth responses scale to the community level remains unknown. Analysis of metagenome-assembled genomes suggests that corrinoids are supplied to the community by members of the archaeal and bacterial phyla Thermoproteota, Actinobacteria, and Proteobacteria. Corrinoids were found largely adhered to the soil matrix in a grassland soil, at levels exceeding those required by cultured bacteria. Enrichment cultures and soil microcosms seeded with different corrinoids showed distinct shifts in bacterial community composition, supporting the hypothesis that corrinoid structure can shape communities. Environmental context influenced both community- and taxon-specific responses to specific corrinoids. These results implicate corrinoids as key determinants of soil microbiome structure and suggest that environmental micronutrient reservoirs promote community stability