A data driven equivariant approach to constrained Gaussian mixture modeling

Maximum likelihood estimation of Gaussian mixture models with different class-specific covariance matrices is known to be problematic. This is due to the unboundedness of the likelihood, together with the presence of spurious maximizers. Existing methods to bypass this obstacle are based on the fact that unboundedness is avoided if the eigenvalues of the covariance matrices are bounded away from zero. This can be done imposing some constraints on the covariance matrices, i.e. by incorporating a priori information on the covariance structure of the mixture components. The present work introduces a constrained equivariant approach, where the class conditional covariance matrices are shrunk towards a pre-specified matrix Psi. Data-driven choices of the matrix Psi, when a priori information is not available, and the optimal amount of shrinkage are investigated. The effectiveness of the proposal is evaluated on the basis of a simulation study and an empirical example

A two-step estimator for multilevel latent class analysis with covariates

We propose a two-step estimator for multilevel latent class analysis (LCA) with covariates. The measurement model for observed items is estimated in its first step, and in the second step covariates are added in the model, keeping the measurement model parameters fixed. We discuss model identification, and derive an Expectation Maximization algorithm for efficient implementation of the estimator. By means of an extensive simulation study we show that (i) this approach performs similarly to existing stepwise estimators for multilevel LCA but with much reduced computing time, and (ii) it yields approximately unbiased parameter estimates with a negligible loss of efficiency compared to the one-step estimator. The proposal is illustrated with a cross-national analysis of predictors of citizenship norms.Comment: Manuscript version accepted for publication in Psychometrik

A two-step estimator for multilevel latent class analysis with covariates

We propose a two-step estimator for multilevel latent class analysis (LCA) with covariates. The measurement model for observed items is estimated in its first step, and in the second step covariates are added in the model, keeping the measurement model parameters fixed. We discuss model identification, and derive an Expectation Maximization algorithm for efficient implementation of the estimator. By means of an extensive simulation study we show that (1) this approach performs similarly to existing stepwise estimators for multilevel LCA but with much reduced computing time, and (2) it yields approximately unbiased parameter estimates with a negligible loss of efficiency compared to the one-step estimator. The proposal is illustrated with a cross-national analysis of predictors of citizenship norms

Multilevel latent class analysis with covariates: Analysis of cross-national citizenship norms with a two-stage approach

This paper focuses on the substantive application of multilevel LCA to the evolution of citizenship norms in a diverse array of democratic countries. To do so, we present a two-stage approach to fit multilevel latent class models: in the first stage (measurement model construction), unconditional class enumeration is done separately on both low and high level latent variables, estimating only a part of the model at a time -- hence keeping the remaining part fixed -- and then updating the full measurement model; in the second stage (structural model construction), individual and/or group covariates are included in the model. By separating the two parts -- first stage and second stage of model building -- the measurement model is stabilized and is allowed to be determined only by it's indicators. Moreover, this two-step approach makes the inclusion/exclusion of a covariate a relatively simple task to handle. Our proposal amends common practice in applied social science research, where simple (low-level) LCA is done to obtain a classification of low-level unit, and this is then related to (low- and high-level) covariates simply including group fixed effects. Our analysis identifies latent classes that score either consistently high or consistently low on all measured items, along with two theoretically important classes that place distinctive emphasis on items related to engaged citizenship, and duty-based norms

Mechanisms of endothelial cell dysfunction in cystic fibrosis

Although cystic fibrosis (CF) patients exhibit signs of endothelial perturbation, the functions of the cystic fibrosis conductance regulator (CFTR) in vascular endothelial cells (EC) are poorly defined. We sought to uncover biological activities of endothelial CFTR, relevant for vascular homeostasis and inflammation. We examined cells from human umbilical cords (HUVEC) and pulmonary artery isolated from non-cystic fibrosis (PAEC) and CF human lungs (CF-PAEC), under static conditions or physiological shear. CFTR activity, clearly detected in HUVEC and PAEC, was markedly reduced in CF-PAEC. CFTR blockade increased endothelial permeability to macromolecules and reduced trans‑endothelial electrical resistance (TEER). Consistent with this, CF-PAEC displayed lower TEER compared to PAEC. Under shear, CFTR blockade reduced VE-cadherin and p120 catenin membrane expression and triggered the formation of paxillin- and vinculin-enriched membrane blebs that evolved in shrinking of the cell body and disruption of cell-cell contacts. These changes were accompanied by enhanced release of microvesicles, which displayed reduced capability to stimulate proliferation in recipient EC. CFTR blockade also suppressed insulin-induced NO generation by EC, likely by inhibiting eNOS and AKT phosphorylation, whereas it enhanced IL-8 release. Remarkably, phosphodiesterase inhibitors in combination with a β2 adrenergic receptor agonist corrected functional and morphological changes triggered by CFTR dysfunction in EC. Our results uncover regulatory functions of CFTR in EC, suggesting a physiological role of CFTR in the maintenance EC homeostasis and its involvement in pathogenetic aspects of CF. Moreover, our findings open avenues for novel pharmacology to control endothelial dysfunction and its consequences in CF

Pegaso: an ultra-light long duration stratospheric

Launched from the Mario Zuccelli Station (Baia Terra Nova) in Antarctica during the 2005/06 austral summer, the PEGASO-D payload lifted into the stratospheric anticyclone over the southern polar region. This effort marks the first Long Duration Scientific payload to be launched from this location and is the fourth such payload launched in the polar regions. Performing in the framework of the NOBILE/AMUNDSEN collaborative LDB development between ASI-ARR. The Italian Institute of Geophysics and Volcanology (INGV), with the sponsorship of the Italian Antarctic Program (PNRA) and the Italian Space Agency (ASI),designed and built the Ultra-Light system together with three Universities in Italy. The Pegaso program has been created to investigate the Earth magnetic field and provide a precursor series of small payload launches for the bigger LDB program such as OLIMPO, BOOMERanG and BArSPOrt through this collaboration between ASI and ARR. The Italian scientific community, aware of the big advantages that LDB balloons can offer to their experiments, proposed to extend the LDB program to Southern polar regions, besides performing launches from the newly initiated Nobile/Amundsen Stratospheric Balloon Center in Svalbard, Norway.Three PEGASO (Polar Explorer for Geomagnetics And other Scientific Observations) payloads have been launched from the Svalbard (No) in collaboration with Andoya Rocket Range, ASI and ISTAR (Operations and logistics) during the past two northern summers. These stratospheric (altitude m.35000) small 10kmc balloons have floated in the stratosphere between 14 to 39 days measuring the magnetic field of polar regions, by means of a 3-axys-fluxgate magnetometer, during a three year campaign. The study of the magnetic field and its variations is done through permanent observatories. They provide us with high quality data but their spatial distribution is not quite regular, specially in Antarctica due to logistic difficulties. The coverage is improved through marine and aeromagnetic surveys, and also through satellite missions. There exists nevertheless a gap in the wavelengths of the magnetic field represented by these kind of measurements. Satellite data are too far away from Earth's surface to individuate wavelengths lower than 1000 km, and near-ground sur- veys are not able to represent wavelengths longer than the dimensions of the surveyed area. Moreover, there is a region empty of data around the geographical pole for the satellite measurements. The size of these gaps depends on the orbital parameters, but it can reach up to 10 degrees around the pole. PEGASO allows to bridge this gap in the measurements of the magnetic field. Surveys carried out at 35 km height allow the study of crustal anomalies in the range between, we can say, 60 and 1000 km. Taking into account that pathfinders (smaller non-recoverable balloon systems) are usually sent to explore the atmospheric currents, the use of PEGASO as pathfinder allows us to obtain all these results at a very affordable cost. The PEGASO payload was also developed as a single source system integrating science, housekeeping and operational control of the entire balloon borne configuration.Satellite telemetry sent the scientific (magnetometric) data, house-keeping (temperature, solar panel voltage and current, altitude and time) and telecommand (four ballast, two parachute release system, system reset), and powered the terminate system. Data flows through the IRIDIUM telephone service. The onboard systems were kept inside a vessel (white painted and pressurizzed vessel due to power dissipation) except for external flexible solar panels and magnetometer, attached to an external boom. Two redundant tracking systems have been used: a first GPS was integrated inside the on-board telemetry system, necessary to reconstruct position and time of scientific data, while an independent GPS-ARGOS system gave the balloon trajectory, including its descent. Continuous trajectory predictions were made during the missions; they have been necessary, in particular, for the flight safety requirements of the northern hemisphere. The evaluation of the statistical error is proposed. The PEGASO payload was developed to be a light, cost effective way to explore the potential of Ultra-Light Long Duration Ballooning for science as well as an introduction to the earth-space possibilities for students.PublishedBeijing, China1A. Geomagnetismo e Paleomagnetism

Prunus spinosa Extract Loaded in Biomimetic Nanoparticles Evokes In Vitro Anti-Inflammatory and Wound Healing Activities

none14sìPrunus spinosa fruits (PSF) contain different phenolic compounds showing antioxidant and anti-inflammatory activities. Innovative drug delivery systems such as biomimetic nanoparticles could improve the activity of PSF extract by promoting (i) the protection of payload into the lipidic bilayer, (ii) increased accumulation to the diseased tissue due to specific targeting properties, (iii) improved biocompatibility, (iv) low toxicity and increased bioavailability. Using membrane proteins extracted from human monocyte cell line THP-1 cells and a mixture of phospholipids, we formulated two types of PSF-extract-loaded biomimetic vesicles differing from each other for the presence of either 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPG). The biological activity of free extract (PSF), compared to both types of extract-loaded vesicles (PSF-DOPCs and PSF-DOPGs) and empty vesicles (DOPCs and DOPGs), was evaluated in vitro on HUVEC cells. PSF-DOPCs showed preferential incorporation of the extract. When enriched into the nanovesicles, the extract showed a significantly increased anti-inflammatory activity, and a pronounced wound-healing effect (with PSF-DOPCs more efficient than PSF-DOPG) compared to free PSF. This innovative drug delivery system, combining nutraceutical active ingredients into a biomimetic formulation, represents a possible adjuvant therapy for the treatment of wound healing. This nanoplatform could be useful for the encapsulation/enrichment of other nutraceutical products with short stability and low bioavailability.openTiboni, Mattia; Coppari, Sofia; Casettari, Luca; Guescini, Michele; Colomba, Mariastella; Fraternale, Daniele; Gorassini, Andrea; Verardo, Giancarlo; Ramakrishna, Seeram; Guidi, Loretta; Di Giacomo, Barbara; Mari, Michele; Molinaro, Roberto; Albertini, Maria CristinaTiboni, Mattia; Coppari, Sofia; Casettari, Luca; Guescini, Michele; Colomba, Mariastella; Fraternale, Daniele; Gorassini, Andrea; Verardo, Giancarlo; Ramakrishna, Seeram; Guidi, Loretta; Di Giacomo, Barbara; Mari, Michele; Molinaro, Roberto; Albertini, Maria Cristin

Evolución ambiental durante el holoceno en la cuenca del río Salto-Arrecifes

La cuenca del río Salto-Arrecifes, se ubica en el NE de la Provincia de Buenos Aires, en la subregión de la Pampa denominada Pampa Ondulada (Pasotti y Castellanos, 1966). Su extensa área de influencia de 2.000 km2 abarca parcial a totalmente el territorio de once Municipios de la Prov. de Buenos Aires. Está integrada por una subcuenca sur, conformada por los ríos Rojas-Salto y gran número de tributarios (Ao Dulce, Ao del Sauce, etc.) y una norte, que corresponde al arroyo Pergamino y tributarios menores. A partir de la confluencia de estas dos subcuentas se desarrolla a lo largo de unos 80 km el río Arrecifes, con vertiente al Paraná de las Palmas. En su sector terminal, un poco antes de desaguar en el río Baradero, unos de sus brazos distributarios se une al curso del arroyo El Tala (Fig.1). Tanto el arroyo Pergamino como los ríos Salto y Arrecifes escurren encajonados entre barrancas de importante desarrollo vertical. Con la finalidad de reconstruir la evolución paleoambiental y paleoclimática del Pleistoceno tardío-Holoceno tardío en los valles de esta región, se realizaron estudios estratigráficos, sedimentológicos y paleoecológicos. Asimismo, se acotaron temporalmente las sucesiones reconocidas en un total de doce localidades de estudio y se realizaron las correlaciones estratigráficas entre las unidades aflorante a lo largo de más de 100 km. En esta presentación, se expondrán los resultados y conclusiones preliminares alcanzadas para el caracterizar el Holoceno en esta cuenca fluvial, y su correlato con las enunciadas para este lapso en otras de la Pampa Ondulada.A lo largo de gran parte del trayecto estudiado, los depósitos del Holoceno se reconocen en la porción media superior de las barrancas y yacen discordantes sobre limos arenosos, de tonalidades verdosas de composición vitroclástica pre-holocenas, a excepción del tramo desarrollado en los últimos 50 km antes de desaguar en el río Baradero. En este sector inferior de la cuenca, los depósitos corresponden al Holoceno medio y apoyan directamente sobre sedimentos del ?Pampeano?.En los canales de mayor numero de orden (ríos Salto y Arrecifes) el inicio de la sedimentación holocena se acota en aproximadamente 11.000 años 14C AP y está representada por depósitos areno limosos vítreos y bioclásticos ricos en materia orgánica. Solo en una de las localidades estudiadas, pudo evidenciarse la existencia de un delgado estrato conglomerádico basal. En tanto, en los cursos de menor orden (Ao Pergamino, Ao Cañete y cabeceras de río Salto), el inicio de la sedimentación holocena ésta representada por la alternancia de estratos muy delgados de arenas limosas, diatomitas y de niveles con alto contenido en materia orgánica, en una sucesión de unos 50 cm a 100 cm de potencia. Hacia el techo, y en todas las columnas analizadas, se observa en contacto neto el desarrollo de un estrato delgado fango arenosos oscuro muy rico en materia orgánica de 10 a 30 cm de potencia y datado en varias secciones en ~7.500 años 14C AP, (Fig.2).Posteriormente, en contacto neto se observan depósitos de limos y margas de coloraciones claras y de variada potencia, los que sustentan un paleosuelo de desarrollo regional datado en ~3.000 años 14C AP (Prieto et al. 2004, Fucks et al. 2011). Sobre éste, yacen aluvios y eolianitas más modernas. Como se mencionó anteriormente, aguas abajo del puente carretero la Eloísa, el Holoceno está representado a partir de acumulaciones vinculadas al evento ingresivo del Holoceno medio, que han sido datadas desde ~ 6.000 años 14C AP y los depósitos más recientes. En las secciones analizadas de este tramo inferior, se identificó también el desarrollo del paleosuelo datado en ~3.000 años 14C AP.En los depósitos holocénicos mencionados, se analizó el contenido bioclástico carbonático (charáceas, gasterópodos, ostrácodos, etc.) y silíceo (fitolítico, diatomológico, etc.), por su importancia como registros o indicadores ?proxies? de condiciones ambientales y climáticas.Se determinó sólo un resto de vertebrado correspondiente a un calcaño asignable a cérvido para ~ 5000 años AP.Se infiere para el comienzo del Holoceno, a los 11.000 años AP, al igual que en otras cuencas fluviales de la región (Areco y Luján), la existencia de cuerpo loticos/lenticos asociados a regiones con balance hídrico positivo (humedad) y temperaturas más cálidas que las precedentes. Los indicadores biológicos analizados permiten reconocer la existencia de ambientes fluvio-límnicos someros de agua salobres (alta conductibilidad), mesotróficas y muy alcalinas desarrolladas durante condiciones climáticas cálidas.A los ~7500 años AP y a través de la identificación del paleosuelo antes mencionado, se registra un evento de estabilidad geomorfológica con reducción de espejos de agua y de actividad fluvial bajo condiciones cálidas-sub-húmedas. Éste suelo también fue reconocido en la Cuenca del río Areco (localidad San Antonio de Areco) (Fucks et al. 2011). En tanto para la cuenca del río Lujan se estimó una contracción de los cuerpos de agua y la presencia, en los terrenos aledaños, de una importante cubierta vegetal (Prieto et al. 2004). Posteriormente entre los 6000 y 3000 años 14C AP, se desarrollaron bajo condiciones climáticas templadas sub-húmedas estacionales, pantanos alcalinos. Esta distrofia de los ambientes lenticos también habría sucedido en otras cuencas de la pampa ondulada. Por último, sobre los depósitos margosos acumulados en los pantanos alcalinos y previo a los 3500-3000 años 14C AP, como así también en los depósitos estúaricos regresivos, se evidencian paleosuelos correlacionables a escala regional con los geosuelos La Pelada-Puesto Berrondo (Fucks et al. 20011, Huarte et al. 2013, Prieto et al. 2004). Los resultados alcanzados nos permiten, por un lado proponer que las aguas mixohalinas de la ingresión Holocena penetraron por curso del río Arrecifes hace ~ 6.000 años 14CAP, quedando sus depósitos expuestos en el tramo final de la cuenca. Por otro, discutir la conformación paleogeográfíca de la cuenca Salto-Arrecifes a lo largo del Pleistoceno tardío-Holoceno y su variabilidad en respuestas a los climáticos acaecidos durante el lapso. Finalmente, analizar los cambios geomorfológicos de esta cuenca hidrológica ante las modificaciones del perfil de equilibrio y/o nivel de base, ejercidos por controles tectónicos

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking