Bayesian Semiparametric Multi-State Models

Multi-state models provide a unified framework for the description of the evolution of discrete phenomena in continuous time. One particular example are Markov processes which can be characterised by a set of time-constant transition intensities between the states. In this paper, we will extend such parametric approaches to semiparametric models with flexible transition intensities based on Bayesian versions of penalised splines. The transition intensities will be modelled as smooth functions of time and can further be related to parametric as well as nonparametric covariate effects. Covariates with time-varying effects and frailty terms can be included in addition. Inference will be conducted either fully Bayesian using Markov chain Monte Carlo simulation techniques or empirically Bayesian based on a mixed model representation. A counting process representation of semiparametric multi-state models provides the likelihood formula and also forms the basis for model validation via martingale residual processes. As an application, we will consider human sleep data with a discrete set of sleep states such as REM and Non-REM phases. In this case, simple parametric approaches are inappropriate since the dynamics underlying human sleep are strongly varying throughout the night and individual-specific variation has to be accounted for using covariate information and frailty terms

Enfermedad de Chagas: Interpretación de pruebas cardiológicas, utilidad de la RMN cardiaca y uso combinado in vitro de benznidazol y corticoide

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 08-10-202

Approximation of An Experimental Model Obtained in A Testing Machine for use in an Industrial Production Machine

Design of experiments (DOE) is a powerful tool that allows performing the modeling and analysis of the influence of factors of the process on the specified variables, which are often called response variables. Being a systematic procedure to analyze the effect of the response variables, and the controllable factor s that are modified during the execution of the experiment.Within the different strategies of the design of experiments, the factorial design is one of the most widely used. The problem with factorial designs is a large number of experiments that may be ne cessary.It is not convenient to perform the tests of experimental designs in an industrial machine, because it is more difficult to control and measure the variables accurately and in an agile way. Moreover, if an industrial machine has to be used, it is n ot feasible to perform a large number of trials, because it would be necessary to interrupt production.Therefore it was decided to conduct an investigation in which experimental models were obtained in a testing machine that was specially developed for tha t purpose. Later, data were collected from an industrial machine that performed the same process, and with the same machining conditions. The problem to be solved is to what extent the models obtained in the testing machine can be adjusted or not to predic t the process in industrial machines.A study was done by means of regression analysis of the correlation between the valuesobtained in the test machine and those obtained in the industrial machine. It was observed that the trends of roughness parameters gi ven by the models obtained in the testing machine are similar to those obtained in the industrial process. For this reason it is feasible to adapt the models obtained in the testing machine for the industrial machinePeer ReviewedPostprint (published version

Inmovilización de una β-xilosidasa de Geobacillus stearothermophilus como CLEAs

Se purificó una β-xilosidasa de la familia 52 de Geobacillus stearothermophilus (XynB2WT) y su mutante Y509E (XynB2Y509E) con actividad dual de β-xilosidasa y xilanasa con el fin de preparar agregados enzimáticos entrecruzados (CLEAs). Se utilizó sulfato de amonio (78%) como agente precipitante y glutaraldehído (25 mM) como agente de reticulación. La reacción de reticulación se llevó a cabo durante 30 minutos a temperatura ambiente y en agitación horizontal. En estas condiciones, los CLEAs producidos para XynB2WT y para XynB2Y509E presentaron un 46% y un 34% de actividad recuperada. La caracterización morfológica realizada a los CLEAs por Microscopía Electrónica de Barrido puso en evidencia una mezcla homogénea de agregados de pequeño tamaño. La caracterización bioquímica de enzimas libres e inmovilizadas demostró que el pH y la temperatura óptimos de reacción eran mayores en XynB2WT libre que en su forma inmovilizada (pH 6,5 frente a 5 y temperatura de 75 °C frente a 65 °C). Sin embargo, en XynB2Y509E libre e inmovilizada permanecieron constantes en términos generales (pH 6,5 para el CLEA y 6 para la libre y una temperatura de 55 °C para ambas). El análisis de los parámetros cinéticos muestra un valor de Km menor para el CLEA de ambas enzimas (2,44 mM para XynB2WT libre frente a 3,86 mM en XynB2WT-CLEA y 2,13 mM para XynB2Y509E libre frente a 3,53 mM para XynB2Y509E -CLEA). La inmovilización mejoró la termoestabilidad en la enzima mutada, presentando una Tm ligeramente mayor en el CLEA de XynB2Y509E. Por último, se comprobó que ambas enzimas mantienen aproximadamente un 50% de actividad al cabo de los 10 ciclos de reacción realizados a pH 6,5 y 60 °C, lo cual sugiere una buena estabilidad operacional de los agregados producidos. A β-xylosidase from the family 52 of Geobacillus stearothermophilus (XynB2WT) and its mutant Y509E (XynB2Y509E) with dual activity of β-xylosidase and xylanase were purified in order to prepare cross- linked enzyme aggregates (CLEAs). Ammonium sulfate (78%) was used as precipitating agent and glutaraldehyde (25 mM) as crosslinking agent. The crosslinking reaction was carried out for 30 minutes at room temperature with horizontal stirring. Under these conditions, the CLEAs produced for XynB2WT and for XynB2Y509E showed 46% and 34% recovered activity. The morphological characterization of the CLEAs carried out by scanning electron microscopy revealed a homogeneous mixture of small-sized aggregates. Biochemical characterization of free and immobilized enzymes showed that the optimal reaction pH and temperature were higher in free XynB2WT than in its immobilized form (pH 6.5 vs. 5 and temperature 75 °C vs. 65 °C). However, free and immobilized XynB2Y509E remained broadly constant (pH 6.5 for CLEA and 6 for free and a temperature of 55 °C for both). The analysis of the kinetic parameters shows a lower Km value for the CLEA of both enzymes (2.44 mM for free XynB2WT versus 3.86 mM in XynB2WT-CLEA and 2.13 mM for free XynB2Y509E versus 3.53 mM for XynB2Y509E -CLEA). The immobilization improved the thermostability in the mutated enzyme, presenting a slightly higher Tm in the CLEA of XynB2Y509E. Finally, it was found that both enzymes maintain approximately 50% activity after the 10 reaction cycles carried out at pH 6.5 and 60 °C, which suggests a good operational stability of the aggregates produced

Estimating the Cost of the Spanish Sustainable Food Basket through the Reference Budgets Approach

Reference budgets (RB) are illustrative priced baskets containing the minimum goods and services necessary for well-described types of families to have adequate social participation. Cross-country comparable food RB with the minimum cost were previously developed in 26 EU countries. However, sustainability was not considered. The aim of this paper is to present the development of healthy and sustainable food baskets for Spanish adults. This work follows the steps proposed in previous European projects to build RB: (1) revision of guidelines on healthy and sustainable eating and expert consultations, (2) translation into a concrete list of foods, (3) pricing. The results indicate that a sustainable diet can be cheaper than current recommendations when only the dietary content is considered, representing monthly savings of about EUR 7.27. This is mainly explained by the shift towards more plant-based proteins. Adding constraints on origin, packaging and seasonality increases the overall cost of the food basket by EUR 12.22/month compared with current recommendations. The Spanish Sustainable Food Reference Budget illustrates the cost of applying different criteria to improve dietary sustainability in the Spanish context, and can be useful to support the ecological transition, since providing different levels of adherence to a sustainable dietary pattern can ease its access across socioeconomic group

Peripheral Inflammation Enhances Microglia Response and Nigral Dopaminergic Cell Death in an in vivo MPTP Model of Parkinson’s Disease

The impact of systemic inflammation in nigral dopaminergic cell loss remains unclear. Here, we have investigated the role of peripheral inflammation induced by systemic lipopolysaccharide (LPS) administration in the MPTP-based model of Parkinson’s disease. Brain inflammation, microglia and astroglia activation, disruption of the blood–brain barrier (BBB) and integrity of the nigrostriatal dopaminergic system were evaluated in response to i.p. injection of LPS, MPTP or the combination of both. Our results showed that combinative treatment exacerbates microglia activation and enhances (i) the appearance of galectin-3-positive microglia, recently identified as microglial disease-associated phenotypic marker, (ii) the up-regulation of pro-inflammatory cytokines, (iii) the occurrence of A1 neurotoxic astrocytes, (iv) the breakdown of the BBB, and (v) the loss of dopaminergic neurons in the substantia nigra. Microglia activation was triggered earlier than other degenerative events, suggesting that over-activation of microglia (including different polarization states) may induce dopaminergic neuron loss by itself, initiating the endless cycle of inflammation/degeneration. Our study revitalizes the importance of peripheral inflammation as a potential risk factor for Parkinson’s disease and raises the possibility of using new anti-inflammatory therapies to improve the course of neurodegenerative diseases, including those directly aimed at modulating the deleterious activity of disease-associated microglia.España MINECO y FEDER SAF2015-64171-

A Conceptual Tool for the Implementation of the Circular Economy Emissions Reuse Closed Loops through Process Equipment

Nowadays industry is immersed in a transition to the Circular Economy (CE) as a way to achieve resource efficiency in production processes. However, the implementation of CE closed loops is still in an initial phase and it focuses mainly on the recycling of components of products instead of the reuse of emissions. The purpose of this study is to explore the possibility of accelerating the transition of the CE in production processes through a conceptual tool that allows the possibility of evaluating the reuse of emissions between the equipment involved in a process. The Environmental Analysis of Relations of Coexistence of the Equipment (EARC) tool is a novelty in the implementation of the CE emissions reuse closed loops at the company level. The EARC tool focuses on the identification and analysis of the equipment involved in a process and in the material inputs and emissions outputs of each of its operations with the objective of evaluating the possibility of reusing emissions among them. This paper presents a conceptual tool as the basis for the development of a redesign methodology for the reuse of emissions in production processes with the objective of reducing the consumption of resources and the generation of emissions as well as the reduction of production costs.Peer ReviewedPostprint (published version

A discontinuous Galerkin solver for Boltzmann Poisson systems in nano devices

In this paper, we present results of a discontinuous Galerkin (DG) scheme applied to deterministic computations of the transients for the Boltzmann-Poisson system describing electron transport in semiconductor devices. The collisional term models optical-phonon interactions which become dominant under strong energetic conditions corresponding to nano-scale active regions under applied bias. The proposed numerical technique is a finite element method using discontinuous piecewise polynomials as basis functions on unstructured meshes. It is applied to simulate hot electron transport in bulk silicon, in a silicon $n^+$-$n$-$n^+$ diode and in a double gated 12nm MOSFET. Additionally, the obtained results are compared to those of a high order WENO scheme simulation and DSMC (Discrete Simulation Monte Carlo) solvers.Comment: 51 pages, 82 figure

Pesquisa com crianças: entre a experiência no campo e a escrita do texto

ResumoA tessitura do texto foca em dois momentos do desenvolvimento da pesquisa com crianças. O primeiro é relativo ao processo de observação: estar com as crianças numa atitude de escuta, marcada pela presença física do pesquisador na captura das cenas e episódios e nos processos de interação entre o pesquisador e os sujeitos da pesquisa. O segundo diz respeito ao processo de distanciamento da escrita, a teorização das ações vivenciadas no campo de pesquisa. Os dados gerados indicam que pesquisar com crianças envolve interações afetivas e corpóreas, ou seja, a presença pessoal afeta e é afetada pelas experiências vividas no campo. Palavras-chave: Pesquisa. Escrita. Educação Infantil. Corporeidade

Modleamiento y predicción de lluvias usando Edge Computing para el entorno colombiano

International audienceNowadays the number of devices connected to internet which offer the possibility to collect data is increasing. The interconnectivity of these new sensors favors the creation of sustainable cities, in which the optimization of resources is based on the collected data. These sensors are also a big source of information for forecasting future values. In this work we present an Edge Computing approach for the analysis and forecasting of rainfall data that is later validated on the CITI Laboratory Youpi Platform. To this end, we built a container image with the necessary tools and libraries to use the time series prediction models SARIMA and Prophet on ARMv7 architectures. A Raspberry Pi 3 node was chosen to evaluate performance on an Edge Computing device. Colombia was chosen due to its tropical location and its variant geography which present a wide range of historical rainfall data. The data we used to train our models consisted on the historical mesures from sensors deployed in Colombia by the "Instituto de Hidrología, Meteorología y es-tudios Ambientales de Colombia-IDEAM". In first place, we selected Bucaramanga to study its data sensors and to define the well-suited parameters for SARIMA and Prophet trend models. The comparison between them presented a high degree of similarity, offering a good prediction of dry and wet seasons. Thereafter, the SARIMA and Prophet model of Bucaramanga were used to observe its adaptability to the cities of Bogotá and Medellín, getting a successful outcome at seasonal predictions. After this estimation of the SARIMA parameters and its analysis offline, a container image was created to simplify and speed up the models implementation in the devices for predicting the two years monthly rainfall for Bucaramanga, Bogotá and Medellín. The container is available for armv7 architectures, that is usually used for IoT nodes on the Youpi platform. The proposed model allows to create a network of sensors, with distributed analysis capacity, that improve the prevention of flood or drought emergencies in Smart Cities on Colombia, helping to manage resources for agriculture or prevent catastrophes