A disease model for wheezing disorders in preschool children based on clinicians' perceptions

BACKGROUND: Wheezing disorders in childhood vary widely in clinical presentation and disease course. During the last years, several ways to classify wheezing children into different disease phenotypes have been proposed and are increasingly used for clinical guidance, but validation of these hypothetical entities is difficult. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to develop a testable disease model which reflects the full spectrum of wheezing illness in preschool children. We performed a qualitative study among a panel of 7 experienced clinicians from 4 European countries working in primary, secondary and tertiary paediatric care. In a series of questionnaire surveys and structured discussions, we found a general consensus that preschool wheezing disorders consist of several phenotypes, with a great heterogeneity of specific disease concepts between clinicians. Initially, 24 disease entities were described among the 7 physicians. In structured discussions, these could be narrowed down to three entities which were linked to proposed mechanisms: a) allergic wheeze, b) non-allergic wheeze due to structural airway narrowing and c) non-allergic wheeze due to increased immune response to viral infections. This disease model will serve to create an artificial dataset that allows the validation of data-driven multidimensional methods, such as cluster analysis, which have been proposed for identification of wheezing phenotypes in children. CONCLUSIONS/SIGNIFICANCE: While there appears to be wide agreement among clinicians that wheezing disorders consist of several diseases, there is less agreement regarding their number and nature. A great diversity of disease concepts exist but a unified phenotype classification reflecting underlying disease mechanisms is lacking. We propose a disease model which may help guide future research so that proposed mechanisms are measured at the right time and their role in disease heterogeneity can be studied.

Distance-based kriging relying on proxy simulations for inverse conditioning

Let us consider a large set of candidate parameter fields, such as hydraulic conductivity maps, on which we can run an accurate forward flow and transport simulation. We address the issue of rapidly identifying a subset of candidates whose response best match a reference response curve. In order to keep the number of calls to the accurate flow simulator computationally tractable, a recent distance-based approach relying on fast proxy simulations is revisited, and turned into a non-stationary kriging method where the covariance kernel is obtained by combining a classical kernel with the proxy. Once the accurate simulator has been run for an initial subset of parameter fields and a kriging metamodel has been inferred, the predictive distributions of misfits for the remaining parameter fields can be used as a guide to select candidate parameter fields in a sequential way. The proposed algorithm, Proxy-based Kriging for Sequential Inversion (ProKSI), relies on a variant of the Expected Improvement, a popular criterion for kriging-based global optimization. A statistical benchmark of ProKSI’s performances illustrates the efficiency and the robustness of the approach when using different kinds of proxies.

DNA-based identification of novel bovine casein gene variants

In cattle, at least 39 variants of the 4 casein proteins (α(S1)-, β-, α(S2)- and κ-casein) have been described to date. Many of these variants are known to affect milk-production traits, cheese-processing properties, and the nutritive value of milk. They also provide valuable information for phylogenetic studies. So far, the majority of studies exploring the genetic variability of bovine caseins considered European taurine cattle breeds and were carried out at the protein level by electrophoretic techniques. This only allows the identification of variants that, due to amino acid exchanges, differ in their electric charge, molecular weight, or isoelectric point. In this study, the open reading frames of the casein genes CSN1S1, CSN2, CSN1S2, and CSN3 of 356 animals belonging to 14 taurine and 3 indicine cattle breeds were sequenced. With this approach, we identified 23 alleles, including 5 new DNA sequence variants, with a predicted effect on the protein sequence. The new variants were only found in indicine breeds and in one local Iranian breed, which has been phenotypically classified as a taurine breed. A multidimensional scaling approach based on available SNP chip data, however, revealed an admixture of taurine and indicine populations in this breed as well as in the local Iranian breed Golpayegani. Specific indicine casein alleles were also identified in a few European taurine breeds, indicating the introgression of indicine breeds into these populations. This study shows the existence of substantial undiscovered genetic variability of bovine casein loci, especially in indicine cattle breeds. The identification of new variants is a valuable tool for phylogenetic studies and investigations into the evolution of the milk protein genes.

A different perspective on poverty in Lao PDR: Multidimensional poverty in Lao PDR for the years 2002/2003 and 2007/2008

This paper presents an indicator for measuring multidimensional poverty in the Lao People’s Democratic Republic applying the Alkire–Foster methodology to the Lao Expenditure and Consumption Survey 2002/2003 and 2007/2008. We calculated a multidimensional poverty index (MPI) that includes three dimensions: education, health, and standard of living. Making use of the MPI’s decomposability, we analyse how much each of the different dimensions and its respective indicators contribute to the overall MPI. We find a marked reduction in the multidimensional poverty headcount ratio over the study period, regardless of how the indicators are weighted or how the deprivation and poverty cut-offs are set. This reduction is based on improvements regarding all indicators except cooking fuel and nutrition. We observe no significant reduction in the intensity of poverty, however; there are wide disparities between the country’s regions and between urban and rural areas. The proportion of poor people in rural areas is more than twice as high as that in urban areas. By complementing the traditional income-based poverty measure, we hope to provide useful information that can support knowledge-based decision-making for poverty alleviation.

Model-based Self-awareness Patterns for Autonomy

Los sistemas técnicos son cada vez más complejos, incorporan funciones más avanzadas, están más integrados con otros sistemas y trabajan en entornos menos controlados. Todo esto supone unas condiciones más exigentes y con mayor incertidumbre para los sistemas de control, a los que además se demanda un comportamiento más autónomo y fiable. La adaptabilidad de manera autónoma es un reto para tecnologías de control actualmente. El proyecto de investigación ASys propone abordarlo trasladando la responsabilidad de la capacidad de adaptación del sistema de los ingenieros en tiempo de diseño al propio sistema en operación. Esta tesis pretende avanzar en la formulación y materialización técnica de los principios de ASys de cognición y auto-consciencia basadas en modelos y autogestión de los sistemas en tiempo de operación para una autonomía robusta. Para ello el trabajo se ha centrado en la capacidad de auto-conciencia, inspirada en los sistemas biológicos, y se ha explorado la posibilidad de integrarla en la arquitectura de los sistemas de control. Además de la auto-consciencia, se han explorado otros temas relevantes: modelado funcional, modelado de software, tecnología de los patrones, tecnología de componentes, tolerancia a fallos. Se ha analizado el estado de la técnica en los ámbitos pertinentes para las cuestiones de la auto-consciencia y la adaptabilidad en sistemas técnicos: arquitecturas cognitivas, control tolerante a fallos, y arquitecturas software dinámicas y computación autonómica. El marco teórico de ASys existente de sistemas autónomos cognitivos ha sido adaptado para servir de base para este análisis de autoconsciencia y adaptación y para dar sustento conceptual al posterior desarrollo de la solución. La tesis propone una solución general de diseño para la construcción de sistemas autónomos auto-conscientes. La idea central es la integración de un meta-controlador en la arquitectura de control del sistema autónomo, capaz de percibir la estado funcional del sistema de control y, si es necesario, reconfigurarlo en tiempo de operación. Esta solución de metacontrol se ha formalizado en cuatro patrones de diseño: i) el Patrón Metacontrol, que define la integración de un subsistema de metacontrol, responsable de controlar al propio sistema de control a través de la interfaz proporcionada por su plataforma de componentes, ii) el patrón Bucle de Control Epistémico, que define un bucle de control cognitivo basado en el modelos y que se puede aplicar al diseño del metacontrol, iii) el patrón de Reflexión basada en Modelo Profundo propone una solución para construir el modelo ejecutable utilizado por el meta-controlador mediante una transformación de modelo a modelo a partir del modelo de ingeniería del sistema, y, finalmente, iv) el Patrón Metacontrol Funcional, que estructura el meta-controlador en dos bucles, uno para el control de la configuración de los componentes del sistema de control, y otro sobre éste, controlando las funciones que realiza dicha configuración de componentes; de esta manera las consideraciones funcionales y estructurales se desacoplan. La Arquitectura OM y el metamodelo TOMASys son las piezas centrales del marco arquitectónico desarrollado para materializar la solución compuesta de los patrones anteriores. El metamodelo TOMASys ha sido desarrollado para la representación de la estructura y su relación con los requisitos funcionales de cualquier sistema autónomo. La Arquitectura OM es un patrón de referencia para la construcción de una metacontrolador integrando los patrones de diseño propuestos. Este meta-controlador se puede integrar en la arquitectura de cualquier sistema control basado en componentes. El elemento clave de su funcionamiento es un modelo TOMASys del sistema decontrol, que el meta-controlador usa para monitorizarlo y calcular las acciones de reconfiguración necesarias para adaptarlo a las circunstancias en cada momento. Un proceso de ingeniería, complementado con otros recursos, ha sido elaborado para guiar la aplicación del marco arquitectónico OM. Dicho Proceso de Ingeniería OM define la metodología a seguir para construir el subsistema de metacontrol para un sistema autónomo a partir del modelo funcional del mismo. La librería OMJava proporciona una implementación del meta-controlador OM que se puede integrar en el control de cualquier sistema autónomo, independientemente del dominio de la aplicación o de su tecnología de implementación. Para concluir, la solución completa ha sido validada con el desarrollo de un robot móvil autónomo que incorpora un meta-controlador con la Arquitectura OM. Las propiedades de auto-consciencia y adaptación proporcionadas por el meta-controlador han sido validadas en diferentes escenarios de operación del robot, en los que el sistema era capaz de sobreponerse a fallos en el sistema de control mediante reconfiguraciones orquestadas por el metacontrolador. ABSTRACT Technical systems are becoming more complex, they incorporate more advanced functionalities, they are more integrated with other systems and they are deployed in less controlled environments. All this supposes a more demanding and uncertain scenario for control systems, which are also required to be more autonomous and dependable. Autonomous adaptivity is a current challenge for extant control technologies. The ASys research project proposes to address it by moving the responsibility for adaptivity from the engineers at design time to the system at run-time. This thesis has intended to advance in the formulation and technical reification of ASys principles of model-based self-cognition and having systems self-handle at runtime for robust autonomy. For that it has focused on the biologically inspired capability of self-awareness, and explored the possibilities to embed it into the very architecture of control systems. Besides self-awareness, other themes related to the envisioned solution have been explored: functional modeling, software modeling, patterns technology, components technology, fault tolerance. The state of the art in fields relevant for the issues of self-awareness and adaptivity has been analysed: cognitive architectures, fault-tolerant control, and software architectural reflection and autonomic computing. The extant and evolving ASys Theoretical Framework for cognitive autonomous systems has been adapted to provide a basement for this selfhood-centred analysis and to conceptually support the subsequent development of our solution. The thesis proposes a general design solution for building self-aware autonomous systems. Its central idea is the integration of a metacontroller in the control architecture of the autonomous system, capable of perceiving the functional state of the control system and reconfiguring it if necessary at run-time. This metacontrol solution has been formalised into four design patterns: i) the Metacontrol Pattern, which defines the integration of a metacontrol subsystem, controlling the domain control system through an interface provided by its implementation component platform, ii) the Epistemic Control Loop pattern, which defines a modelbased cognitive control loop that can be applied to the design of such a metacontroller, iii) the Deep Model Reflection pattern proposes a solution to produce the online executable model used by the metacontroller by model-to-model transformation from the engineering model, and, finally, iv) the Functional Metacontrol pattern, which proposes to structure the metacontroller in two loops, one for controlling the configuration of components of the controller, and another one on top of the former, controlling the functions being realised by that configuration; this way the functional and structural concerns become decoupled. The OM Architecture and the TOMASys metamodel are the core pieces of the architectural framework developed to reify this patterned solution. The TOMASys metamodel has been developed for representing the structure and its relation to the functional requirements of any autonomous system. The OM architecture is a blueprint for building a metacontroller according to the patterns. This metacontroller can be integrated on top of any component-based control architecture. At the core of its operation lies a TOMASys model of the control system. An engineering process and accompanying assets have been constructed to complete and exploit the architectural framework. The OM Engineering Process defines the process to follow to develop the metacontrol subsystem from the functional model of the controller of the autonomous system. The OMJava library provides a domain and application-independent implementation of an OM Metacontroller than can be used in the implementation phase of OMEP. Finally, the complete solution has been validated in the development of an autonomous mobile robot that incorporates an OM metacontroller. The functional selfawareness and adaptivity properties achieved thanks to the metacontrol system have been validated in different scenarios. In these scenarios the robot was able to overcome failures in the control system thanks to reconfigurations performed by the metacontroller.

Heavyweight extensions to the UML metamodel to describe the C3 architectural style

UML is widely accepted as the standard for representing the various software artifacts generated by a development process. For this reason, there have been attempts to use this language to represent the software architecture of systems as well. Unfortunately, these attempts have ended in the same representations (boxes and lines) already criticized by the software architecture community.In this work we propose an extension to the UML metamodel that is able to represent the syntactics and semantics of the C3 architectural style. This style is derived from C2. The modifications to define C3 are described in section 4. This proposal is innovative regarding UML extensions for software architectures, since previous proposals where based on light extensions to the UML meta-model, while we propose a heavyweight extension of the metamodel. On the other hand, this proposal is less ambitious than previous proposals, since we do not want to represent in UML any architectural style, but only one: C3.

Event-based time series data preprocessing: application to traffic flow time series

Traffic flow time series data are usually high dimensional and very complex. Also they are sometimes imprecise and distorted due to data collection sensor malfunction. Additionally, events like congestion caused by traffic accidents add more uncertainty to real-time traffic conditions, making traffic flow forecasting a complicated task. This article presents a new data preprocessing method targeting multidimensional time series with a very high number of dimensions and shows its application to real traffic flow time series from the California Department of Transportation (PEMS web site). The proposed method consists of three main steps. First, based on a language for defining events in multidimensional time series, mTESL, we identify a number of types of events in time series that corresponding to either incorrect data or data with interference. Second, each event type is restored utilizing an original method that combines real observations, local forecasted values and historical data. Third, an exponential smoothing procedure is applied globally to eliminate noise interference and other random errors so as to provide good quality source data for future work.

MedVir: an interactive representation system of multidimensional medical data applied to Traumatic Brain Injury's rehabilitation prediction

Clinicians could model the brain injury of a patient through his brain activity. However, how this model is defined and how it changes when the patient is recovering are questions yet unanswered. In this paper, the use of MedVir framework is proposed with the aim of answering these questions. Based on complex data mining techniques, this provides not only the differentiation between TBI patients and control subjects (with a 72% of accuracy using 0.632 Bootstrap validation), but also the ability to detect whether a patient may recover or not, and all of that in a quick and easy way through a visualization technique which allows interaction.

Contribución al estudio de las metodologías de cálculo realista con incertidumbre (BEPU), dentro del análisis determinista de seguridad de plantas nucleares

El análisis determinista de seguridad (DSA) es el procedimiento que sirve para diseñar sistemas, estructuras y componentes relacionados con la seguridad en las plantas nucleares. El DSA se basa en simulaciones computacionales de una serie de hipotéticos accidentes representativos de la instalación, llamados escenarios base de diseño (DBS). Los organismos reguladores señalan una serie de magnitudes de seguridad que deben calcularse en las simulaciones, y establecen unos criterios reguladores de aceptación (CRA), que son restricciones que deben cumplir los valores de esas magnitudes. Las metodologías para realizar los DSA pueden ser de 2 tipos: conservadoras o realistas. Las metodologías conservadoras utilizan modelos predictivos e hipótesis marcadamente pesimistas, y, por ello, relativamente simples. No necesitan incluir un análisis de incertidumbre de sus resultados. Las metodologías realistas se basan en hipótesis y modelos predictivos realistas, generalmente mecanicistas, y se suplementan con un análisis de incertidumbre de sus principales resultados. Se les denomina también metodologías BEPU (“Best Estimate Plus Uncertainty”). En ellas, la incertidumbre se representa, básicamente, de manera probabilista. Para metodologías conservadores, los CRA son, simplemente, restricciones sobre valores calculados de las magnitudes de seguridad, que deben quedar confinados en una “región de aceptación” de su recorrido. Para metodologías BEPU, el CRA no puede ser tan sencillo, porque las magnitudes de seguridad son ahora variables inciertas. En la tesis se desarrolla la manera de introducción de la incertidumbre en los CRA. Básicamente, se mantiene el confinamiento a la misma región de aceptación, establecida por el regulador. Pero no se exige el cumplimiento estricto sino un alto nivel de certidumbre. En el formalismo adoptado, se entiende por ello un “alto nivel de probabilidad”, y ésta corresponde a la incertidumbre de cálculo de las magnitudes de seguridad. Tal incertidumbre puede considerarse como originada en los inputs al modelo de cálculo, y propagada a través de dicho modelo. Los inputs inciertos incluyen las condiciones iniciales y de frontera al cálculo, y los parámetros empíricos de modelo, que se utilizan para incorporar la incertidumbre debida a la imperfección del modelo. Se exige, por tanto, el cumplimiento del CRA con una probabilidad no menor a un valor P0 cercano a 1 y definido por el regulador (nivel de probabilidad o cobertura). Sin embargo, la de cálculo de la magnitud no es la única incertidumbre existente. Aunque un modelo (sus ecuaciones básicas) se conozca a la perfección, la aplicación input-output que produce se conoce de manera imperfecta (salvo que el modelo sea muy simple). La incertidumbre debida la ignorancia sobre la acción del modelo se denomina epistémica; también se puede decir que es incertidumbre respecto a la propagación. La consecuencia es que la probabilidad de cumplimiento del CRA no se puede conocer a la perfección; es una magnitud incierta. Y así se justifica otro término usado aquí para esta incertidumbre epistémica: metaincertidumbre. Los CRA deben incorporar los dos tipos de incertidumbre: la de cálculo de la magnitud de seguridad (aquí llamada aleatoria) y la de cálculo de la probabilidad (llamada epistémica o metaincertidumbre). Ambas incertidumbres pueden introducirse de dos maneras: separadas o combinadas. En ambos casos, el CRA se convierte en un criterio probabilista. Si se separan incertidumbres, se utiliza una probabilidad de segundo orden; si se combinan, se utiliza una probabilidad única. Si se emplea la probabilidad de segundo orden, es necesario que el regulador imponga un segundo nivel de cumplimiento, referido a la incertidumbre epistémica. Se denomina nivel regulador de confianza, y debe ser un número cercano a 1. Al par formado por los dos niveles reguladores (de probabilidad y de confianza) se le llama nivel regulador de tolerancia. En la Tesis se razona que la mejor manera de construir el CRA BEPU es separando las incertidumbres, por dos motivos. Primero, los expertos defienden el tratamiento por separado de incertidumbre aleatoria y epistémica. Segundo, el CRA separado es (salvo en casos excepcionales) más conservador que el CRA combinado. El CRA BEPU no es otra cosa que una hipótesis sobre una distribución de probabilidad, y su comprobación se realiza de forma estadística. En la tesis, los métodos estadísticos para comprobar el CRA BEPU en 3 categorías, según estén basados en construcción de regiones de tolerancia, en estimaciones de cuantiles o en estimaciones de probabilidades (ya sea de cumplimiento, ya sea de excedencia de límites reguladores). Según denominación propuesta recientemente, las dos primeras categorías corresponden a los métodos Q, y la tercera, a los métodos P. El propósito de la clasificación no es hacer un inventario de los distintos métodos en cada categoría, que son muy numerosos y variados, sino de relacionar las distintas categorías y citar los métodos más utilizados y los mejor considerados desde el punto de vista regulador. Se hace mención especial del método más utilizado hasta el momento: el método no paramétrico de Wilks, junto con su extensión, hecha por Wald, al caso multidimensional. Se decribe su método P homólogo, el intervalo de Clopper-Pearson, típicamente ignorado en el ámbito BEPU. En este contexto, se menciona el problema del coste computacional del análisis de incertidumbre. Los métodos de Wilks, Wald y Clopper-Pearson requieren que la muestra aleatortia utilizada tenga un tamaño mínimo, tanto mayor cuanto mayor el nivel de tolerancia exigido. El tamaño de muestra es un indicador del coste computacional, porque cada elemento muestral es un valor de la magnitud de seguridad, que requiere un cálculo con modelos predictivos. Se hace especial énfasis en el coste computacional cuando la magnitud de seguridad es multidimensional; es decir, cuando el CRA es un criterio múltiple. Se demuestra que, cuando las distintas componentes de la magnitud se obtienen de un mismo cálculo, el carácter multidimensional no introduce ningún coste computacional adicional. Se prueba así la falsedad de una creencia habitual en el ámbito BEPU: que el problema multidimensional sólo es atacable desde la extensión de Wald, que tiene un coste de computación creciente con la dimensión del problema. En el caso (que se da a veces) en que cada componente de la magnitud se calcula independientemente de los demás, la influencia de la dimensión en el coste no se puede evitar. Las primeras metodologías BEPU hacían la propagación de incertidumbres a través de un modelo sustitutivo (metamodelo o emulador) del modelo predictivo o código. El objetivo del metamodelo no es su capacidad predictiva, muy inferior a la del modelo original, sino reemplazar a éste exclusivamente en la propagación de incertidumbres. Para ello, el metamodelo se debe construir con los parámetros de input que más contribuyan a la incertidumbre del resultado, y eso requiere un análisis de importancia o de sensibilidad previo. Por su simplicidad, el modelo sustitutivo apenas supone coste computacional, y puede estudiarse exhaustivamente, por ejemplo mediante muestras aleatorias. En consecuencia, la incertidumbre epistémica o metaincertidumbre desaparece, y el criterio BEPU para metamodelos se convierte en una probabilidad simple. En un resumen rápido, el regulador aceptará con más facilidad los métodos estadísticos que menos hipótesis necesiten; los exactos más que los aproximados; los no paramétricos más que los paramétricos, y los frecuentistas más que los bayesianos. El criterio BEPU se basa en una probabilidad de segundo orden. La probabilidad de que las magnitudes de seguridad estén en la región de aceptación no sólo puede asimilarse a una probabilidad de éxito o un grado de cumplimiento del CRA. También tiene una interpretación métrica: representa una distancia (dentro del recorrido de las magnitudes) desde la magnitud calculada hasta los límites reguladores de aceptación. Esta interpretación da pie a una definición que propone esta tesis: la de margen de seguridad probabilista. Dada una magnitud de seguridad escalar con un límite superior de aceptación, se define el margen de seguridad (MS) entre dos valores A y B de la misma como la probabilidad de que A sea menor que B, obtenida a partir de las incertidumbres de A y B. La definición probabilista de MS tiene varias ventajas: es adimensional, puede combinarse de acuerdo con las leyes de la probabilidad y es fácilmente generalizable a varias dimensiones. Además, no cumple la propiedad simétrica. El término margen de seguridad puede aplicarse a distintas situaciones: distancia de una magnitud calculada a un límite regulador (margen de licencia); distancia del valor real de la magnitud a su valor calculado (margen analítico); distancia desde un límite regulador hasta el valor umbral de daño a una barrera (margen de barrera). Esta idea de representar distancias (en el recorrido de magnitudes de seguridad) mediante probabilidades puede aplicarse al estudio del conservadurismo. El margen analítico puede interpretarse como el grado de conservadurismo (GC) de la metodología de cálculo. Utilizando la probabilidad, se puede cuantificar el conservadurismo de límites de tolerancia de una magnitud, y se pueden establecer indicadores de conservadurismo que sirvan para comparar diferentes métodos de construcción de límites y regiones de tolerancia. Un tópico que nunca se abordado de manera rigurosa es el de la validación de metodologías BEPU. Como cualquier otro instrumento de cálculo, una metodología, antes de poder aplicarse a análisis de licencia, tiene que validarse, mediante la comparación entre sus predicciones y valores reales de las magnitudes de seguridad. Tal comparación sólo puede hacerse en escenarios de accidente para los que existan valores medidos de las magnitudes de seguridad, y eso ocurre, básicamente en instalaciones experimentales. El objetivo último del establecimiento de los CRA consiste en verificar que se cumplen para los valores reales de las magnitudes de seguridad, y no sólo para sus valores calculados. En la tesis se demuestra que una condición suficiente para este objetivo último es la conjunción del cumplimiento de 2 criterios: el CRA BEPU de licencia y un criterio análogo, pero aplicado a validación. Y el criterio de validación debe demostrarse en escenarios experimentales y extrapolarse a plantas nucleares. El criterio de licencia exige un valor mínimo (P0) del margen probabilista de licencia; el criterio de validación exige un valor mínimo del margen analítico (el GC). Esos niveles mínimos son básicamente complementarios; cuanto mayor uno, menor el otro. La práctica reguladora actual impone un valor alto al margen de licencia, y eso supone que el GC exigido es pequeño. Adoptar valores menores para P0 supone menor exigencia sobre el cumplimiento del CRA, y, en cambio, más exigencia sobre el GC de la metodología. Y es importante destacar que cuanto mayor sea el valor mínimo del margen (de licencia o analítico) mayor es el coste computacional para demostrarlo. Así que los esfuerzos computacionales también son complementarios: si uno de los niveles es alto (lo que aumenta la exigencia en el cumplimiento del criterio) aumenta el coste computacional. Si se adopta un valor medio de P0, el GC exigido también es medio, con lo que la metodología no tiene que ser muy conservadora, y el coste computacional total (licencia más validación) puede optimizarse. ABSTRACT Deterministic Safety Analysis (DSA) is the procedure used in the design of safety-related systems, structures and components of nuclear power plants (NPPs). DSA is based on computational simulations of a set of hypothetical accidents of the plant, named Design Basis Scenarios (DBS). Nuclear regulatory authorities require the calculation of a set of safety magnitudes, and define the regulatory acceptance criteria (RAC) that must be fulfilled by them. Methodologies for performing DSA van be categorized as conservative or realistic. Conservative methodologies make use of pessimistic model and assumptions, and are relatively simple. They do not need an uncertainty analysis of their results. Realistic methodologies are based on realistic (usually mechanistic) predictive models and assumptions, and need to be supplemented with uncertainty analyses of their results. They are also termed BEPU (“Best Estimate Plus Uncertainty”) methodologies, and are typically based on a probabilistic representation of the uncertainty. For conservative methodologies, the RAC are simply the restriction of calculated values of safety magnitudes to “acceptance regions” defined on their range. For BEPU methodologies, the RAC cannot be so simple, because the safety magnitudes are now uncertain. In the present Thesis, the inclusion of uncertainty in RAC is studied. Basically, the restriction to the acceptance region must be fulfilled “with a high certainty level”. Specifically, a high probability of fulfillment is required. The calculation uncertainty of the magnitudes is considered as propagated from inputs through the predictive model. Uncertain inputs include model empirical parameters, which store the uncertainty due to the model imperfection. The fulfillment of the RAC is required with a probability not less than a value P0 close to 1 and defined by the regulator (probability or coverage level). Calculation uncertainty is not the only one involved. Even if a model (i.e. the basic equations) is perfectly known, the input-output mapping produced by the model is imperfectly known (unless the model is very simple). This ignorance is called epistemic uncertainty, and it is associated to the process of propagation). In fact, it is propagated to the probability of fulfilling the RAC. Another term used on the Thesis for this epistemic uncertainty is metauncertainty. The RAC must include the two types of uncertainty: one for the calculation of the magnitude (aleatory uncertainty); the other one, for the calculation of the probability (epistemic uncertainty). The two uncertainties can be taken into account in a separate fashion, or can be combined. In any case the RAC becomes a probabilistic criterion. If uncertainties are separated, a second-order probability is used; of both are combined, a single probability is used. On the first case, the regulator must define a level of fulfillment for the epistemic uncertainty, termed regulatory confidence level, as a value close to 1. The pair of regulatory levels (probability and confidence) is termed the regulatory tolerance level. The Thesis concludes that the adequate way of setting the BEPU RAC is by separating the uncertainties. There are two reasons to do so: experts recommend the separation of aleatory and epistemic uncertainty; and the separated RAC is in general more conservative than the joint RAC. The BEPU RAC is a hypothesis on a probability distribution, and must be statistically tested. The Thesis classifies the statistical methods to verify the RAC fulfillment in 3 categories: methods based on tolerance regions, in quantile estimators and on probability (of success or failure) estimators. The former two have been termed Q-methods, whereas those in the third category are termed P-methods. The purpose of our categorization is not to make an exhaustive survey of the very numerous existing methods. Rather, the goal is to relate the three categories and examine the most used methods from a regulatory standpoint. Special mention deserves the most used method, due to Wilks, and its extension to multidimensional variables (due to Wald). The counterpart P-method of Wilks’ is Clopper-Pearson interval, typically ignored in the BEPU realm. The problem of the computational cost of an uncertainty analysis is tackled. Wilks’, Wald’s and Clopper-Pearson methods require a minimum sample size, which is a growing function of the tolerance level. The sample size is an indicator of the computational cost, because each element of the sample must be calculated with the predictive models (codes). When the RAC is a multiple criteria, the safety magnitude becomes multidimensional. When all its components are output of the same calculation, the multidimensional character does not introduce additional computational cost. In this way, an extended idea in the BEPU realm, stating that the multi-D problem can only be tackled with the Wald extension, is proven to be false. When the components of the magnitude are independently calculated, the influence of the problem dimension on the cost cannot be avoided. The former BEPU methodologies performed the uncertainty propagation through a surrogate model of the code, also termed emulator or metamodel. The goal of a metamodel is not the predictive capability, clearly worse to the original code, but the capacity to propagate uncertainties with a lower computational cost. The emulator must contain the input parameters contributing the most to the output uncertainty, and this requires a previous importance analysis. The surrogate model is practically inexpensive to run, so that it can be exhaustively analyzed through Monte Carlo. Therefore, the epistemic uncertainty due to sampling will be reduced to almost zero, and the BEPU RAC for metamodels includes a simple probability. The regulatory authority will tend to accept the use of statistical methods which need a minimum of assumptions: exact, nonparametric and frequentist methods rather than approximate, parametric and bayesian methods, respectively. The BEPU RAC is based on a second-order probability. The probability of the safety magnitudes being inside the acceptance region is a success probability and can be interpreted as a fulfillment degree if the RAC. Furthermore, it has a metric interpretation, as a distance (in the range of magnitudes) from calculated values of the magnitudes to acceptance regulatory limits. A probabilistic definition of safety margin (SM) is proposed in the thesis. The same from a value A to other value B of a safety magnitude is defined as the probability that A is less severe than B, obtained from the uncertainties if A and B. The probabilistic definition of SM has several advantages: it is nondimensional, ranges in the interval (0,1) and can be easily generalized to multiple dimensions. Furthermore, probabilistic SM are combined according to the probability laws. And a basic property: probabilistic SM are not symmetric. There are several types of SM: distance from a calculated value to a regulatory limit (licensing margin); or from the real value to the calculated value of a magnitude (analytical margin); or from the regulatory limit to the damage threshold (barrier margin). These representations of distances (in the magnitudes’ range) as probabilities can be applied to the quantification of conservativeness. Analytical margins can be interpreted as the degree of conservativeness (DG) of the computational methodology. Conservativeness indicators are established in the Thesis, useful in the comparison of different methods of constructing tolerance limits and regions. There is a topic which has not been rigorously tackled to the date: the validation of BEPU methodologies. Before being applied in licensing, methodologies must be validated, on the basis of comparisons of their predictions ad real values of the safety magnitudes. Real data are obtained, basically, in experimental facilities. The ultimate goal of establishing RAC is to verify that real values (aside from calculated values) fulfill them. In the Thesis it is proved that a sufficient condition for this goal is the conjunction of 2 criteria: the BEPU RAC and an analogous criterion for validation. And this las criterion must be proved in experimental scenarios and extrapolated to NPPs. The licensing RAC requires a minimum value (P0) of the probabilistic licensing margin; the validation criterion requires a minimum value of the analytical margin (i.e., of the DG). These minimum values are basically complementary; the higher one of them, the lower the other one. The regulatory practice sets a high value on the licensing margin, so that the required DG is low. The possible adoption of lower values for P0 would imply weaker exigence on the RCA fulfillment and, on the other hand, higher exigence on the conservativeness of the methodology. It is important to highlight that a higher minimum value of the licensing or analytical margin requires a higher computational cost. Therefore, the computational efforts are also complementary. If medium levels are adopted, the required DG is also medium, and the methodology does not need to be very conservative. The total computational effort (licensing plus validation) could be optimized.

Modelo multidimensional de los factores que afectan la interacción entre marketing y ventas en el lanzamiento de nuevos productos en Latino América

Esta tesis se centra en la identificación y análisis de los factores que pueden favorecer o actuar como barreras del éxito de la implementación de la innovación y las relaciones entre sí, desde el enfoque de la interface marketing-ventas. El trabajo empírico se enmarca en el vacío de investigación existente en el campo del proceso de lanzamiento de nuevos productos en los mercados donde operan subsidiarias de empresas multinacionales de consumo masivo (FMCG). Las empresas FMCG son altamente dependientes de la innovación como proceso clave determinante del crecimiento competitivo de mediano y largo plazo. En un contexto de acortamiento del ciclo de vida de los productos, como resultado del desarrollo tecnológico y científico que impactan en el comportamiento de los consumidores, las empresas invierten un mayor nivel de recursos en el desarrollo de nuevos productos, reingeniería y programas de innovación (Mundra, Gulati y Gupta, 2013). Sin embargo, a pesar del aumento en la inversión, las tasas de éxito de la innovación reportadas son inferiores al 25% (Evanschitzky, Eisend, Calantone y Jiang, 2012). Aumentar las tasas de éxito de los proyectos de innovación es reconocida en la literatura como un elemento clave para la supervivencia y competitividad de las empresas, para ser superiores a su competencia y desarrollar nuevos modelos de negocios. A pesar de la existencia de estudios que intentan comprender el proceso de lanzamiento de nuevos productos, no se ha identificado un claro prototipo de gestión de la innovación (Gupta et al, 2007). Profundizando en los factores de éxito, los autores Keupp, Palmié y Gassman (2012) reconocen que la innovación exitosa no depende solamente de la estrategia de selección de los proyectos de innovación, sino también la forma en que los mismos son implementados (Klein and Sorra, 1996; Repenning, 2002; Keupp, Palmié y Gassmann, 2012). Al analizar la implementación de los proyectos de lanzamiento de nuevos productos al mercado, en empresas FMCG, dicho proceso es responsabilidad principalmente de las funciones de marketing y ventas a través de la comunicación con los consumidores y los clientes respectivamente (Ernst, Hoyer y Rubsaamen, 2010). Es decir que el éxito en la implementación de la innovación requiere la gestión efectiva de la relación inter-funcional entre marketing y ventas (Ernst, Hoyer y Rubsaamen, 2010; Hughes, Le Bon y Malshe, 2012). A pesar de la importancia de la integración entre marketing y ventas en la conceptualización e implementación de la innovación, este tema no ha sido estudiado en profundidad (Hughes, Le Bon y Malshe, 2012; Keupp, Palmié y Gassmann, 2012). En las empresas multinacionales, está demostrado que el desempeño de las subsidiarias determinan el éxito competitivo de la empresa a nivel global. El desafío de dichas subsidiarias es conjugar el desarrollo global de innovación y comunicación con las características locales de comportamiento del consumidor y el mercado. Por lo tanto, esta investigación empírica responde a la pregunta académica y de gestión acerca de cómo mejorar las tasas de éxito de lanzamiento de nuevos productos al mercado en subsidiarias de empresas de consumo masivo, desde la perspectiva de la relación entre marketing y ventas. En particular analiza cómo afectan la formalización de los procesos y los mecanismos de comunicación a la confianza interpersonal y a la efectividad de la interface marketing-ventas y dichos factores a su vez sobre la planificación integrada de la implementación de la innovación. La determinación de los factores o ítems que conforman cada uno de los constructos del proceso de ejecución de la innovación, se llevó a cabo a partir de una revisión exhaustiva del estado del arte de la literatura sobre las interfaces funcionales y el proceso de innovación. Posteriormente, los ítems seleccionados (más de 50 en total) fueron validados por referentes de marketing y ventas de Argentina y Uruguay a través de entrevistas en profundidad. A partir de los factores identificados se construyeron dos modelos teóricos: • (1) relativo a la influencia de las dimensiones de confianza interpersonal sobre la efectividad de las uniones inter-funcionales y como los mecanismos organizacionales, tales como la frecuencia y la calidad de la comunicación entre las áreas, afectan la confianza y la relación entre ellas; • (2) relativo a la dimensión planificación integrada de la implementación de la innovación, ya que durante el lanzamiento de nuevos productos al mercado, marketing y ventas utilizan procesos formales que facilitan la comunicación frecuente y efectiva, desarrollando confianza inter-personal que no solamente afecta la efectividad de su relación sino también el desarrollo de planes integrados entre ambas áreas. El estudio fue llevado a cabo en una empresa multinacional de consumo masivo que integra la lista Global 500 (Fortune, 2015), presente en todo el mundo con más de 25 marcas participantes en más de 15 categorías, implementando 150 proyectos de innovación en el último año. El grupo de subsidiarias en estudio fue reconocido a nivel mundial por su desempeño en crecimiento competitivo y su alta contribución al crecimiento total. El modelo analizado en esta tesis fue expandido al resto de América Latina, tratándose entonces de un caso ejemplar que representa una práctica de excelencia en la implementación de la innovación en subsidiarias de una empresa multinacional. La recolección de los datos fue llevado a cabo a través de un cuestionario estructurado y confidencial, enviado a la base de datos de todo el universo de directores y gerentes de marketing y ventas. El nivel de respuesta fue muy elevado (70%), logrando 152 casos válidos. El análisis de datos comprendió el análisis descriptivo de los mismos, estimación de fiabilidad y análisis factorial exploratorio a través del software SPSS v.20. El análisis factorial confirmatorio y el análisis de senderos para examinar las relaciones entre los factores se estudiaron mediante el software R (Package 2.15.1., R Core Team, 2012) (Fox, 2006). Finalmente se llevaron a cabo entrevistas en profundidad a gerentes de marketing y ventas de cada uno de los seis países con el fin de profundizar en los constructos y sus relaciones. Los resultados de los modelos demuestran que la frecuencia de comunicación impacta positivamente en la calidad de la misma, que a su vez afecta directamente la relación entre marketing y ventas. Adicionalmente, la calidad de la comunicación impacta sobre la confianza cognitiva, que a su vez se relaciona no solamente con la confianza afectiva sino también con la relación entre ambas áreas. Esto significa que para mejorar la implementación de la innovación, los gerentes deberían orientarse a reforzar la relación entre marketing y ventas facilitando la construcción de confianza interpersonal primero cognitiva y luego afectiva, incrementando la frecuencia de la comunicación que alimenta la calidad de la comunicación entre ambas áreas. A través del segundo modelo se demuestra que durante el lanzamiento de nuevos productos al mercado, marketing y ventas necesitan emplear procesos formales que faciliten la comunicación frecuente y efectiva. De esta forma se contrarresta el efecto negativo de la formalización sobre la planificación integrada entre ambas áreas. Adicionalmente, los gerentes de ambos departamentos deberían promover la construcción de confianza interpersonal, no solamente para mejorar la efectividad de la relación, sino también para desarrollar planes integrados de implementación de nuevos productos. Finalmente, se valida que la frecuencia de la comunicación, la confianza afectiva y la relación marketing-ventas, se relacionan positivamente con la planificación integrada en la implementación de la innovación. El estudio contribuye a la comprensión de los factores que las empresas pueden emplear para mejorar la relación inter-funcional entre marketing y ventas y la implementación de la innovación en empresas de consumo masivo. El aporte de esta investigación puede ser valorado de dos maneras, los aportes a la gestión y a la academia. Desde el punto de vista empresarial, provee a los líderes al frente de empresas de consumo masivo, del conocimiento sobre los factores que afectan la implementación de la innovación y en definitiva el éxito del negocio a mediano y largo plazo. Desde el punto de vista académico aporta al conocimiento del proceso de implementación de la innovación y en la efectividad de la interface marketing y ventas en un caso de buenas prácticas en el mercado de consumo masivo. A su vez incorpora por primera vez un estudio empírico en geografías emergentes capaces de recuperar el camino de crecimiento posterior a una profunda crisis económica a través de la exitosa implementación de la innovación en sus mercados. ABSTRACT This thesis is focused on the identification, analysis and relationship study of factors which may benefit or hinder the successful deployment of innovation, from a marketing-sales interface perspective. Considering the non-existent investigation dedicated to the study of new products launches into markets in which Fast Moving Consumer Goods (FMCG) companies’ subsidiaries operate, it is that this investigation has been carried out. FMCG companies rely on innovation as their key process for a competitive growth on a medium and long term basis. Nowadays, the life-cycle of products is getting shorter as a result of new technological and scientific development, having impact on consumer behavior, and therefore companies are forced to dedicating more resources to the development of new products, reengineering and innovation programs (Mundra, Gulati and Gupta, 2013). However, in spite of the investment increase, the innovation success rates have been reported to be lower than 25% (Evanschitzky, Eisend, Calantone y Jiang, 2012). Increasing success rates on innovation processes has been considered as a key element on the survival and competitiveness of companies, outperforming competitors and developing new business models. Despite new studies which try to comprehend the process of new products launch, a prototype of innovation management has not yet been identified (Gupta et al, 2007). Emphasizing on success factors, authors Keupp, Palmié and Gassman (2012) recognize that successful innovation does not solely depend on innovation processes’ selection strategy, but it is also based on the way in which these are implemented (Klein and Sorra, 1996; Repenning, 2002; Keupp, Palmié y Gassmann, 2012). While analyzing the implementation of projects for new products releases on massive consumption companies, the two departments in charge of taking this forward are marketing and sales, by focusing on communication strategies with consumers and clients respectively (Ernst, Hoyer y Rubsaamen, 2010). This means that having success on innovation implementation requires an effective management of inter-functional relationship among marketing and sales (Ernst, Hoyer y Rubsaamen, 2010; Hughes, Le Bon y Malshe, 2012). In spite of the importance on the integration between marketing and sales on the conceptualization and implementation of innovation, this subject has not been studied in depth (Hughes, Le Bon y Malshe, 2012; Keupp, Palmié y Gassmann, 2012). In multinational companies, previous research has confirmed that the performance of their subsidiaries determine the competitive success of the company on a global scale. The challenge of said subsidiaries is to conjugate the global innovation development and communication with the local consumer and market behavior. Therefore, this empirical study aims to respond to the academic and management question of how to improve the success rates of new product launches into MNE subsidiary’ markets, from a marketing-sales relationship perspective. Particularly, this investigation analyses how the formalization of products and communication mechanisms affect interpersonal trust and marketing-sales interface effectiveness and also on how these factors affect the overall planning of the implementation of innovation. The determination of which factors build the hypothesis of the innovation execution process was taken forward through an extensive research on the extant literature on functional interfaces and innovation processes. More than 50 items were selected which were in turn validated by marketing and sales referents on Uruguay and Argentina through in depth interviews. Based on the identified factors, two theoretical models were proposed: (1) Relative to the influence that interpersonal trust dimensions have on inter functional linkages effectiveness and how organizational mechanisms such as frequency and quality of communication between departments affect trust and their relationship. (2) Relative to the integrated planning and innovation implementation dimensions. Marketing and sales department use formal process thus allowing inter-personal trust, which affects positively their relationship and also enables the development of integrated planning between them. The study was performed within a massive consumption company which is part of the “Global 500” (Fortune, 2015), with subsidiaries all over the world and more than 25 participant brands in 15 categories, having implemented over 150 innovation projects in the year under study. The analyzed subsidiary group has been awarded worldwide for their performance in competitive growth and their high contribution to the total growth. The model being analyzed in this thesis was implemented throughout Latin America, representing a remarkable case of innovation implementation excellence for subsidiaries of multinational companies. Data recollection was carried out through a structured and confidential questionnaire, sent to the universe of marketing-sales directors and managers’ database available with a high level of responsiveness of 70%, resulting in 152 valid cases. Data exploration involved a descriptive analysis, followed by a reliability estimation and an exploratory factorial analysis carried out through SPSS v.20. Confirmatory factorial analysis and path analysis (to examine relations between the different study factors) were studied using “R” software (Package 2.15.1., R Core Team, 2012) (Fox, 2006). Finally, in depth interviews were carried out to several marketing and sales managers in each of the six countries so as to further confirm the hypothesis and their relations. The models results prove that communication frequency has a positive impact on the quality of the same, which in turn has direct effects on the marketing-sales relations. Additionally, communication quality has an impact on the cognitive trust, which also relates not only to affective trust, but also to the relation between both areas. This means that in order to improve the implementation of innovation, managers should strive to enforce marketing-sales relations, facilitating the interpersonal trust construction (firstly cognitive, followed by affective trust), increasing the communication frequency, and therefore nurturing the communication quality among both areas. Through the second model, the results confirm the importance of creating effective relationships between sales and marketing to facilitate planning integrated new product implementations. While formalized new product development processes provide opportunities for sales and marketing to communicate, this does not directly influence the planning of integrated new product implementations. By using these formal opportunities to communicate to create information quality, it is possible to improve sales and marketing’s ability to integrate information during the planning process. Further, communication quality creates inter-personal trust in the other party’s competences (cognitive-based trust), leading to affect-based trust. Affect-based inter-personal trust, not only to improve the overall effectiveness of the sales and marketing relationship, but also helps in planning integrated new product implementations. This study contributes to the understanding of factors which enterprises can use to improve the inter-functional relations between marketing and sales, and the implementation of innovation in FMCG companies. The contribution of this investigation can be measured in two ways: enrichment of management and contribution to the academic area. From a business perspective, it provides massive consumption businesses leaders with knowledge on which factors affect innovation implementation, which results on mid and long-term success for the company. From an academic point of view, it provides knowledge on a prototype of successful innovation implementation management based on the marketing-sales interface effectiveness through a case study in the FMCG consumption market. Last but not least, it incorporates for the first time an empiric study on emerging geographies capable of recovery post a deep economic crisis through successful innovation implementation on their markets.

Enriching the integration of semantic resources based on WordNet

In this paper we present the enrichment of the Integration of Semantic Resources based in WordNet (ISR-WN Enriched). This new proposal improves the previous one where several semantic resources such as SUMO, WordNet Domains and WordNet Affects were related, adding other semantic resources such as Semantic Classes and SentiWordNet. Firstly, the paper describes the architecture of this proposal explaining the particularities of each integrated resource. After that, we analyze some problems related to the mappings of different versions and how we solve them. Moreover, we show the advantages that this kind of tool can provide to different applications of Natural Language Processing. Related to that question, we can demonstrate that the integration of semantic resources allows acquiring a multidimensional vision in the analysis of natural language.

Assessing participation in online discussion forums: a proposal for multidimensional analysis

This paper aims to assess the discussion forums being used in the programme Especialista Universitario online sobre Tecnologías de la Información y la Comunicación, taught at the University of Alicante, on the basis of the analysis model suggested by Kay (2004). In such a model, it is essential to represent graphically the forum activity so that the visual representation may improve analysis. This research has allowed reaching results which define the forum activity and has contributed with a proposal for multi analysis in the area of assessing participation in communication within online discussion forums.

Phrase-based statistical machine translation: explanation of its processes and statistical models and evaluation of the English to Spanish translations produced

Statistical machine translation (SMT) is an approach to Machine Translation (MT) that uses statistical models whose parameter estimation is based on the analysis of existing human translations (contained in bilingual corpora). From a translation student’s standpoint, this dissertation aims to explain how a phrase-based SMT system works, to determine the role of the statistical models it uses in the translation process and to assess the quality of the translations provided that system is trained with in-domain goodquality corpora. To that end, a phrase-based SMT system based on Moses has been trained and subsequently used for the English to Spanish translation of two texts related in topic to the training data. Finally, the quality of this output texts produced by the system has been assessed through a quantitative evaluation carried out with three different automatic evaluation measures and a qualitative evaluation based on the Multidimensional Quality Metrics (MQM).

A genetic two-factor model of the covariation among a subset of Multidimensional Aptitude Battery and Wechsler Adult Intelligence Scale - Revised subtests

The phenotypic and genetic factor structure of performance on five Multidimensional Aptitude Battery (MAB) subtests and one Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtest was explored in 390 adolescent twin pairs (184 monozygotic [MZ]; 206 dizygotic (DZ)). The temporal stability of these measures was derived from a subsample of 49 twin pairs, with test-retest correlations ranging from .67 to .85. A phenotypic factor model, in which performance and verbal factors were correlated, provided a good fit to the data. Genetic modeling was based on the phenotypic factor structure, but also took into account the additive genetic (A), common environmental (C), and unique environmental (E) parameters derived from a fully saturated ACE model. The best fitting model was characterized by a genetic correlated two-factor structure with specific effects, a general common environmental factor, and overlapping unique environmental effects. Results are compared to multivariate genetic models reported in children and adults, with the most notable difference being the growing importance of common genes influencing diverse abilities in adolescence. (C) 2003 Elsevier Inc. All rights reserved.

Multidimensional modelling to investigate interspecies hydrogen transfer in anaerobic biofilms

Anaerobic digestion is a multistep process, mediated by a functionally and phylogenetically diverse microbial population. One of the crucial steps is oxidation of organic acids, with electron transfer via hydrogen or formate from acetogenic bacteria to methanogens. This syntrophic microbiological process is strongly restricted by a thermodynamic limitation on the allowable hydrogen or formate concentration. In order to study this process in more detail, we developed an individual-based biofilm model which enables to describe the processes at a microbial resolution. The biochemical model is the ADM1, implemented in a multidimensional domain. With this model, we evaluated three important issues for the syntrophic relationship: (i) is there a fundamental difference in using hydrogen or formate as electron carrier? (ii) Does a thermodynamic-based inhibition function produced substantially different results from an empirical function? and; (iii) Does the physical colocation of acetogens and methanogens follow directly from a general model. Hydrogen or formate as electron carrier had no substantial impact on model results. Standard inhibition functions or thermodynamic inhibition function gave similar results at larger substrate field grid sizes (> 10 mu m), but at smaller grid sizes, the thermodynamic-based function reduced the number of cells with long interspecies distances (> 2.5 mu m). Therefore, a very fine grid resolution is needed to reflect differences between the thermodynamic function, and a more generic inhibition form. The co-location of syntrophic bacteria was well predicted without a need to assume a microbiological based mechanism (e.g., through chemotaxis) of biofilm formation.