Computational fluid dynamics modelling in cardiovascular medicine.

This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges.

Comparative carbon cycle dynamics of the present and last interglacial

Changes in temperature and carbon dioxide during glacial cycles recorded in Antarctic ice cores are tightly coupled. However, this relationship does not hold for interglacials. While climate cooled towards the end of both the last (Eemian) and present (Holocene) interglacials, CO₂ remained stable during the Eemian while rising in the Holocene. We identify and review twelve biogeochemical mechanisms of terrestrial (vegetation dynamics and CO₂ fertilization, land use, wild fire, accumulation of peat, changes in permafrost carbon, subaerial volcanic outgassing) and marine origin (changes in sea surface temperature, carbonate compensation to deglaciation and terrestrial biosphere regrowth, shallow-water carbonate sedimentation, changes in the soft tissue pump, and methane hydrates), which potentially may have contributed to the CO₂ dynamics during interglacials but which remain not well quantified. We use three Earth System Models (ESMs) of intermediate complexity to compare effects of selected mechanisms on the interglacial CO₂ and δ¹³ CO₂ changes, focusing on those with substantial potential impacts: namely carbonate sedimentation in shallow waters, peat growth, and (in the case of the Holocene) human land use. A set of specified carbon cycle forcings could qualitatively explain atmospheric CO₂ dynamics from 8ka BP to the pre-industrial. However, when applied to Eemian boundary conditions from 126 to 115 ka BP, the same set of forcings led to disagreement with the observed direction of CO₂ changes after 122 ka BP. This failure to simulate late-Eemian CO₂ dynamics could be a result of the imposed forcings such as prescribed CaCO₃ accumulation and/or an incorrect response of simulated terrestrial carbon to the surface cooling at the end of the interglacial. These experiments also reveal that key natural processes of interglacial CO₂ dynamics eshallow water CaCO₃ accumulation, peat and permafrost carbon dynamics are not well represented in the current ESMs. Global-scale modeling of these long-term carbon cycle components started only in the last decade, and uncertainty in parameterization of these mechanisms is a main limitation in the successful modeling of interglacial CO₂ dynamics.

Global Optimization with Sparse and Local Gaussian Process Models

We present a novel surrogate model-based global optimization framework allowing a large number of function evaluations. The method, called SpLEGO, is based on a multi-scale expected improvement (EI) framework relying on both sparse and local Gaussian process (GP) models. First, a bi-objective approach relying on a global sparse GP model is used to determine potential next sampling regions. Local GP models are then constructed within each selected region. The method subsequently employs the standard expected improvement criterion to deal with the exploration-exploitation trade-off within selected local models, leading to a decision on where to perform the next function evaluation(s). The potential of our approach is demonstrated using the so-called Sparse Pseudo-input GP as a global model. The algorithm is tested on four benchmark problems, whose number of starting points ranges from 102 to 104. Our results show that SpLEGO is effective and capable of solving problems with large number of starting points, and it even provides significant advantages when compared with state-of-the-art EI algorithms.

Importance of Nuclear Data Uncertainties in Criticality Calculations

To study the propagation of the uncertainty from basic data across different scale and physics phenomena -> through complex coupled multi-physics and multi-scale simulations

On the Extension of the Analytic Nodal Diffusion Solver ANDES to Sodium Fast Reactors

Within the framework of the Collaborative Project for a European Sodium Fast Reactor, the reactor physics group at UPM is working on the extension of its in-house multi-scale advanced deterministic code COBAYA3 to Sodium Fast Reactors (SFR). COBAYA3 is a 3D multigroup neutron kinetics diffusion code that can be used either as a pin-by-pin code or as a stand-alone nodal code by using the analytic nodal diffusion solver ANDES. It is coupled with thermalhydraulics codes such as COBRA-TF and FLICA, allowing transient analysis of LWR at both fine-mesh and coarse-mesh scales. In order to enable also 3D pin-by-pin and nodal coupled NK-TH simulations of SFR, different developments are in progress. This paper presents the first steps towards the application of COBAYA3 to this type of reactors. ANDES solver, already extended to triangular-Z geometry, has been applied to fast reactor steady-state calculations. The required cross section libraries were generated with ERANOS code for several configurations. The limitations encountered in the application of the Analytic Coarse Mesh Finite Difference (ACMFD) method –implemented inside ANDES– to fast reactors are presented and the sensitivity of the method when using a high number of energy groups is studied. ANDES performance is assessed by comparison with the results provided by ERANOS, using a mini-core model in 33 energy groups. Furthermore, a benchmark from the NEA for a small 3D FBR in hexagonal-Z geometry and 4 energy groups is also employed to verify the behavior of the code with few energy groups.

Hydration of C3S, C2S and their Blends. Micro- and Nanoscale Characterization

This study forms part of wider research conducted under a EU 7 th Framework Programme (COmputationally Driven design of Innovative CEment-based materials or CODICE). The ultimate aim is the multi-scale modelling of the variations in mechanical performance in degraded and non-degraded cementitious matrices. The model is being experimentally validated by hydrating the main tri-calcium silicate (T1-C3S) and bi-calcium silicate (β-C2S), phases present in Portland cement and their blends. The present paper discusses micro- and nanoscale studies of the cementitious skeletons forming during the hydration of C3S, C2S and 70 % / 30 % blends of both C3S/C2S and C2S/C3S with a water/cement ratio of 0.4. The hydrated pastes were characterized at different curing ages with 29 Si NMR, SEM/TEM/EDS, BET, and nanoindentation. The findings served as a basis for the micro- and nanoscale characterization of the hydration products formed, especially C-S-H gels. Differences were identified in composition, structure and mechanical behaviour (nanoindentation), depending on whether the gels formed in C3S or C2S pastes. The C3S gels had more compact morphologies, smaller BET-N2 specific surface area and lesser porosity than the gels from C2S-rich pastes. The results of nanoindentation tests appear to indicate that the various C-S-H phases formed in hydrated C3S and C2S have the same mechanical properties as those formed in Portland cement paste. Compared to the C3S sample, the hydrated C2S specimen was dominated by the loose-packed (LP) and the low-density (LD) C-S-H phases, and had a much lower content of the high density (HD) C-S-H phase

Mapping of mechanical properties of cement paste microstructures

The presented study is related to the EU 7 th Framework Programme CODICE (COmputationally Driven design of Innovative CEment-based materials). The main aim of the project is the development of a multi-scale model for the computer based simulation of mechanical and durability performance of cementitious materials. This paper reports results of micro/nano scale characterisation and mechanical property mapping of cementitious skeletons formed by the cement hydration at different ages. Using the statistical nanoindentation and micro-mechanical property mapping technique, intrinsic properties of different hydrate phases, and also the possible interaction (or overlapping) of different phases (e.g. calcium-silcate-hydrates) has been studied. Results of the mapping and statistical indentation testing appear to suggest the possible existence of more hydrate phases than the commonly reported LD and HD C-S-H and CH phases

Fractal Behaviour and Irregularity of Wetting Fronts in Heterogeneous Porous Media

The wetting front is the zone where water invades and advances into an initially dry porous material and it plays a crucial role in solute transport through the unsaturated zone. Water is an essential part of the physiological process of all plants. Through water, necessary minerals are moved from the roots to the parts of the plants that require them. Water moves chemicals from one part of the plant to another. It is also required for photosynthesis, for metabolism and for transpiration. The leaching of chemicals by wetting fronts is influenced by two major factors, namely: the irregularity of the fronts and heterogeneity in the distribution of chemicals, both of which have been described by using fractal techniques. Soil structure can significantly modify infiltration rates and flow pathways in soils. Relations between features of soil structure and features of infiltration could be elucidated from the velocities and the structure of wetting fronts. When rainwater falls onto soil, it doesn?t just pool on surfaces. Water ?or another fluid- acts differently on porous surfaces. If the surface is permeable (porous) it seeps down through layers of soil, filling that layer to capacity. Once that layer is filled, it moves down into the next layer. In sandy soil, water moves quickly, while it moves much slower through clay soil. The movement of water through soil layers is called the the wetting front. Our research concerns the motion of a liquid into an initially dry porous medium. Our work presents a theoretical framework for studying the physical interplay between a stationary wetting front of fractal dimension D with different porous materials. The aim was to model the mass geometry interplay by using the fractal dimension D of a stationary wetting front. The plane corresponding to the image is divided in several squares (the minimum correspond to the pixel size) of size length ". We acknowledge the help of Prof. M. García Velarde and the facilities offered by the Pluri-Disciplinary Institute of the Complutense University of Madrid. We also acknowledge the help of European Community under project Multi-scale complex fluid flows and interfacial phenomena (PITN-GA-2008-214919). Thanks are also due to ERCOFTAC (PELNoT, SIG 14)

Computational methods to create and analyze a digital gene expression atlas of embryo development from microscopy images

Abstract The creation of atlases, or digital models where information from different subjects can be combined, is a field of increasing interest in biomedical imaging. When a single image does not contain enough information to appropriately describe the organism under study, it is then necessary to acquire images of several individuals, each of them containing complementary data with respect to the rest of the components in the cohort. This approach allows creating digital prototypes, ranging from anatomical atlases of human patients and organs, obtained for instance from Magnetic Resonance Imaging, to gene expression cartographies of embryo development, typically achieved from Light Microscopy. Within such context, in this PhD Thesis we propose, develop and validate new dedicated image processing methodologies that, based on image registration techniques, bring information from multiple individuals into alignment within a single digital atlas model. We also elaborate a dedicated software visualization platform to explore the resulting wealth of multi-dimensional data and novel analysis algo-rithms to automatically mine the generated resource in search of bio¬logical insights. In particular, this work focuses on gene expression data from developing zebrafish embryos imaged at the cellular resolution level with Two-Photon Laser Scanning Microscopy. Disposing of quantitative measurements relating multiple gene expressions to cell position and their evolution in time is a fundamental prerequisite to understand embryogenesis multi-scale processes. However, the number of gene expressions that can be simultaneously stained in one acquisition is limited due to optical and labeling constraints. These limitations motivate the implementation of atlasing strategies that can recreate a virtual gene expression multiplex. The developed computational tools have been tested in two different scenarios. The first one is the early zebrafish embryogenesis where the resulting atlas constitutes a link between the phenotype and the genotype at the cellular level. The second one is the late zebrafish brain where the resulting atlas allows studies relating gene expression to brain regionalization and neurogenesis. The proposed computational frameworks have been adapted to the requirements of both scenarios, such as the integration of partial views of the embryo into a whole embryo model with cellular resolution or the registration of anatom¬ical traits with deformable transformation models non-dependent on any specific labeling. The software implementation of the atlas generation tool (Match-IT) and the visualization platform (Atlas-IT) together with the gene expression atlas resources developed in this Thesis are to be made freely available to the scientific community. Lastly, a novel proof-of-concept experiment integrates for the first time 3D gene expression atlas resources with cell lineages extracted from live embryos, opening up the door to correlate genetic and cellular spatio-temporal dynamics. La creación de atlas, o modelos digitales, donde la información de distintos sujetos puede ser combinada, es un campo de creciente interés en imagen biomédica. Cuando una sola imagen no contiene suficientes datos como para describir apropiadamente el organismo objeto de estudio, se hace necesario adquirir imágenes de varios individuos, cada una de las cuales contiene información complementaria respecto al resto de componentes del grupo. De este modo, es posible crear prototipos digitales, que pueden ir desde atlas anatómicos de órganos y pacientes humanos, adquiridos por ejemplo mediante Resonancia Magnética, hasta cartografías de la expresión genética del desarrollo de embrionario, típicamente adquiridas mediante Microscopía Optica. Dentro de este contexto, en esta Tesis Doctoral se introducen, desarrollan y validan nuevos métodos de procesado de imagen que, basándose en técnicas de registro de imagen, son capaces de alinear imágenes y datos provenientes de múltiples individuos en un solo atlas digital. Además, se ha elaborado una plataforma de visualization específicamente diseñada para explorar la gran cantidad de datos, caracterizados por su multi-dimensionalidad, que resulta de estos métodos. Asimismo, se han propuesto novedosos algoritmos de análisis y minería de datos que permiten inspeccionar automáticamente los atlas generados en busca de conclusiones biológicas significativas. En particular, este trabajo se centra en datos de expresión genética del desarrollo embrionario del pez cebra, adquiridos mediante Microscopía dos fotones con resolución celular. Disponer de medidas cuantitativas que relacionen estas expresiones genéticas con las posiciones celulares y su evolución en el tiempo es un prerrequisito fundamental para comprender los procesos multi-escala característicos de la morfogénesis. Sin embargo, el número de expresiones genéticos que pueden ser simultáneamente etiquetados en una sola adquisición es reducido debido a limitaciones tanto ópticas como del etiquetado. Estas limitaciones requieren la implementación de estrategias de creación de atlas que puedan recrear un multiplexado virtual de expresiones genéticas. Las herramientas computacionales desarrolladas han sido validadas en dos escenarios distintos. El primer escenario es el desarrollo embrionario temprano del pez cebra, donde el atlas resultante permite constituir un vínculo, a nivel celular, entre el fenotipo y el genotipo de este organismo modelo. El segundo escenario corresponde a estadios tardíos del desarrollo del cerebro del pez cebra, donde el atlas resultante permite relacionar expresiones genéticas con la regionalización del cerebro y la formación de neuronas. La plataforma computacional desarrollada ha sido adaptada a los requisitos y retos planteados en ambos escenarios, como la integración, a resolución celular, de vistas parciales dentro de un modelo consistente en un embrión completo, o el alineamiento entre estructuras de referencia anatómica equivalentes, logrado mediante el uso de modelos de transformación deformables que no requieren ningún marcador específico. Está previsto poner a disposición de la comunidad científica tanto la herramienta de generación de atlas (Match-IT), como su plataforma de visualización (Atlas-IT), así como las bases de datos de expresión genética creadas a partir de estas herramientas. Por último, dentro de la presente Tesis Doctoral, se ha incluido una prueba conceptual innovadora que permite integrar los mencionados atlas de expresión genética tridimensionales dentro del linaje celular extraído de una adquisición in vivo de un embrión. Esta prueba conceptual abre la puerta a la posibilidad de correlar, por primera vez, las dinámicas espacio-temporales de genes y células.

Caracterización multiescala de objetos como herramienta para la clasificación de imágenes de alta resolución espacial

This paper presents a new methodology, simple and affordable, for the definition and characterization of objects at different scales in high spatial resolution images. The objects have been generated by integrating texturally and spectrally homogeneous segments. The former have been obtained from the segmentation of Wavelet coefficients of the panchromatic image. The multi-scale character of this transform has yielded texturally homogeneous segments of different sizes for each of the scales. The spectrally homogeneous segments have been obtained by segmenting the classified corresponding multispectral image. In this way, it has been defined a set of objects characterized by different attributes, which give to the objects a semantic meaning, allowing to determine the similarities and differences between them. To demonstrate the capabilities of the methodology proposed, different experiments of unsupervised classification of a Quickbird image have been carried out, using different subsets of attributes and 1-D ascendant hierarchical classifier. Obtained results have shown the capability of the proposed methodology for separating semantic objects at different scales, as well as, its advantages against pixel-based image interpretation.

Water scarcity and climate change impact and vulnerability in irrigated agriculture in Mediterranean river basins

Actualmente, la escasez de agua constituye un importante problema en muchos lugares del mundo. El crecimiento de la población, la creciente necesidad de alimentos, el desarrollo socio-económico y el cambio climático ejercen una importante y cada vez mayor presión sobre los recursos hídricos, a la que muchos países van a tener que enfrentarse en los próximos anos. La región Mediterránea es una de las regiones del mundo de mayor escasez de recursos hídricos, y es además una de las zonas más vulnerables al cambio climático. La mayoría de estudios sobre cambio climático prevén mayores temperaturas y una disminución de las precipitaciones, y una creciente escasez de agua debida a la disminución de recursos disponibles y al aumento de las demandas de riego. En el contexto actual de desarrollo de políticas se demanda cada vez más una mayor consideración del cambio climático en el marco de las políticas sectoriales. Sin embargo, los estudios enfocados a un solo sector no reflejan las múltiples dimensiones del los efectos del cambio climático. Numerosos estudios científicos han demostrado que el cambio climático es un fenómeno de naturaleza multi-dimensional y cuyos efectos se transmiten a múltiples escalas. Por tanto, es necesaria la producción de estudios y herramientas de análisis capaces de reflejar todas estas dimensiones y que contribuyan a la elaboración de políticas robustas en un contexto de cambio climático. Esta investigación pretende aportar una visión global de la problemática de la escasez de agua y los impactos, la vulnerabilidad y la adaptación al cambio climático en el contexto de la región mediterránea. La investigación presenta un marco integrado de modelización que se va ampliando progresivamente en un proceso secuencial y multi-escalar en el que en cada etapa se incorpora una nueva dimensión. La investigación consta de cuatro etapas que se abordan a lo largo de cuatro capítulos. En primer lugar, se estudia la vulnerabilidad económica de las explotaciones de regadío del Medio Guadiana, en España. Para ello, se utiliza un modelo de programación matemática en combinación con un modelo econométrico. A continuación, en la segunda etapa, se utiliza un modelo hidro-económico que incluye un modelo de cultivo para analizar los procesos que tienen lugar a escala de cultivo, explotación y cuenca teniendo en cuenta distintas escalas geográficas y de toma de decisiones. Esta herramienta permite el análisis de escenarios de cambio climático y la evaluación de posibles medidas de adaptación. La tercera fase consiste en el análisis de las barreras que dificultan la aplicación de procesos de adaptación para lo cual se analizan las redes socio-institucionales en la cuenca. Finalmente, la cuarta etapa aporta una visión sobre la escasez de agua y el cambio climático a escala nacional y regional mediante el estudio de distintos escenarios de futuro plausibles y los posibles efectos de las políticas en la escasez de agua. Para este análisis se utiliza un modelo econométrico de datos de panel para la región mediterránea y un modelo hidro-económico que se aplica a los casos de estudio de España y Jordania. Los resultados del estudio ponen de relieve la importancia de considerar múltiples escalas y múltiples dimensiones en el estudio de la gestión de los recursos hídricos y la adaptación al cambio climático en los contextos mediterráneos de escasez de agua estudiados. Los resultados muestran que los impactos del cambio climático en la cuenca del Guadiana y en el conjunto de España pueden comprometer la sostenibilidad del regadío y de los ecosistemas. El análisis a escala de cuenca hidrográfica resalta la importancia de las interacciones entre los distintos usuarios del agua y en concreto entre distintas comunidades de regantes, así como la necesidad de fortalecer el papel de las instituciones y de fomentar la creación de una visión común en la cuenca para facilitar la aplicación de los procesos de adaptación. Asimismo, los resultados de este trabajo evidencian también la capacidad y el papel fundamental de las políticas para lograr un desarrollo sostenible y la adaptación al cambio climático es regiones de escasez de agua tales como la región mediterránea. Especialmente, este trabajo pone de manifiesto el potencial de la Directiva Marco del Agua de la Unión Europea para lograr una efectiva adaptación al cambio climático. Sin embargo, en Jordania, además de la adaptación al cambio climático, es preciso diseñar estrategias de desarrollo sostenible más ambiciosas que contribuyan a reducir el riesgo futuro de escasez de agua. ABSTRACT Water scarcity is becoming a major concern in many parts of the world. Population growth, increasing needs for food production, socio-economic development and climate change represent pressures on water resources that many countries around the world will have to deal in the coming years. The Mediterranean region is one of the most water scarce regions of the world and is considered a climate change hotspot. Most projections of climate change envisage an increase in temperatures and a decrease in precipitation and a resulting reduction in water resources availability as a consequence of both reduced water availability and increased irrigation demands. Current policy development processes require the integration of climate change concerns into sectoral policies. However, sector-oriented studies often fail to address all the dimensions of climate change implications. Climate change research in the last years has evidenced the need for more integrated studies and methodologies that are capable of addressing the multi-scale and multi-dimensional nature of climate change. This research attempts to provide a comprehensive view of water scarcity and climate change impacts, vulnerability and adaptation in Mediterranean contexts. It presents an integrated modelling framework that is progressively enlarged in a sequential multi-scale process in which a new dimension of climate change and water resources is addressed at every stage. It is comprised of four stages, each one explained in a different chapter. The first stage explores farm-level economic vulnerability in the Spanish Guadiana basin using a mathematical programming model in combination with an econometric model. Then, in a second stage, the use of a hydro-economic modelling framework that includes a crop growth model allows for the analysis of crop, farm and basin level processes taking into account different geographical and decision-making scales. This integrated tool is used for the analysis of climate change scenarios and for the assessment of potential adaptation options. The third stage includes the analysis of barriers to the effective implementation of adaptation processes based on socioinstitutional network analysis. Finally, a regional and country level perspective of water scarcity and climate change is provided focusing on different possible socio-economic development pathways and the effect of policies on future water scarcity. For this analysis, a panel-data econometric model and a hydro-economic model are applied for the analysis of the Mediterranean region and country level case studies in Spain and Jordan. The overall results of the study demonstrate the value of considering multiple scales and multiple dimensions in water management and climate change adaptation in the Mediterranean water scarce contexts analysed. Results show that climate change impacts in the Guadiana basin and in Spain may compromise the sustainability of irrigation systems and ecosystems. The analysis at the basin level highlights the prominent role of interactions between different water users and irrigation districts and the need to strengthen institutional capacity and common understanding in the basin to enhance the implementation of adaptation processes. The results of this research also illustrate the relevance of water policies in achieving sustainable development and climate change adaptation in water scarce areas such as the Mediterranean region. Specifically, the EU Water Framework Directive emerges as a powerful trigger for climate change adaptation. However, in Jordan, outreaching sustainable development strategies are required in addition to climate change adaptation to reduce future risk of water scarcity.

1H HR MAS NMR metabolomic and non-destructive 2D NMR relaxometry to assess internal quality in apples.

NMR can be considered a multi-scale multidimensional technology in the sense that it provides both spatial insight at macroscopic (MRI) or microscopic level (relaxometry), together with chemical characterization (HR-MAS). In this study 296 apples (from 4 cultivars) were MRI screened (20 slices per fruit) among which 7 fruits were used for metabolomic study by 1H HR MAS in order to assess various chemical shifts: malic acid, sucrose, glucose, fructose and ethanol. On the first season, tissue samples were taken from the sound and affected apples (near the core, centre and outer part of the mesocarp) belonging to sound and affected locations, while on the second season, tissue samples were focused on the comparison between sound and affected tissue. Beside, MRI and 2D non-destructive relaxometry (on whole fruits, and localized tissue) where performed on 72 and 12 apples respectively in order to compare features at macroscopic (tissue) and microscopic (subcellular) level. HR MAS shows higher content of ?-glucose, ?-glucose, malic acid and aromatic compounds in watercore affected tissues from both seasons, while sound tissue reflects higher sucrose. Microscopic (subcellular) degradation of tissue varies according to disorder development and is in good accordance with macroscopic characterization with MRI.