Bone marrow-derived mesenchymal stromal cells improve vascular regeneration and reduce leukocyte-endothelium activation in critical ischemic murine skin in a dose-dependent manner

BACKGROUND AIMS Stem cells participate in vascular regeneration following critical ischemia. However, their angiogenic and remodeling properties, as well as their role in ischemia-related endothelial leukocyte activation, need to be further elucidated. Herein, we investigated the effect of bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a critically ischemic murine skin flap model. METHODS Groups received either 1 × 10(5), 5 × 10(5), or 1 × 10(6) BM-MSCs or cell-free conditioned medium (CM). Controls received sodium chloride. Intravital fluorescence microscopy was performed for morphological and quantitative assessment of micro-hemodynamic parameters over 12 days. RESULTS Tortuosity and diameter of conduit-arterioles were pronounced in the MSC groups (P < 0.01), whereas vasodilation was shifted to the end arteriolar level in the CM group (P < 0.01). These effects were accompanied by angiopoietin-2 expression. Functional capillary density and red blood cell velocity were enhanced in all treatment groups (P < 0.01). Although a significant reduction of rolling and sticking leukocytes was observed in the MSC groups with a reduction of diameter in postcapillary venules (P < 0.01), animals receiving CM exhibited a leukocyte-endothelium interaction similar to controls. This correlated with leukocyte common antigen expression in tissue sections (P < 0.01) and p38 mitogen-activated protein kinase expression from tissue samples. Cytokine analysis from BM-MSC culture medium revealed a 50% reduction of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-12, tumor necrosis factor-α, interferon-γ) and chemokines (keratinocyte chemoattractant, granulocyte colony-stimulating factor) under hypoxic conditions. DISCUSSION We demonstrated positive effects of BM-MSCs on vascular regeneration and modulation of endothelial leukocyte adhesion in critical ischemic skin. The improvements after MSC application were dose-dependent and superior to the use of CM alone.

Resolving diffusion in clay minerals at different time scales: Combination of experimental and modeling approaches

Since no single experimental or modeling technique provides data that allow a description of transport processes in clays and clay minerals at all relevant scales, several complementary approaches have to be combined to understand and explain the interplay between transport relevant phenomena. In this paper molecular dynamics simulations (MD) were used to investigate the mobility of water in the interlayer of montmorillonite (Mt), and to estimate the influence of mineral surfaces and interlayer ions on the water diffusion. Random Walk (RW) simulations based on a simplified representation of pore space in Mt were used to estimate and understand the effect of the arrangement of Mt particles on the meso- to macroscopic diffusivity of water. These theoretical calculations were complemented with quasielastic neutron scattering (QENS) measurements of aqueous diffusion in Mt with two pseudo-layers of water performed at four significantly different energy resolutions (i.e. observation times). The size of the interlayer and the size of Mt particles are two characteristic dimensions which determine the time dependent behavior of water diffusion in Mt. MD simulations show that at very short time scales water dynamics has the characteristic features of an oscillatory motion in the cage formed by neighbors in the first coordination shell. At longer time scales, the interaction of water with the surface determines the water dynamics, and the effect of confinement on the overall water mobility within the interlayer becomes evident. At time scales corresponding to an average water displacement equivalent to the average size of Mt particles, the effects of tortuosity are observed in the meso- to macroscopic pore scale simulations. Consistent with the picture obtained in the simulations, the QENS data can be described using a (local) 3D diffusion at short observation times, whereas at sufficiently long observation times a 2D diffusive motion is clearly observed. The effects of tortuosity measured in macroscopic tracer diffusion experiments are in qualitative agreement with RW simulations. By using experimental data to calibrate molecular and mesoscopic theoretical models, a consistent description of water mobility in clay minerals from the molecular to the macroscopic scale can be achieved. In turn, simulations help in choosing optimal conditions for the experimental measurements and the data interpretation. (C) 2014 Elsevier B.V. All rights reserved.

Diffusion transport of water in basalts

Studying diffusive transport in porous rocks is of fundamental importance in understanding a variety of geochemical processes including: element transfer, primary mineral dissolution kinetics and precipitation of secondary phases. Here we report new findings on the relationship between diffusive transport and textural characteristics of the pore systems on the example of mid-oceanic ridge basalts having different degree of alteration but very similar bulk pore volume. Diffusion processes in porous basalts were studied in situ using H2O -> D2O exchange experiments. The effective diffusion coefficients of water molecules increase systematically from 5.05*10**-11 to 1.19*10**-10 m**2/s for fresh and moderately altered basalts and from 2.40*10**-11 to 6.72*10**-11 m**2/s for completely altered basalt as temperature increases from 5 to 50 °C. The activation energy of the diffusion process increases from 12.29 ± 0.71 kJ/mol for fresh and moderately altered basalts to 14.3 ± 1.33 kJ/mol for completely altered basalt. The results indicate that neither the bulk porosity nor the degree of alteration can be used as proxies for the efficiency of element transport during MORB-water interaction. The formation of secondary phases that replace primary minerals and fill the pore space in the rock leads to the formation of tiny pores and phases with large specific surface area. These factors might have a dominant control on the transport properties of altered basaltic rocks.

Modelling of chloride transport in non-saturated concrete : from microscale to macroscale

Corrosion of steel bars embedded in concrete has a great influence on structural performance and durability of reinforced concrete. Chloride penetration is considered to be a primary cause of concrete deterioration in a vast majority of structures. Therefore, modelling of chloride penetration into concrete has become an area of great interest. The present work focuses on modelling of chloride transport in concrete. The differential macroscopic equations which govern the problem were derived from the equations at the microscopic scale by comparing the porous network with a single equivalent pore whose properties are the same as the average properties of the real porous network. The resulting transport model, which accounts for diffusion, migration, advection, chloride binding and chloride precipitation, consists of three coupled differential equations. The first equation models the transport of chloride ions, while the other two model the flow of the pore water and the heat transfer. In order to calibrate the model, the material parameters to determine experimentally were identified. The differential equations were solved by means of the finite element method. The classical Galerkin method was employed for the pore solution flow and the heat transfer equations, while the streamline upwind Petrov Galerkin method was adopted for the transport equation in order to avoid spatial instabilities for advection dominated problems. The finite element codes are implemented in Matlab® . To retrieve a good understanding of the influence of each variable and parameter, a detailed sensitivity analysis of the model was carried out. In order to determine the diffusive and hygroscopic properties of the studied concretes, as well as their chloride binding capacity, an experimental analysis was performed. The model was successfully compared with experimental data obtained from an offshore oil platform located in Brazil. Moreover, apart from the main objectives, numerous results were obtained throughout this work. For instance, several diffusion coefficients and the relation between them are discussed. It is shown how the electric field set up between the ionic species depends on the gradient of the species’ concentrations. Furthermore, the capillary hysteresis effects are illustrated by a proposed model, which leads to the determination of several microstructure properties, such as the pore size distribution and the tortuosity-connectivity of the porous network. El fenómeno de corrosión del acero de refuerzo embebido en el hormigón ha tenido gran influencia en estructuras de hormigón armado, tanto en su funcionalidad estructural como en aspectos de durabilidad. La penetración de cloruros en el interior del hormigón esta considerada como el factor principal en el deterioro de la gran mayoría de estructuras. Por lo tanto, la modelización numérica de dicho fenómeno ha generado gran interés. El presente trabajo de investigación se centra en la modelización del transporte de cloruros en el interior del hormigón. Las ecuaciones diferenciales que gobiernan los fenómenos a nivel macroscópico se deducen de ecuaciones planteadas a nivel microscópico. Esto se obtiene comparando la red porosa con un poro equivalente, el cual mantiene las mismas propiedades de la red porosa real. El modelo está constituido por tres ecuaciones diferenciales acopladas que consideran el transporte de cloruros, el flujo de la solución de poro y la transferencia de calor. Con estas ecuaciones se tienen en cuenta los fenómenos de difusión, migración, advección, combinación y precipitación de cloruros. El análisis llevado a cabo en este trabajo ha definido los parámetros necesarios para calibrar el modelo. De acuerdo con ellas, se seleccionaron los ensayos experimentales a realizar. Las ecuaciones diferenciales se resolvieron mediante el método de elementos finitos. El método clásico de Galerkin se empleó para solucionar las ecuaciones de flujo de la solución de poro y de la transferencia de calor, mientras que el método streamline upwind Petrov-Galerkin se utilizó para resolver la ecuación de transporte de cloruros con la finalidad de evitar inestabilidades espaciales en problemas con advección dominante. El código de elementos finitos está implementado en Matlab® . Con el objetivo de facilitar la comprensión del grado de influencia de cada variable y parámetro, se realizó un análisis de sensibilidad detallado del modelo. Se llevó a cabo una campaña experimental sobre los hormigones estudiados, con el objeto de obtener sus propiedades difusivas, químicas e higroscópicas. El modelo se contrastó con datos experimentales obtenidos en una plataforma petrolera localizada en Brasil. Las simulaciones numéricas corroboraron los datos experimentales. Además, durante el desarrollo de la investigación se obtuvieron resultados paralelos a los planteados inicialmente. Por ejemplo, el análisis de diferentes coeficientes de difusión y la relación entre ellos. Así como también se observó que el campo eléctrico establecido entre las especies iónicas disueltas en la solución de poro depende del gradiente de concentración de las mismas. Los efectos de histéresis capilar son expresados por el modelo propuesto, el cual conduce a la determinación de una serie de propiedades microscópicas, tales como la distribución del tamaño de poro, además de la tortuosidad y conectividad de la red porosa.

Quantitative evaluation of patient-specific conforming hexahedral meshes of abdominal aortic aneurysms and intraluminal thrombus generated from MRI

A novel method for generating patient-specific high quality conforming hexahedral meshes is presented. The meshes are directly obtained from the segmentation of patient magnetic resonance (MR) images of abdominal aortic aneu-rysms (AAA). The MRI permits distinguishing between struc-tures of interest in soft tissue. Being so, the contours of the lumen, the aortic wall and the intraluminal thrombus (ILT) are available and thus the meshes represent the actual anato-my of the patient?s aneurysm, including the layered morpholo-gies of these structures. Most AAAs are located in the lower part of the aorta and the upper section of the iliac arteries, where the inherent tortuosity of the anatomy and the presence of the ILT makes the generation of high-quality elements at the bifurcation is a challenging task. In this work we propose a novel approach for building quadrilateral meshes for each surface of the sectioned geometry, and generating conforming hexahedral meshes by combining the quadrilateral meshes. Conforming hexahedral meshes are created for the wall and the ILT. The resulting elements are evaluated on four patients? datasets using the Scaled Jacobian metric. Hexahedral meshes of 25,000 elements with 94.8% of elements well-suited for FE analysis are generated.

Caracterización del hormigón en relación a la difusión de gases y su correlación con el radón

Radon gas (Rn) is a natural radioactive gas present in some soils and able to penetrate buildings through the building envelope in contact with the soil. Radon can accumulate within buildings and consequently be inhaled by their occupants. Because it is a radioactive gas, its disintegration process produces alpha particles that, in contact with the lung epithelia, can produce alterations potentially giving rise to cancer. Many international organizations related to health protection, such as WHO, confirm this causality. One way to avoid the accumulation of radon in buildings is to use the building envelope as a radon barrier. The extent to which concrete provides such a barrier is described by its radon diffusion coefficient (DRn), a parameter closely related to porosity (ɛ) and tortuosity factor (τ). The measurement of the radon diffusion coefficient presents challenges, due to the absence of standard procedures, the requirement to establish adequate airtightness in testing apparatus (referred to here as the diffusion cell), and due to the fact that measurement has to be carried out in an environment certified for use of radon calibrated sources. In addition to this calibrated radon sources are costly. The measurement of the diffusion coefficient for non-radioactive gas is less complex, but nevertheless retains a degree of difficulty due to the need to provide reliably airtight apparatus for all tests. Other parameters that can characterize and describe the process of gas transport through concrete include the permeability coefficient (K) and the electrical resistivity (ρe), both of which can be measured relatively easily with standardized procedure. The use of these parameters would simplify the characterization of concrete behaviour as a radon barrier. Although earlier studies exist, describing correlation among these parameters, there is, as has been observed in the literature, little common ground between the various research efforts. For precisely this reason, prior to any attempt to measure radon diffusion, it was deemed necessary to carry out further research in this area, as a foundation to the current work, to explore potential relationships among the following parameters: porosity-tortuosity, oxygen diffusion coefficient, permeability coefficient and resistivity. Permeability coefficient measurement (m2) presents a more straightforward challenge than diffusion coefficient measurement. Some authors identify a relationship between both coefficients, including Gaber (1988), who proposes: k= a•Dn Equation 1 Where: a=A/(8ΠD020), A = sample cross-section, D020 = diffusion coefficient in air (m2/s). Other studies (Klink et al. 1999, Gaber and Schlattner 1997, Gräf and Grube et al. 1986), experimentally relate both coefficients of different types of concrete confirming that this relationship exists, as represented by the simplified expression: k≈Dn Equation 2 In each particular study a different value for n was established, varying from 1.3 to 2.5, but this requires determination of a value for n in a more general way because these proposed models cannot estimate diffusion coefficient. If diffusion coefficient has to be measured to be able to establish n, these relationships are not interesting. The measurement of electric resistivity is easier than diffusion coefficient measurement. Correlation between the parameters can be established via Einstein´s law that relates movement of electrical charges to media conductivity according to the expression: D_e=k/ρ Equation 3 Where: De = diffusion coefficient (cm2/s), K = constant, ρ = electric resistivity (Ω•cm). The tortuosity factor is used to represent the uneven geometry of concrete pores, which are described as being not straight, but tortuous. This factor was first introduced in the literature to relate global porosity with fluid transport in a porous media, and can be formulated in a number of different ways. For example, it can take the form of equation 4 (Mason y Malinauskas), which combines molecular and Knudsen diffusion using the tortuosity factor: D=ε^τ (3/2r √(πM/8RT+1/D_0 ))^(-1) Equation 4 Where: r = medium radius obtained from MIP (µm), M = gas molecular mass, R = ideal gases constant, T = temperature (K), D0 = coefficient diffusion in the air (m2/s). Few studies provide any insight as to how to obtain the tortuosity factor. The work of Andrade (2012) is exceptional in this sense, as it outlines how the tortuosity factor can be deduced from pore size distribution (from MIP) from the equation: ∅_th=∅_0•ε^(-τ). Equation 5 Where: Øth = threshold diameter (µm), Ø0 = minimum diameter (µm), ɛ = global porosity, τ = tortuosity factor. Alternatively, the following equation may be used to obtain the tortuosity factor: DO2=D0*ɛτ Equation 6 Where: DO2 = oxygen diffusion coefficient obtained experimentally (m2/s), DO20 = oxygen diffusion coefficient in the air (m2/s). This equation has been inferred from Archie´s law ρ_e=〖a•ρ〗_0•ɛ^(-m) and from the Einstein law mentioned above, using the values of oxygen diffusion coefficient obtained experimentally. The principal objective of the current study was to establish correlations between the different parameters that characterize gas transport through concrete. The achievement of this goal will facilitate the assessment of the useful life of concrete, as well as open the door to the pro-active planning for the use of concrete as a radon barrier. Two further objectives were formulated within the current study: 1.- To develop a method for measurement of gas coefficient diffusion in concrete. 2.- To model an analytic estimation of radon diffusion coefficient from parameters related to concrete porosity and tortuosity factor. In order to assess the possible correlations, parameters have been measured using the standardized procedures or purpose-built in the laboratory for the study of equations 1, 2 y 3. To measure the gas diffusion coefficient, a diffusion cell was designed and manufactured, with the design evolving over several cycles of research, leading ultimately to a unit that is reliably air tight. The analytic estimation of the radon diffusion coefficient DRn in concrete is based on concrete global porosity (ɛ), whose values may be experimentally obtained from a mercury intrusion porosimetry test (MIP), and from its tortuosity factor (τ), derived using the relations expressed in equations 5 y 6. The conclusions of the study are: Several models based on regressions, for concrete with a relative humidity of 50%, have been proposed to obtain the diffusion coefficient following the equations K=Dn, K=a*Dn y D=n/ρe. The final of these three relations is the one with the determination coefficient closest to a value of 1: D=(19,997*LNɛ+59,354)/ρe Equation 7 The values of the obtained oxygen diffusion coefficient adjust quite well to those experimentally measured. The proposed method for the measurement of the gas coefficient diffusion is considered to be adequate. The values obtained for the oxygen diffusion coefficient are within the range of those proposed by the literature (10-7 a 10-8 m2/s), and are consistent with the other studied parameters. Tortuosity factors obtained using pore distribution and the expression Ø=Ø0*ɛ-τ are inferior to those from resistivity ρ=ρ0*ɛ-τ. The closest relationship to it is the one with porosity of pore diameter 1 µm (τ=2,07), being 7,21% inferior. Tortuosity factors obtained from the expression DO2=D0*ɛτ are similar to those from resistivity: for global tortuosity τ=2,26 and for the rest of porosities τ=0,7. Estimated radon diffusion coefficients are within the range of those consulted in literature (10-8 a 10-10 m2/s).ABSTRACT El gas radón (Rn) es un gas natural radioactivo presente en algunos terrenos que puede penetrar en los edificios a través de los cerramientos en contacto con el mismo. En los espacios interiores se puede acumular y ser inhalado por las personas. Al ser un gas radioactivo, en su proceso de desintegración emite partículas alfa que, al entrar en contacto con el epitelio pulmonar, pueden producir alteraciones del mismo causando cáncer. Muchos organismos internacionales relacionados con la protección de la salud, como es la OMS, confirman esta causalidad. Una de las formas de evitar que el radón penetre en los edificios es utilizando las propiedades de barrera frente al radón de su propia envolvente en contacto con el terreno. La principal característica del hormigón que confiere la propiedad de barrera frente al radón cuando conforma esta envolvente es su permeabilidad que se puede caracterizar mediante su coeficiente de difusión (DRn). El coeficiente de difusión de un gas en el hormigón es un parámetro que está muy relacionado con su porosidad (ɛ) y su tortuosidad (τ). La medida del coeficiente de difusión del radón resulta bastante complicada debido a que el procedimiento no está normalizado, a que es necesario asegurar una estanquidad a la celda de medida de la difusión y a que la medida tiene que ser realizada en un laboratorio cualificado para el uso de fuentes de radón calibradas, que además son muy caras. La medida del coeficiente de difusión de gases no radioactivos es menos compleja, pero sigue teniendo un alto grado de dificultad puesto que tampoco está normalizada, y se sigue teniendo el problema de lograr una estanqueidad adecuada de la celda de difusión. Otros parámetros que pueden caracterizar el proceso son el coeficiente de permeabilidad (K) y la resistividad eléctrica (ρe), que son más fáciles de determinar mediante ensayos que sí están normalizados. El uso de estos parámetros facilitaría la caracterización del hormigón como barrera frente al radón, pero aunque existen algunos estudios que proponen correlaciones entre estos parámetros, en general existe divergencias entre los investigadores, como se ha podido comprobar en la revisión bibliográfica realizada. Por ello, antes de tratar de medir la difusión del radón se ha considerado necesario realizar más estudios que puedan clarificar las posibles relaciones entre los parámetros: porosidad-tortuosidad, coeficiente de difusión del oxígeno, coeficiente de permeabilidad y resistividad. La medida del coeficiente de permeabilidad (m2) es más sencilla que el de difusión. Hay autores que relacionan el coeficiente de permeabilidad con el de difusión. Gaber (1988) propone la siguiente relación: k= a•Dn Ecuación 1 En donde: a=A/(8ΠD020), A = sección de la muestra, D020 = coeficiente de difusión en el aire (m2/s). Otros estudios (Klink et al. 1999, Gaber y Schlattner 1997, Gräf y Grube et al. 1986) relacionan de forma experimental los coeficientes de difusión de radón y de permeabilidad de distintos hormigones confirmando que existe una relación entre ambos parámetros, utilizando la expresión simplificada: k≈Dn Ecuación 2 En cada estudio concreto se han encontrado distintos valores para n que van desde 1,3 a 2,5 lo que lleva a la necesidad de determinar n porque no hay métodos que eviten la determinación del coeficiente de difusión. Si se mide la difusión ya deja de ser de interés la medida indirecta a través de la permeabilidad. La medida de la resistividad eléctrica es muchísimo más sencilla que la de la difusión. La relación entre ambos parámetros se puede establecer a través de una de las leyes de Einstein que relaciona el movimiento de cargas eléctricas con la conductividad del medio según la siguiente expresión: D_e=k/ρ_e Ecuación 3 En donde: De = coeficiente de difusión (cm2/s), K = constante, ρe = resistividad eléctrica (Ω•cm). El factor de tortuosidad es un factor de forma que representa la irregular geometría de los poros del hormigón, al no ser rectos sino tener una forma tortuosa. Este factor se introduce en la literatura para relacionar la porosidad total con el transporte de un fluido en un medio poroso y se puede formular de distintas formas. Por ejemplo se destaca la ecuación 4 (Mason y Malinauskas) que combina la difusión molecular y la de Knudsen utilizando el factor de tortuosidad: D=ε^τ (3/2r √(πM/8RT+1/D_0 ))^(-1) Ecuación 4 En donde: r = radio medio obtenido del MIP (µm), M = peso molecular del gas, R = constante de los gases ideales, T = temperatura (K), D0 = coeficiente de difusión de un gas en el aire (m2/s). No hay muchos estudios que proporcionen una forma de obtener este factor de tortuosidad. Destaca el estudio de Andrade (2012) en el que deduce el factor de tortuosidad de la distribución del tamaño de poros (curva de porosidad por intrusión de mercurio) a partir de la ecuación: ∅_th=∅_0•ε^(-τ) Ecuación 5 En donde: Øth = diámetro umbral (µm), Ø0 = diámetro mínimo (µm), ɛ = porosidad global, τ = factor de tortuosidad. Por otro lado, se podría utilizar también para obtener el factor de tortuosidad la relación: DO2=D0*-τ Ecuación 6 En donde: DO2 = coeficiente de difusión del oxígeno experimental (m2/s), DO20 = coeficiente de difusión del oxígeno en el aire (m2/s). Esta ecuación está inferida de la ley de Archie ρ_e=〖a•ρ〗_0•ɛ^(-m) y la de Einstein mencionada anteriormente, utilizando valores del coeficiente de difusión del oxígeno DO2 obtenidos experimentalmente. El objetivo fundamental de la tesis es encontrar correlaciones entre los distintos parámetros que caracterizan el transporte de gases a través del hormigón. La consecución de este objetivo facilitará la evaluación de la vida útil del hormigón así como otras posibilidades, como la evaluación del hormigón como elemento que pueda ser utilizado en la construcción de nuevos edificios como barrera frente al gas radón presente en el terreno. Se plantean también los siguientes objetivos parciales en la tesis: 1.- Elaborar una metodología para la medida del coeficiente de difusión de los gases en el hormigón. 2.- Plantear una estimación analítica del coeficiente de difusión del radón a partir de parámetros relacionados con su porosidad y su factor de tortuosidad. Para el estudio de las correlaciones posibles, se han medido los parámetros con los procedimientos normalizados o puestos a punto en el propio Instituto, y se han estudiado las reflejadas en las ecuaciones 1, 2 y 3. Para la medida del coeficiente de difusión de gases se ha fabricado una celda que ha exigido una gran variedad de detalles experimentales con el fin de hacerla estanca. Para la estimación analítica del coeficiente de difusión del radón DRn en el hormigón se ha partido de su porosidad global (ɛ), que se obtiene experimentalmente del ensayo de porosimetría por intrusión de mercurio (MIP), y de su factor de tortuosidad (τ), que se ha obtenido a partir de las relaciones reflejadas en las ecuaciones 5 y 6. Las principales conclusiones obtenidas son las siguientes: Se proponen modelos basados en regresiones, para un acondicionamiento con humedad relativa de 50%, para obtener el coeficiente de difusión del oxígeno según las relaciones: K=Dn, K=a*Dn y D=n/ρe. La propuesta para esta última relación es la que tiene un mejor ajuste con R2=0,999: D=(19,997*LNɛ+59,354)/ρe Ecuación 7 Los valores del coeficiente de difusión del oxígeno así estimados se ajustan a los obtenidos experimentalmente. Se considera adecuado el método propuesto de medida del coeficiente de difusión para gases. Los resultados obtenidos para el coeficiente de difusión del oxígeno se encuentran dentro del rango de los consultados en la literatura (10-7 a 10-8 m2/s) y son coherentes con el resto de parámetros estudiados. Los resultados de los factores de tortuosidad obtenidos de la relación Ø=Ø0*ɛ-τ son inferiores a la de la resistividad (ρ=ρ0*ɛ-τ). La relación que más se ajusta a ésta, siendo un 7,21% inferior, es la de la porosidad correspondiente al diámetro 1 µm con τ=2,07. Los resultados de los factores de tortuosidad obtenidos de la relación DO2=D0*ɛτ son similares a la de la resistividad: para la porosidad global τ=2,26 y para el resto de porosidades τ=0,7. Los coeficientes de difusión de radón estimados mediante estos factores de tortuosidad están dentro del rango de los consultados en la literatura (10-8 a 10-10 m2/s).

Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: Role of vascular endothelial growth factor

The sequence of events that leads to tumor vessel regression and the functional characteristics of these vessels during hormone–ablation therapy are not known. This is because of the lack of an appropriate animal model and monitoring technology. By using in vivo microscopy and in situ molecular analysis of the androgen-dependent Shionogi carcinoma grown in severe combined immunodeficient mice, we show that castration of these mice leads to tumor regression and a concomitant decrease in vascular endothelial growth factor (VEGF) expression. Androgen withdrawal is known to induce apoptosis in Shionogi tumor cells. Surprisingly, tumor endothelial cells begin to undergo apoptosis before neoplastic cells, and rarefaction of tumor vessels precedes the decrease in tumor size. The regressing vessels begin to exhibit normal phenotype, i.e., lower diameter, tortuosity, vascular permeability, and leukocyte adhesion. Two weeks after castration, a second wave of angiogenesis and tumor growth begins with a concomitant increase in VEGF expression. Because human tumors often relapse following hormone–ablation therapy, our data suggest that these patients may benefit from combined anti-VEGF therapy.

Development and characterization of a rodent model of immune-mediated cholangitis.

The cholangiopathies are a group of hepatobiliary diseases in which intrahepatic bile duct epithelial cells, or cholangiocytes, are the target for a variety of destructive processes, including immune-mediated damage. We tested the hypothesis that cholangitis could be induced in rodents by immunization with highly purified cholangiocytes. Inbred Wistar rats were immunized with purified hyperplastic cholangiocytes isolated after bile duct ligation from either syngeneic Wistar or allogeneic Fischer 344 rats; control rats were immunized with bovine serum albumin (BSA) or hepatocytes. After immunization with cholangiocytes, recipient animals developed histologic evidence of nonsuppurative cholangitis without inflammation in other organs; groups immunized with BSA or hepatocytes showed no cholangitis. Immunohistochemical studies revealed that portal tract infiltrates around bile ducts consisted of CD3-positive lymphocytes, some of which expressed major histocompatibility complex class II antigen; B cells and exogenous monocytes/macrophages were essentially absent. Transfer of unfractionated ConA-stimulated spleen cells from cholangiocyte-immunized (but not BSA-immunized) rats into recipients also caused nonsuppurative cholangitis. Moreover, these splenocytes from cholangiocyte-immunized (but not BSA-immunized) rats were cytotoxic in vitro for cultured rodent cholangiocytes; no cytotoxicity was observed against a rat hepatocyte cell line. Also, a specific antibody response in sera of cholangiocyte-immunized rats was demonstrated by immunoblots against cholangiocyte proteins. Finally, cholangiograms in cholangiocyte-immunized rats showed distortion and tortuosity of the entire intrahepatic biliary ductal system. This unique rodent model of experimental cholangitis demonstrates the importance of immune mechanisms in the pathogenesis of cholangitis and will prove useful in exploring the mechanisms by which the immune system targets and damages cholangiocytes.

Coupled heat and mass transfer in concrete exposed to fire

The first investigation of this study is concerned with the reasonableness of the assumptions related to diffusion of water vapour in concrete and with the development of a diffusivity equation for heated concrete. It has been demonstrated that diffusion of water vapour does occur in concrete at all temperatures and that the type of diffusion is concrete is Knudsen diffusion. Neglecting diffusion leads to underestimating the pressure. It results in a maximum pore pressure of less than 1 MPa. It has also been shown that the assumption that diffusion in concrete is molecular is unreasonable even when the tortuosity is considered. Molecular diffusivity leads to overestimating the pressure. It results in a maximum pore pressure of 2.7 MPa of which the vapour pressure is 1.5 MPa while the air pressure is 1.2 MPa. Also, the first diffusivity equation, appropriately named 'concrete diffusivity', has been developed specifically for concrete that determines the effective diffusivity of any gas in concrete at any temperature. In thick walls and columns exposed to fire, concrete diffusivity leads to a maximum pore pressures of 1.5 and 2.2 MPa (along diagonals), respectively, that are almost entirely due to water vapour pressure. Also, spalling is exacerbated, and thus higher pressures may occur, in thin heated sections, since there is less of a cool reservoir towards which vapour can migrate. Furthermore, the reduction of the cool reservoir is affected not only by the thickness, but also by the time of exposure to fire and by the type of exposure, i.e. whether the concrete member is exposed to fire from one or more sides. The second investigation is concerned with examining the effects of thickness and exposure time and type. It has been demonstrated that the build up of pore pressure is low in thick members, since there is a substantial cool zone towards which water vapour can migrate. Thus, if surface and/or explosive spalling occur on a thick member, then such spalling must be due to high thermal stresses, but corner spalling is likely to be pore pressure spalling. However, depending on the exposure time and type, the pore pressures can be more than twice those occurring in thick members and thought to be the maximum that can occur so far, and thus the enhanced propensity of pore pressure spalling occurring on thin sections heated on opposite sides has been conclusively demonstrated to be due to the lack of a cool zone towards which moisture can migrate. Expressions were developed for the determination of the maximum pore pressures that can occur in different concrete walls and columns exposed to fire and of the corresponding times of exposure.

The clinical assessment of systemic hypertension in optometric practice

This thesis sets out to examine in detail the condition of systemic hypertension (high Blood Pressure) in relation to optometric practice in the United Kingdom. Systemic hypertension, which is asymptomatic in the early stages, is diagnosed from the Blood Pressure (BP) measurement recorded by a sphygmomanometer and/or from the complications that have developed in target organs. Optometric practice based surveys revealed that diagnosed systemic hypertension was the most prevalent cardiovascular medical condition (20.5%). Measurement of BP of patients in this sample revealed that if an optometrist included sphygmomanometry into the sight examination then at least one patient each day would be referred for suspect systemic hypertension. Optometric opinion felt that the measurement of BP in optometric practice would advance the profession, being appreciated by both patients and General Practitioners (GPs), but was felt to be an unnecessary routine procedure. The present sight examination for the systemic hypertensive is similar to that of the normotensive patient, but may involve an altered fundus examination and a visual field test. The GPs were in favour of optometric BP measurement and a future role in the share care management of the systemic hypertensive. The application of a new pictorial grading scale for the grading of vascular changes associated with pre-malignant systemic hypertension was found to be both accurate and reliable. Clinical trial of the grading scale in optometric practice found positive correlations between BP and increasing severity of the retinal vascular features. The subtle pre-malignant vascular changes require reliable accurate detection and analysis to assist in the management of the systemic hypertensive patient. Vessel width was shown to decrease with increasing age. Image analysis of the A/V ratio, arteriolar tortuosity and focal calibre changes revealed a positive correlation to the patient's BP (p<0.001). The retinal vasculature is relatively stable longitudinally with only minor changes in response to early disease states. Age and elevated BP increased a patient's risk of developing systemic medical conditions over a two-year period. The application of the pictorial grading scale to optometric practice and training the optometrist in the use of sphygmomanometry would improve the management of the systemic hypertensive patient in optometric practice. Future advances in image analysis hold substantial benefits for the detection and monitoring of subtle vascular changes associated with systemic hypertension.

Improving the description of the retinal vasculature and patient history taking for monitoring systemic hypertension

Systemic hypertension is an important public health concern. If optometrists are to perform a more active role in the detection and monitoring of high blood pressure (BP), there is a need to improve the consistency of describing the retinal vasculature and to assess patient's ability to correctly report the diagnosis of hypertension, its control and medication. One hundred and one patients aged >40 years were dilated and had fundus photography performed. BP was measured and a self-reported history of general health and current medication was compared with the records of their general practitioner (GP). The status of the retinal vasculature was quantified using a numeric scale by five clinicians and this was compared to the same evaluation performed with the aid of a basic pictorial grading scale. Image analysis was used to objectively measure the artery-to-vein (A/V) ratio and arterial reflex. Arteriolar tortuosity and calibre changes were found to be the most sensitive retinal signs of high BP. Using the grading scale to describe the retinal vasculature significantly improved inter- and intra-observer repeatability. Almost half the patients examined were on medication for high BP or cardiovascular disease. Patients' ability to give their complete medical history was poor, as was their ability to recall what medication they had been prescribed. GPs indicated it was useful to receive details of their patient's BP when it was >140/90 mmHg. The use of improved description of the retinal vasculature and stronger links between optometrists and GPs may enhance future patient care. © 2001 The College of Optometrists. Published by Elsevier Science Ltd. All rights reserved.

An artificial neural network stratifies the risks of reintervention and mortality after endovascular aneurysm repair:a retrospective observational study

Background Lifelong surveillance after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) is considered mandatory to detect potentially life-threatening endograft complications. A minority of patients require reintervention but cannot be predictively identified by existing methods. This study aimed to improve the prediction of endograft complications and mortality, through the application of machine-learning techniques. Methods Patients undergoing EVAR at 2 centres were studied from 2004-2010. Pre-operative aneurysm morphology was quantified and endograft complications were recorded up to 5 years following surgery. An artificial neural networks (ANN) approach was used to predict whether patients would be at low- or high-risk of endograft complications (aortic/limb) or mortality. Centre 1 data were used for training and centre 2 data for validation. ANN performance was assessed by Kaplan-Meier analysis to compare the incidence of aortic complications, limb complications, and mortality; in patients predicted to be low-risk, versus those predicted to be high-risk. Results 761 patients aged 75 +/- 7 years underwent EVAR. Mean follow-up was 36+/- 20 months. An ANN was created from morphological features including angulation/length/areas/diameters/ volume/tortuosity of the aneurysm neck/sac/iliac segments. ANN models predicted endograft complications and mortality with excellent discrimination between a low-risk and high-risk group. In external validation, the 5-year rates of freedom from aortic complications, limb complications and mortality were 95.9% vs 67.9%; 99.3% vs 92.0%; and 87.9% vs 79.3% respectively (p0.001) Conclusion This study presents ANN models that stratify the 5-year risk of endograft complications or mortality using routinely available pre-operative data.

A Bayesian neural network algorithm identifies patients in whom post-EVAR surveillance may be unnecessary

Lifelong surveillance is not cost-effective after endovascular aneurysm repair (EVAR), but is required to detect aortic complications which are fatal if untreated (type 1/3 endoleak, sac expansion, device migration). Aneurysm morphology determines the probability of aortic complications and therefore the need for surveillance, but existing analyses have proven incapable of identifying patients at sufficiently low risk to justify abandoning surveillance. This study aimed to improve the prediction of aortic complications, through the application of machine-learning techniques. Patients undergoing EVAR at 2 centres were studied from 2004–2010. Aneurysm morphology had previously been studied to derive the SGVI Score for predicting aortic complications. Bayesian Neural Networks were designed using the same data, to dichotomise patients into groups at low- or high-risk of aortic complications. Network training was performed only on patients treated at centre 1. External validation was performed by assessing network performance independently of network training, on patients treated at centre 2. Discrimination was assessed by Kaplan-Meier analysis to compare aortic complications in predicted low-risk versus predicted high-risk patients. 761 patients aged 75 +/− 7 years underwent EVAR in 2 centres. Mean follow-up was 36+/− 20 months. Neural networks were created incorporating neck angu- lation/length/diameter/volume; AAA diameter/area/volume/length/tortuosity; and common iliac tortuosity/diameter. A 19-feature network predicted aor- tic complications with excellent discrimination and external validation (5-year freedom from aortic complications in predicted low-risk vs predicted high-risk patients: 97.9% vs. 63%; p < 0.0001). A Bayesian Neural-Network algorithm can identify patients in whom it may be safe to abandon surveillance after EVAR. This proposal requires prospective study.

Repeated, long-distance migrations by a philopatric predator targeting highly contrasting ecosystems

Long-distance movements of animals are an important driver of population spatial dynamics and determine the extent of overlap with area-focused human activities, such as fishing. Despite global concerns of declining shark populations, a major limitation in assessments of population trends or spatial management options is the lack of information on their long-term migratory behaviour. For a large marine predator, the tiger shark Galeocerdo cuvier, we show from individuals satellite-tracked for multiple years (up to 1101 days) that adult males undertake annually repeated, round-trip migrations of over 7,500 km in the northwest Atlantic. Notably, these migrations occurred between the highly disparate ecosystems of Caribbean coral reef regions in winter and high latitude oceanic areas in summer, with strong, repeated philopatry to specific overwintering insular habitat. Partial migration also occurred, with smaller, immature individuals displaying reduced migration propensity. Foraging may be a putative motivation for these oceanic migrations, with summer behaviour showing higher path tortuosity at the oceanic range extremes. The predictable migratory patterns and use of highly divergent ecosystems shown by male tiger sharks appear broadly similar to migrations seen in birds, reptiles and mammals, and highlight opportunities for dynamic spatial management and conservation measures of highly mobile sharks.