Nötige und unnötige Behandlungen beim Hämorrhoidalleiden: Der Patient bestimmt mit

Up to one third of the general population suffers from symptoms caused by hemorrhoids. Conservative treatment comes first unless the patient presents with an acute hemorrhoidal prolapse or a thrombosis. A fiber enriched diet is the primary treatment option, recommended in the perioperative period as well as a long-term prophylaxis. A timely limited application of topical ointments or suppositories and/or flavonoids are further treatment options. When symptoms persist interventional procedures for grade I-II hemorrhoids, and surgery for grade III-IV hemorrhoids should be considered. Rubber band ligation is the interventional treatment of choice. A comparable efficacy using sclerosing or infrared therapy has not yet been demonstrated. We therefore do not recommend these treatment options for the cure of hemorrhoids. Self-treatment by anal insertion of bougies is of lowrisk and may be successful, particularly in the setting of an elevated sphincter pressure. Anal dilation, sphincterotomy, cryosurgery, bipolar diathermy, galvanic electrotherapy, and heat therapy should be regarded as obsolete given the poor or missing data reported for these methods. For a long time, the classic excisional hemorrhoidectomy was considered to be the gold standard as far as surgical procedures are concerned. Primary closure (Ferguson) seems to be superior compared to the "open" version (Milligan Morgan) with respect to postoperative pain and wound healing. The more recently proposed stapled hemorrhoidopexy (Longo) is particularly advisable for circular hemorrhoids. Compared to excisional hemorrhoidectomy the Longo-operation is associated with reduced postoperative pain, shorter operation time and hospital stay as well as a faster recovery, with the disadvantage though of a higher recurrence rate. Data from Hemorrhoidal Artery Ligation (HAL)-, if appropriate in combination with a Recto-Anal Repair (HAL/RAR)-, demonstrates a similar trend towards a better tolerance of the procedure at the expense of a higher recurrence rate. These relatively "new" procedures equally qualify for the treatment of grade III and IV hemorrhoids, and, in the case of stapled hemorrhoidopexy, may even be employed in the emergency situation of an acute anal prolapse. While under certain circumstances different treatment options are equivalent, there is a clear specificity with respect to the application of those procedures in other situations. The respective pros and cons need to be discussed separately with every patient. According to their own requirements a treatment strategy has to be defined according to their individual requirements.

Eigenvalue estimates for non-selfadjoint Dirac operators on the real line

We show that the non-embedded eigenvalues of the Dirac operator on the real line with complex mass and non-Hermitian potential V lie in the disjoint union of two disks, provided that the L1-norm of V is bounded from above by the speed of light times the reduced Planck constant. The result is sharp; moreover, the analogous sharp result for the Schrödinger operator, originally proved by Abramov, Aslanyan and Davies, emerges in the nonrelativistic limit. For massless Dirac operators, the condition on V implies the absence of non-real eigenvalues. Our results are further generalized to potentials with slower decay at infinity. As an application, we determine bounds on resonances and embedded eigenvalues of Dirac operators with Hermitian dilation-analytic potentials.

Hemodynamic Performance of Edwards Intuity Valve in a Compliant Aortic Root Model

Numerous designs of bioprosthetic valves exist. The sutureless surgical valve is a newer design concept which combines elements of the transcatheter valve technology with surgical valves. This design aims at shorter and easier implantation. It was the aim of this study to perform hemodynamic and kinematic measurements for this type of valves to serve as a baseline for following studies which investigate the effect of the aortic root on the valve performance. To this end, the Edwards Intuity aortic valve was investigated in a new in vitro flow loop mimicking the left heart. The valve was implanted in a transparent, compliant aortic root model, and the valve kinematics was investigated using a high speed camera together with synchronized hemodynamic measurements of pressures and flows. The valve closure was asynchronous (one by one leaflet), and the valve started to close before the deceleration of the fluid. The aortic root model showed a dilation of the sinuses which was different to the ascending aorta, and the annulus was found to move towards the left ventricle during diastole and towards the aorta during systole.

Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI in dachshunds (L326P) as well as in humans (one single case with a L78P mutation). To elucidate the disease mechanism underlying OI in the dog model, we applied a range of biochemical assays to mutant and control skin fibroblasts as well as on bone samples. These experiments revealed that type I collagen synthesized by mutant cells had decreased electrophoretic mobility. Procollagen was retained intracellularly with concomitant dilation of ER cisternae and activation of the ER stress response markers GRP78 and phospho-eIF2α, thus suggesting a defect in procollagen processing. In line with the migration shift detected on SDS-PAGE of cell culture collagen, extracts of bone collagen from the OI dog showed a similar mobility shift, and on tandem mass spectrometry, the chains were post-translationally overmodified. The bone collagen had a higher content of pyridinoline than control dog bone. We conclude that the SERPINH1 mutation in this naturally occurring model of OI impairs how HSP47 acts as a chaperone in the ER. This results in abnormal post-translational modification and cross-linking of the bone collagen.

Estradiol-induced alopecia in five dogs after contact with a transdermal gel used for the treatment of postmenopausal symptoms in women

BACKGROUND Noninflammatory alopecia is a frequent problem in dogs. Estrogen-induced alopecia is well described in dogs, with estrogen producing testicular tumors and canine female hyperestrogenism. OBJECTIVES To increase awareness that extensive alopecia in dogs can be caused by exposure to estradiol gel used by owners to treat their postmenopausal symptoms. ANIMALS Skin biopsies from five dogs with extensive alopecia were examined. METHODS Owners were asked for a thorough case history, including possible exposure to an estradiol gel. Complete blood work and serum chemistry panel analysis were performed to investigate possible underlying causes. Formalin-fixed skin biopsy samples were obtained from lesional skin and histopathology was performed. RESULTS All owners confirmed the use of a transdermal estradiol gel and close contact with the affected dogs before development of alopecia. Histopathologic examination showed a similar picture in all five dogs. Most hair follicles were predominantly either in kenogen or telogen and hair follicle infundibula showed mild to moderate dilation. Hair regrowth was present in all five dogs after the exposure to the estradiol gel was stopped or minimized. Blood work and serum chemistry panel were within normal limits in all cases. One dog had elevated estradiol concentrations, whereas in another dog estradiol concentrations were within normal limits. CONCLUSION AND CLINICAL IMPORTANCE Alopecia can occur after contact with a transdermal gel used as treatment for postmenopausal symptoms in women. Estradiol gel used by female owners therefore represents a possible cause for noninflammatory alopecia in dogs. Estradiol concentrations are not necessarily elevated in affected dogs.

Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.

Reactive oxygen species-dependent mechanisms of N-(4-hydroxyphenyl)retinamide (4HPR)-induced apoptosis in human carcinoma cells

4HPR is a synthetic retinoid that has shown chemopreventive and therapeutic efficacy against premalignant and malignant lesions including oral leukoplakia, ovarian and breast cancer, and neuroblastoma. 4HPR induces apoptosis in various cancer cells and production of reactive oxygen species (ROS) has been suggested as a possible cause underlying these effects. However, the mechanisms governing these effects by 4HPR are not fully elucidated. In this study, we explored the mechanisms of 4HPR-induced ROS increase and apoptosis in human cancer cells. ^ First, we identified genes modulated by 4HPR using oligonucleotide gene expression arrays and found that they fall into specific functional canonical pathways and gene networks using Ingenuity Pathways Analysis®. Further analysis has shown that 4HPR induced up-regulation of Endoplasmic Reticulum (ER)-related genes such as Heat shock proteins 70 and 90 and the transcriptional factor, GADD153. These findings were validated using quantitative real-time PCR. ^ Second, we found that 4HPR induced extensive ER stress evidenced by dilation of the ER and endoribonuclease-mediated splicing and activation of the transcriptional factor, XBP-1. In addition, 4HPR induced the up-regulation of various ER stress-related genes and their protein products, as well as cleavage and activation of the ER specific Caspase-4. Concomitantly with XBP-1 splicing, all of these effects were dependent on ROS generation by 4HPR. Furthermore, chemical inhibition and RNA interference studies revealed a novel pro-apoptotic role for HSP70/A1A in 4HPR-mediated apoptosis. ^ Third, we observed rapid activation of the small GTPase Rac by 4HPR which was upstream of ROS generation. Inhibition of Rac activity or silencing of its expression by RNA interference inhibited ROS generation and apoptosis induction by 4HPR. siRNA targeting PAK1 and expression of a dominant negative Rac, decreased 4HPR-mediated ROS generation, while expression of a constitutive active Rac increased basal and 4HPR-induced ROS generation and PARP cleavage. Furthermore, metastatic cancer cells exhibited higher Rac activation, ROS generation, and cell growth inhibition due to 4HPR exposure compared to their primary cancer cell counterparts. ^ These findings provide novel insights into 4HPR-mediated ROS generation and apoptosis induction and support the use of ROS inducing agents such as 4HPR against metastatic cancer cells. ^

Two Obstetrical Heresies

Dr. Silas F. Starley deplores what he considered errors generally taught and accepted in the late 19th century in Two Obstetrical Heresies . “The first is the part that membranes containing the amniotic fluid and the foetus play in effecting dilation of the os uteri in the first stage of labor.The second is the supposed necessity for waiting for their rupture and the escape of the waters before applying the forceps, in every case, without exception.” Silas F. Starley (1823-1887) was born in Alabama and moved to Texas with his family in 1837. He graduated from the University of Louisville School of Medicine in 1854 and spent his professional career in Texas, ending his career in Corsicana. He was President of the State Medical Association of Texas (Texas Medical Association) in 1883 and wrote articles in Texas medical journals on various topics including obstetrics, vascular tumor, and pneumonia. Texas State Historical Association, http://www.tshaonline.org/handbook/online/articles/sat05 , accessed 10/16/2012. Texas Physicians Historical Biographical Database, http://www4.utsouthwestern.edu/library/doctors/doctors.cfm?DoctorID=16809 , accessed 10/16/12.

Morphological Functions to Quantify Three-Dimensional Tomograms of Macropore Structure in a Vineyard Soil with Two Different Management Regimes

Soil tomography and morphological functions built over Minkowski functionals were used to describe the impact on pore structure of two soil management practices in a Mediterranean vineyard. Soil structure controls important physical and biological processes in soil–plant–microbial systems. Those processes are dominated by the geometry of soil pore structure, and a correct model of this geometry is critical for understanding them. Soil tomography has been shown to provide rich three-dimensional digital information on soil pore geometry. Recently, mathematical morphological techniques have been proposed as powerful tools to analyze and quantify the geometrical features of porous media. Minkowski functionals and morphological functions built over Minkowski functionals provide computationally efficient means to measure four fundamental geometrical features of three-dimensional geometrical objects, that is, volume, boundary surface, mean boundary surface curvature, and connectivity. We used the threshold and the dilation and erosion of three-dimensional images to generate morphological functions and explore the evolution of Minkowski functionals as the threshold and as the degree of dilation and erosion changes. We analyzed the three-dimensional geometry of soil pore space with X-ray computed tomography (CT) of intact soil columns from a Spanish Mediterranean vineyard by using two different management practices (conventional tillage versus permanent cover crop of resident vegetation). Our results suggested that morphological functions built over Minkowski functionals provide promising tools to characterize soil macropore structure and that the evolution of morphological features with dilation and erosion is more informative as an indicator of structure than moving threshold for both soil managements studied.

Preliminary mineralogy and ore petrology of the intermediate-sulfidation pallancata deposit, Ayacucho, Peru

Se investiga la compleja mineralogía del Yacimiento de Pallancata (6º productor de plata del mundo) y se establecen las condiciones de formación (P.T) basadas en la petrología de las menas comparada con los datos de mineralogía experimental y en la petrografía y microtermometría de inclusiones fluídas en la ganga silicatada, resultando un depósito típicamente caracterizado como epitermal de sulfuración intermedia.ABSTRACT:Pallancata is a world-class intermediate-sulfidation epithermal deposit, hosted by upper Miocene volcanics of the south-central Peruvian Andes in a sinuous N70ºW, ∼75º SW strike-slip structure, with wide (up to 35 m) pull-apart dilation zones related to bends of the vein strike. The structural evolution of the vein from earlier brecciation to later open space infill resembles the Shila Paula district (Chauvet et al. 2006). Fluid inclusion petrography and microthermometry show that ore deposition is related to protracted boiling of very diluted, mainly meteoric fluids, starting at 250–260 ºC, under ∼300 m hydrostatic head. The mineralogical-petrological study reveals a complex sequence of mineralization (eight stages) and mineral reactions consistent with Ag2S enrichment or Sb2S3 depletion, or both, during cooling over the temperature range 250–200 ºC: pyrite, sphalerite, galena, miargyrite, pyrargyrite-proustite, chalcopyrite, polybasite-pearceite, argentite (now acanthite), and Au–Ag alloy (“electrum”). This Ag2S enrichment and Sb2S3depletion during cooling may be explained by decay of a Ag-rich galena precursor at deeper levels (Pb2S2–AgSbS2 solid solution), which rapidly becomes unstable with decreasing temperature, producing residual (stoichiometric) PbS and more mobile Ag and Sb sulfide phases, which migrated upward and laterally away from the thermal core of the system. The core is still undisclosed by mining works, but the available geochemical evidence (logAg/log Pb ratios decreasing at depth) is consistent with this interpretation, implying a deeper potential resource. Data from sulfide geothermometry, based on mineral equilibria, document the thermal evolution of the system below 200 ºC (stephanite, uytenbogaardtite, jalpaite, stromeyerite, mckinstryite, among others). The end of the most productive stages (3, 4, and 5) is marked by the precipitation of stephanite at temperatures below 197 ± 5 ºC, but precipitation of residual silver continues through the waning stages of the hydrothermal system down to <93.3 ºC (stromeyerite) or in a supergene redistribution (stage 8, acanthite II).

A comparative analysis of visual strategy in elite and amateur handball goalkeepers

The aim of the present study was to analyze the visual strategies prior to a throw from 7 metres in elite and amateur handball goalkeepers. To this end we analyzed the visual fixations in number and order of 10 goalkeepers (29.7±5.4 years; 14.7±8.6 years of experience), 3 elite and 7 amateurs, during the life size projection of 14 different throws, made by different players. During each throw the movement of the eyeballs, the dilation of the pupil (pupillometry) and the subject?s blinking were recorded thanks to a technological system which permitted eye tracking with high speed cameras, and the subsequent presentation of the visual data for each action studied. The elite goalkeepers performed a greater number of visual fixations than the amateur goalkeepers, revealing large and significant differences. Equally the priority zones observed were differed, with the amateur goalkeepers fixating more on the thrower?s face, and the elite goalkeepers paying more attention to the area of the arm/ball. It can therefore be inferred that elite goalkeepers have a greater perceptive capacity and also use different visual strategies from the amateur goalkeepers.

Evaluación de la seguridad al deslizamiento de una presa de fábrica en un cimiento con una familia de discontinuidades y con un criterio de rotura con ley de fluencia no asociada

En España existen del orden de 1,300 grandes presas, de las cuales un 20% fueron construidas antes de los años 60. El hecho de que existan actualmente una gran cantidad de presas antiguas aún en operación, ha producido un creciente interés en reevaluar su seguridad empleando herramientas nuevas o modificadas que incorporan modelos de fallo teóricos más completos, conceptos geotécnicos más complejos y nuevas técnicas de evaluación de la seguridad. Una manera muy común de abordar el análisis de estabilidad de presas de gravedad es, por ejemplo, considerar el deslizamiento a través de la interfase presa-cimiento empleando el criterio de rotura lineal de Mohr-Coulomb, en donde la cohesión y el ángulo de rozamiento son los parámetros que definen la resistencia al corte de la superficie de contacto. Sin embargo la influencia de aspectos como la presencia de planos de debilidad en el macizo rocoso de cimentación; la influencia de otros criterios de rotura para la junta y para el macizo rocoso (ej. el criterio de rotura de Hoek-Brown); las deformaciones volumétricas que ocurren durante la deformación plástica en el fallo del macizo rocoso (i.e., influencia de la dilatancia) no son usualmente consideradas durante el diseño original de la presa. En este contexto, en la presente tesis doctoral se propone una metodología analítica para el análisis de la estabilidad al deslizamiento de presas de hormigón, considerando un mecanismo de fallo en la cimentación caracterizado por la presencia de una familia de discontinuidades. En particular, se considera la posibilidad de que exista una junta sub-horizontal, preexistente y persistente en el macizo rocoso de la cimentación, con una superficie potencial de fallo que se extiende a través del macizo rocoso. El coeficiente de seguridad es entonces estimado usando una combinación de las resistencias a lo largo de los planos de rotura, cuyas resistencias son evaluadas empleando los criterios de rotura no lineales de Barton y Choubey (1977) y Barton y Bandis (1990), a lo largo del plano de deslizamiento de la junta; y el criterio de rotura de Hoek y Brown (1980) en su versión generalizada (Hoek et al. 2002), a lo largo del macizo rocoso. La metodología propuesta también considera la influencia del comportamiento del macizo rocoso cuando este sigue una ley de flujo no asociada con ángulo de dilatancia constante (Hoek y Brown 1997). La nueva metodología analítica propuesta es usada para evaluar las condiciones de estabilidad empleando dos modelos: un modelo determinista y un modelo probabilista, cuyos resultados son el valor del coeficiente de seguridad y la probabilidad de fallo al deslizamiento, respectivamente. El modelo determinista, implementado en MATLAB, es validado usando soluciones numéricas calculadas mediante el método de las diferencias finitas, empleando el código FLAC 6.0. El modelo propuesto proporciona resultados que son bastante similares a aquellos calculados con FLAC; sin embargo, los costos computacionales de la formulación propuesta son significativamente menores, facilitando el análisis de sensibilidad de la influencia de los diferentes parámetros de entrada sobre la seguridad de la presa, de cuyos resultados se obtienen los parámetros que más peso tienen en la estabilidad al deslizamiento de la estructura, manifestándose además la influencia de la ley de flujo en la rotura del macizo rocoso. La probabilidad de fallo es obtenida empleando el método de fiabilidad de primer orden (First Order Reliability Method; FORM), y los resultados de FORM son posteriormente validados mediante simulaciones de Monte Carlo. Los resultados obtenidos mediante ambas metodologías demuestran que, para el caso no asociado, los valores de probabilidad de fallo se ajustan de manera satisfactoria a los obtenidos mediante las simulaciones de Monte Carlo. Los resultados del caso asociado no son tan buenos, ya que producen resultados con errores del 0.7% al 66%, en los que no obstante se obtiene una buena concordancia cuando los casos se encuentran en, o cerca de, la situación de equilibrio límite. La eficiencia computacional es la principal ventaja que ofrece el método FORM para el análisis de la estabilidad de presas de hormigón, a diferencia de las simulaciones de Monte Carlo (que requiere de al menos 4 horas por cada ejecución) FORM requiere tan solo de 1 a 3 minutos en cada ejecución. There are 1,300 large dams in Spain, 20% of which were built before 1960. The fact that there are still many old dams in operation has produced an interest of reevaluate their safety using new or updated tools that incorporate state-of-the-art failure modes, geotechnical concepts and new safety assessment techniques. For instance, for gravity dams one common design approach considers the sliding through the dam-foundation interface, using a simple linear Mohr-Coulomb failure criterion with constant friction angle and cohesion parameters. But the influence of aspects such as the persistence of joint sets in the rock mass below the dam foundation; of the influence of others failure criteria proposed for rock joint and rock masses (e.g. the Hoek-Brown criterion); or the volumetric strains that occur during plastic failure of rock masses (i.e., the influence of dilatancy) are often no considered during the original dam design. In this context, an analytical methodology is proposed herein to assess the sliding stability of concrete dams, considering an extended failure mechanism in its rock foundation, which is characterized by the presence of an inclined, and impersistent joint set. In particular, the possibility of a preexisting sub-horizontal and impersistent joint set is considered, with a potential failure surface that could extend through the rock mass; the safety factor is therefore computed using a combination of strength along the rock joint (using the nonlinear Barton and Choubey (1977) and Barton and Bandis (1990) failure criteria) and along the rock mass (using the nonlinear failure criterion of Hoek and Brown (1980) in its generalized expression from Hoek et al. (2002)). The proposed methodology also considers the influence of a non-associative flow rule that has been incorporated using a (constant) dilation angle (Hoek and Brown 1997). The newly proposed analytical methodology is used to assess the dam stability conditions, employing for this purpose the deterministic and probabilistic models, resulting in the sliding safety factor and the probability of failure respectively. The deterministic model, implemented in MATLAB, is validated using numerical solution computed with the finite difference code FLAC 6.0. The proposed deterministic model provides results that are very similar to those computed with FLAC; however, since the new formulation can be implemented in a spreadsheet, the computational cost of the proposed model is significantly smaller, hence allowing to more easily conduct parametric analyses of the influence of the different input parameters on the dam’s safety. Once the model is validated, parametric analyses are conducting using the main parameters that describe the dam’s foundation. From this study, the impact of the more influential parameters on the sliding stability analysis is obtained and the error of considering the flow rule is assessed. The probability of failure is obtained employing the First Order Reliability Method (FORM). The probabilistic model is then validated using the Monte Carlo simulation method. Results obtained using both methodologies show good agreement for cases in which the rock mass has a nonassociate flow rule. For cases with an associated flow rule errors between 0.70% and 66% are obtained, so that the better adjustments are obtained for cases with, or close to, limit equilibrium conditions. The main advantage of FORM on sliding stability analyses of gravity dams is its computational efficiency, so that Monte Carlo simulations require at least 4 hours on each execution, whereas FORM requires only 1 to 3 minutes on each execution.

Ajuste del modelo de Drucker Prager extendido para la simulación de la respuesta mecánica de un vertisol mediante el método de elementos finitos

La mecanización de las labores del suelo es la causa, por su consumo energético e impacto directo sobre el medio ambiente, que más afecta a la degradación y pérdida de productividad de los suelos. Entre los factores de disminución de la productividad se deben considerar la compactación, la erosión, el encostramiento y la pérdida de estructura. Todo esto obliga a cuidar el manejo agrícola de los suelos tratando de mejorar las condiciones del suelo y elevar sus rendimientos sin comprometer aspectos económicos, ecológicos y ambientales. En el presente trabajo se adecuan los parámetros constitutivos del modelo de Drucker Prager Extendido (DPE) que definen la fricción y la dilatancia del suelo en la fase de deformación plástica, para minimizar los errores en las predicciones durante la simulación de la respuesta mecánica de un Vertisol mediante el Método de Elementos Finitos. Para lo cual inicialmente se analizaron las bases teóricas que soportan este modelo, se determinaron las propiedades y parámetros físico-mecánicos del suelo requeridos como datos de entrada por el modelo, se determinó la exactitud de este modelo en las predicciones de la respuesta mecánica del suelo, se estimaron mediante el método de aproximación de funciones de Levenberg-Marquardt los parámetros constitutivos que definen la trayectoria de la curva esfuerzo-deformación plástica. Finalmente se comprobó la exactitud de las predicciones a partir de las adecuaciones realizadas al modelo. Los resultados permitieron determinar las propiedades y parámetros del suelo, requeridos como datos de entrada por el modelo, mostrando que su magnitud está en función su estado de humedad y densidad, además se obtuvieron los modelos empíricos de estas relaciones exhibiendo un R2>94%. Se definieron las variables que provocan las inexactitudes del modelo constitutivo (ángulo de fricción y dilatancia), mostrando que las mismas están relacionadas con la etapa de falla y deformación plástica. Finalmente se estimaron los valores óptimos de estos ángulos, disminuyendo los errores en las predicciones del modelo DPE por debajo del 4,35% haciéndelo adecuado para la simulación de la respuesta mecánica del suelo investigado. ABSTRACT The mechanization using farming techniques is one of the main factors that affects the most the soil, causing its degradation and loss of productivity, because of its energy consumption and direct impact on the environment. Compaction, erosion, crusting and loss of structure should be considered among the factors that decrease productivity. All this forces the necessity to take care of the agricultural-land management trying to improve soil conditions and increase yields without compromising economic, ecological and environmental aspects. The present study was aimed to adjust the parameters of the Drucker-Prager Extended Model (DPE), defining friction and dilation of soil in plastic deformation phase, in order to minimize the error of prediction when simulating the mechanical response of a Vertisol through the fine element method. First of all the theoretic fundamentals that withstand the model were analyzed. The properties and physical-mechanical parameters of the soil needed as input data to initialize the model, were established. And the precision of the predictions for the mechanical response of the soil was assessed. Then the constitutive parameters which define the path of the plastic stress-strain curve were estimated through Levenberg-Marquardt method of function approximations. Lastly the accuracy of the predictions from the adequacies made to the model was tested. The results permitted to determine those properties and parameters of the soil, needed in order to initialize the model. It showed that their magnitude is in function of density and humidity. Moreover, the empirical models from these relations were obtained: R2>94%. The variables producing inaccuracies in the constitutive model (angle of repose and dilation) were defined, and there was showed that they are linked with the plastic deformation and rupture point. Finally the optimal values of these angles were established, obtaining thereafter error values for the DPE model under 4, 35%, and making it suitable for the simulation of the mechanical response of the soil under study.

Estudio del flujo sanguíneo para diferentes técnicas de implantación de stents en bifurcaciones coronarias

Las enfermedades arteriales vienen presididas por la aterosclerosis, que es un proceso crónico de degeneración, que evoluciona hacia la obstrucción de la luz arterial. La pared de la arteria se engrosa debido al depósito de elementos grasos tales como el colesterol. Los stents intraluminales son diminutas estructuras tubulares autoexpandibles de malla de metal, que se colocan dentro de la arteria coronaria después de una angioplastia con balón para prevenir el cierre de dicha arteria. A pesar de estar diseñados para ser compatibles con el tejido humano, a menudo se da una reacción en cadena de consecuencias indeseables. La reestenosis intra-stent es un problema creciente debido al importante incremento que se ha producido en la utilización del stent intracoronario como forma de revascularización percutánea. Se habla de una incidencia global del 28%, siendo la causa principal de su aparición la proliferación neointimal a través de una compleja cascada de sucesos que pueden tardar meses en desarrollarse. Una de las reacciones más importantes es la trombosis o la formación de una fina capa de coágulo como respuesta a la presencia de un material extraño. Este proceso es multifactorial, y en él intervienen la regresión de la pared como consecuencia del estiramiento previo, la denudación endotelial, lo que permite la agregación plaquetaria, la proliferación neointimal, lo que facilita a los receptores de membrana desencadenar un proceso de agregación posterior y, por último, el remodelado negativo inadecuado de la pared, lo que produce pérdida de luz arterial. Se ha observado frecuentemente que el depósito de ateroma en la pared arterial está relacionado con el valor de los esfuerzos cortantes en la misma. Hay mayores probabilidades de engrosamiento de la pared en las zonas donde son bajos los esfuerzos cortantes, quizá por el mayor tiempo de residencia de las partículas circulantes por el torrente sanguíneo. Si nos centramos en la afirmación anterior, el siguiente paso sería buscar las zonas susceptibles de presentar un valor bajo de dichos esfuerzos. Las zonas potencialmente peligrosas son los codos y bifurcaciones, entre otras. Nos hemos centrado en una bifurcación coronaria, ya que los patrones de flujo que se suelen presentar, tales como recirculación y desprendimiento de vórtices están íntimamente relacionados con las técnicas de implantación de stents en esta zona. Proyectamos nuestros esfuerzos en el estudio de dos técnicas de implante, utilizando un único stent y una tercera a través de una configuración de culotte con el uso de dos stents. El primer caso trata de una bifurcación con un único stent en la rama principal cuyos struts cierran el orificio lateral que da salida a la rama secundaria de la bifurcación, es decir sería un stent sin orificio. El segundo consiste en un único stent también, pero con la diferencia de que éste presenta un orificio de comunicación con la rama lateral. Todas estas técnicas se aplicaron a bifurcaciones de 45º y de 90º. Introdujimos las geometrías -una vez confeccionadas con el código comercial Gambit- en el programa Ansys-Fluent contemplando régimen estacionario. Los resultados obtenidos fueron cotejados con los experimentales, que se realizaron paralelamente, con el fin de corroborarlos. Una vez validados, el estudio computacional ya contó con la fiabilidad suficiente como para abordar el régimen no estacionario, tanto en la versión de reposo como en la de ejercicio –hiperemia- El comportamiento reológico de la sangre para régimen no estacionario en estado de reposo es otra de las tareas abordadas, realizando una comparativa de los modelos Newtoniano, Carreau y Ley de Potencias. Finalmente, en una última etapa, debido a la reciente incursión de los stents diseñados específicamente frente a los convencionales, se aborda el comportamiento hemodinámico de los mismos. Concretamente, se comparó el patrón de flujo en un modelo de bifurcación coronaria con los nuevos stents (Stentys) y los convencionales. Se estudiaron cuatro modelos, a saber, stent simple en la rama principal, stent simple en la rama secundaria, culotte desplegando el primer stent en la rama principal y culotte desplegando el primer stent en la rama secundaria. La bifurcación estudiada presenta un ángulo de apertura de 45º y la relación de diámetros de las ramas hija se ajustaron de acuerdo a la ley de Finet. Se recogieron resultados experimentales en el laboratorio y se corrieron simulaciones numéricas con Ansys Fluent paralelamente. Las magnitudes que se tuvieron en cuenta con el fin de ubicar las regiones potencialmente ateroscleróticas fueron los esfuerzos cortantes, vorticidad y caída de presión. ABSTRACT Nowadays, restenosis after percutaneous dilation is the major drawback of coronary angioplasty. It represents a special form of atherosclerosis due to the healing process secondary to extensive vessel trauma induced after intracoronary balloon inflation. The use of coronary stents may decrease the incidence of this phenomenon. Unfortunately, intra-stent restenosis still occurs in 20-30% of the cases following the stent implantation. Most experiments suggest a correlation between low wall shear stress and wall thickness. The preferential locations for the atherosclerotic plaque are bifurcations. The objective of this work is to analyze the local hemodynamic changes caused in a coronary bifurcation by three different stenting techniques: simple stenting of the main vessel, simple stenting of the main vessel with kissing balloon in the side branch and culotte. To carry out this study an idealized geometry of a coronary bifurcation is used, and two bifurcation angles, 45º and 90º, are chosen as representative of the wide variety of real configurations. Both numerical simulations and experimental measurements are performed. First, steady simulations are carried out with the commercial code Ansys-Fluent, then, experimental measurements with PIV (Particle Image Velocimetry), obtained in the laboratory, are used to validate the numerical simulations. The steady computational simulations show a good overall agreement with the experimental data. Then, pulsatile flow is considered to take into account the transient effects. The time averaged wall shear stress, oscillatory shear index and pressure drop obtained numerically are used to compare the behavior of the stenting techniques. In a second step, the rheologic behavior of blood was considered comparing Newtonian, Carreau and Power Law models. Finally, as a result of previous investigations with conventional stents and after the recent emergence of several devices specifically designed for coronary bifurcations angioplasty, the hemodynamic performance of these new devices (Stentys) was compared to conventional ones and techniques in a coronary bifurcation model. Four different stenting techniques: simple stenting of the main vessel, simple stenting of the side vessel, culotte deploying the first stent in the main vessel and culotte deploying the first stent in the side vessel have been considered. To carry out this study an idealized geometry of a coronary bifurcation is used. A 45 degrees bifurcation angle is considered and the daughter branches diameters are obtained according to the Finet law. Both experiments in the laboratory and numerical simulations were used , focusing on important factors for the atherosclerosis development, like the wall shear stress, the oscillation shear index, the pressure loss and the vorticity.

Cardiac βARK1 inhibition prolongs survival and augments β blocker therapy in a mouse model of severe heart failure

Chronic human heart failure is characterized by abnormalities in β-adrenergic receptor (βAR) signaling, including increased levels of βAR kinase 1 (βARK1), which seems critical to the pathogenesis of the disease. To determine whether inhibition of βARK1 is sufficient to rescue a model of severe heart failure, we mated transgenic mice overexpressing a peptide inhibitor of βARK1 (βARKct) with transgenic mice overexpressing the sarcoplasmic reticulum Ca2+-binding protein, calsequestrin (CSQ). CSQ mice have a severe cardiomyopathy and markedly shortened survival (9 ± 1 weeks). In contrast, CSQ/βARKct mice exhibited a significant increase in mean survival age (15 ± 1 weeks; P < 0.0001) and showed less cardiac dilation, and cardiac function was significantly improved (CSQ vs. CSQ/βARKct, left ventricular end diastolic dimension 5.60 ± 0.17 mm vs. 4.19 ± 0.09 mm, P < 0.005; % fractional shortening, 15 ± 2 vs. 36 ± 2, P < 0.005). The enhancement of the survival rate in CSQ/βARKct mice was substantially potentiated by chronic treatment with the βAR antagonist metoprolol (CSQ/βARKct nontreated vs. CSQ/βARKct metoprolol treated, 15 ± 1 weeks vs. 25 ± 2 weeks, P < 0.0001). Thus, overexpression of the βARKct resulted in a marked prolongation in survival and improved cardiac function in a mouse model of severe cardiomyopathy that can be potentiated with β-blocker therapy. These data demonstrate a significant synergy between an established heart-failure treatment and the strategy of βARK1 inhibition.