Principal response curves technique for the analysis of multivariate biomonitoring time series

Although chemical and biological monitoring is often used to evaluate the quality of surface waters for regulatory purposes and/or to evaluate environmental status and trends, the resulting biological and chemical data sets are large and difficult to evaluate. Multivariate techniques have long been used to analyse complex data sets. This paper discusses the methods currently in use and introduces the principal response curves method, which overcomes the problem of cluttered graphical results representation that is a great drawback of most conventional methods. To illustrate this, two example data sets are analysed using two ordination techniques, principal component analysis and principal response curves. Whereas PCA results in a difficult-to-interpret diagram, principal response curves related methods are able to show changes in community composition in a diagram that is easy to read. The principal response curves method is used to show trends over time with an internal reference (overall mean or reference year) or external reference (e.g. preferred water quality or reference site). Advantages and disadvantages of both methods are discussed and illustrate

Afwegingskader sanering waterbodem, oever en/of landbodem; beoordeling fysische, milieuchemische en ecologische aspecten

Door RIZA en DWW is een systematiek ontwikkeld waarmee stapsgewijs een aantal aspecten kan worden beoordeeld die relevant zijn voor de afweging of voor een specifiek verontreinigingsgeval een integrale sanering van waterbodem, oever en landbodem wenselijk is. In twee deelstudies is de huidige stand van kennis geïnventariseerd op het gebied van de beoordeling van ecologische risico's en de fysische en milieuchemische relaties tussen compartimenten van een watersysteem. In dit rapport worden de resultaten van deze deelstudies samengevat en wordt een systematiek gepresenteerd om stapsgewijs bovengenoemde afweging uit te voeren

Bioassay responses and effects on benthos after pilot remediations in the delta of the rivers Rhine and Meuse

Chemical and biological monitoring was carried out for 5 years following pilot remediations at two locations in the Rhine-Meuse delta. The remediations consisted of partial excavation of the contaminated sediments, followed by applying a clean layer of sandy material on top. After the remediation, a new silty sediment top layer was formed exhibiting a lower toxicity in five sediment/sediment pore water bioassays. Compared to the unremediated sites, lower metal and PAH concentrations were found at the remediated sites, but in one location at the same time elevated HCH, PCB and HCB levels were recorded. One year after the remediation, the differences became smaller, although effects-based classification showed that the remediated site showed a higher quality up to the last year. In both remediated sites a rapid recolonization of nematodes, oligochaetes and chironomids was observed, while the recolonization by bivalves was slower. A few years after the remediation the differences decrease

Neurodegeneration as an early event in the pathogenesis of diabetic retinopathy: therapeutic implications

La Retinopatía Diabética (RD) es la complicación más común de la diabetes y una de las principales causas de ceguera. La RD se ha considerado clásicamente como una enfermedad microcirculatoria de la retina. No obstante, antes de que las anormalidades microcirculatorias se puedan detectar en un examen oftalmoscópico, la neurodegeneración ya está presente. Esto significa que la neurodegeneración es un acontecimiento temprano en la patogenia de la RD. Por tanto, existe la necesidad de tener buenos modelos animales donde se puedan testar fármacos potencialmente neuroprotectores y entender sus mecanismos de acción. En el primer capítulo de la tesis el objetivo fue caracterizar los acontecimientos secuenciales que tienen lugar en la neurodegeneración retiniana en un modelo murino de diabetes tipo 2, el ratón db/db. Se encontró un incremento progresivo con la edad de los marcadores de neurodegeneración (activación glial y apoptosis) en todas las etapas estudiadas. Se observaron anormalidades electroretinográficas en ratones de 16 y 24 pero no a 8 semanas de edad. Además, se observó una acumulación progresiva de glutamato en ratones diabéticos asociada con la disminución de su transportador GLAST. Todas estas anormalidades fueron abolidas al reducir los niveles de glucosa en sangre. Finalmente, a 8 semanas de edad, se encontraron alteraciones en la expresión de varios genes relacionados con la neurotransmisión y el estrés oxidativo como por ejemplo UCP2. Estos resultados sugieren que el ratón db/db reproduce las características del proceso neurodegenerativo que tiene lugar en el ojo diabético humano. Por tanto éste es un modelo apropiado para investigar los mecanismos subyacentes de la neurodegeneración retiniana inducida por la diabetes y para testar fármacos neuroprotectores. En el segundo capítulo se evalúan los efectos potenciales del ácido fenofíbrico (el metabolito activo del fenofibrato) en la prevención de la neurodegeneración retiniana que presenta el ratón db/db. El tratamiento oral durante una semana resultó en la reducción de la activación glial y de la apoptosis en comparación con los ratones tratados con vehículo. Las anormalidades funcionales mejoraron y el tratamiento con ácido fenofíbrico también previno la disminución de GLAST producida por la diabetes. Estos resultados sugieren que la neuroprotección es uno de los mecanismos subyacentes por los cuales el ácido fenofíbrico ejerce sus acciones beneficiosas en la retinopatía diabética. El tercer capítulo se centra en GLP-1 y sus efectos neuroprotectores en la retina. Se ha demostrado que GLP-1 ejerce efectos neuroprotecotres en el sistema nervioso central. El objetivo fue examinar la expresión y contenido de GLP-1R en retinas humanas y de ratón db/db, determinar los efectos neuroprotectores en la retina después de un tratamiento sistémico y otro tópico ocular (colirio) y examinar los mecanismos neuroprotectores subyacentes. Se encontró abundante expresión de GLP-1R en las retinas humanas y de ratón db/db. Además, se demostró que la administración sistémica de agonistas de GLP-1R (liraglutide) previene la neurodegeneración en la retina (activación glial, apoptosis neuronal y anormalidades electroretinográficas). Este efecto puede ser atribuido a una reducción significativa de glutamato extracelular y a un incremento de las vías de señalización pro-supervivencia. Se encontró un nivel similar de neuroprotección usando administración tópica ocular de GLP-1 nativo y de otros agonistas de GLP-1R (liraglutide, lixisenatide y exenatide). Cabe destacar que esta acción neuroprotectora fue observada sin reducción en los niveles de glucosa en sangre. Estos resultados sugieren que la activación de GLP-1R por si misma previene la neurodegeneración en la retina inducida por la diabetes.Diabetic retinopathy (DR) is the most common complication of diabetes and one of the leading causes of preventable blindness. DR has been classically considered to be a microcirculatory disease of the retina. However, before any microcirculatory abnormalities can be detected under ophthalmoscopic examination, retinal neurodegeneration is already present. This is to say that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy. There is a need to have a good animal model where potentially neuroprotective drugs could be tested on and understand their mechanisms of action. In the first chapter of this thesis the main aim was to characterize the sequential events that take place in retinal neurodegeneration in a murine model of spontaneous type 2 diabetes, the db/db mouse. We found progressively increased levels of the histological markers of neurodegeneration (glial activation and apoptosis) at all stages studied worsening with age. Significant electroretinographic abnormalities were present in diabetic mice at weeks 16 and 24 but not at week 8. Moreover it was observed a progressive accumulation of glutamate in diabetic mice associated with an early downregulation of its transporter GLAST. All this abnormalities were abrogated by lowering blood glucose levels. Finally, a dysregulation of several genes related to neurotransmission and oxidative stress such as UCP2 were found at week 8. All these results suggest that db/db mouse reproduce the features of the neurodegenerative process that occurs in the human diabetic eye. Therefore it is an appropriate model for investigating the underlying mechanisms of diabetes induced retinal neurodegeneration and for testing neuroprotective drugs. In the second chapter the potential effects of fenofibric acid (FA) (the active metabolite of fenofibrate) in preventing retinal neurodegeneration in the db/db mouse are evaluated. Oral treatment for one week resulted in a reduction of glial activation and apoptosis in comparison to vehicle-treated mice. Functional abnormalities were ameliorated and FA treatment also prevented GLAST downregulation induced by diabetes. Our results suggest that neuroprotection is one of the underlying mechanisms by which FA exerts its beneficial actions in diabetic retinopathy. The third chapter is focused on GLP-1 and its neuroprotective effects in the retina. GLP-1 has been demonstrated to have neuroprotective effects in the central nervous system. We sought to examine the expression and content of GLP-1R in human and db/db mice retinas, to determine the retinal neuroprotective effects of systemic and topical administration of GLP-1R agonists in db/db mice and, to examine the underlying neuroprotective mechanisms. We found abundant expression of GLP-1R in the human retina and retinas from db/db mice. Moreover, it has been demonstrated that systemic administration of GLP-1R agonists (liraglutide) prevents retinal neurodegeneration (glial activation, neural apoptosis and electroretinographical abnormalities). This effect can be attributed to a significant reduction of extracellular glutamate and to an increase of prosurvival signalling pathways. We have found a similar neuroprotective effect using topical administration of native GLP-1 and several GLP-1R agonists (liraglutide, lixisenatide and exenatide). Notably, this neuroprotective action was observed without any reduction in blood glucose levels. These results suggest that GLP-1R activation itself prevents diabetes induced retinal neurodegeneration

Statistical analysis of sediment toxicity by additive monotone regression splines

Modeling nonlinearity and thresholds in dose-effect relations is a major challenge, particularly in noisy data sets. Here we show the utility of nonlinear regression with additive monotone regression splines. These splines lead almost automatically to the estimation of thresholds. We applied this novel method to explore the relation between the toxicity of aquatic sediments, as observed in bioassays with Daphnia magna, Chironomus riparius and Vibrio fischeri, and the degree of contamination of the sediments. Despite the low signal-to-noise ratio in the data, some interesting thresholds and (non)linear effects were found. The method has added value compared to the linear multivariate methods applied earlier to these data. Percentages of explained variance remained low, but could be doubled by diminishing the effect of local variabilit

BEM–FEM coupling for the analysis of flexible propellers in non-uniform flows and validation with full-scale measurements

The first part of the paper presents a partitioned fluid–structure interaction (FSI) coupling for the non-uniform flow hydro-elastic analysis of highly flexible propellers in cavitating and non-cavitating conditions. The chosen fluid model is a potential flow solved with a boundary element method (BEM). The structural sub-problem has been modelled with a finite element method (FEM). In the present method, the fully partitioned framework allows one to use another flow or structural solver. An important feature of the present method is the time periodic way of solving the FSI problem. In a time periodic coupling, the coupling iterations are not performed per time step but on a periodic level, which is necessary for the present BEM–FEM coupling, but can also offer an improved convergence rate compared to a time step coupled method. Thus, it allows to solve the structural problem in the frequency domain, meaning that any transients, which slow down the convergence process, are not computed. As proposed in the method, the structural equations of motion can be solved in modal space, which allows for a model reduction by involving only a limited number of mode shapes. The second part of the paper includes a validation study on full-scale. For the full-scale validation study a purposely designed composite propeller with a diameter of 1 m has been manufactured. Also an underwater measurement set-up including a stereo camera system, remote control of the optics and illumination system has been developed. The propeller design and the underwater measurement set-up are described in the paper. During sea trials blade deflections have been measured in three different positions. A comparison between measured and calculated torque shows that the measured torque is much larger than computed. This is attributed to the differences between effective and nominal wakefields, where the latter one has been used for the calculations. To correct for the differences between measured and computed torque the calculated pressures have been amplified accordingly. In that way the deformations which have been computed with the BEM–FEM coupling for non-uniform flows became very similar to the measured results.</p

Boundary element modelling aspects for the hydro-elastic analysis of flexible marine propellers

Boundary element methods (BEM) have been used for propeller hydrodynamic calculations since the 1990s. More recently, these methods are being used in combination with finite element methods (FEM) in order to calculate flexible propeller fluid–structure interaction (FSI) response. The main advantage of using BEM for flexible propeller FSI calculations is the relatively low computational demand in comparison with higher fidelity methods. However, the BEM modelling of flexible propellers is not straightforward and requires several important modelling decisions. The consequences of such modelling choices depend significantly on propeller structural behaviour and flow condition. The two dimensionless quantities that characterise structural behaviour and flow condition are the structural frequency ratio (the ratio between the lowest excitation frequency and the fundamental wet blade natural frequency) and the reduced frequency. For both, general expressions have been derived for (flexible) marine propellers. This work shows that these expressions can be effectively used to estimate the dry and wet fundamental blade frequencies and the structural frequency ratio. This last parameter and the reduced frequency of vibrating blade flows is independent of the geometrical blade scale as shown in this work. Regarding the BEM-FEM coupled analyses, it is shown that a quasi-static FEM modelling does not suffice, particularly due to the fluid-added mass and hydrodynamic damping contributions that are not negligible. It is demonstrated that approximating the hydro-elastic blade response by using closed form expressions for the fluid added mass and hydrodynamic damping terms provides reasonable results, since the structural response of flexible propellers is stiffness dominated, meaning that the importance of modelling errors in fluid added mass and hydrodynamic damping is small. Finally, it is shown that the significance of recalculating the hydrodynamic influence coefficients is relatively small. This fact might be utilized, possibly in combination with the use of the closed form expressions for fluid added mass and hydrodynamic damping contributions, to significantly reduce the computation time of flexible propeller FSI calculationsShip Hydromechanics and Structure