Dynamic contrast agent -enhanced magnetic resonance imaging assessment of tumor microvasculature

Dynamic contrast agent-enhanced magnetic resonance imaging (DCE MRI) data, when analyzed with the appropriate pharmacokinetic models, have been shown to provide quantitative estimates of microvascular parameters important in characterizing the angiogenic activity of malignant tissue. These parameters consist of the whole blood volume per unit volume of tissue, v b, transport constant from the plasma to the extravascular, extracellular space (EES), k1 and the transport constant from the EES to the plasma, k2. Parameters vb and k1 are expected to correlate with microvascular density (MVD) and vascular permeability, respectively, which have been suggested to serve as surrogate markers for angiogenesis. In addition to being a marker for angiogenesis, vascular permeability is also useful in estimating tumor penetration potential of chemotherapeutic agents. ^ Histological measurements of the intratumoral microvascular environment are limited by their invasiveness and susceptibility to sampling errors. Also, MVD and vascular permeability, while useful for characterizing tumors at a single time point, have shown less utility in longitudinal studies, particularly when used to monitor the efficacy of antiangiogenic and traditional chemotherapeutic agents. These limitations led to a search for a non-invasive means of characterizing the microvascular environment of an entire tumor. ^ The overall goal of this project was to determine the utility of DCE MRI for monitoring the effect of antiangiogenic agents. Further applications of a validated DCE MRI technique include in vivo measurements of tumor microvascular characteristics to aid in determining prognosis at presentation and in estimating drug penetration. DCE MRI data were generated using single- and dual-tracer pharmacokinetic models with different molecular-weight contrast agents. The resulting pharmacokinetic parameters were compared to immunohistochemical measurements. The model and contrast agent combination yielding the best correlation between the pharmacokinetic parameters and histological measures was further evaluated in a longitudinal study to evaluate the efficacy of DCE MRI in monitoring the intratumoral microvascular environment following antiangiogenic treatment. ^

(Table 1) Lipid content and organohalogen contaminant concentration in captive sledge dogs (Canis familiaris) and wild female polar bears (Ursus maritimus) from Greenland

The limited knowledge and/or the inability to control physiological condition parameters that influence the fate of organohalogen contaminants (OHCs) has been the foremost confounding aspect in monitoring programs and health risk assessments of wild top predators in the Arctic such as the polar bear (Ursus maritimus). In the present comparative study, we used a potential surrogate Canoidea species for the East Greenland polar bear, the captive sledge dog (Canis familiaris), to investigate some factors that may influence the bioaccumulation and biotransformation of major chlorinated and brominated OHCs in adipose tissue and blood (plasma) of control (fed commercial pork fat) and exposed (fed West Greenland minke whale (Balaenoptera acutorostrata) blubber) adult female sledge dogs. Furthermore, we compared the patterns and concentrations of OHCs and their known or suggested hydroxylated (OH) metabolites (e.g., OH-PCBs) in sledge dogs with those in adipose tissue and blood (plasma) of East Greenland adult female polar bears, and blubber of their main prey species, the ringed seal (Pusa hispida). The two-year feeding regime conducted with sledge dogs led to marked differences in overall adipose tissue (and plasma) OHC residue accumulation between the control and exposed groups. Characteristic prey-to-predator OHC bioaccumulation dynamics for major PCB and PBDE congeners (patterns and concentrations) and biotransformation capacity with respect to PCB metabolite formation and OH-PCB retention distinguished, to some extent, captive sledge dogs and wild polar bears. Based on the present findings, we conclude that the use of surrogate species in toxicological investigations for species in the Canoidea family should be done with great caution, although they remain essential in the context of contaminants research with sensitive arctic top carnivore species such as the polar bear.

La palabra de los "naturales" en la justicia : Posibilidades y limitaciones en el análisis de la documentación judicial referida a indígenas (Jujuy, siglo XVII)

El presente artículo se propone establecer variables de análisis en lo que respecta al rol de los indígenas en la documentación judicial colonial. En ese sentido, el corpus principal de análisis lo constituye el Pleito de los indios de Paipaya contra Francisco Salas Valdez (1671) a través del cual vislumbraremos las condiciones de producción del documento, el rol de los mediadores, la distancia cultural o la influencia de las condiciones de subordinación actuantes en el mismo. Consideramos al presente trabajo una aproximación que no pretende ser definitiva, si no abrir un panorama a la reflexión sobre la temática ya que este extenso documento nos brindará elementos de reflexión metodológica y heurística con que abordar el estudio de los indígenas a través de la fuente judicial

EPANET Input Files of New York tunnels and Pacific City used in a metamodel-based optimization study

Metamodels have proven be very useful when it comes to reducing the computational requirements of Evolutionary Algorithm-based optimization by acting as quick-solving surrogates for slow-solving fitness functions. The relationship between metamodel scope and objective function varies between applications, that is, in some cases the metamodel acts as a surrogate for the whole fitness function, whereas in other cases it replaces only a component of the fitness function. This paper presents a formalized qualitative process to evaluate a fitness function to determine the most suitable metamodel scope so as to increase the likelihood of calibrating a high-fidelity metamodel and hence obtain good optimization results in a reasonable amount of time. The process is applied to the risk-based optimization of water distribution systems; a very computationally-intensive problem for real-world systems. The process is validated with a simple case study (modified New York Tunnels) and the power of metamodelling is demonstrated on a real-world case study (Pacific City) with a computational speed-up of several orders of magnitude.

La palabra de los "naturales" en la justicia : Posibilidades y limitaciones en el análisis de la documentación judicial referida a indígenas (Jujuy, siglo XVII)

El presente artículo se propone establecer variables de análisis en lo que respecta al rol de los indígenas en la documentación judicial colonial. En ese sentido, el corpus principal de análisis lo constituye el Pleito de los indios de Paipaya contra Francisco Salas Valdez (1671) a través del cual vislumbraremos las condiciones de producción del documento, el rol de los mediadores, la distancia cultural o la influencia de las condiciones de subordinación actuantes en el mismo. Consideramos al presente trabajo una aproximación que no pretende ser definitiva, si no abrir un panorama a la reflexión sobre la temática ya que este extenso documento nos brindará elementos de reflexión metodológica y heurística con que abordar el estudio de los indígenas a través de la fuente judicial