Image segmentation methods for intracranial aneurysm haemodynamic research

Patient-specific haemodynamic technology is being increasingly utilised in clinical applications. Under normal circumstances, computational haemodynamic simulation is performed using geometric results obtained via medical image segmentation. However, even when employed upon the same set of medical imaging data, both the geometry and volume of intracranial aneurysm models are highly dependent upon varying insufficiently validated vascular segmentation methods. In this study, we compared three segmentation methods to segment the geometry of the aneurysm. These include: the Region Growing Threshold (RGT), Chan-Vese model (CV) and Threshold-Based Level Set (TLS). The results obtained were evaluated via measurement of arterial volume differences (VD), local geometric shapes, and haemodynamic simulation results. In total, 45 patient-specific aneurysm cases with three different anatomy locations were assessed in this study. From this, we discovered that the average VD of all three segmentation methods lay in the vicinity of 9.3% (SD=±4.6%). The computational haemodynamic simulation was performed via the use of the vessel geometries. Analyses produced an average of 23.2% (SD=±8.7%) difference in energy loss (EL) between the varying segmentation methods, with the difference in Wall Shear Stress (WSS) averaging 24.0% (SD=±8.5%) and 126.4% (SD=±124.4%) for the highest and lowest volumes of WSS respectively. The results of the lowest WSS, was seen to be significantly dependent upon the geometry of the aneurysm surface. It is therefore essential, in order to confirm the quality of segmentation processes in the application of patient-specific analyses of cerebrovascular haemodynamics – to validate these individual segmentation methods.     

Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs

The most common primary central nervous system tumor in adults is the glioblastoma multiforme (GBM). The highly invasive nature of GBM cells is a significant factor resulting in the inevitable tumor recurrence and poor patient prognosis. Tumor cells utilize structures known as invadopodia to faciliate their invasive phenotype. In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme. Furthermore, these cellular activities were augmented in cells that survived radiotherapy and temozolomide treatment, indicating that surviving cells may possess a more invasive phenotype posttherapy. We performed a screen of FDA-approved agents not previously used for treating GBM patients with the aim of investigating their “anti-invadopodia” and cytotoxic effects in GBM cell lines and identified a number that reduced cell viability, as well as agents which also reduced invadopodia activity. Importantly, two of these, pacilitaxel and vinorelbine tartrate, reduced radiation/temozolomide-induced invadopodia activity. Our data demonstrate the value of testing previously approved drugs (repurposing) as potential adjuvant agents for the treatment of GBM patients to reduce invadopodia activity, inhibit GBM cell invasion, and potentially improve patient outcome.     

Bacterial communities associated with the rhizosphere of transgenic Bt 176 maize (Zea mays) and its non transgenic counterpart

The effect of transgenic Bt 176 maize on the rhizosphere bacterial community has been studied with a polyphasic approach by comparing the rhizosphere of Bt maize cultivated in greenhouse with that of its non transgenic counterpart grown in the same conditions. In the two plants the bacterial counts of the copiotrophic, oligotrophic and sporeforming bacteria, and the community level catabolic profiling, showed no significant differences; differences between the rhizosphere and bulk soil bacterial communities were evidenced. Automated ribosomal intergenic spacer analysis (ARISA) showed differences also in the rhizosphere communities at different plant ages, as well as between the two plant types. ARISA fingerprinting patterns of soil bacterial communities exposed to root growth solutions, collected from transgenic and non transgenic plants grown in hydroponic conditions, were grouped separately by principal component analysis suggesting that root exudates could determine the selection of different bacterial communities.     

A nonparametric approach to the analysis of longitudinal data via a set of level crossing problems with application to the analysis of microarray time course experiments

Here we develop a completely nonparametric method for comparing two groups on a set of longitudinal measurements. No assumptions are made about the form of the mean response function, the covariance structure or the distributional form of disturbances around the mean response function. The solution proposed here is based on the realization that every longitudinal data set can also be thought of as a collection of survival data sets where the events of interest are level crossings. The method for testing for differences in the longitudinal measurements then is as follows: for an arbitrarily large set of levels, for each subject determine the first time the subject has an upcrossing and a downcrossing for each level. For each level one then computes the log rank statistic and uses the maximum in absolute value of all these statistics as the test statistic. By permuting group labels we obtain a permutation test of the hypothesis that the joint distribution of the measurements over time does not depend on group membership. Simulations are performed to investigate the power and it is applied to the area that motivated the method-the analysis of microarrays. In this area small sample sizes, few time points and far too many genes to consider genuine gene level longitudinal modeling have created a need for a simple, model free test to screen for interesting features in the data.     

Le bassin lacustre miocène de Bes-Konak (anatolie-turquie): Géologie et introduction a la paléontologie des vertébrés

The tertiary lacustrine and marshy facies ofBes-Konak (Ankara-district) has provided a rich fauna of Vertebrates preserved as molds and casts in Diatomites and volcano-sedimentary beds.In this assemblage are: Cyprinid fishes (Leuciscus(P.) etiliusRückert Ulkümen) with among them a new species of Barbus, some Amphibians both Urodela (mature Triturinae) and Anura (larval forms of Pelobates sp. and mature Rana sp.), a Turtle (Chelydridae-Chelydropsis sp.) a Snake (Colubroïde-Colubridae or Viperidae) and Birds (among them a new species of cormorant).According to the others various data resulting from palaebotanical, palynological and structural investigations, this fauna is clearly suggestive of a lower or middle Miocene deposit. It supports readily the climatic features (local sub-tropical microclimate inside a regional hot-temperate context) as invertebrates, macro and microflora and sedimentology had already shown.Once more, it points out the peculiar trophic type of the limnic area of Bes-Konak and its evolution to a well-marked eutrophic condition.     

Testing the ratio of two poisson rates

In this paper we compare the properties of four different general approaches for testing the ratio of two Poisson rates. Asymptotically normal tests, tests based on approximate p -values, exact conditional tests, and a likelihood ratio test are considered. The properties and power performance of these tests are studied by a Monte Carlo simulation experiment. Sample size calculation formulae are given for each of the test procedures and their validities are studied. Some recommendations favoring the likelihood ratio and certain asymptotic tests are based on these simulation results. Finally, all of the test procedures are illustrated with two real life medical examples.     

A computational model of intussusceptive microvascular growth and remodeling

Non-sprouting angiogenesis, also known as intussusceptive angiogenesis (IA), is an important modality of blood vessel morphogenesis in growing tissues. We present a novel computational framework for simulation of IA to answer some of the questions concerning the underlying mechanisms of the remodeling process. The model relies on mechanical interactions between blood and tissue, includes the structural maturation of the vessel wall, and is controlled by stimulating or inhibiting chemical agents. The model provides a simple explanation for the formation of microvessels and bifurcations from capillaries via IA, allowing for both maintenance and avoidance of shunt vessels. Detailed hemodynamic and transport properties for oxygen, metabolites or growth factors can be predicted. The model is an in silico framework for testing certain conceptual ideas about the mechanisms of intussusceptive growth and remodeling, in particular those related to mechanical and transport phenomena.