FCNN-based axon segmentation for convection-enhanced delivery optimization

Purpose: Glioblastoma multiforme treatment is a challenging task in clinical oncology. Convection- enhanced delivery (CED) is showing encouraging but still suboptimal results due to drug leakages. Numerical models can predict drug distribution within the brain, but require retrieving brain physical properties, such as the axon diameter distribution (ADD), through axon architecture analysis. The goal of this work was to provide an automatic, accurate and fast method for axon segmentation in electronic microscopy images based on fully convolutional neural network (FCNN) as to allow automatic ADD computation. Methods: The segmentation was performed using a residual FCNN inspired by U-Net and Resnet. The FCNN training was performed exploiting mini-batch gradient descent and the Adam optimizer. The Dice coefficient was chosen as loss function. Results: The proposed segmentation method achieved results comparable with already existing methods for axon segmentation in terms of Information Theoretic Scoring (0.98 %) with a faster training (5 h on the deployed GPU) and without requiring heavy post-processing (testing time was 0.2 s with a non-optimized code). The ADDs computed from the segmented and ground-truth images were statistically equivalent. Conclusions: The algorithm proposed in this work allowed fast and accurate axon segmentation and ADD computation, showing promising performance for brain microstructure analysis for CED delivery optimization

Vino e Ambiente: sostenibilità e qualità primaria nel sottobacino Iudeo-Bucari (TP).

In questa raccolta di scritti, vengono riportati i risultati dell’attività di ricerca realizzata con la collaborazione della cantina UVAM e dell’Istituto Regionale Vino e Olio di Sicili

Microstructure and Mechanical Properties of the in situ Β-Si 3 N 4 /Α′-SiAlON Composite

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65911/1/j.1151-2916.1994.tb04604.x.pd

Chronic Losartan Administration Reduces Mortality and Preserves Cardiac but Not Skeletal Muscle Function in Dystrophic Mice

Duchenne muscular dystrophy (DMD) is a degenerative disorder affecting skeletal and cardiac muscle for which there is no effective therapy. Angiotension receptor blockade (ARB) has excellent therapeutic potential in DMD based on recent data demonstrating attenuation of skeletal muscle disease progression during 6–9 months of therapy in the mdx mouse model of DMD. Since cardiac-related death is major cause of mortality in DMD, it is important to evaluate the effect of any novel treatment on the heart. Therefore, we evaluated the long-term impact of ARB on both the skeletal muscle and cardiac phenotype of the mdx mouse. Mdx mice received either losartan (0.6 g/L) (n = 8) or standard drinking water (n = 9) for two years, after which echocardiography was performed to assess cardiac function. Skeletal muscle weight, morphology, and function were assessed. Fibrosis was evaluated in the diaphragm and heart by Trichrome stain and by determination of tissue hydroxyproline content. By the study endpoint, 88% of treated mice were alive compared to only 44% of untreated (p = 0.05). No difference in skeletal muscle morphology, function, or fibrosis was noted in losartan-treated animals. Cardiac function was significantly preserved with losartan treatment, with a trend towards reduction in cardiac fibrosis. We saw no impact on the skeletal muscle disease progression, suggesting that other pathways that trigger fibrosis dominate over angiotensin II in skeletal muscle long term, unlike the situation in the heart. Our study suggests that ARB may be an important prophylactic treatment for DMD-associated cardiomyopathy, but will not impact skeletal muscle disease

Mutator dynamics in sexual and asexual experimental populations of yeast

<p>Abstract</p> <p>Background</p> <p>In asexual populations, mutators may be expected to hitchhike with associated beneficial mutations. In sexual populations, recombination is predicted to erode such associations, inhibiting mutator hitchhiking. To investigate the effect of recombination on mutators experimentally, we compared the frequency dynamics of a mutator allele (<it>msh2</it>Δ) in sexual and asexual populations of <it>Saccharomyces cerevisiae</it>.</p> <p>Results</p> <p>Mutator strains increased in frequency at the expense of wild-type strains in all asexual diploid populations, with some approaching fixation in 150 generations of propagation. Over the same period of time, mutators declined toward loss in all corresponding sexual diploid populations as well as in haploid populations propagated asexually.</p> <p>Conclusions</p> <p>We report the first experimental investigation of mutator dynamics in sexual populations. We show that a strong mutator quickly declines in sexual populations while hitchhiking to high frequency in asexual diploid populations, as predicted by theory. We also show that the <it>msh2Δ </it>mutator has a high and immediate realized cost that is alone sufficient to explain its decline in sexual populations. We postulate that this cost is indirect; namely, that it is due to a very high rate of recessive lethal or strongly deleterious mutation. However, we cannot rule out the possibility that <it>msh2</it>Δ also has unknown directly deleterious effects on fitness, and that these effects may differ between haploid asexual and sexual populations. Despite these reservations, our results prompt us to speculate that the short-term cost of highly deleterious recessive mutations can be as important as recombination in preventing mutator hitchhiking in sexual populations.</p

LDL-C-lowering efficacy of the ezetimibe/simvastatin single tablet compared with atorvastatin or roslivastatin in elderly patients with hype rcholesterolemia

Background: Cardiovascular disease occurs with increasing frequency with advancing age. However, despite increasing risk, the likelihood of statin use decreases with age. Co-administration of statin therapy with the cholesterol absorption inhibitor ezetimibe has been shown to increase LDL-C-lowering efficacy without requiring titration to a higher statin dose.We evaluated the LDL-C-lowering efficacy of the ezetimibe/simvastatin (E/S) single tablet vs 2 high efficacy monotherapies, atorvastatin (A) or rosuvastatin (R), in patients (pts) <65 and 6565 yrs with hypercholesterolemia using the results from 2 clinical trials. Methods: This was a side-by-side comparison of 2 similarly-designed, randomized, double-blind, 6-week, comparator studies: E/S vs A, and E/S vs R. In E/S vs A, pts (N=1321 <65 yrs, N=581 6565 yrs) were randomized equally to: E/S (10/10, 10/20, 10/40, 10/80 mg) or A (10, 20, 40, 80 mg). In E/S vs R, pts (N=2369 <65 yrs, N=590 6565 yrs) were randomized equally to: E/S (10/20, 10/40, 10/80 mg) or R (10, 20, 40 mg).The primary endpoint in each study was % change from baseline in LDL-C for E/S vs A or E/S vs R, pooled across all doses. Safety monitoring was also conducted. Results: In both the E/S vs A and the E/S vs R comparisons, E/S produced significantly greater reduction in LDL-C in both age groups, pooled across all doses (see Table). In both studies, E/S, A, and R were well tolerated by pts in both age groups. Conclusion: E/S, through inhibition of two sources of cholesterol, offers a highly efficacious option as LDL-C-lowering therapy for the treatment of hypercholesterolemia in elderly pts