Assessment of treatment response in tuberculosis

Antibiotic treatment of tuberculosis has a duration of several months. There is significant variability of the host immune response and the pharmacokinetic-pharmacodynamic properties of Mycobacterium tuberculosis sub-populations at the site of disease. A limitation of sputum-based measures of treatment response may be sub-optimal detection and monitoring of Mycobacterium tuberculosis sub-populations. Potential biomarkers and surrogate endpoints should be benchmarked against hard clinical outcomes (failure/relapse/death) and may need tailoring to specific patient populations. Here, we assess the evidence supporting currently utilized and future potential host and pathogen-based models and biomarkers for monitoring treatment response in active and latent tuberculosis. Biomarkers for monitoring treatment response in extrapulmonary, pediatric and drug resistant tuberculosis are research priorities

Investigation of charge sharing among electrode strips for a CdZnTe detector

We have investigated charge sharing among the anode strips of a CdZnTe (CZT) detector using a 30 micrometer collimated gamma-ray beam. We compared the laboratory measurements with the predictions from our modeling of the charge transport within the detector. The results indicate that charge sharing is a function of the interaction depth and the energy of the incoming photon. Also, depending on depth, a fraction of the electrons might drift to the inter-anode region causing incomplete charge collection. Here, we show that photoelectron range and diffusion of the charge cloud are the principal causes of charge sharing and obtain limits on the size of the electron cloud as a function of position in the detector.Comment: 16 pages 10 figures. Accepted for publication in Nuclear Instruments and Methods -

Nifurtimox Is Effective Against Neural Tumor Cells and Is Synergistic with Buthionine Sulfoximine.

Children with aggressive neural tumors have poor survival rates and novel therapies are needed. Previous studies have identified nifurtimox and buthionine sulfoximine (BSO) as effective agents in children with neuroblastoma and medulloblastoma. We hypothesized that nifurtimox would be effective against other neural tumor cells and would be synergistic with BSO. We determined neural tumor cell viability before and after treatment with nifurtimox using MTT assays. Assays for DNA ladder formation and poly-ADP ribose polymerase (PARP) cleavage were performed to measure the induction of apoptosis after nifurtimox treatment. Inhibition of intracellular signaling was measured by Western blot analysis of treated and untreated cells. Tumor cells were then treated with combinations of nifurtimox and BSO and evaluated for viability using MTT assays. All neural tumor cell lines were sensitive to nifurtimox, and IC50 values ranged from approximately 20 to 210 μM. Nifurtimox treatment inhibited ERK phosphorylation and induced apoptosis in tumor cells. Furthermore, the combination of nifurtimox and BSO demonstrated significant synergistic efficacy in all tested cell lines. Additional preclinical and clinical studies of the combination of nifurtimox and BSO in patients with neural tumors are warranted

A preliminary systems study of interface equipment for digitally programmed flight simulators

Design study of digitally programmed supersonic transport flight simulato

Toolbox value creation final report (WP-101)

This document contains the deliverables of TransForum project WP-101, Toolbox Value Creation. Its contents allow users to use a summary analysis toolbox made for charting and improving value chains in the areas of People, Planet and Profit. Features of the toolbox are: Guidance in organizing a quick scan and change process. Create summary graphic overview of the materials balance of a production network. Model People and Planet and Profit separately but in conjunction. Allow flexible inclusion or omission of actors, processes and products. Analyze value of improvements