Health, Wealth, and the 21st Century Cures Act

Americans are increasingly apprehensive about our future, so it is inspiring when Congress produces legislation intended to both enhance our health and expand our economy. The 21st Century Cures Act,1 recently passed by the House with an impressive bipartisan majority vote of 344 to 77, intends to accelerate the many-step process of drug discovery and development, from basic scientific research to clinical development to delivery, distribution, and ongoing monitoring. Among other things, the legislation boosts National Institute of Health funding, dramatically speeds up the US Food and Drug Administration (FDA) approval process, and aims to make use of new information technology to better monitor the performance of medical products after they reach the market. This landmark bill now awaits a comparable piece of legislation being developed by the Senate Health Education, Labor, and Pensions Committee. Together, they will transform the biomedical ecosystem and provide the foundation for the next several decades of innovative life-saving and health-enhancing solutions for our nation and the world

CaGrid Workflow Toolkit: A taverna based workflow tool for cancer grid

SOFTWAR

Could an open-source clinical trial data-management system be what we have all been looking for?

The authors argue that research organizations and funders should combine efforts to produce an open-source solution for trial data management

Are dual isotope and isotopomer ratios of N2O useful indicators for N2O turnover during denitrification in nitrate-contaminated aquifers?

Denitrifying aquifers are sources of the greenhouse gas N2O. Isotopic signatures reflect processes of production and reduction of N2O, but it is not clear to which extent these can be used to quantify those processes. We investigated the spatial distribution of isotopologue values of N2O (delta O-18, average delta N-15, and N-15 site preference, SP) in two denitrifying sandy aquifers to study N2O production and reduction and associated isotope effects in groundwater. For the first time, we combined this approach with direct estimation of N2O reduction from excess-N-2 analysis. Groundwater samples were collected from 15 monitoring wells and four multilevel sampling wells and analysed for NO3-, dissolved N2O, dissolved O-2, excess N-2 from denitrification and isotopic signatures of NO3- and N2O. Both aquifers exhibited high NO3- concentrations with average concentrations of 22 and 15 mg N L-1, respectively. Evidence of intense denitrification with associated N2O formation was obtained from mean excess-N-2 of 3.5 and 4.3 mg N L-1, respectively. Isotopic signatures of N2O were highly variable with ranges of 17.6-113.2 parts per thousand (delta O-18), 55.4 to 89.4 parts per thousand (delta N-15(bulk)) and 1.8-97.9 parts per thousand (SP). delta N-15 and delta O-18 of NO3- ranged from 2.1 parts per thousand to 65.5 parts per thousand and from -5 parts per thousand to 33.5 parts per thousand, respectively.The relationships between delta N-15 of NO3- , delta N-15(bulk) and SP were not in good agreement with the distribution predicted by a Rayleigh-model of isotope fractionation. The large ranges of delta O-18 and SP of N2O as well as the close correlation between these values could be explained by the fact that N2O reduction to N-2 was strongly progressed but variable.We confirm and explain that a large range in SP and delta O-18 is typical for N2O from denitrifying aquifers, showing that this source signature can be distinguished from the isotopic fingerprint of N2O emitted from soils without water-logging. We conclude that isotopologue values of N2O in our sites were not suitable to quantify production or reduction of N2O or the contribution of different processes to the total N2O flux, apparently because these values were not only governed by individual pathways but eventually also by the spatial distribution of substrates and activity within the aquifers. These observations could be explained by the dynamics of N2O production, reduction and transport in water-saturated systems with heterogenic distribution of microbial activity and by a combination of diffusive and enzymatic isotope effects. (C) 2012 Elsevier Ltd. All rights reserved

Cell ‘guidling'

A binary logic to explain cell genesi

Significance of tumor angiogenesis in clinically localized prostate carcinoma treated with external beam radiotherapy

To determine the prognostic significance of microvessel density (a measure of tumor angiogenesis) in comparison with other prognostic factors for patients with clinically localized prostatic carcinoma treated with external beam radiotherapy. Microvessel density was quantified within the initial invasive carcinoma from the diagnostic transurethral resection specimen of 25 patients with a mean follow-up of 44 months. Microvessels were identified by immunohistochemical staining of endothelial cells for factor VIII-related antigen in formalin-fixed, paraffin-embedded tissue. Microvessels were counted in a x200 field (0.754 mm2) in the area of maximal angiogenesis. Microvessel density correlated with several pretreatment prognostic factors, including prostate-specific antigen (PSA) (p < 0.0001), tumor grade (p = 0.006), and ploidy (p = 0.016). The degree of tumor angiogenesis also correlated with outcome following external beam radiotherapy. The mean microvessel count in the nine tumors from patients who failed radiotherapy (ie, had rising PSA and/or clinical relapse) was 97.0 +/- 33.6 (+/- SD) per x200 field compared with 46.1 +/- 17.1 for the 16 patients with no evidence of failure (p < 0.0001). Increased microvessel density was also associated with a significantly worse actuarial outcome at 4 years using either biochemical relapse (rising PSA) or a composite endpoint of rising PSA or clinical relapse (p = 0.0003). The intratumoral quantification of tumor angiogenesis may prove valuable as a prognostic indicator in patients with clinically localized prostate cancer treated with radiotherapy