A noninvasive multi-analyte diagnostic assay: Combining protein and DNA markers to stratify bladder cancer patients

Purpose: The authors recently reported the development of a noninvasive diagnostic assay using urinary matrix metalloproteinases (MMPs) as monitors of disease-free status and bladder cancer in high-risk populations. Using an approach called clinical intervention determining diagnostic (CIDD), they identified with high confidence those patients who could be excluded from additional intervention. To maximize performance, MMPs were combined with DNAbased markers and CIDD was applied to a population of patients undergoing monitoring for recurrence. Patients and methods: Urine samples were obtained from 323 patients, 48 of whom had a recurrence and 275 of whom did not have cancer upon cytoscopic evaluation. Twist1 and Nid2 methylation status was determined using methylation-specific polymerase chain reaction, FGFR3 mutational status by quantitative PCR, and MMP levels by enzyme-linked immunosorbent assay. Results: Using a combination of these DNA and protein markers, the authors identified with high confidence (97% negative predicted value) those patients who do not have cancer. Cutoffs were adjusted such that at 92% sensitivity, 51% of disease-free patients might be triaged from receiving further tests. Conclusion: The multi-analyte diagnostic readout assay described here is the first to combine protein and DNA biomarkers into one assay for optimal clinical performance. Using this approach, the detection of FGFR3 mutations and Twist1 and Nid2 methylation in the urine of patients undergoing bladder cancer recurrence screening increase the sensitivity and negative predictive value at an established MMP protein cutoff. This noninvasive urinary diagnostic assay could lead to the more efficient triage of patients undergoing recurrence monitoring

Heliospheric Transport of Neutron-Decay Protons

We report on new simulations of the transport of energetic protons originating from the decay of energetic neutrons produced in solar flares. Because the neutrons are fast-moving but insensitive to the solar wind magnetic field, the decay protons are produced over a wide region of space, and they should be detectable by current instruments over a broad range of longitudes for many hours after a sufficiently large gamma-ray flare. Spacecraft closer to the Sun are expected to see orders-of magnitude higher intensities than those at the Earth-Sun distance. The current solar cycle should present an excellent opportunity to observe neutron-decay protons with multiple spacecraft over different heliographic longitudes and distances from the Sun.Comment: 12 pages, 4 figures, to be published in special issue of Solar Physic

Coronal Diagnostics from Narrowband Images around 30.4 nm

Images taken in the band centered at 30.4 nm are routinely used to map the radiance of the He II Ly alpha line on the solar disk. That line is one of the strongest, if not the strongest, line in the EUV observed in the solar spectrum, and one of the few lines in that wavelength range providing information on the upper chromosphere or lower transition region. However, when observing the off-limb corona the contribution from the nearby Si XI 30.3 nm line can become significant. In this work we aim at estimating the relative contribution of those two lines in the solar corona around the minimum of solar activity. We combine measurements from CDS taken in August 2008 with temperature and density profiles from semiempirical models of the corona to compute the radiances of the two lines, and of other representative coronal lines (e.g., Mg X 62.5 nm, Si XII 52.1 nm). Considering both diagnosed quantities from line ratios (temperatures and densities) and line radiances in absolute units, we obtain a good overall match between observations and models. We find that the Si XI line dominates the He II line from just above the limb up to ~2 R_Sun in streamers, while its contribution to narrowband imaging in the 30.4 nm band is expected to become smaller, even negligible in the corona beyond ~2 - 3 R_Sun, the precise value being strongly dependent on the coronal temperature profile.Comment: 26 pages, 11 figures; to be published in: Solar Physic

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Enabling and Enhancing Science Exploration Across the Solar System: Aerocapture Technology for SmallSat to Flagship Missions

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