Portable near-infrared diffusive light imager for breast cancer detection

We present a frequency-domain near-infrared optical tomography system designed for breast cancer detection, in conjunction with conventional ultrasound. It features fast optical switching, three-wavelength excitations, and avalanche photodiode as detectors. Laser diodes at 660, 780, and 830 nm are used as light sources and their outputs are distributed sequentially to one of nine source fibers. An equivalent 130-dB isolation between electrical signals from different source channels is achieved with the optical switches of very low crosstalk. Ten detection channels, each of which includes a silicon avalanche photodiode, detect diffusive photon density waves simultaneously. The dynamic range of an avalanche photodiode is about 20 to 30 dB higher than that of a photomultiplier tube, thus eliminating the need for multistep system gain control. The entire system is compact in size (<0.051 m(3)) and fast in data acquisition (less than 2 sec for a complete scan). Calibration and the clinical experiment results are presented in the paper.     

Age-conditional probabilities of developing cancer

We propose an estimator of the probability of developing a disease in a given age range, conditional on never having developed the disease prior to the beginning of the age range. Our estimator improves the one described by Wun, Merrill and Feuer ( Lifetime Data Analysis 1998; 4, 169-186) that is currently used by the U.S. National Cancer Institute for the SEER Cancer Statistics Review. Both estimators use cross-sectional disease rates and provide an interpretation of these rates in terms of the age-conditional probability of developing disease in a hypothetical cohort. The difficulty of this problem is that rates are not available per person-years alive and disease free, but only per person-years alive. Wun et al. used ad hoc methods to handle this problem which did not properly account for competing risks, did not provide a measure of variability, and only allowed age ranges using prespecified 5-year age intervals. Here we solve the problem under a unified competing risks framework, which allows the calculation of the age-conditional probabilities for any age range. We generalize gamma confidence intervals to apply to our new statistic. Although our new method provides estimates which are numerically similar to that of Wun et al., this paper provides a comprehensive theoretical basis for estimation and inference about the age-conditional probability of developing a disease.     

Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs

This article provides an overview of methods for reliability assessment of quantitative structure-activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation.     

Solid-organ transplant recipients treated with drotrecogin alfa (activated) for severe sepsis

Severe sepsis in immunosuppressed recipients of solid-organ transplants is associated with a high mortality. Conventional management of sepsis in this patient population has not specifically attempted to treat the underlying inflammatory or procoagulant responses that contribute to the development of multisystem organ failure. Drotrecogin alfa (activated, human activated protein C) has been shown to be a safe and effective adjuvant in the treatment of severe sepsis; however, experience in recipients of solid-organ transplants has not been addressed. The treatments and outcomes of three solid-organ transplant recipients (liver, kidney, and kidney-pancreas) who experienced episodes of severe sepsis are presented and demonstrate initial success with the use of drotrecogin alfa (activated).