Symposium on integrating the science of environmental justice into decision-making at the Environmental Protection Agency: an overview.

In March 2010, the Environmental Protection Agency (EPA) collaborated with government and nongovernmental organizations to host a groundbreaking symposium, "Strengthening Environmental Justice Research and Decision Making: A Symposium on the Science of Disproportionate Environmental Health Impacts." The symposium provided a forum for discourse on the state of scientific knowledge about factors identified by EPA that may contribute to higher burdens of environmental exposure or risk in racial/ethnic minorities and low-income populations. Also featured were discussions on how environmental justice considerations may be integrated into EPA's analytical and decision-making frameworks and on research needs for advancing the integration of environmental justice into environmental policymaking. We summarize key discussions and conclusions from the symposium and briefly introduce the articles in this issue.

Modern environmental health hazards: a public health issue of increasing significance in Africa.

OBJECTIVES: Traditional hazards such as poor sanitation currently account for most of Africa's environmentally related disease burden. However, with rapid development absent appropriate safeguards for environment and health, modern environmental health hazards (MEHHs) may emerge as critical contributors to the continent's disease burden. We review recent evidence of human exposure to and health effects from MEHHs, and their occurrence in environmental media and consumer products. Our purpose is to highlight the growing significance of these hazards as African countries experience urbanization, industrial growth, and development. DATA SOURCES: We reviewed published epidemiologic, exposure, and environmental studies of chemical agents such as heavy metals and pesticides. DATA SYNTHESIS: The body of evidence demonstrates ongoing environmental releases of MEHHs and human exposures sometimes at toxicologically relevant levels. Several sources of MEHHs in environmental media have been identified, including natural resource mining and processing and automobile exhaust. Biomonitoring studies provided direct evidence of human exposure to metals such as mercury and lead and pesticides such as p,p'-dichlorodiphenyltrichloroethane (DDT) and organophosphates. Land and water resource pollution and industrial air toxics are areas of significant data gaps, notwithstanding the presence of several emitting sources. CONCLUSION: Unmitigated MEHH releases and human exposure have implications for Africa's disease burden. For Africans encumbered by conditions such as malnutrition that impair resilience to toxicologic challenges, the burden may be higher. A shift in public health policy toward accommodating the emerging diversity in Africa's environmental health issues is necessary to successfully alleviate the burden of avoidable ill health and premature death for all its communities now and in the future.

Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer.

PURPOSE: The study aims to evaluate the efficacy and toxicity of fenretinide in preventing tumor recurrence in patients with transitional cell carcinoma (TCC) of the bladder. EXPERIMENTAL DESIGN: We conducted a multicenter phase III, randomized, placebo-controlled trial of fenretinide (200 mg/day orally for 12 months) in patients with non-muscle-invasive bladder TCC (stages Ta, Tis, or T1) after transurethral resection with or without adjuvant intravesical Bacillus Calmette-Guerin (BCG). Patients received cystoscopic evaluation and bladder cytology every 3 months during the 1-year on study drug and a final evaluation at 15 months. The primary endpoint was time to recurrence. RESULTS: A total of 149 patients were enrolled; 137 were evaluable for recurrence. The risk of recurrence was considered to be "low" in 72% (no prior BCG) and intermediate or high in 32% (prior BCG) of the evaluable patients. Of the lower-risk group, 68% had solitary tumors and 32% had multifocal, low-grade papillary (Ta, grade 1 or grade 2) tumors. The 1-year recurrence rates by Kaplan-Meier estimate were 32.3% (placebo) versus 31.5% (fenretinide; P = 0.88 log-rank test). Fenretinide was well tolerated and had no unexpected toxic effects; only elevated serum triglyceride levels were significantly more frequent on fenretinide (versus placebo). The Data Safety and Monitoring Board recommended study closure at 149 patients (before reaching the accrual goal of 160 patients) because an interim review of the data showed a low likelihood of detecting a difference between the two arms, even if the original accrual goal was met. CONCLUSIONS: Although well tolerated, fenretinide did not reduce the time-to-recurrence in patients with Ta, T1, or Tis TCC of the bladder.

Möbius: an integrated discrete-event modeling environment.

UNLABELLED: Möbius has found numerous applications in computational biology to build and solve stochastic models of biological processes. It provides the user with a modeling workflow and several sophisticated features that are not available in the simulation tools commonly used by computational biologists. AVAILABILITY: Möbius is free for academic users. It can be downloaded from www.mobius.uiuc.edu

Dynamic partitioning for hybrid simulation of the bistable HIV-1 transactivation network.

MOTIVATION: The stochastic kinetics of a well-mixed chemical system, governed by the chemical Master equation, can be simulated using the exact methods of Gillespie. However, these methods do not scale well as systems become more complex and larger models are built to include reactions with widely varying rates, since the computational burden of simulation increases with the number of reaction events. Continuous models may provide an approximate solution and are computationally less costly, but they fail to capture the stochastic behavior of small populations of macromolecules. RESULTS: In this article we present a hybrid simulation algorithm that dynamically partitions the system into subsets of continuous and discrete reactions, approximates the continuous reactions deterministically as a system of ordinary differential equations (ODE) and uses a Monte Carlo method for generating discrete reaction events according to a time-dependent propensity. Our approach to partitioning is improved such that we dynamically partition the system of reactions, based on a threshold relative to the distribution of propensities in the discrete subset. We have implemented the hybrid algorithm in an extensible framework, utilizing two rigorous ODE solvers to approximate the continuous reactions, and use an example model to illustrate the accuracy and potential speedup of the algorithm when compared with exact stochastic simulation. AVAILABILITY: Software and benchmark models used for this publication can be made available upon request from the authors.