The tumorigenicity, migration, growth and invasiveness of certain tumor cells is stimulated by basement membranes. Here we have examined the effect of Matrigel, an extract of basement membrane proteins, on the behavior of several prostate cancer cell lines, testing their growth and invasiveness in vitro and in vivo. Cells of the Tsu-prI line were more invasive than PC-3, Du-145, or LNCaP cells. Peptide inhibitors implicated laminin in the migration and invasion of these cells. When these cells were suspended in Matrigel and injected into nude mice, their growth was greatly enhanced, since large tumors formed in athymic nude mice whereas virtually no tumors were observed in the absence of Matrigel. The growth of a slowly growing line, LNCaP, was increased by exogenous basic fibroblast growth factor when injected with Matrigel. A laminin cell adhesion peptide, YIGSR, was a potent inhibitor of Matrigel-stimulated tumor growth implicating cell-laminin interactions in this process. These results suggest that tumor growth of prostate adenocarcinoma cells may be dependent both on cellular growth factors and on cell-matrix interactions mediated by laminin which facilitate the development of transplanted tumors in nude mice.

Implementation of the Affordable Care Act is unleashing historic new efforts aimed at reforming the US health system. Many important incremental improvements are under way, yet there is a growing recognition that more transformative changes are necessary if the health care system is to do a better job of optimizing population health. While the concept of the Triple Aim-dedicated to improving the experience of care, the health of populations, and lowering per capita costs of care-has been used to help health care providers and health care systems focus their efforts on costs, quality, and outcomes, it does not provide a roadmap for a new system. In this article we describe the 3.0 Transformation Framework we developed to stimulate thinking and support the planning and development of the new roadmap for the next generation of the US health care system. With a focus on optimizing population health over the life span, the framework suggests how a system designed to better manage chronic disease care could evolve into a system designed to enhance population health. We describe how the 3.0 Transformation Framework has been used and applied in national, state, and local settings, and we suggest potential next steps for its wider application and use.

Health impact assessment (HIA) has been advanced as a means of bringing potential health impacts to the attention of policy makers, particularly in sectors where health impacts may not otherwise be considered. This article examines lessons for HIA in the United States from the related and relatively well-developed field of environmental impact assessment (EIA). We reviewed the EIA literature and conducted twenty phone interviews with EIA professionals. Successes of EIA cited by respondents included integration of environmental goals into decision making, improved planning, and greater transparency and public involvement. Reported shortcomings included the length and complexity of EIA documents, limited and adversarial public participation, and an emphasis on procedure over substance. Presently, EIAs consider few, if any, health outcomes. Respondents differed on the prospects for HIA. Most agreed that HIA could contribute to EIA in several areas, including assessment of cumulative impacts and impacts to environmental justice. Reasons given for not incorporating HIA into EIA were uncertainties about interpreting estimated health impacts, that EIA documents would become even longer and more complicated, and that HIA would gain little from the procedural and legal emphasis in EIA. We conclude that for HIA to advance, whether as part of or separate from EIA, well-formulated methodologies need to be developed and tested in real-world situations. When possible, HIA should build on the methods that have been utilized successfully in EIA. The most fruitful avenue is demonstration projects that test, refine, and demonstrate different methods and models to maximize their utility and acceptance.Health impact assessment (HIA) has been advanced in a number of different nations and by the World Health Organization (WHO) as a means to facilitate the consideration of potential health consequences of proposed

This publication is part of the National Academy of Medicine's Vital Directions for Health and Health Care Initiative, which called on more than 150 leading researchers, scientists, and policy makers from across the United States to assess and provide expert guidance on 19 priority issues for U.S. health policy. The views presented in this publication and others in the series are those of the authors and do not represent formal consensus positions of the NAM, the National Academies of Sciences, Engineering, and Medicine, or the authors' organizations. Learn more: nam.edu/VitalDirections.