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Decision-makers in public and private sectors are deciding how to invest in rebuilding and modernizing their crumbling infrastructure to support economic growth amidst changing social, technological, and environmental pressures. Informing these complex infrastructure investment decisions critically depends on making strategic shifts in science policy to support the development and brokering of usable knowledge including strengthening science-policy-practice connections. Numerous weaknesses at this interface stymie uptake of potentially useful knowledge and lead to a persistent “knowledge-action gap”. Specific reasons for this gap are varied and include challenges to the supply of information, differences in culture, priorities, and communication between scientists and decision makers. We identify evidence-based strategies and tactics available to science policy-makers and program managers that could help foster more usable knowledge to guide 21st century infrastructure investments.