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One of the most destructive natural hazards, tropical cyclone (TC)–induced coastal flooding, will worsen under climate change. Here we conduct climatology–hydrodynamic modeling to quantify the effects of sea level rise (SLR) and TC climatology change (under RCP 8.5) on late 21st century flood hazards at the county level along the US Atlantic and Gulf Coasts. We find that, under the compound effects of SLR and TC climatology change, the historical 100-year flood level would occur annually in New England and mid-Atlantic regions and every 1–30 years in southeast Atlantic and Gulf of Mexico regions in the late 21st century. The relative effect of TC climatology change increases continuously from New England, mid-Atlantic, southeast Atlantic, to the Gulf of Mexico, and the effect of TC climatology change is likely to be larger than the effect of SLR for over 40% of coastal counties in the Gulf of Mexico.

Developing a user-friendly platform that can handle a vast number of complex physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models both for conventional small molecules and larger biologic drugs is a substantial challenge. Over the last decade the Simcyp Population Based Simulator has gained popularity in major pharmaceutical companies (70% of top 40 - in term of R&D spending). Under the Simcyp Consortium guidance, it has evolved from a simple drug-drug interaction tool to a sophisticated and comprehensive Model Based Drug Development (MBDD) platform that covers a broad range of applications spanning from early drug discovery to late drug development. This article provides an update on the latest architectural and implementation developments within the Simulator. Interconnection between peripheral modules, the dynamic model building process and compound and population data handling are all described. The Simcyp Data Management (SDM) system, which contains the system and drug databases, can help with implementing quality standards by seamless integration and tracking of any changes. This also helps with internal approval procedures, validation and auto-testing of the new implemented models and algorithms, an area of high interest to regulatory bodies.

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