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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.

Floodplain areas comprise some 30% of the area in the Amazon, but are currently under severe anthropogenic threat. Across the Amazon Basin, forest-dwelling non-volant mammals play crucial roles in maintaining the integrity of forest functionality, yet have been poorly studied in fluvial island forests. Mammal assemblages may be affected by edaphic characteristics that operate indirectly via food nutritional quality, by patch attributes, and/or can be modulated by anthropogenic disturbances. Here, we conducted systematic and quantitative mammal surveys across fluvial islands of an Amazonian archipelago, to assess the influence of edaphic factors (soil fertility), island attributes (island area and degree of isolation) and anthropogenic characteristics (distance from human settlement and logging) on the patterns of mammal species composition and richness. On 28 islands, we conducted spoor surveys and deployed 49 camera traps (total effort of 2940 camera trap-days). Subsequently, we performed multiple regression analysis to investigate the influence of environmental and anthropogenic predictors on mammal species richness, while dbRDA (distance-based redundancy analysis) was used for species composition. We found that mammal species richness was positively correlated with soil fertility, and in combination with anthropogenic characteristics, both variables affected the species assemblage composition. In particular, smaller species were found across a variety of levels of soil fertility and anthropogenic disturbances, while larger mammals were mostly recorded at sites with higher soil fertility and low levels of anthropogenic disturbances. Understanding the contribution of environmental and anthropogenic characteristics to the observed mammalian species richness and assemblage composition patterns will help optimise management and conservation efforts on Amazonian fluvial islands. In particular, we suggest enforcing hunting and logging restrictions within fluvial islands through surveillance activities, especially in more fertile islands.

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