PDE solvers using Adaptive Mesh Refinement on block structured grids are some of the most challenging applications to adapt to massively parallel computing environments. We describe optimizations to the Chombo AMR framework that enable it to scale efficiently to thousands of processors on the Cray XT4. The optimization process also uncovered OS-related performance variations that were not explained by conventional OS interference benchmarks. Ultimately the variability was traced back to complex interactions between the application, system software, and the memory hierarchy. Once identified, software modifications to control the variability improved performance by 20% and decreased the variation in computation time across processors by a factor of 3. These newly identified sources of variation will impact many applications and suggest new benchmarks for OS-services be developed.