While the simulated data is in agreement with anticipated parameters, it is important to note that experimental measures of coincidence loss are often greater than those simulated here. This is due to many factors including the fact that non-uniform illumination can lead to local loss of electron counts due to hard limits on count rates during sensing. This is evidenced in diffraction data collected at increasing incident electron flux from dose-insensitive, well-diffracting crystals of Co(II) mesotetraphenyl porphyrin, which we used as a diffraction standard. In that case, an approximately fourfold increase in incident flux does not result in a fourfold increase in observed diffraction counts across all measured signal pixels (Supplementary Figure ), and a nearly 9-fold increase in flux, from ~0.01 to ~0.084 e -/Å 2 /s, showed a pronounced loss of counts at the brightest reflections. This was observed in scatterplots of counts at 0.01 e -/Å 2 /s vs higher incident flux values, and histograms of count ratios across those conditions. Based on that experiment, we elected to limit our incident flux for subsequent experiments to less than 0.05 e -/Å 2 /s.