Best-fit orientation matrices for each frame were determined by nXDS, and orientation matrix components were compared for each frame in a dose series. nXDS would often find crystallographically equivalent orientations for different frames in the same series. We treated these symmetry-related orientations by using the initial orientation as a reference and iteratively correcting each subsequent frame to its symmetry-equivalent orientation nearest that of the preceding frame. Frames were considered mis-indexed when any of their orientation matrix components differed from those of adjacent frames by greater than two standard deviations of the population of all measured matrix components of that index. Such frames were excluded from further analysis. For beam-sensitive samples, where substantial non-monotonic intensity fluctuations had been measured, reflection positions predicted by nXDS matched reflections in the first frame of a series well, but agreed poorly with reflections on later frames. Figure ) illustrates an example of these indexing disagreements for a room temperature Cu(II)-serine crystal illuminated at 200 kV, which, following the delivery of only 1.5 e -/Å 2 , produced reflections clearly inconsistent with its initial orientation. Nearby orientations, determined by nXDS indexing of subsequent frames in the series, produced predictions better matching the observed diffraction.