The problem is intermittent, which causes me to lean more towards a hardware failure. The client also has 3 datasets operating concurrently and only experiences the problems in one (the other two are considerably smaller). They are even getting these errors when running integrity checks, normally with the adjunct "Unable to read unopened file [insert random file name here]".
The errors have been occurring randomly (making it hard to reproduce) in OE with increasing frequency for some time, they have only just started occurring in AP.
I am currently running a full set of integrity checks locally on a separate computer...but the dataset is over 2GB, so that may take some time...