In reply to:

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With the O/U this difference between the barrels, causes it's own set of problems, but only when regulateing, and it is true the change of bullet weight, in an O/U, is not as drastic a change to the regulation as it is with the S/S.

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Mac, I think you have forgotten an important point here.
Every double rifle is an individual!
Some are more forgiving than others, both SxS and O/U.
I've seen SxS and O/U doubles which would shoot a variety of different bullet weights well.
On the other hand I've seen O/U doubles which will go right off the paper (shooting apart) at 50 yards with a change in bullet weight.