If a file is uniquely held in DT, can it be accessed by other applications?
I moved a PDF of a book to DT and deleted it from the finder, it was then no longer possible to open the PDF from Calibre, so the answer would appear to be no.
If files have been indexed by DT are they fully searchable or is it only their meta-data?
My understanding is that only the meta-data is searchable
Conclusion
If you want the omniscient power to search all the data within files on your mac and you want to access those files from other applications (eg Calibre & Skim) then you have no choice but to duplicate data.
You can open documents in other applications via Data > Open With. But you shouldn’t reference their path, you have to use item links (see Edit > Copy Item Link) instead to reference them from other apps.
No, the only difference between indexing and importing is the file location. The search is identical.
Indeed, as Christian noted, right-click>”Open In” is your friend (and CMD-shift-O will open a file in the default application).
So if you have a book in DEVONthink you want to open in Calibre, right click it and choose “Open In… Calbre”.
If Skim is your default PDF reader, CMD-shift-O in DEVONthink will open it directly in Skim (or whatever the default is).