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Andy2 - When a program runs in Safe Mode but not in Normal Mode that often indicates some sort of interference from an external program.
If other suggestions don't fix the problem, try disabling startup programs. You can do that via Task Manager or CCleaner, the latter also allows shell extensions (right click menu items) to be disabled. If calibre runs you'll need to find the culprit by via a process of elimination.
Oh, and close any other desktop tasks you started before you tried calibre - browser, mail client, newsfeed, spreadsheet etc.
BR