Is there an issue if you DON'T start from "SIMULATION" when changing?

[sandmac]

I swear there must be a "game-to-game variance" factor coded in this game that prohibits sliders from absolute consistency.

Slider testers:

Something I've always wondered...

SIMULATION sliders:

Once the sliders are started with a base from the SIMULATION SETTING, is there a rule when making even simple changes that you have to select SIMULATION and start over?

The game doesn't FORCE you to start over but I wonder if it's a good idea?

Does anyone notice in-game sliders taking affect more or less than slider changes from the menu?