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I have been trying various single-player modes and during main gameplay, at random times my keyboard suddenly loses all functionality. No key or key combination works, including OS gestures like ALT-F4 and even CTRL-ALT-DEL. The keyboard is completely unresponsive.

All USB peripherals (Mouse, Gamepad, etc) continue to work fine. Theoretically I could continue to play with just the peripherals except that without the "ESC" key available, there is no way to exit a game.

All attempts to cleanly quit a game or the application itself do not work. Every time this happens I am forced to hold the power button on my laptop until the power cuts (I REALLY hate doing that). I tried windowed mode but it still completely captures the mouse, and this doesn't solve the problem.

I am running on a Lenovo Ideapad w/ fully up-to-date Windows 10, 16GB RAM , and Nvidia GeForce GTX960; the hardware and OS shouldn't be a problem. I've tried running the executable under Windows 7 compatibility mode. Tried changing preferred graphics adapter to the high performace option, as well as enabling "Stereo Mix" on my Recording Devices (All things I found online purporting to fix issues with this program).

I would be very grateful to anyone who has a way to solve this issue. This is such an amazing game in every respect, and it is so sad that this one tiny glitch prevents me from playing it. Thanks guys.
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Install the June 2010 DirectX runtime package, then use the DirectX web installer, as your current DirectX may have become corrupt over time.
You can find the ZIP file containing the 2010 package installation files here:
http://www.microsoft.com/downloads/en/details.aspx?FamilyID=3b170b25-abab-4bc3-ae91-50ceb6d8fa8d
You will have to extract the files into some folder, then open that folder and launch the DXSETUP.exe file in order to proceed with the installation.
Afterwards, download the latest DirectX web installer use it as well:
http://www.microsoft.com/en-us/download/details.aspx?id=35

Other than that, all I could suggest would be to search a solution online. I don't think the issue you're experiencing is specific to this game, so you could probably find (a) fix(es) online somewhere.