Hello,
I've experienced a problem similar to the one in this closed issue.
I'm using the latest version of IronPython (2.7.7), on a windows10 64 bit.

I'm calling to python from C#, in a multi-threaded environment.
My python code uses a lot of isinstance calls, and some of them (about once every 10,000 times) raise either a "SystemError: Handle is not initialized." or a "ValueError: Index was out of range. Must be non-negative and less than the size of the collection.\nParameter name: index".

By catching the exception in python I was able to locate the source to the same lines in _weakrefset.py, as described here:

On "Lib\_weakrefset.py"

35 :class WeakSet(object):
....
68 : def __contains__(self, item):
69 : try:
**70*: wr = ref(item) # <- here is raised "ValueError"

Exception ("Index was out of range")

71 : except TypeError:
72 : return False
**73*: return wr in self.data # <- here is raised "SystemError"

Exception ("Handle is not initialized")

I've tried using the script given in the original issue to recreate the problem, but that didn't work.
The C# code I'm using is open-source, and I don't know C# enough to understand where exactly my python is being called and in what context.
Please, If someone could help me recreate the problem, I will upload a detailed script that raises the same exceptions.
Thanks!