We establish a "second vanishing theorem" for local cohomology modules over regular rings of unramified mixed characteristic, which relates the connectedness of the spectrum of a ring with the vanishing of local cohomology. Applying this, and new results on the mixed characteristic Lyubeznik numbers, we further study connectedness properties of the spectra of a certain class of rings.1 I (S) = E S (K) ⊕t−1 by induction on t, noting that the result follows from Theorem 3.8 if t = 1. Fix t > 1, and assume that for any ideal J of S for which dim(S/q) ≥ 3 for every minimal prime q of J, if Spec • (S/J) has t − 1 connected components, then H n−1 J (S) = E S (K) ⊕t−2 . In particular, this holds forConsider the following piece of the Mayer-Vietoris sequence in local cohomology associated to J and J t :