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The Quaternary period saw the extinctions of numerous predominantly larger, especially megafaunal, species, many of which occurred during the transition from the Pleistocene to the Holocene epoch. However, the extinction wave did not stop at the end of the Pleistocene, but continued especially on isolated Islands in Holocene extinctions. Among the main causes hypothesized by paleontologists are natural climate change and overkill by humans, who appeared during the Middle Pleistocene and migrated to many regions of the world during the Late Pleistocene and Holocene. A variant of the latter possibility is the second-order predation hypothesis, which focuses more on the indirect damage caused by overcompetition with nonhuman predators. The spread of disease is also discussed as a possible reason.