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Medical students begin to explore the realm of near death experiences, hoping for insights. Each has their heart stopped and is revived. They begin having flashes of walking nightmares from their childhood, reflecting sins they committed or had committed against them. The experiences continue to intensify, and they begin to be physically beaten by their visions as they try and go deeper into the death experience to find a cure.

After a terrible air disaster, survivor Max Klein emerges a changed person. Unable to connect to his former life or to wife Laura, he feels godlike and invulnerable. When psychologist Bill Perlman is unable to help Max, he has Max meet another survivor, Carla Rodrigo, who is racked with grief and guilt since her baby died in the crash which she and Max survived.

The major sub-plot circles around the youngest Griffin, Stewie, who has a near-death experience at a pool when a lifeguard chair falls on him, but he survives. After having a vision of being in Hell, he decides to change his ways, but this doesn’t last long. While watching television, he and Brian spot a man that looks like Stewie. Brian is convinced that he is Stewie’s real father, until Stewie learns that the man is actually himself as an adult, taking a vacation from his own time period. Baby Stewie visits thirty years later to discover that his adult self, going by the name Stu, is a single blue-collar middle-aged virgin working at a Circuit City-type store. Meanwhile, Peter and Lois are trying to teach their two older kids, Meg and Chris, to date. In the future, Chris, who hasn’t changed much, is working as a cop and is married to a foul-mouthed hustler named Vanessa. Meg is now called Ron, since she had a sex-change after college.

Manny (Ray Ramono), Sid (John Leguizamo), and Diego (Denis Leary) are currently living in a large valley surrounded by an enormously high ice wall on all sides. When a waterpark begins to form, the trio discovers that the ice wall is actually a wall that is barely holding a massive body of water that could flood the valley to nearly a mile underwater. A vulture tells them that there is a boat at the other end of the valley that may save them all, but they only have 3 days to make it or die. Manny is having trouble facing the fact that he may be the last mammoth left. Along the way, they meet Ellie (Queen Latifah), a mammoth who thinks she is a possum, and her possum brothers Crash (Sean William Scott) and Eddie (Josh Peck). As they begin to travel together, Manny learns, with help from Diego and Sid, that having this new mammoth with them, may not be as bad as Manny makes it out to be while they try to escape the oncoming and continually threatening flood. During their journey, Scrat the sabre-toothed squirrel has his own hilarious adventures that eventually leads to something else entirely.

Joe Hickley thinks he’s got a great scheme: kidnap the child of rich parents, hold it for 24 hours, keeping the mother under his control while an accomplice gets the ransom from the father, who is on a trip. But things go very wrong when he tries this scheme on the Jennings family, in part because their daughter Abby is asthmatic, and in part because the Jennings’ find out more than Hickley wants them to know.

Eight years after the InGen incident, Dr. Alan Grant is happy with his life far from any dinosaurs other than fossilized. Unfortunately, he is extremely short in research money, and therefore accepts the offer of wealthy businessman Paul Kirby: A low flight over isolated Isla Sorna, where InGen’s second research site was located, and Dr. Grant can fund his future research for a long time. What Dr. Grant didn’t know is that Kirby just needs a dinosaur expert to help him and his wife find their 14-year-old son Eric, who crashed on the island while paragliding. What he did suspect, but never wanted to witness, is that the Velociraptors have evolved into a communicating species (and seemingly all along had the capability to do so), now being smarter than primates.