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In Knockemstiff, Ohio, war veteran Willard can't save his beautiful wife, Charlotte, from a slow death by cancer no matter how much sacrificial blood he pours on his 'prayer log'. Carl and Sandy Henderson, a husband-and-wife team of serial killers, trawl America's highways searching for suitable models to photograph and exterminate. Preacher Roy and his crippled virtuoso-guitar-playing sidekick are running from the law. And caught in the middle of all this is Arvin, Willard and Charlotte's orphaned son, looking for answers....