New York State Police say a preliminary investigation determined the crash happened just after 12:30 p.m. on the New York State Thruway as the bus was heading westbound near exit 40 (Weedsport) in the town of Brutus.
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Authorites say the bus exited the roadway for an unknown reason and rolled over onto the grassy shoulder.
There were a total of 57 passengers, including the driver, and all were taken to the hospital for injuries ranging from minor to serious.
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The name of the tour bus company is unknown, but police say the bus was headed to the Niagara Falls.
The investigation is ongoing.