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President Barack Obama has said the biggest threat to US security is the possibility of a terrorist organisation obtaining a nuclear weapon.
Speaking on the eve of a nuclear security summit in Washington, he said leaders from 40 states should focus on how to secure nuclear material.
He said groups like al-Qaeda would not hesitate to use nuclear devices.
Neither North Korea nor Iran, two states with disputed nuclear ambitions, have been invited to the summit.
The two countries are viewed by the US as violators of the non-proliferation agreement.
Syria was also left off the invitation list because the US believes Damascus has nuclear ambitions, the Associated Press news agency notes.
But the leaders of nuclear states like India, China and Pakistan are among those coming to Washington for the biggest gathering of world leaders in the US capital in decades, says the BBC's Mark Mardell.
While the issue of what to do about Iran's nuclear ambitions is not on the agenda, it will be at the centre of many discussions, our North America editor adds.
"The single biggest threat to US security, both short-term, medium-term and long-term, would be the possibility of a terrorist organisation obtaining a nuclear weapon," Mr Obama said.
"This is something that could change the security landscape in this country and around the world for years to come.
"If there was ever a detonation in New York City, or London, or Johannesburg, the ramifications economically, politically and from a security perspective would be devastating."