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Speaking at the Vital Voices conference she said it was imperative that Mrs Nelson's killers did not succeed, and that her murder stood as a final rebuke to all who would try to derail the peace process.
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She told the 400 delegates at the conference, aimed at strengthening the roles of women in democracy, and another 800 delegates who took part by video link from Craigavon, Londonderry and Cavan, that peace was about taking risks, making compromises and moving forward.
She said: "There have been setbacks along the road. I think particularly today of the murder of Rosemary Nelson.
"It was an effort to derail the common efforts that people of both traditions across the community have been making to bring about peace and inclusion in Northern Ireland.
"Obviously it is imperative that her killers must not be allowed to succeed. They must be brought to justice. More than that, her murder must stand as a final rebuke to all who would try to derail the peace process."
America 'will support' Northern Ireland
The First Lady also stressed America's continued support for Northern Ireland.
She said, "We will stand with you. We will stand with all who take risks for peace. We will stand with all who are interested in building opportunities and accepting responsibility for the future."
Mrs Clinton praised the First Minister of the Assembly in Northern Ireland David Trimble and Deputy First Minister Seamus Mallon, who both spoke at the event, and Northern Ireland Secretary Mo Mowlam, who sent her apologies for not attending, for their commitment to the peace process.
This was Mrs Clinton's fourth visit to Northern Ireland since her husband was elected US President.
Her speech at the women's conference underlined her continuing interest in the role that women are playing in the Northern Ireland peace process. She received two standing ovations, as she took the stage and when she finished speaking.
Trimble praises role of women
First Minister David Trimble praised Mrs Clinton and the Vital Voices project for helping provide resources and partnerships to further the role of women.
He said the "courage and commitment" of Northern Ireland women had done much to "maintain the fabric of civic society through the many dark days of the last 30 years."
Mrs Clinton flew to London to meet UK Prime Minister, Tony Blair's wife Cherie, and to attend a children's rights conference later on Thursday.
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