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James Anderson bowled seven immaculate overs which cost only 17 and included the wicket of Herschelle Gibbs, who stabbed a back-of-a-length delivery straight to short cover.
BBC: England win seals one-day series
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Home supporters were hoping for a partnership of the magnitude of the one between Amla and De Villiers, but it ended on 69 when David drove the innocuous-looking off-spin of Duminy straight to short cover.
BBC: S Africa top rankings after win
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Kieswetter's luck ran out when he called for a suicidal run having hit straight to short mid-wicket, Kevin Pietersen rightly refused and the wicketkeeper-batsman was given out after lengthy video referrals which finally concluded his bat had bounced into the air when he dived for his crease as Niall O'Brien whipped off the bails.
BBC: England through as rain wipes out Ireland match