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Highlights: London Irish 23-19 Ospreys
London Irish (17) 23
Tries: Mapusua, Tagicakibau Cons: Hewat 2 Pens: Hewat 3
Ospreys (6) 19
Try: Walker Con: Hook Pens: Hook 4
EDF Cup holders Ospreys are through to the semi-finals after picking up a losing bonus point at London Irish.
Nikki Walker's converted try and a long-distance James Hook penalty was enough to see the visitors through.
Irish did have one foot in the last four themselves when tries from Seilala Mapusua and Sailosi Tagicakibau helped build a 20-6 lead.
But Walker and Hook made sure it was the Welsh region who were the ones to go through as Group C winners.
The Ospreys only needed a losing bonus point to qualify, but it did not look like they would need it early on.
Hook put them 6-0 up inside the opening 20 minutes kicking two penalties.
But Irish took control of the game and turned it on its head with two good tries.
First Shane Geraghty switched inside to centre Seilala Mapusua who dived over in the 26th minute at the mercy of Ian Gough.
Peter Hewat converted and went on to add another three points after the Ospreys were caught offside.
And that lead was extended six minutes before the break when wing Tagicakibau pounced on a loose ball to race through under the posts for the hosts' second try.
The Samoan took advantage after Gavin Henson's pass failed to reach Tommy Bowe and he skipped past a challenge from Walker to get the converted score and a 17-6 lead.
The Ospreys had to come out and attack in the second half to keep alive their hopes of defending the Cup.
But they fell further behind five minutes after the restart with Hewart kicking his second penalty.
Hook cut that lead soon after with a kick of his own as Irish were penalised for failing to roll away.
The Ospreys then threw on captain Ryan Jones and lock Alun Wyn Jones as they looked for some urgency.
And on 55 minutes, Walker put them in the driving seat.
Henson sent a wide ball to Andrew Bishop, who offloaded to Walker to go over in the corner with Hook converting.
Wyn Jones cost the Ospreys another three points for using his head while taking out of the ruck.
But Hook went on to keep his head and tremendously kicked a 52-metre penalty.
Marty Holah did go over, which would have put the Ospreys in front, but his try was controversially ruled out for an apparent forward pass.
And they had to survive a late onslaught from Irish deep into overtime as the ball stayed alive.
London Irish player coach Mike Catt: "I thought we did enough to deserve to win it, but unfortunately they crept back and got the valuable bonus point that they desperately needed.
"To come and beat the Ospreys who are a top team with a lot of international players is a huge plus for us.
"We took the game to them...but unfortunately it was not enough."
Ospreys try-scorer Nikki Walker: "They are a good side and we knew they were going to come out and play.
"We were caught sleeping in the first half, but we went out there and performed better in the second half.
"London Irish are a dangerous side, but the boys managed to dig in and get there in the end."
London Irish: Hewat, Ojo, Seveali'i, Mapusua, Tagicakibau, Geraghty, Hodgson, Dermody, Paice, Rautenbach, Hudson, Casey, Thorpe, S. Armitage, Hala'ufia.
Replacements: Catt for Geraghty (60), Richards for Hodgson (74), Buckland for Paice (74), Lea'aetoa for Rautenbach (74), Roche for Hudson (57).
Not Used: Danaher, Bailey.
Ospreys: Vaughton, Walker, Bowe, Henson, Williams, Hook, Nutbrown, James, Bennett, A. Jones, Gough, Bateman, Smith, Holah, Tiatia.
Replacements: A. Bishop for Vaughton (40), Hibbard for Bennett (56), A. Jones for Bateman (52), R. Jones for Smith (52).
Not Used: Mitchell, Webb, Biggar.
Ref: Andrew Small (RFU).