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You have done all the caching tricks in the book on the server side: memcache, apc, database cache and so on and squeezed every millisecond out of it, now your site is as fast as it will ever get. Well guess again !
Too often people forget that what you are effectively caching and creating with those technologies is the HTML part of the user response time, now if they are done correctly then HTML is 10 - 20% of your users response time, so there is room for a whole lot of improvements on those other 80 - 90%.
After having attended this talk you will not only have learned to make your sites faster for your long term users but also people coming for the first time as well as people on slower connections.