Audiences need to know right up front why they are going to sit and listen to you. Define the overarching question of the talk very early. You will have a chance to redefine the question in more detail as the talk proceeds, but get it out in a simple way early in the talk.
One technique I use is the "set up" slide. This may be the first slide in a presentation that established the problem and sets up a tension that will be resolved in the talk.
One example is shown below. Herceptin is an effective therapeutic for breast tumors that overexpress the Her2 protein. However most Her2 positive tumors are quite heterogeneous, with the criteria for using Herceptin being as low as 10% of the cells over-expressing the protein. Core A and B below are from the same tumor but illustrate that different parts of the tumor have radically different Her2 expression profiles. This leads to a bit of a paradox as to why Herceptin is effective in these tumors.
This can be the first slide in a presentation. It sets up the overarching question. People know why they are sitting there and what they will learn. The speaker will have a chance later in the talk to define the issue more precisely.
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