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Given two random variables $X$ and $Y$, an operational approach is undertaken to quantify the ``leakage of information from $X$ to $Y$. The resulting measure $mathcal{L}(X !! to !! Y)$ is called emph{maximal leakage}, and is defined as the multiplicative increase, upon observing $Y$, of the probability of correctly guessing a randomized function of $X$, maximized over all such randomized functions. A closed-form expression for $mathcal{L}(X !! to !! Y)$ is given for discrete $X$ and $Y$, and it is subsequently generalized to handle a large class of random variables. The resulting properties are shown to be consistent with an axiomatic view of a leakage measure, and the definition is shown to be robust to variations in the setup. Moreover, a variant of the Shannon cipher system is studied, in which performance of an encryption scheme is measured using maximal leakage. A single-letter characterization of the optimal limit of (normalized) maximal leakage is derived and asymptotically-optimal encryption schemes are demonstrated. Furthermore, the sample complexity of estimating maximal leakage from data is characterized up to subpolynomial factors. Finally, the emph{guessing} framework used to define maximal leakage is used to give operational interpretations of commonly used leakage measures, such as Shannon capacity, maximal correlation, and local differential privacy.
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