Labeled cells were analysed using the ThermoFisher Cellomics ArrayScan VTI, a high content scanning (vHCS) microscope, using version 6.6.2.0 software. The ArrayScan VTI captures images using an ORCA-ER camera in two channels applicable to the assay. XF-53 filters for 405 and 488 nm were used in automated image analysis to quantify nuclei number, and cleaved lamin A, respectively. The Cellomics toolbox, Compartmental Analysis, used an algorithm to encircle perinuclear staining of cleaved lamin A. The primary object in the Hoechst channel was identified as the nucleus of the cell of which 500 total were counted per well. In channels 2, the perinucleus was identified as a ''circ'', which was 3 pixels outside the primary object, where the algorithm measured pixel intensity above background staining. The ''MEAN_AvgCirIntensity'' for each channel was used for analysis, under the vHCS analysis tool, and exported to Microsoft Excel spreadsheets and GraphPad Prism for further analysis. Figure S1 Active site titrations for caspases -3, -6, 7. The exact active site concentration of each caspase used was determined by titrating the enzymes against the pan-caspase inhibitor zVAD-fmk [27] . (TIF) Figure S2 Km determination for lamin A. A: The indicated concentrations of lamin A protein were digested with 20 nM caspase-6 and samples were analysed with the Mesoscale ELISA system. B: Cleavage rates were determined as the slope of the curves in (A) and plotted against the lamin A concentration to obtain values for Km and kcat through curve fitting using the built-in function of the GraphPad Prism 5.0 software package. (TIF) Quantifying social distancing arising from pandemic influenza Local epidemic curves during the 1918–1919 influenza pandemic were often characterized by multiple epidemic waves. Identifying the underlying cause(s) of such waves may help manage future pandemics. We investigate the hypothesis that these waves were caused by people avoiding potentially infectious contacts—a behaviour termed ‘social distancing’. We estimate the effective disease reproduction number and from it infer the maximum degree of social distancing that occurred during the course of the multiple-wave epidemic in Sydney, Australia. We estimate that, on average across the city, people reduced their infectious contact rate by as much as 38%, and that this was sufficient to explain the multiple waves of this epidemic. The basic reproduction number, R(0), was estimated to be in the range of 1.6–2.0 with a preferred estimate of 1.8, in line with other recent estimates for the 1918–1919 influenza pandemic. The data are also consistent with a high proportion (more than 90%) of the population being initially susceptible to clinical infection, and the proportion of infections that were asymptomatic (if this occurs) being no higher than approximately 9%. The observed clinical attack rate of 36.6% was substantially lower than the 59% expected based on the estimated value of R(0), implying that approximately 22% of the population were spared from clinical infection. This reduction in the clinical attack rate translates to an estimated 260 per 100 000 lives having been saved, and suggests that social distancing interventions could play a major role in mitigating the public health impact of future influenza pandemics. Infectious diseases are commonly controlled by minimizing contact between infectious and susceptible individuals. Personal measures to reduce potentially infectious contacts are sometimes referred to as 'social distancing'. It has been suggested that policies encouraging social distancing may be effective against pandemic influenza (Bell et al. 2006; Glass et al. 2006) . It is unclear, however, whether individuals can reduce their infectious contact rate to a level low enough to return a worthwhile public health outcome. An examination of levels of social distancing actually achieved during previous epidemics can provide useful guidance as to the effectiveness of social distancing interventions during future influenza pandemics.