Systemic inflammatory biology was assessed by circulating levels of CRP. Blood spot samples obtained during study years 2, 3, and 4 were analyzed using a high-sensitivity enzyme immunoassay [66], and longitudinal observations on each participant were analyzed using a mixed effect linear model (SAS PROC MIXED) in a Year (2, 3, and 4, treated as a repeated measure) × Loneliness (high versus low) factorial design. Aberrantly high CRP values were identified by standard outlier detection algorithms (SAS PROC UNIVARIATE) and excluded from analysis because they were likely to reflect the effect of acute infection rather than chronic inflammation.