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The process of tumorigenesis leaves a series of indelible genetic changes in tumor cells, that when expressed, have the potential to be tumor-specific immune targets. Neoantigen vaccines that capitalize on this potential immunogenicity have shown efficacy in preclinical models and have now entered clinical trials. Here we discuss the status of personalized neoantigen vaccines and the current major challenges to this nascent field. In particular, we focus on the types of antigens that can be targeted by vaccination and on the role that preexisting immunosuppression, and in particular T-cell exhaustion, will play in the development of effective cancer vaccines.

To determine longitudinal predictors of incident and persistent fear of falling (FOF) in older women.Longitudinal study.Clinical research center based at a university hospital.One thousand two hundred eighty-two community-dwelling women aged 70 to 85.FOF at baseline and after 3 years of follow-up; a range of baseline demographic and clinical variables, including mobility, balance, and depression.FOF was present in 418 subjects (33%) at baseline, developed in 30% of women who had been free of the symptom at baseline, and was reported by a total of 46% of the sample after 3 years of follow-up. In cross-sectional multivariable analysis, baseline FOF was independently associated with a range of variables, including living alone, obesity, cognitive impairment, depression, and impairments in balance and mobility. Baseline predictors of FOF that persisted after 3 years were similar, whereas obesity and slower timed up and go test scores predicted new-onset FOF.FOF in older women is a common and persistent complaint that is caused mainly by impairments of balance and mobility. A range of social, psychological, and physical risk factors for disability are associated with persistence of FOF. These results imply that early intervention may be important for the prevention of persistent FOF.