Predicting anti-cancer drug combination responses with a temporal cell state network model.

Cancer chemotherapy combines multiple drugs, but predicting the effects of drug combinations on cancer cell proliferation remains challenging, even for simple in vitro systems. We hypothesized that by combining knowledge of single drug dose responses and cell state transition network dynamics, we could predict how a population of cancer cells will respond to drug combinations. We tested this hypothesis here using three targeted inhibitors of different cell cycle states in two different cell lines in vitro. We formulated a Markov model to capture temporal cell state transitions between different cell cycle phases, with single drug data constraining how drug doses affect transition rates. This model was able to predict the landscape of all three different pairwise drug combinations across all dose ranges for both cell lines with no additional data. While further application to different cell lines, more drugs, additional cell state networks, and more complex co-culture or in vivo systems remain, this work demonstrates how currently available or attainable information could be sufficient for prediction of drug combination response for single cell lines in vitro.

Early and surgical menopause associated with higher Framingham Risk Scores for cardiovascular disease in the Canadian Longitudinal Study on Aging.

OBJECTIVE: In women, the risk of cardiovascular disease (CVD) is higher in the postmenopausal period. The effect that menopausal type, natural versus surgical, or the age at natural menopause has on CVD needs further investigation. To this end, we assessed the association between menopausal type and timing and the 10-year office-based Framingham Risk Score (FRS) in women from the Canadian Longitudinal Study on Aging. METHODS: We included women aged 45 to 85 years from the Canadian Longitudinal Study on Aging Comprehensive cohort of seven Canadian provinces who were menopausal at the time of recruitment and had no prior CVD. Poisson regressions were used to evaluate the association between menopausal characteristics and the FRS. Natural menopause was defined as the cessation of menstrual periods for at least 1 year in women with no history of hysterectomy. Surgical menopause was defined as hysterectomy with or without oophorectomy prior to natural menopause. As main covariates, we examined age, education, province of residency, and hormone therapy. RESULTS: A total of 10,090 women (8,200 natural menopausal and 1,890 surgical menopausal) were eligible for the study. In the multivariable model, surgical menopause was associated with a higher mean FRS compared with natural menopause (CVD risk 12.4% vs 10.8%, P < 0.001). Compared with women with age at natural menopause from 50 to 54 years (CVD risk 10.2%), natural menopause before age 40, 40 to 44, or 45 to 49 had a higher CVD risk (12.2%, 11.4%, and 10.6%, respectively, P < 0.001). CONCLUSIONS: Our study supports an association between menopausal type and timing on CVD risk prediction and highlights the need to be judicious about surgical menopause. Preventative interventions for CVD should be considered in surgical menopausal women and women with an age at natural menopause less than 45 years.

Video Summary:http://links.lww.com/MENO/A701 .

How are important life events disclosed on facebook? Relationships with likelihood of sharing and privacy.

This study examined an aspect of Facebook disclosure that has as yet gone unexplored: whether a user prefers to share information directly, for example, through status updates, or indirectly, via photos with no caption or relationship status changes without context or explanation. The focus was on the sharing of important positive and negative life events related to romantic relationships, health, and work/school in relation to likelihood of sharing this type of information on Facebook and general attitudes toward privacy. An online survey of 599 adult Facebook users found that when positive life events were shared, users preferred to do so indirectly, whereas negative life events were more likely to be disclosed directly. Privacy shared little association with how information was shared. Implications for understanding the finer nuances of how news is shared on Facebook are discussed.