The site of breast cancer metastases dictates their clonal composition and reversible transcriptomic profile.

Intratumoral heterogeneity is a driver of breast cancer progression, but the nature of the clonal interactive network involved in this process remains unclear. Here, we optimized the use of optical barcoding to visualize and characterize 31 cancer subclones in vivo. By mapping the clonal composition of thousands of metastases in two clinically relevant sites, the lungs and liver, we found that metastases were highly polyclonal in lungs but not in the liver. Furthermore, the transcriptome of the subclones varied according to their metastatic niche. We also identified a reversible niche-driven signature that was conserved in lung and liver metastases collected during patient autopsies. Among this signature, we found that the tumor necrosis factor-α pathway was up-regulated in lung compared to liver metastases, and inhibition of this pathway affected metastasis diversity. These results highlight that the cellular and molecular heterogeneity observed in metastases is largely dictated by the tumor microenvironment.

The link between intravenous multiple pump flow errors and infusion system mechanical compliance.

IV drug delivery in intensive care often takes the form of simultaneous multiple infusions from separate infusion devices via either shared or individual fluid pathways. Because of the potency of the drugs administered and the acuity of the patients, accurate drug delivery is required. Instances of unexpected and unacceptable accuracy degradation have been reported when the equilibrium of the infusion system is disturbed. We describe a mathematical model of a simple infusion system used to investigate and verify results reported from a simple experimental multiple pump fault scenario. The results suggest that flow degradation is attributable to small changes in infusion system extracorporeal volume, referred to as "compliance." The model may, by expansion, be used to determine the nature of fluid flow within other multiple pump systems, be applied to the design of future IV systems, and explain the need for small-volume infusion systems with small mechanical compliance.