Parasitic behavior in competing chemically fueled reaction cycles.

Non-equilibrium, fuel-driven reaction cycles serve as model systems of the intricate reaction networks of life. Rich and dynamic behavior is observed when reaction cycles regulate assembly processes, such as phase separation. However, it remains unclear how the interplay between multiple reaction cycles affects the success of emergent assemblies. To tackle this question, we created a library of molecules that compete for a common fuel that transiently activates products. Often, the competition for fuel implies that a competitor decreases the lifetime of these products. However, in cases where the transient competitor product can phase-separate, such a competitor can increase the survival time of one product. Moreover, in the presence of oscillatory fueling, the same mechanism reduces variations in the product concentration while the concentration variations of the competitor product are enhanced. Like a parasite, the product benefits from the protection of the host against deactivation and increases its robustness against fuel variations at the expense of the robustness of the host. Such a parasitic behavior in multiple fuel-driven reaction cycles represents a lifelike trait, paving the way for the bottom-up design of synthetic life.

Learning the distribution of single-cell chromosome conformations in bacteria reveals emergent order across genomic scales.

The order and variability of bacterial chromosome organization, contained within the distribution of chromosome conformations, are unclear. Here, we develop a fully data-driven maximum entropy approach to extract single-cell 3D chromosome conformations from Hi-C experiments on the model organism Caulobacter crescentus. The predictive power of our model is validated by independent experiments. We find that on large genomic scales, organizational features are predominantly present along the long cell axis: chromosomal loci exhibit striking long-ranged two-point axial correlations, indicating emergent order. This organization is associated with large genomic clusters we term Super Domains (SuDs), whose existence we support with super-resolution microscopy. On smaller genomic scales, our model reveals chromosome extensions that correlate with transcriptional and loop extrusion activity. Finally, we quantify the information contained in chromosome organization that may guide cellular processes. Our approach can be extended to other species, providing a general strategy to resolve variability in single-cell chromosomal organization.

Echocardiography in extracorporeal life support: A key player in procedural guidance, tailoring and monitoring.

Extracorporeal life support (ECLS) is a mainstay of current practice in severe respiratory, circulatory or cardiac failure refractory to conventional management. The inherent complexity of different ECLS modes and their influence on the native pulmonary and cardiovascular system require patient-specific tailoring to optimize outcome. Echocardiography plays a key role throughout the ECLS care, including patient selection, adequate placement of cannulas, monitoring, weaning and follow-up after decannulation. For this purpose, echocardiographers require specific ECLS-related knowledge and skills, which are outlined here.

Implementation of medication reviews in community pharmacies and their effect on potentially inappropriate drug use in elderly patients.

BACKGROUND: In 2008 recommendations were launched to prevent medication-related hospital admissions in the Netherlands. Elderly patients using several drugs on a chronic basis were among the target group. Pharmacy-led medication reviews (MRs) were identified as having potential for improving patient safety. OBJECTIVE: This observational study evaluated the implementation success rate of performing all five steps of a complete MR for patients and changes in the presence of nine issues of potentially inappropriate medication (PIM) use. This change was compared between patients with a complete MR (intervention group, IG) and a reference group (RG) who attended the same pharmacy; all patients were eligible for MR, but only selected patients formed the IG. SETTING: Dutch community pharmacy. METHOD: After appropriate training, the rate of IG with complete MRs was measured by pharmacists registering the various MR steps in the MR tool. Patients were eligible for a MR if aged ≥ 65 years with ≥ 5 drugs being used chronically. MAIN OUTCOME MEASURES: The success rate of implementing MRs with five steps completed; the presence of nine PIMs for both study groups. RESULTS: In pharmacies with specifically trained pharmacists, 63 % of selected patients received a complete MR. This was 12 % higher than in pharmacies without trained pharmacists. PIMs reported at study start declined in the IG and at study end had decreased by an average of 19 % (with a range between 34 and 100 % per PIM); this decrease did not significantly differ from the RG. CONCLUSION: Additional efforts are needed to improve the implementation of pharmacist-led MRs in order to realize its full potential in general practice, and for a substantial decrease of PIMs to occur in susceptible patients. These efforts should focus on training courses and additional support using computerized systems to share information with GPs and to register MR activities, together with sufficient financial reimbursement.