Studies performed in absence of gravitational constraint show that a living system is unable to choose between two different phenotypes, thus leading cells to segregate into different, alternative stable states. This finding demonstrates that the genotype does not determine by itself the phenotype but requires additional, physical constraints to finalize cell differentiation. Constraints belong to two classes holonomic (independent of the system’s dynamical states, as being established by the space-time geometry of the field) and non-holonomic (modified during those biological processes to which they contribute in shaping). This latter kind of “constraints”, in which dynamics works on the constraint to recreate them, have emerged as critical determinants of self-organizing systems, by manifesting a “closure of constraints.” Overall, the constraints act by harnessing the “randomness” represented by the simultaneous presence of equiprobable events restraining the system within one attractor. These results cast doubt on the mainstream scientific concept and call for a better understanding of causation in cell biology. © 2020 WILEY Periodicals, Inc.Efforts to decipher the processes underpinning biological systems now have a plethora of approaches from which to choose. Transcriptomics and proteomics provide a global snapshot of the abundance of gene products in a sample, from which researchers can learn a great deal about the inner machinations of a cell. this website However, when attempting to piece together a roadmap of an organism’s metabolism, these strategies illuminate only a portion of the cellular landscape, and the evidence provided is often once- or even twice-removed from the actual players (the metabolites) involved. In this issue of Physiologia Plantarum, Jia et al. (2020) used metabolomic approaches to directly analyse the molecular soup of substrates and products contained in plant cells (known as the metabolome) to unravel the metabolic and physiological differences separating a drought-sensitive and a drought-tolerant species of the ecologically and economically important woody plant, poplar. © 2020 Scandinavian Plant Physiology Society.BACKGROUND Parental drinking and parent alcohol use disorder (AUD) are known predictors of adolescent positive alcohol expectancies, but their link to negative expectancies is unclear. Research suggests that parent drinking may indirectly predict adolescent expectancies through exposure to parental drinking events. However, exposure to parent negative alcohol consequences may be more relevant to adolescents’ expectancies. The present study tested the mediating effect of parent observable negative alcohol consequences in the association between parent AUD and adolescent expectancies. METHODS This study used parent and adolescent data from the Adult and Family Development Project. A total of 581 adolescents reported on their alcohol expectancies across 2 waves of data, and their parents reported on potentially observable alcohol-related negative consequences during the first wave. Past-year and lifetime parent AUD were assessed with diagnostic interviews across 6 waves of data. RESULTS Mothers’ observable consequences mediated the effect of her past-year AUD on adolescent negative expectancies in adolescence, but this effect did not hold at a 1.5-year follow-up. Mothers’ lifetime AUD was the only prospective predictor of later adolescent negative expectancies. No father drinking variables predicted expectancies, and all models were invariant across child biological sex. Finally, older adolescent age prospectively predicted higher positive expectancies, whereas the adolescents’ own drinking predicted lower negative expectancies. CONCLUSIONS These findings, in line with other recent studies, suggest that exposure to mothers’ negative experiences with alcohol may counterintuitively normalize negative alcohol effects. This may paradoxically increase risk for adolescents rather than buffering the effects of a family history of parental AUD. © 2020 by the Research Society on Alcoholism.OBJECTIVES To develop a competency-based, adaptable home visit curricula and clinical framework for family medicine (FM) residents, and to examine resident attitudes, self-efficacy, and skills following implementation. DESIGN Quantitative analysis of resident survey responses and qualitative thematic analysis of written resident reflections. SETTING Urban FM residency program. PARTICIPANTS A total of 43 residents and 20 homebound patients in a home-based primary care program. INTERVENTION A home-based primary care practice and accompanying curriculum for FM residents was developed and implemented to improve learners’ confidence and skills to perform home visits. MEASUREMENTS A 10-question survey with a 4-point Likert scale and open-ended responses. Written resident reflections following home visits. RESULTS Over 3 years, 43 unique respondents completed a total of 79 surveys evaluating attitudes, skills, and barriers to home care. Some residents may have completed the survey more than once at different stages in their training. Overall, 86% are interested in home visits in future practice, and 78% of survey responses indicated an increased likelihood to perform home visits with more training. Learners with two or more home visits reported significantly improved confidence. Themes across all resident reflections included social determinants of health, patient-physician relationship, patient-home assessment, patient autonomy/independence, and physician wellness/attitudes. Residents described how home visits encourage more holistic care to improve outcomes for patients who are homebound. CONCLUSION Our home visit curriculum provided new learning, an enhanced desire to practice home-based primary care, improved learner confidence, and could help residents meet the need of a growing population of adults who are homebound. © 2020 The American Geriatrics Society.OBJECTIVES Older adults are often prescribed potentially inappropriate medications associated with adverse health outcomes and increased health services utilization. Developing Pharmacist-led Research to Educate and Sensitize Community Residents to the Inappropriate Prescriptions Burden in the Elderly (D-PRESCRIBE), a pragmatic randomized clinical trial, demonstrated how a community pharmacist-led evidence-based educational intervention successfully empowered community-dwelling older adults and their physicians to reduce chronic use of inappropriate medications. The objective of this study was to evaluate the cost-effectiveness of the D-PRESCRIBE intervention for discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs). DESIGN Cost-effectiveness analysis. SETTING Canada. PARTICIPANTS Community-dwelling adults aged 65 years and older. MEASUREMENTS Decision analysis combining decision tree and Markov state transition modeling was developed to estimate the cost-effectiveness of D-PRESCRIBE (NSAIDs) compared with usual care from a Canadian healthcare system perspective with a time horizon of 1 year.