A unifying framework for understanding ecological and evolutionary population connectivity

Although the concept of connectivity is ubiquitous in ecology and evolution, its definition is often inconsistent, particularly in interdisciplinary research. In an ecological context, population connectivity refers to the movement of individuals or species across a landscape. It is measured by locating organisms and tracking their occurrence across space and time. In an evolutionary context, connectivity is typically used to describe levels of current and past gene flow, calculated from the degree of genetic similarity between populations. Both connectivity definitions are useful in their specific contexts, but rarely are these two perspectives combined. Different definitions of connectivity could result in misunderstandings across subdisciplines. Here, we unite ecological and evolutionary perspectives into a single unifying framework by advocating for connectivity to be conceptualized as a generational continuum. Within this framework, connectivity can be subdivided into three timescales: (1) within a generation (e.g., movement), (2) across one parent-offspring generation (e.g., dispersal), and (3) across two or more generations (e.g., gene flow), with each timescale determining the relevant context and dictating whether the connectivity has ecological or evolutionary consequences. Applying our framework to real-world connectivity questions can help to identify sampling limitations associated with a particular methodology, further develop research questions and hypotheses, and investigate eco-evolutionary feedback interactions that span the connectivity continuum. We hope this framework will serve as a foundation for conducting and communicating research across subdisciplines, resulting in a more holistic understanding of connectivity in natural systems

Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks

Specific Immunologic Countermeasure Protocol for Deep-Space Exploration Missions

Historically, serious illness of astronauts on orbit is rare, however clinical episodes requiring therapeutic intervention have occurred during International Space Station (ISS) missions at a noteworthy rate (1, 2). Persistent exposure to the space environment exacerbates perturbations to the immune system (3). In support, the NASA “twins” study—an evaluation of a crewmember during a 1-year ISS mission—revealed significant changes between in-flight and non-flight time points in the gene expression patterns of several immune response pathways, DNA methylation patterns of genes that regulate T cell responses, and the signatures of plasma cytokines, to promote during spaceflight decreased cellular responsiveness and increased inflammation (4). Because future deep-space exploration missions will endure for an unprecedented amount of time, with increased magnitude of mission-associated stressors, it is reasonable to expect a higher incidence of morbidities. Previously, we published a comprehensive review of potential countermeasures to obviate the immune “problem” associated with spaceflight. Now, we present a specific and personalized immune countermeasure prescription for prospective astronauts embarking on deep-space voyageGerman National Space Program [50WB1622]; European Space Agency (ESA)'s Topical Team Stress and Immunity - ESA ELIPS 4 program; European Space Agency (ESA)'s Topical Team Stress and Immunity - ESA SciSpacE programOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]