Operationalizing and selecting outcome measures for the HEALing Communities Study.

BACKGROUND: The Helping to End Addiction Long-termSM (HEALing) Communities Study (HCS) is a multisite, parallel-group, cluster randomized wait-list controlled trial evaluating the impact of the Communities That HEAL intervention to reduce opioid overdose deaths and associated adverse outcomes. This paper presents the approach used to define and align administrative data across the four research sites to measure key study outcomes. METHODS: Priority was given to using administrative data and established data collection infrastructure to ensure reliable, timely, and sustainable measures and to harmonize study outcomes across the HCS sites. RESULTS: The research teams established multiple data use agreements and developed technical specifications for more than 80 study measures. The primary outcome, number of opioid overdose deaths, will be measured from death certificate data. Three secondary outcome measures will support hypothesis testing for specific evidence-based practices known to decrease opioid overdose deaths: (1) number of naloxone units distributed in HCS communities; (2) number of unique HCS residents receiving Food and Drug Administration-approved buprenorphine products for treatment of opioid use disorder; and (3) number of HCS residents with new incidents of high-risk opioid prescribing. CONCLUSIONS: The HCS has already made an impact on existing data capacity in the four states. In addition to providing data needed to measure study outcomes, the HCS will provide methodology and tools to facilitate data-driven responses to the opioid epidemic, and establish a central repository for community-level longitudinal data to help researchers and public health practitioners study and understand different aspects of the Communities That HEAL framework.

The Modern Synthesis in the Light of Microbial Genomics.

We review the theoretical implications of findings in genomics for evolutionary biology since the Modern Synthesis. We examine the ways in which microbial genomics has influenced our understanding of the last universal common ancestor, the tree of life, species, lineages, and evolutionary transitions. We conclude by advocating a piecemeal toolkit approach to evolutionary biology, in lieu of any grand unified theory updated to include microbial genomics.

Eukaryogenesis, how special really?

Eukaryogenesis is widely viewed as an improbable evolutionary transition uniquely affecting the evolution of life on this planet. However, scientific and popular rhetoric extolling this event as a singularity lacks rigorous evidential and statistical support. Here, we question several of the usual claims about the specialness of eukaryogenesis, focusing on both eukaryogenesis as a process and its outcome, the eukaryotic cell. We argue in favor of four ideas. First, the criteria by which we judge eukaryogenesis to have required a genuinely unlikely series of events 2 billion years in the making are being eroded by discoveries that fill in the gaps of the prokaryote:eukaryote "discontinuity." Second, eukaryogenesis confronts evolutionary theory in ways not different from other evolutionary transitions in individuality; parallel systems can be found at several hierarchical levels. Third, identifying which of several complex cellular features confer on eukaryotes a putative richer evolutionary potential remains an area of speculation: various keys to success have been proposed and rejected over the five-decade history of research in this area. Fourth, and perhaps most importantly, it is difficult and may be impossible to eliminate eukaryocentric bias from the measures by which eukaryotes as a whole are judged to have achieved greater success than prokaryotes as a whole. Overall, we question whether premises of existing theories about the uniqueness of eukaryogenesis and the greater evolutionary potential of eukaryotes have been objectively formulated and whether, despite widespread acceptance that eukaryogenesis was "special," any such notion has more than rhetorical value.