Risk Attenuation and Amplification in the U.S. Opioid Crisis.

The evolution of risk identification and ultimately the public and private responses that have become known collectively as the "opioid crisis" is an important case study in risk management due to the reach and magnitude of its impacts. This article examines a number of "signals" related to opioid risks using the social amplification of risk framework (SARF) to investigate a limited set of public-sector activities and policy responses. We evaluate whether the SARF presents an effective lens to examine the serious shortcomings of risk management of opioid use, which has a history of risk attenuation and, more recently, evidence of risk amplification. Our goal in this article is limited to addressing "goodness of fit" of the SARF as a descriptive tool. We consider whether the SARF effectively reveals important gaps in public risk management responses for the opioid example and other similarly situated societal risk problems. Applying SARF supports that its suggested relationship between risk signals and inappropriate attenuated public response does generate useful insights into regulatory efficacy for examples of public risk management. Similar such conclusions about inappropriate public responses stemming from the amplification factors are less supported because, in this case, the risk is, and continues to be, large. Overall, we find that the SARF's particular focus on the signaling function of risk information performs best as an organizational aid to study historical information rather than as a predictive tool for determining inappropriate risk management responses.

Integrins Have Cell-Type-Specific Roles in the Development of Motor Neuron Connectivity.

Formation of the nervous system requires a complex series of events including proper extension and guidance of neuronal axons and dendrites. Here we investigate the requirement for integrins, a class of transmembrane cell adhesion receptors, in regulating these processes across classes of C. elegans motor neurons. We show α integrin/ina-1 is expressed by both GABAergic and cholinergic motor neurons. Despite this, our analysis of hypomorphic ina-1(gm144) mutants indicates preferential involvement of α integrin/ina-1 in GABAergic commissural development, without obvious involvement in cholinergic commissural development. The defects in GABAergic commissures of ina-1(gm144) mutants included both premature termination and guidance errors and were reversed by expression of wild type ina-1 under control of the native ina-1 promoter. Our results also show that α integrin/ina-1 is important for proper outgrowth and guidance of commissures from both embryonic and post-embryonic born GABAergic motor neurons, indicating an ongoing requirement for integrin through two phases of GABAergic neuron development. Our findings provide insights into neuron-specific roles for integrin that would not be predicted based solely upon expression analysis.