Placebo-controlled trials are the gold standard of evaluating treatment efficacy in clinical research. Neuromodulation is emerging as an important treatment pathway for many neuropsychiatric conditions, and placebo control arms of these trials require careful design with unique considerations (e.g., sham devices that mimic active stimulation, blinding effectiveness). Inherent to placebo-controlled trials are ethical concerns, such as deception, and potential harm of not receiving the active treatment. In this article, we outline important ethical considerations of placebo-controlled trials across neuromodulation approaches and provide recommendations on how ethical principles can be adhered to going forward. We specifically address issues of autonomy and respect for persons, beneficence, and justice. Within the context of this ethical framework, we also discuss factors influencing placebo effects in neuromodulation, the importance of adequate blinding, and alternative trial designs that could be considered.

Suppose that advanced civilizations, separated by a cosmological distance and time, wish to maximize their access to cosmic resources by rapidly expanding into the universe. How does the presence of one limit the expansionistic ambitions of another, and what sort of boundary forms between their expanding domains? We describe a general scenario for any expansion speed, separation distance and time. We then specialize to a question of particular interest: What are the future prospects for a young and ambitious civilization if they can observe the presence of another at a cosmological distance? We treat cases involving the observation of one or two expanding domains. In the single-observation case, we find that almost any plausible detection will limit one's future cosmic expansion to some extent. Also, practical technological limits to expansion speed (well below the speed of light) play an interesting role. If a domain is visible at the time one embarks on cosmic expansion, higher practical limits to expansion speed are beneficial only up to a certain point. Beyond this point, a higher speed limit means that gains in the ability to expand are more than offset by the first-mover advantage of the observed domain. In the case of two visible domains, it is possible to be ‘trapped’ by them if the practical speed limit is high enough and their angular separation in the sky is large enough, i.e. one's expansion in any direction will terminate at a boundary with the two visible civilizations. Detection at an extreme cosmological distance has surprisingly little mitigating effect on our conclusions.

If advanced civilizations appear in the universe with an ability and desire to expand, the entire universe can become saturated with life on a short timescale, even if such expanders appear rarely. Our presence in an apparently untouched Milky Way thus constrains the appearance rate of galaxy-spanning Kardashev type III (K3) civilizations, if it is assumed that some fraction of K3 civilizations will continue their expansion at intergalactic distances. We use this constraint to estimate the appearance rate of K3 civilizations for 81 cosmological scenarios by specifying the extent to which humanity is a statistical outlier. We find that in nearly all plausible scenarios, the distance to the nearest visible K3 is cosmological. In searches for K3 galaxies where the observable range is limited, we also find that the most likely detections tend to be expanding civilizations who have entered the observable range from farther away. An observation of K3 clusters is thus more likely than isolated K3 galaxies.