Severe cutaneous and neurologic toxicity in melanoma patients during vemurafenib administration following anti-PD-1 therapy.

Immune checkpoint inhibitors such as ipilimumab and targeted BRAF inhibitors have dramatically altered the landscape of melanoma therapeutics over the past few years. Agents targeting the programmed cell death-1/ligand (PD-1/PD-L1) axis are now being developed and appear to be highly active clinically with favorable toxicity profiles. We report two patients with BRAF V600E mutant melanoma who were treated with anti-PD-1 agents as first-line therapy without significant toxicity, followed by vemurafenib at disease progression. Both patients developed severe hypersensitivity drug eruptions with multi-organ injury early in their BRAF inhibitor treatment course. One patient subsequently developed acute inflammatory demyelinating polyneuropathy (AIDP) and the other developed anaphylaxis upon low-dose vemurafenib rechallenge. Further investigation of the immune response during combination or sequences of melanoma therapeutics is warranted. Furthermore, clinicians should maintain a high index of suspicion for these toxicities when vemurafenib is administered following an anti-PD-1 agent.

Does swarming cause honey bees to update their solar ephemerides?

Spatial orientation in the social insects offers several examples of specialized learning mechanisms that underlie complex learning tasks. Here we study one of these systems: the processes by which honey bees update, or fail to update, their memories of the sun's daily pattern of movement (the solar ephemeris function) in relation to the landscape. Specifically, we ask whether bees that have initially learned the solar ephemeris function relative to a conspicuous treeline at their natal site can later realign the ephemeris to a differently oriented treeline. We first confirm and clarify an earlier finding that bees transplanted passively (by being carried) do not re-learn the solar ephemeris in relation to the new treeline. When they cannot detect the sun directly, as on overcast days, these transplanted bees use a solar ephemeris function appropriate for their natal site, despite days or weeks of experience at the new site. We then ask whether bees put through a swarming process as they are transplanted are induced to re-learn the solar ephemeris function at the new site, as swarming is a natural process wherein bees transplant themselves. Most of the swarmed bees failed to re-learn, even though they did extensive learning flights (in comparison with those of non-swarmed controls) as they first emerged from the hive at the new site. We hypothesize that the bees' representation of the solar ephemeris function is stored in an encapsulated cognitive module in which the ephemeris is inextricably linked to the reference landscape in which it was learned.