We propose that status influences individuals' use of dominant versus submissive laughter, and that individuals are conferred status based on the way they laugh. In Study 1, naturally occurring laughter was observed while low- and high-status individuals teased one another. The use of dominant and submissive laughter corresponded to hierarchical variables: High-status individuals and teasers displayed more dominant, disinhibited laughs, whereas low-status individuals and targets of teases displayed more submissive, inhibited laughs. Further, low-status individuals were more likely to vary the form of their laughter between contexts than high-status individuals. Study 2 demonstrated that laughter influences perceptions of status by naïve observers. Individuals who laughed dominantly were afforded higher status than individuals who laughed submissively, regardless of their actual status. Moreover, low-status laughers were perceived to be significantly higher in status, and to have as much status as high-status laughers, when laughing dominantly versus submissively. Finally, exploratory analyses suggest that the positive emotional reactions of observers of laughter can help explain the link between laugh type and status perceptions.

PURPOSE: AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory hematologic malignancies. PATIENTS AND METHODS: In the monotherapy cohort (n = 61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, during a 3-week cycle. In the combination cohort (n = 17), patients with acute myeloid leukemia and myelodysplastic syndrome received escalating doses of AZD5991 and venetoclax during either a 3- or 4-week cycle. Primary objectives were safety and maximum tolerated dose; secondary objectives included plasma pharmacokinetics and antitumor activity. RESULTS: The most common (≥30%) adverse events were diarrhea (59.0%), nausea (55.1%), and vomiting (47.4%). Four deaths occurred because of adverse events: cardiac arrest, sepsis, tumor lysis syndrome, and acute respiratory failure; only tumor lysis syndrome was related to AZD5991. Dose-limiting toxicities occurred in five patients. Three patients with myelodysplastic syndrome achieved an objective response: one marrow complete remission without hematologic improvement, one partial remission with AZD5991 monotherapy, and one marrow complete remission with AZD5991 + venetoclax. Asymptomatic elevations of troponin I or T were observed in eight (10.3%) patients. Post hoc retrospective analysis revealed elevated troponin T in 14/31 patients before any AZD5991 dose and in 54/65 patients after any AZD5991 dose at or after Cycle 1. No associations were found between elevated troponin and cardiovascular risk factors. CONCLUSIONS: Treatment with AZD5991 was associated with high incidence of laboratory troponin elevation and a low overall response rate.