ABSTRACT High-throughput screening, in which large numbers of compounds are traditionally studied one-at-a-time in multiwell plates against specific targets, is widely used across many areas of the biological sciences, including drug discovery. To improve the effectiveness of these screens, we propose a new class of supersaturated designs that guide the construction of pools of compounds in each well. Because the size of the pools is typically limited by the particular application, the new designs accommodate this…

Introduction Critically ill patients commonly develop acquired neutrophil dysfunction, which increases susceptibility to intensive care unit-acquired infection (ICU-AI). This study aimed to assess whether interferon gamma (IFN-γ) can restore function in dysfunctional neutrophils from critically ill patients and to uncover potential underlying mechanisms. Methods This was an observational cohort study. Neutrophils were isolated from whole blood donated by critically ill patients (n=31) in four separate teaching hos…

Abstract Maternal age can influence reproductive success and offspring fitness, but the timing, magnitude and direction of those impacts are not well understood. Evolutionary theory predicts that selection on fertility senescence is stronger than maternal effect senescence, and therefore, the rate of maternal effect senescence will be faster than fertility senescence. We used a 36‐year study of northern elephant seals ( Mirounga angustirostris ) to investigate reproductive senescence. Our dataset included 103,746 …

High-throughput screening, in which multiwell plates are used to test large numbers of compounds against specific targets, is widely used across many areas of the biological sciences and most prominently in drug discovery. We propose a statistically principled approach to these screening experiments, using the machinery of supersaturated designs and the Lasso. To accommodate limitations on the number of biological entities that can be applied to a single microplate well, we present a new class of row-constrained s…

Objectives The use of immunotherapies in the treatment of melanoma has significantly improved the survival of patients with advanced disease. Historically, histamine has been implicated in the pathogenesis of several cancers. Cimetidine does play a role in modulating the immune system and was advocated as an immunotherapeutic agent since the 1970s. Cimetidine has been showing promise in conjunction with standard care in many cancers in vitro and in vivo. However, its effects in melanoma have not been explored yet.…