Alemtuzumab is used as part of reduced-intensity and reduced-toxicity transplant conditioning regimens for nonmalignant diseases. Prior studies identified an ideal target concentration range of 0... Show moreAlemtuzumab is used as part of reduced-intensity and reduced-toxicity transplant conditioning regimens for nonmalignant diseases. Prior studies identified an ideal target concentration range of 0.15-0.6 mcg/mL at day 0. However, only 24% of patients fall within this window using standard intermediate dosing. We performed a pilot study of a novel target concentration intervention strategy to target day 0 alemtuzumab concentrations to 0.15-0.6 mcg/mL. Twelve patients received model-informed alemtuzumab dosing of 0.5-0.6 mcg/kg divided over days -14 to -12. Alemtuzumab concentrations were measured, and pharmacokinetic (PK) modeling was performed on day -5 to predict day 0 concentrations. If the day 0 alemtuzumab concentration was predicted to fall below 0.15 mcg/mL, simulations were performed to identify the individual "top-up" dose needed to achieve the target day 0 concentration window. Six (50%) patients achieved day 0 alemtuzumab concentrations between 0.15 and 0.6 mcg/mL (4 received a top-up dose). Five patients had day 0 concentrations above the target window (no top-up doses). One patient had a day 0 concentration below the target range in the presence of anti-alemtuzumab antibodies. A concentration intervention strategy approach to alemtuzumab treatment can successfully target a greater proportion of patients into the ideal therapeutic window. Additional dose-reduction studies are needed to further optimize the initial dosing and achieve target attainment in all patients. Show less
Van Lange, P.A.M.; Manesi, Z.; Meershoek, R.W.J.; Yuan, M.; Dong, M.; Doesum, N.J. van 2018
Acting prosocially can be quite challenging in one of the most salient intergroup contexts in contemporary society: Soccer. When winning is the ultimate goal, balancing self-interest with helping a... Show moreActing prosocially can be quite challenging in one of the most salient intergroup contexts in contemporary society: Soccer. When winning is the ultimate goal, balancing self-interest with helping a fellow player in distress can be a tough decision; yet it happens. To date, we know little about what motivates soccer players to offer such help in the heat of the game. We propose that sex and what is at stake will matter in such prosocial dilemma situations. A pilot study (N = 107) indicated that female players may be more likely to help than male players, but this difference was only observed when the players are close to scoring position rather than far away from the goal (midfield). The main study (N = 366) finds that young soccer players show elevated inclinations to help in low-stakes situations, for example when their team is winning or when the outcome of the game seems pretty much decided. Contrariwise, helping intentions decline in high-stakes situations, for example when one’s own team is losing, when one is close to a scoring position in the offense (rather than at the midfield), or when the outcome of the game is still uncertain. Furthermore, female players show somewhat greater inclinations to help than their male counterparts. The current data point at some differences for male and female soccer players, albeit small in effect size. In contrast, we conclude that especially quick cost-benefit judgments regarding the stakes can play a major role in decisions to help or not to help another player on the soccer field. Show less
