Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions.

The oral Bruton's tyrosine kinase inhibitor, ibrutinib, has recently demonstrated high efficiency in patients with relapsed B-cell malignancies. Occurrence of bleeding events has been reported in a subgroup of ibrutinib-treated patients. We demonstrate that ibrutinib selectively inhibits platelet signaling and functions downstream of the collagen receptor glycoprotein VI and strongly affects firm platelet adhesion on von Willebrand factor (VWF) under arterial flow. A longitudinal study of 14 patients indicated a correlation between occurrence of bleeding events and decreased platelet aggregation in response to collagen in platelet-rich plasma and firm adhesion on VWF under arterial flow. The addition of 50% untreated platelets was sufficient to efficiently reverse the effects of ibrutinib, and platelet functions recovered after treatment interruption as physiological platelet renewal occurred. These data have important clinical implications and provide a basis for hemostasis management during ibrutinib treatment.

Perceptual-motor constraints on decision making: the case of the manual search behavior for hidden objects in toddlers.

In the C-not-B task, 2.5-year-old children tend to look for an object in a location to which the hiding agent moved his hand (C) after moving an object from A to B. In three experiments, the authors investigated the nature of the constraints underlying toddlers' performance in this task. In Experiment 1, 2.5-year-olds were tested in a new version of the C-not-B task to investigate whether reaching with a detour leads to inhibition of direct visuomotor activation. The findings show that toddlers succeed more in the C-not-B task when a transparent barrier obstructs the path of the reaching movement. The results of Experiment 2 indicate that the successful performance of the children with a barrier cannot merely be the consequence of the longer duration of arm movements. In Experiment 3, pointing responses generated more toddlers' success in the C-not-B task than did reaching responses. These experiments suggest that decision-making processes and judgments in toddlers are affected by constraints intrinsic to the perceptual-motor system.

Benefits of napping and an extended duration of recovery sleep on alertness and immune cells after acute sleep restriction.

Understanding the interactions between sleep and the immune system may offer insight into why short sleep duration has been linked to negative health outcomes. We, therefore, investigated the effects of napping and extended recovery sleep after sleep restriction on the immune and inflammatory systems and sleepiness. After a baseline night, healthy young men slept for a 2-h night followed by either a standard 8-h recovery night (n=12), a 30-min nap (at 1 p.m.) in addition to an 8-h recovery night (n=10), or a 10-h extended recovery night (n=9). A control group slept 3 consecutive 8-h nights (n=9). Subjects underwent continuous electroencephalogram polysomnography and blood was sampled every day at 7 a.m. Leukocytes, inflammatory and atherogenesis biomarkers (high-sensitivity C-reactive protein, interleukin-8, myeloperoxidase, fibrinogen and apolipoproteins ApoB/ApoA), sleep patterns and sleepiness were investigated. All parameters remained unchanged in the control group. After sleep restriction, leukocyte and - among leukocyte subsets - neutrophil counts were increased, an effect that persisted after the 8-h recovery sleep, but, in subjects who had a nap or a 10-h recovery sleep, these values returned nearly to baseline. Inflammatory and atherogenesis biomarkers were unchanged except for higher myeloperoxidase levels after sleep restriction. The increased sleepiness after sleep restriction was reversed better in the nap and extended sleep recovery conditions. Saliva cortisol decreased immediately after the nap. Our results indicate that additional recovery sleep after sleep restriction provided by a midday nap prior to recovery sleep or a sleep extended night can improve alertness and return leukocyte counts to baseline values.

Undetected changes in visible stimuli influence subsequent decisions.

Change blindness-our inability to detect changes in a stimulus-occurs even when the change takes place gradually, without any disruption [Simons, D. J., Franconeri, S. L., & Reimer, R. L. (2000). Change blindness in the absence of a visual disruption. Perception, 29(10), 1143-1154]. Such gradual changes are more difficult to detect than changes that involve a disruption. Using this method, David et al. [David, E., Laloyaux, C., Devue, C., & Cleeremans, A. (in press). Change blindness to gradual changes in facial expressions. Psychologica Belgica] recently showed substantial blindness to changes that involve facial expressions of emotion. In this experiment, we show that people who failed to detect any change in the displays were (1) nevertheless influenced by the changing information in subsequent recognition decisions about which facial expression they had seen, and (2) that their confidence in their decisions was lower after exposure to changing vs. static displays. The findings therefore support the notion that undetected changes that occur in highly salient stimuli may be causally efficacious and influence subsequent behavior. Implications concerning the nature of the representations associated with undetected changes are discussed.