The dynamics of proactive and reactive cognitive control processes in the human brain.

In this study, we leveraged the high temporal resolution of EEG to examine the neural mechanisms underlying the flexible regulation of cognitive control that unfolds over different timescales. We measured behavioral and neural effects of color-word incongruency, as different groups of participants performed three different versions of color-word Stroop tasks in which the relative timing of the color and word features varied from trial to trial. For this purpose, we used a standard Stroop color identification task with equal congruent-to-incongruent proportions (50%/50%), along with two versions of the "Reverse Stroop" word identification tasks, for which we manipulated the incongruency proportion (50%/50% and 80%/20%). Two canonical ERP markers of neural processing of stimulus incongruency, the frontocentral negative polarity incongruency wave (NINC) and the late positive component (LPC), were evoked across the various conditions. Results indicated that color-word incongruency interacted with the relative feature timing, producing greater neural and behavioral effects when the task-irrelevant stimulus preceded the target, but still significant effects when it followed. Additionally, both behavioral and neural incongruency effects were reduced by nearly half in the word identification task (Reverse Stroop 50/50) relative to the color identification task (Stroop 50/50), with these effects essentially fully recovering when incongruent trials appeared only infrequently (Reverse Stroop 80/20). Across the conditions, NINC amplitudes closely paralleled RTs, indicating this component is sensitive to the overall level of stimulus conflict. In contrast, LPC amplitudes were largest with infrequent incongruent trials, suggesting a possible readjustment role when proactive control is reduced. These findings thus unveil distinct control mechanisms that unfold over time in response to conflicting stimulus input under different contexts.

Population pharmacokinetics of milrinone in neonates with hypoplastic left heart syndrome undergoing stage I reconstruction.

We performed a blinded, randomized pharmacokinetic study of milrinone in 16 neonates with hypoplastic left heart undergoing stage I reconstruction to determine the impact of cardiopulmonary bypass and modified ultrafiltration on drug disposition and to define the drug exposure during a continuous IV infusion of drug postoperatively. Neonates received an initial dose of either a 100 or 250 microg/kg of milrinone into the cardiopulmonary bypass circuit at the start of rewarming. Postoperatively, milrinone was infused to clinical needs. A mixed-effect modeling approach was used to characterize milrinone pharmacokinetics during cardiopulmonary bypass, modified ultrafiltration, and postoperatively using the NONMEM algorithm. All patients in this study demonstrated a modified ultrafiltration concentrating effect that occurred despite a modified ultrafiltration drug clearance of 3.3 mL x kg(-1) x min(-1). The infants in this study demonstrated an impaired renal clearance during the immediate postoperative period. A constant infusion of 0.5 microg x kg(-1) x min(-1) resulted in drug accumulation during the initial 12 h of drug administration. Postoperatively, milrinone clearance was significantly impaired (0.4 mL x kg(-1) x min(-1)), improved by the 12th postoperative hour, and approached steady-state clearance (2.6 mL x kg(-1) x min(-1)) by postoperative day 4. In the postoperative setting of markedly impaired renal function, an infusion rate of 0.2 microg x kg(-1) x min(-1) should be considered.

Drug utilization in the pediatric intensive care unit: monitoring prescribing trends and establishing prioritization of pharmacotherapeutic evaluation of critically ill children.

The primary objective of this study was to characterize the drug exposure for children hospitalized in the authors' institution's pediatric intensive care unit for the year 2002. Secondary objectives included the examination of drug utilization differences among various age criteria and the suitability of the most prevalent resources for pediatric dosing guidance. Many of the most commonly prescribed agents in the pediatric intensive care unit fall into the broad categories of pain management/sedation and anti-infectives. Based on the generally narrow windows afforded by each of these drug classes, it is obvious that more, well-defined investigations in critically ill children are warranted. The existing dosing guidance for many of these agents is neither generalizable nor sufficient to accommodate the diversity in pediatric intensive care unit patients, and the current drug monographs fall short of any practical dosing information.