We assessed the effects of felbamate (FBM) on the disposition of valpr oic acid (VPA) in healthy volunteer men. Eighteen subjects received sodium VPA, 400 mg/day for 21 days. Plasma and urine samples were taken on day 7 to document the steady-state disposition of VPA alone. From day 8 to day 21, subjects received placebo or FBM at the following doses (mg/day): 1,200, 2,400, 3,000, or 3,600 (n = 2-4 per group). Many adverse events (AE) occurred from about day 10; 2 subjects dropped out and 1 continued on a reduced FBM dose. Pharmacokinetic studies were repeated on day 21 for the 16 subjects who completed the study. FBM was measured in plasma and urine by high-performance liquid chromatography (HPLC). VPA and its 2-en, 4-en, and 3-oxo metabolites in plasma, and VPA (nonconjugated and total), and its 3-oxo and 4-hydroxy metabolites in urine were measured by gas chromatography/mass spectrometry (GC/MS). Mean plasma FBM trough concentrations on day 21 ranged from 26.9 mu g/ml (1,200 mg dose) to 76.8 mu g/ml (3,600-mg dose). Mean plasma VPA C max values were 32-42 mu g/ml in the various subgroups when VPA only was administered. Higher plasma VPA levels were observed when FBM was administered concurrently (55.4-63.8 mu g/ml). The excretion of 3-oxo-VPA in urine was significantly lower on day 21 than on day 7, whereas VPA-glucuronide was significantly increased. The effects of FBM on VPA disposition were dose dependent and were maximal at approximately 2400 mg/day. FBM has caused significant inhibition of the beta-oxidation pathway for VPA metabolic clearance, and this had been largely compensated by increased VPA glucuronidation.

Integrating evidence from multiple sources to guide decisions is something humans do on a daily basis. Existing research suggests that not all sources of information are weighted equally in decision-making tasks, and that observers are subject to biases in the face of internal and external noise. Here we describe two experiments that measured observers' ability to integrate successive visual signals. Participants viewed pairs of gratings presented sequentially and reproduced their average orientation. Experiment 1 revealed a recency bias in evidence integration, such that observers' average judgments were closer to the orientation of the second grating than the first. Mixture distribution modeling revealed that this was caused by a recency bias in averaging, as well as a tendency to disregard the first stimulus altogether in some trials. In Experiment 2 we replicated these findings, and quantified orientation-specific patterns of neural activity recorded during the task using population-tuning curve modeling of electroencephalography data. This analysis yielded robust orientation tuning to both the presented gratings and observers' decisions, and suggested that observers were storing both grating stimuli for subsequent averaging rather than computing a running average. The neural representation of the second grating was not reliably stronger than that of the first, suggesting that the recency bias is not due to a difference in the strength of encoding of the second stimulus, and instead may arise at a later decision stage where information is retrieved or integrated.

Polyacrylamide-based friction reducers (FRs) are widely used in hydraulic fracturing to reduce friction created within fluid as it flows through tubulars or other restrictions. These polymers generally add viscosity to the fluid to reduce the turbulence induced as fluid flows. Type and amount of total dissolved solids (TDS) in source water have significant impact on performance of FRs. This study investigates these effects and evaluates various types of FRs applied to the Marcellus Shale region. It was found that increase in salinity often causes significant performance degradation (Mantell et al., 2011). This is especially critical for application of FRs in Marcellus shale that is known for challenging brine contents. This effect is more pronounced for some divalent cations than for monovalent ones. Addition of surfactant systems can improve FR performance by extending the salt tolerance. Overall, it can be concluded that FR optimization for given water content and proppant can be done by adjusting FR type and/or concentration. For special applications, when higher proppant loading is desired, applying Viscosifying Friction Reducers (VFRs) and High Viscosity Friction Reducers (HVFRs) are proven to be preferable. It was demonstrated that slickwater viscosity tend to increase exponentially with VFR concentration increase. At the same time VFRs should be breakable to ensure high regained proppant conductivity and minimization of formation damage. Such result would further justify the transition from traditional gelled fluids to FR-based viscous slickwater. This comprehensive review explores the application of various types of FRs for Marcellus shale region. It defines the critical TDS levels, and types of cations that require changes in FR type or dosage. This data can benefit operators in (1) optimizing performance of the FR-based completion fluid; (2) avoiding formation damage associated with usage of unjustified additives; and (3) comparing/qualifying FRs based on their optimal range of application and economical dosage.

When a moving surface alternates in colour and direction, perceptual couplings of colour and motion can differ from their physical correspondence. Periods of motion tend to be perceptually bound with physically delayed colours - a colour/motion perceptual asynchrony. This can be eliminated by motion transparency. Here we show that the colour/motion perceptual asynchrony is not invariably eliminated by motion transparency. Nor is it an inevitable consequence given a particular physical input. Instead, it can emerge when moving surfaces are perceived as alternating in direction, even if those surfaces seem transparent, and it is eliminated when surfaces are perceived as moving invariably. For a given observer either situation can result from exposure to a common input. Our findings suggest that neural events that promote the perception of motion reversals are causal of the colour/motion perceptual asynchrony. Moreover, they suggest that motion transparency and coherence can be signalled simultaneously by subpopulations of direction-selective neurons, with this conflict instantaneously resolved by a competitive winner-takes-all interaction, which can instantiate or eliminate colour/motion perceptual asynchrony.