Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam

The purpose of this study was to model pharmacodynamically the reversal of midazolam sedation with flumazenil. Ten human volunteers underwent four different sessions. In session 1, individual midazolam pharmacokinetics and electroencephalographic pharmacodynamics were determined. In sessions 2 and 3, a computer-controlled infusion of midazolam with individual volunteer pharmacokinetic data was administered, targeting a plasma concentration corresponding to a light or deep level of sedation (20% or 80% of the maximal midazolam electroencephalographic effect) for a period of 210 minutes. After obtaining a stable electroencephalographic effect and constant midazolam plasma concentrations, a zero-order infusion of flumazenil was started until complete reversal of midazolam electroencephalographic effect was obtained. The flumazenil infusion was then stopped and the volunteer was allowed to resedate because of the constant midazolam drug effect. The electroencephalographic response was measured during a 180-minute period and analyzed by aperiodic analysis and fast-Fourier transforms. In session 4, a midazolam plasma concentration corresponding to a deep level of sedation was targeted for 210 minutes to examine for the possible development of acute tolerance. No flumazenil was given in session 4. For a light sedation level, with a mean midazolam plasma concentration of 160 +/- 64 ng/ml, the mean half-life of the equilibration rate constant of flumazenil reversal is 5.0 +/- 2.5 minutes, and the mean effect site concentration causing 50% of Emax is 13.7 +/- 5.8 ng/ml. For a deep level of sedation, with a mean midazolam plasma concentration of 551 +/- 196 ng/ml, the mean half-life of the equilibration rate constant is 3.9 +/- 1.5 minutes, and the mean effect site concentration causing 50% of Emax is 20.6 +/- 6.8 ng/ml. This study provides an estimate of the magnitude of the blood/central nervous system equilibration delay for flumazenil antagonism of midazolam sedation and further defines the usefulness of the electroencephalogram as a measure of midazolam pharmacodynamic effect.     

Psychosocial causes and consequences of pathological gaming

Pathological use of computer and video games has been associated with indicators of psychosocial well-being, such as loneliness, low self-esteem, low social competence, and low life satisfaction. However, few studies have decisively demonstrated whether these indicators of psychosocial well-being are causes or consequences of pathological gaming. To address this gap in the literature, we conducted a two-wave panel study among 851 Dutch adolescents (543 gamers). Causal relations were analyzed using autoregressive structural equation models. These analyses indicated that social competence, self-esteem, and loneliness were significant predictors of pathological gaming six months later. Thus, lower psychosocial well-being can be considered an antecedent of pathological gaming among adolescent gamers. Our analyses further indicated that loneliness was also a consequence of pathological gaming. This suggests that displacement of real-world social interaction resulting from pathological use of video games may deteriorate existing relationships, which could explain the increase in adolescent gamers’ feelings of loneliness.     

Emotionally charged earcons reveal affective congruency effects

In the present study, the affective impact of earcons on stimulus classification is investigated. We show, using a picture-categorization task, that the affective connotation of earcons in major and minor mode (representing positive and negative valence, respectively) can be congruent or incongruent with response valence. Twenty participants classified pictures of animals and instruments in 256 trials, using positive and negative Yes or No responses. Together with the pictures, either a chord in major mode or minor mode was played. The affective valence of the chords either did or did not match the valence of responses. Response-time latencies show congruency effects of the matching and non matching sound and response valences, indicating that it is important to carefully investigate human-computer interfaces for potential affective congruency effects, as these can either facilitate or inhibit user performance.     

UO2 dissolution in Boom Clay conditions

The solubility of uranium dioxide (UO₂) was measured in real and synthetic Boom Clay waters with varying concentrations of humic acids and carbonate under reducing conditions at 20 °C. Uranium concentrations in function of time suggest the reduction of U(VI) to U(IV) by the humic acids which is occurring faster in real clay water than in synthetic clay waters. Humic acids induce also a competition to complex U(VI) in carbonate-containing solution, but they are not able to control the uranium concentration at high bicarbonate concentration (0.02 mol dm⁻³). Nevertheless they may play a role at low carbonate concentration. In our experimental conditions, the geochemical calculations indicate that two uranium secondary phases (U₄O₉ and UO_2(c)) are susceptible to control the uranium concentration in solution. These calculations are in good agreement with results of the X-ray photoelectron spectroscopy. At the end of tests, uranium concentrations reach steady-state values between 3 × 10⁻⁸ and 5 × 10⁻⁸ mol dm⁻³ in the bicarbonate-rich solutions. Although these concentrations are considered as conservative, they are 10-100 times higher than in natural Boom Clay. The consequence is that spent fuel could slowly dissolve in the interstitial clay water undersaturated with respect to UO₂/UO_2+x of the fuel.     

Carotene Degradation and Isomerization during Thermal Processing: A Review on the Kinetic Aspects

Kinetic models are important tools for process design and optimization to balance desired and undesired reactions taking place in complex food systems during food processing and preservation. This review covers the state of the art on kinetic models available to describe heat-induced conversion of carotenoids, in particular lycopene and β-carotene. First, relevant properties of these carotenoids are discussed. Second, some general aspects of kinetic modeling are introduced, including both empirical single-response modeling and mechanism-based multi-response modeling. The merits of multi-response modeling to simultaneously describe carotene degradation and isomerization are demonstrated. The future challenge in this research field lies in the extension of the current multi-response models to better approach the real reaction pathway and in the integration of kinetic models with mass transfer models in case of reaction in multi-phase food systems.     

Pulsed corona for breaking up air bubbles in water

The injection of gas into water, through a hollow needle, gives a stream of bubbles. These bubbles can be effectively broken up by application of HV pulses. Our experimental work shows that this mechanism works in demineralized water and even in conducting tap water if the pulses have a short rise time. Bubble diameters are as low as 50 μm. Our pulse source uses either a HV tetrode or a spark gap as switching element. Extremely small bubbles are produced at a high rate and a low power input. Applications for this method can be found in chemical process technology     

Molecular characterization of pneumococcal nasopharynx isolates collected from children during their first 2 years of life

Pneumococcal colonization was studied in 19 children monitored from birth through the age of 2 years. For this purpose, pneumococcal isolates were characterized by capsular typing, restriction fragment end labeling (RFEL), and penicillin-binding protein (PBP) genotyping. Fifty-eight isolates were collected and were found to belong to 10 capsular types, 31 RFEL types, and 7 PBP genotypes. Thirty-nine percent of the isolates had reduced susceptibility to penicillin. All seven highly resistant strains (MICs, > 1 microgram/ml) were identical to the pandemic clone 23F. Children were culture positive between one and eight times at 13 scheduled visits. Although the infants were frequently recolonized with different strains, colonization with one particular strain often persisted for several months. Isolation of a previously detected capsular type was common, and the chromosomal homogeneity tended to be high when it occurred. Horizontal transfer of capsular genes between strains of different RFEL types was demonstrated in one child. The ecological advantage of transfer of capsular genes is unclear unless survival of the organism on a mucosal surface may be linked to immunoprotective pressure against particular capsular types.