Humans quickly learn to blink strategically in response to environmental task demands.

Eye blinking is one of the most frequent human actions. The control of blinking is thought to reflect complex interactions between maintaining clear and healthy vision and influences tied to central dopaminergic functions including cognitive states, psychological factors, and medical conditions. The most imminent consequence of blinking is a temporary loss of vision. Minimizing this loss of information is a prominent explanation for changes in blink rates and temporarily suppressed blinks, but quantifying this loss is difficult, as environmental regularities are usually complex and unknown. Here we used a controlled detection experiment with parametrically generated event statistics to investigate human blinking control. Subjects were able to learn environmental regularities and adapted their blinking behavior strategically to better detect future events. Crucially, our design enabled us to develop a computational model that allows quantifying the consequence of blinking in terms of task performance. The model formalizes ideas from active perception by describing blinking in terms of optimal control in trading off intrinsic costs for blink suppression with task-related costs for missing an event under perceptual uncertainty. Remarkably, this model not only is sufficient to reproduce key characteristics of the observed blinking behavior such as blink suppression and blink compensation but also predicts without further assumptions the well-known and diverse distributions of time intervals between blinks, for which an explanation has long been elusive.

Learning rational temporal eye movement strategies.

During active behavior humans redirect their gaze several times every second within the visual environment. Where we look within static images is highly efficient, as quantified by computational models of human gaze shifts in visual search and face recognition tasks. However, when we shift gaze is mostly unknown despite its fundamental importance for survival in a dynamic world. It has been suggested that during naturalistic visuomotor behavior gaze deployment is coordinated with task-relevant events, often predictive of future events, and studies in sportsmen suggest that timing of eye movements is learned. Here we establish that humans efficiently learn to adjust the timing of eye movements in response to environmental regularities when monitoring locations in the visual scene to detect probabilistically occurring events. To detect the events humans adopt strategies that can be understood through a computational model that includes perceptual and acting uncertainties, a minimal processing time, and, crucially, the intrinsic costs of gaze behavior. Thus, subjects traded off event detection rate with behavioral costs of carrying out eye movements. Remarkably, based on this rational bounded actor model the time course of learning the gaze strategies is fully explained by an optimal Bayesian learner with humans' characteristic uncertainty in time estimation, the well-known scalar law of biological timing. Taken together, these findings establish that the human visual system is highly efficient in learning temporal regularities in the environment and that it can use these regularities to control the timing of eye movements to detect behaviorally relevant events.

Comparison of different methods to study effects of silver nanoparticles on the pro- and antioxidant status of human keratinocytes and fibroblasts.

In times of antibiotic-resistant bacteria new strategies to avoid the septic-inducing threat of dangerous microorganisms are needed. Silver ions (Ag+) in the forms of silver nitrate or silver sulfadiazine have been used as antimicrobial agents for years. A step further was the development of micro and silver particles (AgNP). In contrast to other Ag+ ion sources, AgNP allow a sustained release of Ag+ ions, due to their high surface to volume ratio. However, AgNP are also toxic to eukaryotic cells and the mechanisms of cytotoxicity have not yet been fully elucidated. In this study, the impact of different AgNP preparations on a human keratinocyte cell line was investigated. The intracellular radical formation was confirmed by the 2',7'-dichlorodihydrofluorescein di-acetate (H2DCF-DA) assay on two cell types (HaCaT cells and normal human dermal fibroblasts) as well as by electron paramagnetic resonance (EPR) spectroscopy, which showed comparable results. EPR spectroscopy was performed for the first time for 24h in experiments using keratinocytes. Drastic changes in the mitochondrial activity were induced in cells incubated with AgNP containing high concentrations of Ag+ ions. It was also possible to show that the quantitative uptake of AgNP was dependent on the AgNP concentration. In addition, the effects of AgNP on the GSH/GSSG system were elucidated. The results showed a batch- and concentration-dependent decrease of the total glutathione concentration which correlated well with the decrease of cell viability. Furthermore, the results suggest a direct reaction of GSH molecules with Ag+ ions. In conclusion, this study proves the efficacy of the H2DCF-DA assay and the EPR spectroscopy. The investigations show that AgNP formulations containing high amounts of released Ag+ ions induce radicals in human keratinocytes and deplete them of their natural anti-oxidative molecules. On the contrary, nanoparticles prepared and stored under argon did not induce significant adverse effects, suggesting that slowing down the release of Ag+ may help to reduce AgNP-related side effects without affecting the antibacterial impact.

Multidisciplinary Delphi Development of a Scale to Evaluate Team Function in Obstetric Emergencies: The PETRA Scale.

OBJECTIVE: The objective of this study was to develop a new interdisciplinary teamwork scale, the Perinatal Emergency: Team Response Assessment (PETRA), for the management of obstetric crises, through consensus agreement of obstetric caregivers. METHODS: This prospective study was performed using expert consensus, based on a Delphi method. The study investigators developed a new PETRA tool, specifically related to obstetric crisis management, based on the existing literature and discussions among themselves. The scale was distributed to a selected panel of experts in the field for the Delphi process. After each round of Delphi, every component of the scale was analyzed quantitatively by the percentage of agreement ratings and each comment reviewed by the blinded investigators. The assessment scale was then modified, with components of less than 80% agreement removed from the scale. The process was repeated on three occasions to reach a consensus and final PETRA scale. RESULTS: Fourteen of 24 invited experts participated in the Delphi process. The original PETRA scale included six categories and 48 items, one global scale item, and a 3-point rubric for rating. The overall percentage agreement by experts in the first, second, and third rounds was 95.0%, 93.2%, and 98.5%, respectively. The final scale after the third round of Delphi consisted of the following seven categories: shared mental model, communication, situational awareness, leadership, followership, workload management, and positive/effective behaviours and attitudes. There were 34 individual items within these categories, each with a 5-point rating rubric (1 = unacceptable to 5 = perfect). CONCLUSION: Using a structured Delphi method, we established the face and content validity of this assessment scale that focuses on important aspects of interdisciplinary teamwork in the management of obstetric crises.

The PETRA (Perinatal Emergency Team Response Assessment) Scale: A High-Fidelity Simulation Validation Study.

OBJECTIVE: The objective of this study was to establish the validity and reliability of a new interdisciplinary teamwork assessment scale, the Perinatal Emergency Team Response Assessment (PETRA), to assess team dynamics during a simulated obstetric crisis. METHODS: This observational cohort study was conducted using high-fidelity simulation and multidisciplinary obstetric teams in order to evaluate the validity and reliability of the previously developed PETRA scale for the assessment of teamwork in the management of obstetric crises. Two high-fidelity simulations of preeclampsia and postpartum hemorrhage (PPH) were conducted 50 times; 42 were performed by multidisciplinary teams and eight (four "good," four "poor") were performed by actors. Five raters used the PETRA tool to assess the simulation video recordings. Three additional raters assessed each performance without the use of PETRA as "good" or "poor" in order to provide an overall rating (referred to as the standardized score). The primary outcome measure was the PETRA score. Cronbach's alpha and intra-class correlation coefficients (2,1) with 95% CIs were calculated to examine internal consistency of the scale and level of agreement among raters, respectively. Construct validity was established by comparing the assessments of the raters with the standardized scores. Generalizability theory analysis was performed to demonstrate PETRA's reliability and to investigate the sources of variation in scores. RESULTS: The simulated emergencies were performed by 119 participants. There was overall high consistency (Cronbach's alpha [95% CI] 0.984 [0.981 to 0.987]) and moderate agreement (intra-class correlation coefficients [95% CI] 0.49 [0.35 to 0.63]) among raters. Significantly higher PETRA scores (mean [standard deviation]) were recorded with "good" versus "poor" performing teams (real scenarios 3.8 [0.7] vs. 2.9 [0.7]; P < 0.001; acted scenarios 4.7 [0.5] vs. 2.2 [0.7]; P < 0.001), suggesting strong construct validity. The overall PETRA scores were not different between the PPH (3.7 [0.7]) and preeclampsia (3.7 [0.8]) scenarios (P = 0.49). Generalizability coefficients were 0.83 for PPH and 0.76 for preeclampsia. CONCLUSION: PETRA is a valid and reliable scale that may be a valuable tool in the assessment and training of multidisciplinary teams in their management of obstetric crises.

A Perioperative Course of Gabapentin Does Not Produce a Clinically Meaningful Improvement in Analgesia after Cesarean Delivery: A Randomized Controlled Trial.

BACKGROUND: Studies examining the efficacy of a single preoperative dose of gabapentin for analgesia after cesarean delivery (CD) have been inconclusive. The authors hypothesized that a perioperative course of gabapentin would improve analgesia after CD. METHODS: This single-center, randomized, double-blind, placebo-controlled, parallel-group, superiority trial was designed to determine the analgesic efficacy of a perioperative course of gabapentin when added to a multimodal analgesic regimen. Women scheduled for elective CD during spinal anesthesia were randomized to receive a perioperative oral course of either gabapentin (600 mg preoperatively followed by 200 mg every 8 h for 2 days) or placebo. Postoperative pain was measured at 24 and 48 h, at rest and on movement, on a visual analogue scale (VAS, 0 to 100 mm). The primary outcome was pain on movement at 24 h. Neonatal outcomes, opiate consumption, VAS satisfaction (0 to 100 mm), adverse effects, and persistent pain were also assessed. RESULTS: Baseline characteristics were similar between groups. There was a statistically significant but small reduction in VAS pain score (mean [95% CI]) on "movement" (40 mm [36 to 45] vs. 47 mm [42 to 51]; difference, -7 mm [-13 to 0]; P = 0.047) at 24 h in the gabapentin (n = 100) compared with control group (n = 97). There was more sedation in the gabapentin group at 24 h (55 vs. 39%, P = 0.026) but greater patient VAS satisfaction (87 vs. 77 mm, P = 0.003). CONCLUSIONS: A perioperative course of gabapentin produces a clinically insignificant improvement in analgesia after CD and is associated with a higher incidence of sedation.

Predictive Factors for Changes in Quality of Life after Steroid Treatment for Active Moderate-to-Severe Graves' Orbitopathy: A Prospective Trial.

OBJECTIVES: To investigate the predictive factors for changes in the quality of life (GO-QoL) of patients with Graves' orbitopathy (GO) prior to and after specific treatment. METHODS: A prospective follow-up study was conducted at an academic tertiary referral orbital center with a joint thyroid-eye clinic on 100 consecutive patients with GO. Before and after the standard 12-week course of weekly intravenous methylprednisolone (cumulative dose 4.5 g), the GO-QoL questionnaire provided by the European Group on Graves' Orbitopathy (EUGOGO) was completed. Endocrine and ophthalmic assessments were performed at each visit. RESULTS: All patients were biochemically euthyroid and untreated for GO at baseline and presented with active and moderate-to-severe disease. Both GO-QoL subscales (visual functioning [VF] and appearance [AP]) significantly increased after immunosuppressive therapy and showed a sustained improvement for 6 months. At baseline, demographic variables (sex, age, and smoking) influenced QoL in the stepwise linear regression (p < 0.01, adjusted R 2 = 0.24 for VF and p < 0.01, adjusted R 2 = 0.21 for AP). In contrast, 6 months after treatment, the improved QoL was now exclusively associated with ophthalmic parameters (p < 0.01, adjusted R 2 = 0.47 for VF; p < 0.01, adjusted R 2 = 0.23 for AP). CONCLUSIONS: Predictive factors for GO-QoL differed not only between the 2 subscales but also before and after the first treatment of GO.

Multi-step planning of eye movements in visual search.

The capability of directing gaze to relevant parts in the environment is crucial for our survival. Computational models have proposed quantitative accounts of human gaze selection in a range of visual search tasks. Initially, models suggested that gaze is directed to the locations in a visual scene at which some criterion such as the probability of target location, the reduction of uncertainty or the maximization of reward appear to be maximal. But subsequent studies established, that in some tasks humans instead direct their gaze to locations, such that after the single next look the criterion is expected to become maximal. However, in tasks going beyond a single action, the entire action sequence may determine future rewards thereby necessitating planning beyond a single next gaze shift. While previous empirical studies have suggested that human gaze sequences are planned, quantitative evidence for whether the human visual system is capable of finding optimal eye movement sequences according to probabilistic planning is missing. Here we employ a series of computational models to investigate whether humans are capable of looking ahead more than the next single eye movement. We found clear evidence that subjects' behavior was better explained by the model of a planning observer compared to a myopic, greedy observer, which selects only a single saccade at a time. In particular, the location of our subjects' first fixation differed depending on the stimulus and the time available for the search, which was well predicted quantitatively by a probabilistic planning model. Overall, our results are the first evidence that the human visual system's gaze selection agrees with optimal planning under uncertainty.