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Objective: The authors describe research and applications in prominent areas of neuroergonomics.Background: Because human factors/ergonomics examines behavior and mind at work, it should include the study of brain mechanisms underlying human performance.Methods: Neuroergonomic studies are reviewed in four areas: workload and vigilance, adaptive automation, neuroengineering, and molecular genetics and individual differences.Results: Neuroimaging studies have helped identify the components of mental workload, workload assessment in complex tasks, and resource depletion in vigilance. Furthermore, real-time neurocognitive assessment of workload can trigger adaptive automation. Neural measures can also drive brain-computer interfaces to provide disabled users new communication channels. Finally, variants of particular genes can be associated with individual differences in specific cognitive functions.Conclusions: Neuroergonomics shows that considering what makes work possible - the human brain - can enrich understanding of the use of technology by humans and can inform technological design.Application: Applications of neuroergonomics include the assessment of operator workload and vigilance, implementation of real-time adaptive automation, neuroengineering for people with disabilities, and design of selection and training methods. [ABSTRACT FROM AUTHOR]

Objectives: Series from high volume oesophageal centres highlight an increasing prevalence of early malignant (EM) lesions. The advent of endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) offer alternatives to traditional surgery. The evolution of this pattern of care in a high volume centre is analysed., Methods: Data were collected from a prospectively maintained database. 96 patients were treated with an EM lesion from 2000 to 2011. Surgery was the standard approach during the initial period (2000-2006). In 2007, with the introduction of EMR±RFA to our Centre, a rising trend toward definitive endoscopic treatment was seen. This study details the selection of cases into treatment groups and their outcomes., Results: From 2000 to 2006, 23 patients were treated with EM lesions, 96% by surgery. Seventy-three were treated from 2007 to 2011, 55% surgically and 45% by EMR±RFA. In the entire experience, there was one death from surgery and morbidity was higher in the surgery group compared with EMR±RFA (p<0.001). Three surgical patients (4.8%) relapsed with HGD or cancer, and one patient with T1N1 disease died of disease recurrence. At a median of 13 months, EMR±RFA offered 100% disease control, 72% had no endoscopic or histological evidence of Barrett's oesophagus and one patient represented with low grade dysplasia., Conclusions: This study highlights the changing pattern of care in the management of early oesophageal cancer. EMR±RFA appears an acceptable alternative to surgery in carefully selected cases. However, long-term outcome analysis using these methods is required and close interdisciplinary collaboration of specialists in gastroenterology, surgery, pathology and radiology is mandatory to achieve optimum outcomes.

Rationale: Cardiomyocytes (CMs) differentiated from human pluripotent stem cells (PSCs) are increasingly being used for cardiovascular research, including disease modeling, and hold promise for clinical applications. Current cardiac differentiation protocols exhibit variable success across different PSC lines and are primarily based on the application of growth factors. However, extracellular matrix is also fundamentally involved in cardiac development from the earliest morphogenetic events, such as gastrulation., Objective: We sought to develop a more effective protocol for cardiac differentiation of human PSCs by using extracellular matrix in combination with growth factors known to promote cardiogenesis., Methods and Results: PSCs were cultured as monolayers on Matrigel, an extracellular matrix preparation, and subsequently overlayed with Matrigel. The matrix sandwich promoted an epithelial-to-mesenchymal transition as in gastrulation with the generation of N-cadherin-positive mesenchymal cells. Combining the matrix sandwich with sequential application of growth factors (Activin A, bone morphogenetic protein 4, and basic fibroblast growth factor) generated CMs with high purity (up to 98%) and yield (up to 11 CMs/input PSC) from multiple PSC lines. The resulting CMs progressively matured over 30 days in culture based on myofilament expression pattern and mitotic activity. Action potentials typical of embryonic nodal, atrial, and ventricular CMs were observed, and monolayers of electrically coupled CMs modeled cardiac tissue and basic arrhythmia mechanisms., Conclusions: Dynamic extracellular matrix application promoted epithelial-mesenchymal transition of human PSCs and complemented growth factor signaling to enable robust cardiac differentiation.

The application of pattern classification techniques to physiological data has undergone rapid expansion. Tasks as varied as the diagnosis of disease from magnetic resonance images, brain-computer interfaces for the disabled, and the decoding of brain functioning based on electrical activity have been accomplished quite successfully with pattern classification. These classifiers have been further applied in complex cognitive tasks to improve performance, in one example as an input to adaptive automation. In order to produce generalizable results and facilitate the development of practical systems, these techniques should be stable across repeated sessions. This paper describes the application of three popular pattern classification techniques to EEG data obtained from asymptotically trained subjects performing a complex multitask across five days in one month. All three classifiers performed well above chance levels. The performance of all three was significantly negatively impacted by classifying across days; however two modifications are presented that substantially reduce misclassifications. The results demonstrate that with proper methods, pattern classification is stable enough across days and weeks to be a valid, useful approach., (Published by Elsevier Inc.)

Human induced pluripotent stem (iPS) cells hold great promise for cardiovascular research and therapeutic applications, but the ability of human iPS cells to differentiate into functional cardiomyocytes has not yet been demonstrated. The aim of this study was to characterize the cardiac differentiation potential of human iPS cells generated using OCT4, SOX2, NANOG, and LIN28 transgenes compared to human embryonic stem (ES) cells. The iPS and ES cells were differentiated using the embryoid body (EB) method. The time course of developing contracting EBs was comparable for the iPS and ES cell lines, although the absolute percentages of contracting EBs differed. RT-PCR analyses of iPS and ES cell-derived cardiomyocytes demonstrated similar cardiac gene expression patterns. The pluripotency genes OCT4 and NANOG were downregulated with cardiac differentiation, but the downregulation was blunted in the iPS cell lines because of residual transgene expression. Proliferation of iPS and ES cell-derived cardiomyocytes based on 5-bromodeoxyuridine labeling was similar, and immunocytochemistry of isolated cardiomyocytes revealed indistinguishable sarcomeric organizations. Electrophysiology studies indicated that iPS cells have a capacity like ES cells for differentiation into nodal-, atrial-, and ventricular-like phenotypes based on action potential characteristics. Both iPS and ES cell-derived cardiomyocytes exhibited responsiveness to beta-adrenergic stimulation manifest by an increase in spontaneous rate and a decrease in action potential duration. We conclude that human iPS cells can differentiate into functional cardiomyocytes, and thus iPS cells are a viable option as an autologous cell source for cardiac repair and a powerful tool for cardiovascular research.

Objective: We show that psychophysiologically driven real-time adaptive aiding significantly enhances performance in a complex aviation task. A further goal was to assess the importance of individual operator capabilities when providing adaptive aiding., Background: Psychophysiological measures are useful for monitoring cognitive workload in laboratory and real-world settings. They can be recorded without intruding into task performance and can be analyzed in real time, making them candidates for providing operator functional state estimates. These estimates could be used to determine if and when system intervention should be provided to assist the operator to improve system performance., Methods: Adaptive automation was implemented while operators performed an uninhabited aerial vehicle task. Psychophysiological data were collected and an artificial neural network was used to detect periods of high and low mental workload in real time. The high-difficulty task levels used to initiate the adaptive automation were determined separately for each operator, and a group-derived mean difficulty level was also used., Results: Psychophysiologically determined aiding significantly improved performance when compared with the no-aiding conditions. Improvement was greater when adaptive aiding was provided based on individualized criteria rather than on group-derived criteria. The improvements were significantly greater than when the aiding was randomly provided., Conclusion: These results show that psychophysiologically determined operator functional state assessment in real time led to performance improvement when included in closed loop adaptive automation with a complex task., Application: Potential future applications of this research include enhanced workstations using adaptive aiding that would be driven by operator functional state.

Voltage-gated channels maintain cellular resting potentials and generate neuronal action potentials by regulating ion flux. Here, we show that Ether-à-go-go (EAG) K+ channels also regulate intracellular signaling pathways by a mechanism that is independent of ion flux and depends on the position of the voltage sensor. Regulation of intracellular signaling was initially inferred from changes in proliferation. Specifically, transfection of NIH 3T3 fibroblasts or C2C12 myoblasts with either wild-type or nonconducting (F456A) eag resulted in dramatic increases in cell density and BrdUrd incorporation over vector- and Shaker-transfected controls. The effect of EAG was independent of serum and unaffected by changes in extracellular calcium. Inhibitors of p38 mitogen-activated protein (MAP) kinases, but not p44/42 MAP kinases (extracellular signal-regulated kinases), blocked the proliferation induced by nonconducting EAG in serum-free media, and EAG increased p38 MAP kinase activity. Importantly, mutations that increased the proportion of channels in the open state inhibited EAG-induced proliferation, and this effect could not be explained by changes in the surface expression of EAG. These results indicate that channel conformation is a switch for the signaling activity of EAG and suggest an alternative mechanism for linking channel activity to the activity of intracellular messengers, a role that previously has been ascribed only to channels that regulate calcium influx.

Signaling complexes are essential for the modulation of excitability within restricted neuronal compartments. Adaptor proteins are the scaffold around which signaling complexes are organized. Here, we demonstrate that the Camguk (CMG)/CASK adaptor protein functionally modulates Drosophila Ether-á-go-go (EAG) potassium channels. Coexpression of CMG with EAG in Xenopus oocytes results in a more than twofold average increase in EAG whole-cell conductance. This effect depends on EAG-T787, the residue phosphorylated by calcium- and calmodulin-dependent protein kinase II (Wang et al., 2002). CMG coimmunoprecipitates with wild-type and EAG-T787A channels, indicating that T787, although necessary for the effect of CMG on EAG current, is not required for the formation of the EAG-CMG complex. Both CMG and phosphorylation of T787 increase the surface expression of EAG channels, and in COS-7 cells, EAG recruits CMG to the plasma membrane. The interaction of EAG with CMG requires a noncanonical Src homology 3-binding site beginning at position R1037 of the EAG sequence. Mutation of basic residues, but not neighboring prolines, prevents binding and prevents the increase in EAG conductance. Our findings demonstrate that membrane-associated guanylate kinase adaptor proteins can modulate ion channel function; in the case of CMG, this occurs via an increase in the surface expression and phosphorylation of the EAG channel.

Introduction: Electroencephalographic (EEG) correlates of Gz-induced loss of consciousness (G-LOC) were examined to better understand the mechanisms of G-LOC., Methods: There were 10 subjects (4 women) who provided 35 G-LOC episodes during which 13 channels of EEG and eye activity were recorded. Subjects simultaneously performed tracking and mathematical tasks prior to and following G-LOC. The performance data and cerebral regional oxygen saturation (rSO2), as measured using near infrared spectroscopy, were correlated with the EEG changes., Results: Across all subjects, seven EEG events were identified and measured. The two most significant were found over widespread scalp sites. They were a 1-2 Hz waveform just prior to G-LOC and a very large, approximately 1 Hz waveform just prior to regaining consciousness. These were associated with a drop of rSO2 levels to approximately 90% of the pre-G-LOC baseline levels. rSO2 levels returned to pre-G-LOC levels within approximately 15 s following G-LOC while EEG and performance measures took approximately 60 s., Discussion: There were two unique EEG waveforms found, one preceding unconsciousness and the other preceding the return to consciousness during G-LOC episodes. Further, the supply of oxygen to the brain was rapidly restored, within approximately 15 s, while the EEG and performance data showed that approximately 60 s were required for the brain to regain functional integrity. The delay in performance and EEG recovery following G-LOC demonstrates that the recovery of brain activity to support cognitive function requires more than just the restoration of normal oxygen levels.

We studied 2 classifiers to determine their ability to discriminate among 4 levels of mental workload during a simulated air traffic control task using psychophysiological measures. Data from 7 air traffic controllers were used to train and test artificial neural network and stepwise discriminant classifiers. Very high levels of classification accuracy were achieved by both classifiers. When the 2 task difficulty manipulations were tested separately, the percentage correct classifications were between 84% and 88%. Feature reduction using saliency analysis for the artificial neural networks resulted in a mean of 90% correct classification accuracy. Considering the data as a 2-class problem, acceptable load versus overload, resulted in almost perfect classification accuracies, with mean percentage correct of 98%. In applied situations, the most important distinction among operator functional states would be to detect mental overload situations. These results suggest that psychophysiological data are capable of such discriminations with high levels of accuracy. Potential applications of this research include test and evaluation of new and modified systems and adaptive aiding.

The functional state of the human operator is critical to optimal system performance. Degraded states of operator functioning can lead to errors and overall suboptimal system performance. Accurate assessment of operator functional state is crucial to the successful implementation of an adaptive aiding system. One method of determining operators' functional state is by monitoring their physiology. In the present study, artificial neural networks using physiological signals were used to continuously monitor, in real time, the functional state of 7 participants while they performed the Multi-Attribute Task Battery with two levels of task difficulty. Six channels of brain electrical activity and eye, heart and respiration measures were evaluated on line. The accuracy of the classifier was determined to test its utility as an on-line measure of operator state. The mean classification accuracies were 85%, 82%, and 86% for the baseline, low task difficulty, and high task difficulty conditions, respectively. The high levels of accuracy suggest that these procedures can be used to provide accurate estimates of operator functional state that can be used to provide adaptive aiding. The relative contribution of each of the 43 psychophysiological features was also determined. Actual or potential applications of this research include test and evaluation and adaptive aiding implementation.

The background to the development of a novel concept for the prepartal activation of calcium absorption capacity as a means of preventing parturient hypocalcaemia and milk fever in grazing ruminants is described. It was hypothesised that this objective could be achieved by decreasing the bio-availability of calcium from pasture for a 3 week period. Soya bean oil was chosen as a supplement, from a number of potential binding agents, to form poorly digestible calcium soaps in the gastrointestinal tract. 28 mature twin-pregnant ewes in late pregnancy were used as assay animals to test the hypothesis, and they proved to be a sensitive experimental model for dairy cows. Following the treatment period, overnight starvation was used to challenge calcium homeostasis. Calcium absorption capacity was assessed indirectly by measuring strontium concentrations in plasma following oral dosing with strontium chloride. Strong support for the hypothesis was obtained as the 14 Treated ewes were protected from severe fasting-induced hypocalcaemia (P = 0.002), and this was associated with a greatly increased capacity of the ewes to absorb calcium. The feeding strategy developed in this experiment led to the production of a Calcigard concentrate supplement which was subsequently shown to protect cows from hypocalcaemia and milk fever, and stimulate production.

Modulation of neuronal excitability is believed to be an important mechanism of plasticity in the nervous system. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been postulated to regulate the ether à go-go (eag) potassium channel in Drosophila. Inhibition of CaMKII and mutation of the eag gene both cause hyperexcitability at the larval neuromuscular junction (NMJ) and memory formation defects in the adult. In this study, we identify a single site, threonine 787, as the major CaMKII phosphorylation site in Eag. This site can be phosphorylated by CaMKII both in a heterologous cell system and in vivo at the larval NMJ. Expression of Eag in Xenopus oocytes was used to assess the function of phosphorylation. Injection of either a specific CaMKII inhibitor peptide or lavendustin C, another CaMKII inhibitor, reduced Eag current amplitude acutely. Mutation of threonine 787 to alanine also reduced amplitude. Moreover, both CaMKII inhibition and the alanine mutation accelerated inactivation. The reduction in current amplitudes and the accelerated inactivation of dephosphorylated Eag channels would result in decreased outward potassium currents and hyperexcitability at presynaptic terminals and, thus, are consistent with the NMJ phenotype observed when CaMKII is inhibited. These results show that Eag is a substrate of CaMKII and suggest that direct modulation of potassium channels may be an important function of this kinase.

Accumulating evidence suggests that many ion channels reside within a multiprotein complex that contains kinases and other signaling molecules. The role of the adaptor proteins that physically link these complexes together for the purposes of ion channel modulation, however, has been little explored. Here, we examine the protein-protein interactions required for regulation of an Aplysia bag cell neuron cation channel by a closely associated protein kinase C (PKC). In inside-out patches, the PKC-dependent enhancement of cation channel open probability could be prevented by the src homology 3 (SH3) domain, presumably by disrupting a link between the channel and the kinase. SH3 and PDZ domains from other proteins were ineffective. Modulation was also prevented by an SH3 motif peptide that preferentially binds the SH3 domain of src. Furthermore, whole-cell depolarizations elicited by cation channel activation were decreased by the src SH3 domain. These data suggest that the cation channel-PKC association may require SH3 domain-mediated interactions to bring about modulation, promote membrane depolarization, and initiate prolonged changes in bag cell neuron excitability. In general, protein-protein interactions between ion channels and protein kinases may be a prominent mechanism underlying neuromodulation.

Background: Instrument selection for recording physiological data in flight studies requires careful attention to subject comfort and non-interference with aircrew activities. Several electrode types and recording sites may be used to examine electrodermal activity (EDA). Placement of electrodes on the foot minimizes interference with physical activity and reduces motion artifacts; however, use of conventional, hard-plastic-encased metal (PEM) electrodes within a flight boot can produce discomfort and pressure-induced artifacts., Hypothesis: When applied with proper electrolyte gels, thin, flexible, silver-impregnated cloth electrodes should acquire EDA signals qualitatively similar to those acquired using conventional, PEM electrodes., Methods: EDA responses evoked by light flashes, auditory stimuli and valsalva maneuvers were recorded with cloth and PEM electrodes simultaneously from both feet of 4 male subjects. Performance of cloth vs. PEM electrodes and variability of signals recorded with the same electrode type were examined by placing pairs of selected electrodes on each foot of the subjects. Placements were balanced with respect to age and handedness of the subject and the number of trials with each electrode type placed on the left or right foot., Results: Qualitatively similar signals were recorded with cloth and PEM electrodes. Cloth electrodes showed more variability between electrodes of the same type., Conclusion: For EDA recording, cloth electrodes can perform at least as well as PEM electrodes, making it practical to take advantage of the cloth electrodes' flexibility and lower profile.

The effects of season of growth and monensin treatment on ruminal digestion of fresh-cut autumn and spring pasture were measured in a single group of ruminally fistulated castrated male sheep, housed indoors in metabolism crates. Responses were assessed in terms of ruminal volatile fatty acid molar proportions, ammonia concentration, pH, apparent digestibility of the pasture, and nitrogen balance of the animals. Blood plasma concentrations of insulin, glucose, beta-hydroxybutyrate, urea, and NEFA were also evaluated. Autumn pasture contained significantly lower proportions of water-soluble carbohydrate (P < 0.05), cellulose (P < 0.05), and lignin (P < 0.05) and increased pectin (P < 0.05), hemicellulose (P < 0.05), and crude protein (P < 0.10) concentrations when compared with spring pasture. Voluntary DMI by sheep of autumn pasture was lower (P < 0.01) than that of spring pasture and was significantly (P < 0.05) reduced by monensin treatment. Monensin treatment significantly decreased the ruminal molar proportions of acetic acid (P < 0.10) and butyric acid (P < 0.001) and increased the molar proportions of propionic acid (P < 0.001) and minor VFA (P < 0.01). Nitrogen retention of the sheep was significantly (P < 0.05) reduced by monensin treatment. Plasma glucose levels were increased (P < 0.10) by monensin treatment during the fourth 5-d collection period in both seasons. Chemical analysis suggested that the composition of autumn pasture was different from that of spring pasture and that this was manifested in vivo by increased DMI and digestibility of spring vs autumn pasture. Ruminal fermentation of autumn pasture also had an increased acetate-to-propionate ratio compared with spring pasture. Monensin treatment acted consistently across seasons by increasing the proportion of propionate and decreasing the proportion of acetate in ruminal fluid.

EEG changes related to the amount of information held in memory during a 4-s retention period were studied. The predictability of the amount of information held in memory was varied. In the weighted condition, 60% of the trials contained only one item and the remaining 40% of the trials were evenly distributed between trials containing 3, 5, 7, or 8 items. In the random condition, the levels were equally represented and randomly presented. In the blocked condition the levels were equally represented but presented in five blocks containing only items from one of the levels. Initial widespread decreases in alpha band power were followed by increased activity in all three conditions. The more difficult of the five levels produced decreased alpha activity in more localized posterior left hemisphere sites. This suggests two alpha mechanisms, one associated with task engagement and the other related to the cognitive demands regardless of the presentation context. Theta band power increased over frontal scalp, and to a lesser extent over left parietal and temporal areas and bilateral occipital sites, during only the weighted condition. These changes were uniform over the entire retention period. Beta 2 activity was also influenced by the task difficulty and the time course of the retention period in the two conditions. Beta 2 activity resembled both alpha and theta in that in levels 1, 2 and 3 it acted like alpha with increasing power over time at numerous widespread sites while the higher difficulty levels showed higher power at the beginning of the retention period and then decreased.

Mutations of eag, first identified in Drosophila on the basis of their leg-shaking phenotype, cause repetitive firing and enhanced transmitter release in motor neurons. The encoded EAG polypeptide is related both to voltage-gated K+ channels and to cyclic nucleotide-gated cation channels. Homology screens identified a family of eag-related channel polypeptides, highly conserved from nematodes to humans, comprising three subfamilies: EAG, ELK, and ERG. When expressed in frog oocytes, EAG channels behave as voltage-dependent, outwardly rectifying K(+)-selective channels. Mutations of the human eag-related gene (HERG) result in a form of cardiac arrhythmia that can lead to ventricular fibrillation and sudden death. Electrophysiological and pharmacological studies have provided evidence that HERG channels specify one component of the delayed rectifier, IKr, that contributes to the repolarization phase of cardiac action potentials. An important role for HERG channels in neuronal excitability is also suggested by the expression of these channels in brain tissue. Moreover, mutations of ERG-type channels in the Drosophila sei mutant cause temperature-induced convulsive seizures associated with aberrant bursting activity in the flight motor pathway. The in vivo function of ELK channels has not yet been established, but when these channels are expressed in frog oocytes, they display properties intermediate between those of EAG- and ERG-type channels. Coexpression of the K(+)-channel beta subunit encoded by Hk with EAG in oocytes dramatically increases current amplitude and also affects the gating and modulation of these currents. Biochemical evidence indicates a direct physical interaction between EAG and HK proteins. Overall, these studies highlight the diverse properties of the eag family of K+ channels, which are likely to subserve diverse functions in vivo.

Background/aims: Our objectives were: (1) to assess the clinical benefits and costs of performing ultrasound-guided liver biopsy with an automated needle compared to blind biopsy with a conventional Trucut needle in patients with chronic hepatitis C; (2) to compare the histological yield of automated needles with Trucut needles., Methods: We prospectively studied 166 patients with hepatitis C virus who underwent either ultrasound-guided biopsy using automated ASAP needles or blind biopsy using conventional Trucut needles. Both groups were matched for age, sex, cirrhosis, needle gauge and operator experience. Patient tolerance, complications and histological adequacy were assessed. In a separate in vitro study, we assessed the histological adequacy of liver biopsy specimens obtained using automated and Trucut needles from 10 fresh autopsy cases., Results: Ultrasound-guided biopsy caused significantly less biopsy pain (36.4% vs. 47.3%; p < 0.0001) and significantly less pain-related morbidity (1.8% vs. 7.7%, p < 0.05). Although, there was no significant difference in diagnostic yield between guided and blind biopsy (98% vs. 94%, p = 0.15), 3 blind biopsies (3.3%), including 2 which yielded extra-hepatic tissue, had to be repeated. The additional expense of performing guided liver biopsy with automated needles was 42 Irish Pounds per patient. In vitro, automated ASAP 15G needles provided liver specimens comparable to Trucut 15G needles and had the highest histopathologic score among the automated needles assessed., Conclusions: Even in the absence of major complications, ultrasound-guided liver biopsy with an automated needle in HCV patients is safer, more comfortable and only marginally more expensive than blind Trucut biopsy.

We performed a preliminary clinical evaluation of digitized mammograms to assess whether digital images suitable for telemammography could be obtained. Thirty mammograms were digitized at a resolution of 4000 x 4000 pixels and 12 bit/pixel. The series contained 17 carcinomas in 16 patients. Five consultant radiologists reported both the original mammograms and the digitized images. There was agreement between the reports of the mammograms and the digitized images in relation to whether a suspicious lesion was present or not in 95% of cases. No study considered benign on viewing the film images was interpreted as malignant on reporting the digitized images. This suggests that film digitizers may allow a digital image of a mammogram of acceptable quality for telemammography to be obtained in the absence of a purpose-built digital mammography system.

This study examined whether alpha event-related desynchronization (ERD) and theta event-related synchronization (ERS) could successfully measure changes in cognitive workload and training while an operator was engaged in a continuous, interactive, control task(s). Alpha 1 (8-10 Hz) ERD, alpha 2 (10-12 Hz) ERD, and theta (3-7 Hz) ERS were determined for a communications event that occurred during multiple task workload conditions or as a single task. Other measures (alpha and theta EEG power, heart rate, respiration, eye blinks, behavioral performance, and subjective workload ratings) were also evaluated. Results showed that alpha 2 EEG, heart rate, behavioral, and subjective measures were sensitive to changes in workload in the multiple tasks. In addition, eye blink rate and behavioral measures were sensitive to training. Alpha ERD and theta ERS were not sensitive to workload and training in our interactive, multiple task environment. However, they were effective indexes of cognitive/behavioral demands within an interactive single task.

Regulation of nonspecific cation channels often underlies neuronal bursting and other prolonged changes in neuronal activity. In bag cell neurons of Aplysia, it recently has been suggested that an intracellular messenger-induced increase in the activity of a nonspecific cation channel may underlie the onset of a 30-min period of spontaneous action potentials referred to as the "afterdischarge. " In patch clamp studies of the channel, we show that the open probability of the channel can be increased by an average of 10. 7-fold by application of ATP to the cytoplasmic side of patches. Duration histograms indicate that the increase is primarily a result of a reduction in the duration and percentage of channel closures described by the slowest time constant. The increase in open probability was not observed using 5'-adenylylimidodiphosphate, a nonhydrolyzable ATP analog, and was blocked in the presence of H7 or the more specific calcium/phospholipid-dependent protein kinase C (PKC) inhibitor peptide(19-36). Because the increase in activity observed in response to ATP occurred without application of protein kinase, our results indicate that a kinase endogenous to excised patches mediates the effect. The effect of ATP could be reversed by exogenously applied protein phosphatase 1 or by a microcystin-sensitive phosphatase also endogenous to excised patches. These results, together with work demonstrating the presence of a protein tyrosine phosphatase in these patches, suggest that the cation channel is part of a regulatory complex including at least three enzymes. This complex may act as a molecular switch to activate the cation channel and, thereby, trigger the afterdischarge.

Background: Mental workload is a major consideration in the design and operation of modern aircraft systems. Objective measures of mental workload that are sensitive and diagnostic are required to meet the needs of both pilots and designers. Due to the multifaceted nature of these complex mental demands multiple measures are required., Hypothesis: Psychophysiological and subjective measures provide unique information about mental workload during flight., Methods: Cardiac, eye, brain and subjective data were collected during an actual flight scenario designed to provide tasks which required different piloting skills at several levels of mental workload., Results: Heart rate was sensitive to the demands of flight but not diagnostic with regard to determining the cause of the workload. Heart rates increased during take offs and landings and to an intermediate level during instrument flight rules (IFR) segments. By showing sensitivity to only the visual demands of the various segments of flight eye activity was more diagnostic. The theta band of the EEG demonstrated increased power during those flight segments which required inflight mental calculations. The subjective measures showed trends suggesting different levels of mental demand but demonstrated few statistically significant differences., Conclusions: Multiple measures, especially psychophysiological measures, provide a comprehensive picture of the mental demands of flight. The measures used in this study were shown to provide unique, non-overlapping information. Because of the continuous nature of the psychophysiological data it may be possible to develop systems which provide on-line monitoring of mental workload that can provide feedback to the pilot and aircraft systems.

Assembly of K channel alpha subunits of the Shaker (Sh) family occurs in a subfamily specific manner. It has been suggested that subfamily specificity also applies in the association of beta subunits with Sh channels (Rhodes, K. J., Keilbaugh, S. A., Barrezueta, N. X., Lopez, K. L., and Trimmer, J. S. (1995) J. Neurosci. 15, 5360-5371; Sewing, S., Roeper, J. and Pongs, O. (1996) Neuron 16, 455-463; Yu, W., Xu, J., and Li, M. (1996) Neuron 16, 441-453). Here we show that the Drosophila beta subunit homologue Hyperkinetic (Hk) associates with members of the ether go-go (eag), as well as Sh, families. Anti-EAG antibody coprecipitates EAG and HK indicating a physical association between proteins. Heterologously expressed Hk dramatically increases the amplitudes of eag currents and also affects gating and modulation by progesterone. Through their ability to interact with a range of alpha subunits, the beta subunits of voltage-gated K channels are likely to have a much broader impact on the signaling properties of neurons and muscle fibers than previously suggested.

A series of experiments were conducted to systematically evaluate the relative contributions of task difficulty and stimulus probability to P300 amplitudes. Scalp event-related potentials (ERPs) were recorded and the topographic distributions were evaluated during a multi-level cognitive task with an antecedent warning. In three separate studies, task difficulty (five levels), probability or expectedness (10-60%), and randomness (random or blocked presentation) were manipulated. Response accuracy, subjective ratings, and reference-free averages of the P300 components elicited by the warning stimuli were evaluated. Statistical analysis indicated that significantly larger P300s were associated with the more difficult task warnings except when memory tasks were presented in a blocked design, suggesting that neither task difficulty nor probability alone can account for variations in the P300 in a multi-level task scenario. Results are discussed with regard to adaptation-level theory.

A case of a chordoma in the thoracic spine is presented. This is a very rare tumour in this location and should be considered in the differential diagnosis of any posterior mediastinal mass. The appearances on CT and MRI were similar to chordomas described in other locations. On T2-weighted images septae of low signal intensity radiated throughout the large high-signal mass. This feature may be of use in differentiating chordomas from other posterior mediastinal masses.

The increased incidence of cerebral toxoplasmosis in AIDS has led to a resurgence in the use of sulphadiazine. One complication of this is acute renal failure secondary to sulphadiazine-induced crystalluria. Three cases are described which demonstrate a spectrum of ultrasound findings ranging from echogenic foci in the renal parenchyma to echogenic material in both dilated and non-dilated collecting systems. In patients with AIDS having sulphadiazine treatment, these ultrasonic findings suggest that sulphadiazine is the cause of the renal failure.

The afterdischarge of Aplysia bag cell neurons has served as a model system for the study of phosphorylation-mediated changes in neuronal excitability. The nature of the depolarization generating the afterdischarge, however, has remained unclear. We now have found that venom from Conus textile triggers a similar prolonged discharge, and we have identified a slow inward current and corresponding channel, the activation of which seems to contribute to the onset of the discharge. The slow inward current is voltage-dependent and Ca(2+)-sensitive, reverses at potentials slightly positive to O mV, exhibits a selectivity of K approximately equal to Na >> Tris > N-methyl-D-glucamine (NMDG), and is blocked by high concentrations of tetrodotoxin. Comparison of these features with those observed in channel recordings provides evidence that a Ca(2+)-sensitive, nonspecific cation channel is responsible for a slow inward current that regulates spontaneous repetitive firing and suggests that modulation of the cation channel underlies prolonged changes in neuronal response properties.

In this investigation, eight Air Force air traffic controllers (ATCs) performed three scenarios on TRACON (Terminal Radar Approach Control), a computer-based air traffic control (ATC) simulation. Two scenarios were used each with three levels of difficulty. One scenario varied traffic volume by manipulating the number of aircraft to be handled and the second scenario varied traffic complexity by manipulating arriving to departing flight ratios, pilot skill and mixture of aircraft types. A third scenario, overload, required subjects to handle a larger number of aircraft in a limited amount of time. The effects of the manipulations on controller workload were assessed using performance, subjective (TLX), and physiological (EEG, eye blink, heart rate, respiration, saccade) measures. Significant main effects of difficulty level were found for TRACON performance, TLX, eye blink, respiration and EEG measures. Only the EEG was associated with main effects for the type of traffic. The results provide support for the differential sensitivity of a variety of workload measures in complex tasks, underscore the importance of traffic complexity in ATC workload, and support the utility of TRACON as a tool for studies of ATC workload.

Genetic and physiological studies of the Drosophila Hyperkinetic (Hk) mutant revealed defects in the function or regulation of K+ channels encoded by the Shaker (Sh) locus. The Hk polypeptide, determined from analysis of cDNA clones, is a homologue of mammalian K+ channel beta subunits (Kv beta). Coexpression of Hk with Sh in Xenopus oocytes increases current amplitudes and changes the voltage dependence and kinetics of activation and inactivation, consistent with predicted functions of Hk in vivo. Sequence alignments show that Hk, together with mammalian Kv beta, represents an additional branch of the aldo-keto reductase superfamily. These results are relevant to understanding the function and evolutionary origin of Kv beta.

EEG from 19 electrodes was used to classify which of 14 tasks each of seven subjects had performed. Stepwise discriminant analysis (SWDA) was used to classify the tasks based upon training on one half of the spectrally analyzed 1 min of data. Eighty six percent correct classification was achieved using principle components analysis (PCA) to determine the EEG bands to be used by the SWDA. Other approaches to deriving the EEG bands met with lower levels of success. The results indicate that frequency and topographical information about the EEG provides useful knowledge with regard to the nature of cognitive activity. Higher frequencies provided much of the information used by the classifier. The utility of this approach is discussed with regard to evaluating operator state in the work environment.

A "same-different" letter pair choice reaction time task was used to compare reaction time, performance accuracy, and P3 amplitude and latency at three levels of task difficulty. Stimulus set was held constant across tasks, and task difficulty was manipulated by instructions to the subject. Subjects delivered a button-press response to designate whether members of each letter pair matched or mismatched on the basis of their physical identity (low difficulty), name identity (medium difficulty), or category identity (vowels/consonants, high difficulty). Task decision difficulty was confirmed by slower reaction times and reduced response accuracy. P3 amplitude was inversely related to task decision difficulty; relatively larger P3s were associated with matched (vs. mismatched) letter pairs. These findings evidence direct effects of task difficulty on P3 amplitude, possibly as the result of "equivocation" related to more difficult task judgments.

Twelve subjects (six female) participated in an experiment designed to separate the effects of perceptual/central and physical demands on psychophysiological measures of peripheral nervous system activity. The difficulty of a single-axis continuous manual tracking task was varied in two ways: order of control was manipulated to vary perceptual/central processing demand, and disturbance amplitude was manipulated to vary physical demand. Physiological measures were sensitive to the imposition of a task and were more sensitive to physical than to perceptual/central demands. A principal components analysis identified five factors (three of them physiological) that accounted for 83.1% of the observed variance. Perceptual/central processing demands specifically affected the component identified with sympathetic cardiovascular control, whereas physical demands were reflected in the component identified with parasympathetic cardiovascular control. This finding suggests that dissociations observed among cardiovascular measures in manual performance tasks are attributable to differential activation of the autonomic control systems.

Objective: The purpose of this study was to demonstrate that gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) could be used as a contrast medium in CT as an alternative to iodine-based compounds., Materials and Methods: Solutions of different concentrations of Gd-DTPA and iopromide were scanned in a tissue equivalent phantom and it was shown that Gd-DTPA caused 2.5 times the attenuation of an equimolar solution of iopromide. From these in vitro studies an in vivo dose of 0.5 mmol/kg Gd-DTPA was calculated to be equivalent to 50 ml iopromide 300., Results: Pre- and postenhancement CT was performed in a volunteer using Gd-DTPA intravenously, and adequate enhancement occurred in intracranial vessels., Conclusion: Gd-DTPA can be used to provide enhancement during CT and might be of value in iodine-sensitive patients.