Simultaneous Separation and Detection of Cations and Anions Ion a Microfluidic Device with Suppressed Electroosmotic Flow and a Single Injection Point

A rapid and simultaneous separation of cationic and anionic peptides and proteins in a glass microfluidic device that has been covalently modified with a neutral poly(ethylene glycol) (PEG) coating to minimize protein adsorption is presented. The features of the device allow samples that contain both anions and cations to be introduced from a central flow stream and separated in different channels with different outlets—all in the presence of low electroosmotic flow (EOF) imparted by the PEG coating. The analytes are electrophoretically extracted from a central hydrodynamic stream and electrophoretically separated in two different channels, in which pressure driven flow has been suppressed through the use of hydrodynamic restrictors. Having different outlets for the electrophoretic separation channels that are spatially separated from the injection enables coupling with further downstream functionalities or off-chip detection, such as mass spectrometry. A plug of charged analyte is hydrodynamically pumped to the sampling intersection and anions from the plug migrate electrophoretically toward the anode in one channel while cations migrate toward the cathode in the other channel due to suppressed EOF from the PEG coating. The separations presented here required less than a minute to complete and produced average separation efficiencies of up to about 3,500 plates from a separation length of 2 cm. The extraction efficiency of both cations and anions from the hydrodynamic stream is determined experimentally and compared with a previously reported model that was used to determine anion extraction efficiency. The extraction efficiency is determined to be 87% and 98% for the two sample mixtures analyzed, and the values predicted by the model are within 3.5% of the experimental data. It is anticipated that this basic approach for simultaneous separation of anions and cations with reduced EOF will be integrated into larger microfluidic systems because the design provides separate outlets that can feed downstream processes or linked to off-chip detection

Validation of a Manually Oscillating Chair for In-The-Field Assessment of Dynamic Visual Acuity on Crewmembers Within Hours of Returning from Long-Duration Spaceflight

Due to the deconditioned state of crewmembers in the initial hours after landing, it is safer and more practical to perform a vision test while seated in a chair versus walking on a treadmill. The purpose of this study was to validate the ability of a manually operated oscillating chair to produce the oscillatory frequency and displacement equivalent of walking on a treadmill at a 4 mph pace. A fast Fourier transform (FFT)was performed on the vertical trunk acceleration to compare the peak and spread of the distribution of oscillation frequencies for each oscillating condition. Peak oscillation frequencies achieved with the manual chair were lower and more variable than those of treadmill walking and the automatic chair. This can mostly be attributed to operator fatigue. However, DVA scores across conditions were not significantly different, indicating that the manual chair can provide adequate vertical oscillation frequency and displacement with the added advantage of being portable enough for testing outside a laboratory. Furthermore the automatic chair very closely matches the oscillation frequency of treadmill walking, making it an ideal method for testing DVA in a laboratory setting

Dynamics of the G-excess illusion

The G-excess illusion is increasingly recognized as a cause of aviation mishaps especially when pilots perform high-speed, steeply banked turns at low altitudes. Centrifuge studies of this illusion have examined the perception of subject orientation and/or target displacement during maintained hypergravity with the subject's head held stationary. The transient illusory perceptions produced by moving the head in hypergravity are difficult to study onboard centrifuges because the high angular velocity ensures the presence of strong Coriolis cross-coupled semicircular canal effects that mask immediate transient otolith-organ effects. The present study reports perceptions following head movements in hypergravity produced by high-speed aircraft maintaining a banked attitude with low angular velocity to minimize cross-coupled effects. Methods: Fourteen subjects flew on the NASA KC-135 and were exposed to resultant gravity forces of 1.3, 1.5, and 1.8 G for 3 minute periods. On command, seated subjects made controlled head movements in roll, pitch, and yaw at 30 second intervals both in the dark and with faint targets at a distance of 5 feet. Results: head movement produced transient perception of target displacement and velocity at levels as low as 1.3 G. Reports of target velocity without appropriate corresponding displacement were common. At 1.8 G when yaw head movements were made from a face down position, 4 subjects reported oscillatory rotational target displacement with fast and slow alternating components suggestive of torsional nystagmus. Head movements evoked symptoms of nausea in most subjects, with 2 subjects and 1 observer vomiting. Conclusions: The transient percepts present conflicting signals, which introduced confusion in target and subject orientation. Repeated head movements in hypergravity generate nausea by mechanisms distinct from cross-coupled Coriolis effects

Effect of Passive Horizontal Rotations and Vertical Oscillations on Dynamic Visual Acuity

Astronauts experience sensorimotor disturbances after long duration space flight. These crewmembers may need to egress the vehicle within a few minutes for safety and operational reasons in various sea state conditions following a water landing. Exposure to even low frequency motions induced by sea conditions surrounding a vessel can cause significant fine and gross motor control problems affecting critical functions. The objective of this study was to document human motor and visual performance during simulated wave motion in the 0.1 to 2.0 Hz range. We examined in 12 healthy subjects the changes in accuracy when performing a seated visual target acquisition task in which the location of target was offset vertically during horizontal full body rotation at an oscillating frequency of 0.8 Hz (peak velocity of 160 deg/s). The main finding was that the accuracy of performance degraded in 7 of 12 subjects when acquiring vertical targets at perturbing frequencies of 0.8 Hz in the horizontal plane by one step size. We also examined in a separate study on 12 healthy subjects seated dynamic visual acuity (DVA) task performance during vertical full body oscillations at perturbing frequencies of 2 Hz (peak to peak motion of 5 cm). The main finding was that DVA was significantly reduced when acquiring targets at perturbing oscillations at frequencies of 2 Hz in the vertical plane by approximately 1 chart line. Thus low frequencies of perturbations in the horizontal and vertical planes can cause decrement in visual performance

Postural Responses Following Space Flight and Ground Based Analogs

With the transition from the Shuttle program to the International Space Station (ISS), the opportunity to fly sensorimotor experiments in a weightless environment has become increasingly more difficult to obtain. As a result, more investigations have turned to ground-based analogs as a way of evaluating an experiment's viability. The two primary analogs available to most investigators are 6deg head down bed rest (HDBR) and dry immersion (DI). For the time being, HDBR investigations have been associated with studies conducted in the United States while the Russians and several other European Union states have concentrated their efforts on using DI as the space flight analog of choice. While either model may be viable for cardiovascular, bone and other system changes, vestibular and sensorimotor investigators have retained serious reservations of either analog's potential to serve as a replacement for a true weightless environment. These reservations have merit, but it is worthwhile to consider that not all changes associated with sensorimotor function during space flight are the result of top-down modifications, but may also be due to the lack, or change, of appropriate support surfaces applying force to the bottom of the feet. To this end we have compared quiet stance postural responses between short duration Space Shuttle flights, long duration ISS flights and HDBR of varying duration. Using these three platforms, representing different modifications of support we investigated postural ataxia using a quiet stance model. Quiet stance was obtained by asking the subjects to stand upright on a force plate, eyes open, arms at the side of the body for three min. From the force plate we obtained average sway velocity in two axes as well as length of line (stabilogram). These parameters were then related to EMG activity recorded from the medial gastrocnemius and lateral tibialis. It is significant to note that postural ataxia measured as quiet stance shows analogous changes between HDBR and space flight. Primary differences across short duration, long duration space flight and HDBR are related to the length of exposure associated with both space flight and HDBR

Walk on Floor Eyes Closed Test as a Measure of Postflight Ataxia

INTRODUCTION: Astronauts returning from space flight universally exhibit impaired posture and locomotion. Measurement of this impairment is an evolving process. The walk on the floor line test with the eyes closed (WOFEC) provides a unique procedure for quantifying postflight ataxia. Data from a modified WOFEC were obtained as part of an ongoing NASA interdisciplinary pre- and postflight study (Functional Task Test, FTT) designed to evaluate astronaut postflight functional performance. METHODS: Seven astronauts (5 short duration with flights of 12-16 days; 2 long duration crewmembers with flights of 6 months) were tested twice before flight, on landing day (short duration only), and 1, 6, and 30 days after flight. The WOFEC consisted of walking for 10 steps (repeated twice) with the feet heel to toe in tandem, arms folded across the chest and the eyes closed. The performance metric (scored by three examiners from video) was the percentage of correct steps completed over the three trials. A step was not counted as correct if the crewmember sidestepped, opened their eyes, or paused for more than three seconds between steps. RESULTS/ CONCLUSIONS: There was a significant decrease in percentage of correct steps on landing day (short duration crew) and on first day following landing (long duration) with partial recovery the following day, and full recovery beginning on day sixth after flight. Both short and long duration fliers appeared to be unaware of foot position relative to their bodies or the floor. Postflight, deviation from a straight path was common, and the test for two crewmembers elicited motion sickness symptoms. These data clearly demonstrate the sensorimotor challenges facing crewmembers after returning from spaceflight. The WOFEC test has value providing the investigator or crew surgeon with a simple method to quantify vestibular ataxia, as well as providing instant feedback of postural ataxia without the use of complex test equipment

The Walk on Floor Eyes Closed Tandem Step Test as a Quantitative Measure of Ataxia After Space Flight

INTRODUCTION Posture and locomotion are among the functions most affected by space flight. Postflight ataxia can be quantified easily by using the walk on the floor line test with the eyes closed (WOFEC). Data from a modified WOFEC were obtained as part of an ongoing interdisciplinary pre- and postflight study (Functional Task Test, FTT) designed to evaluate both postflight functional performance of astronauts and related physiological changes. METHODS Five astronauts with flight durations of 12 to 16 days participated in this study. Performance measurements were obtained in 2 preflight sessions, on landing day, and 1, 6, and 30 days after landing. The WOFEC test consisted of walking with the feet placed heel to toe in tandem, arms folded across the chest and eyes closed, for 10 steps. A trial was initiated after the eyes were closed and the front foot was aligned with the rear foot. The performance metric was the average percentage of correct steps completed over 3 trials. A step was not counted as correct if the crewmember sidestepped, opened eyes, or paused for more than 3 seconds between steps. Step accuracy was scored independently by 3 examiners. RESULTS Immediately after landing subjects seemed to be unaware of their foot position relative to their body or the floor. The percentage of correct steps was significantly decreased on landing day. Partial recovery was observed the next day, and full recovery to baseline on the sixth day post landing. CONCLUSION These data clearly demonstrate the sensorimotor challenges facing crewmembers after they return from space flight. Although this simple test is intended to complement the FTT battery of tests, it has some stand-alone value as it provides investigators with a means to quantify vestibular ataxia as well as provide instant feedback on postural stability without the use of complex test equipment

Jump-Down Performance Alterations after Space Flight

INTRODUCTION: Successful jump performance requires functional coordination of visual, vestibular, and somatosensory systems, which are affected by prolonged exposure to microgravity. Astronauts returning from space flight exhibit impaired ability to coordinate effective landing strategies when jumping from a platform to the ground. This study compares jump strategies used by astronauts before and after flight, changes to those strategies within a test session, and recoveries in jump-down performance parameters across several postflight test sessions. These data were obtained as part of an ongoing interdisciplinary study (Functional Task Test, FTT) designed to evaluate both astronaut postflight functional performance and related physiological changes. METHODS: Seven astronauts from short-duration (Shuttle) and three from long-duration (International Space Station) flights performed 3 two-footed jumps from a platform 30 cm high onto a force plate that measured the ground reaction forces and center-of-pressure displacement from the landings. Neuromuscular activation data were collected from the medial gastrocnemius and anterior tibialis of both legs using surface electromyography electrodes. Two load cells in the platform measured the load exerted by each foot during the takeoff phase of the jump. Data were collected in 2 preflight sessions, on landing day (Shuttle only), and 1, 6, and 30 days after flight. RESULTS: Postural settling time was significantly increased on the first postflight test session and many of the astronauts tested were unable to maintain balance on their first jump landing but recovered by the third jump, showing a learning progression in which performance improvements could be attributed to adjustments in takeoff or landing strategy. Jump strategy changes were evident in reduced air time (time between takeoff and landing) and also in increased asymmetry in foot latencies on takeoff. CONCLUSIONS: The test results revealed significant decrements in astronauts abilities to maintain balance and achieve a postural stability upon landing from a jump early after flight. However, the jump landing adaptation process often begins after the first jump with full recovery of most performance parameters within days after space flight. As expected, performance of ISS astronauts on the first day after flight was similar to that of Shuttle crewmembers on landing day

Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

BACKGROUND: Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. METHODS: We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. RESULTS: Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. CONCLUSION: It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations