Hemodynamic Effects of Midodrine After Space Flight in Astronauts Without Orthostatic Hypotension

Orthostatic hypotension and presyncope are common and potentially serious risks for astronauts returning from space. Susceptible subjects fail to generate an adequate adrenergic response to upright posture. The -1 adrenergic agonist, midodrine, may be an effective countermeasure. We tested the hypothesis that midodrine would have no negative hemodynamic effect on healthy astronauts returning from space. Five male astronauts participated in preflight and postflight tilt testing on a control flight as well as on the test flights, where midodrine (10 mg, orally) was administered after landing, approximately 1 hour before testing. None of these astronauts exhibited orthostatic hypotension or presyncope before or after either flight. Midodrine did not cause any untoward reactions in these subjects before or after flight, in fact a modest beneficial effect was seen on postflight tachycardia (p=0.036). These data show that midodrine protected against post-spaceflight increases in heart rate, without having any adverse hemodynamic effects on non-presyncopal, male astronauts. Among these subjects, midodrine was a safe cardiovascular countermeasure

Contingent negative variation and its relation to time estimation: a theoretical evaluation

The relation between the contingent negative variation (CNV) and time estimation is evaluated in terms of temporal accumulation and preparation processes. The conclusion is that the CNV as measured from the electroencephalogram (EEG) recorded at fronto-central and parietal-central areas is not a direct reflection of the underlying interval timing mechanism(s), but more likely represents a time-based response preparation/decision-making process

ExoPranayama: a biofeedback-driven actuated environment for supporting yoga breathing practices

Both breathing and internal self-awareness are an integral part of any yoga practice. We describe and discuss the development of ExoPranayama, an actuated environment that physically manifests users’ breathing in yoga. Through a series of trials with yoga practitioners and expert teachers, we explore its role in the practice of yoga. Our interview results reveal that biofeedback through the environment supported teaching and improved self-awareness, but it impacted group cohesion. Two practical uses of the technology emerged for supporting breath control in yoga: (1) biofeedback can provide new information about users’ current internal states; (2) machine-driven feedback provides users with a future state or goal, and leads to improved cohesiveness

Hypovolemia Induced Orthostatic Hypotension in Presyncopal Astronauts and Normal Subjects Related to Hypoadrenergic Responsiveness

Circulating blood volume is reduced during spaceflight, making astronauts hemodynamically compromised. After landing, astronauts separate into two groups. One group compensates for the hypovolemia with a hyper-sympathetic response during upright tilt testing and can complete a tilt test with few symptoms. The other group is unable to mount a hyper-sympathetic response and experiences orthostatic hypotension and presyncope during upright tilt tests. We tested the hypothesis that hypovolemia alone, in the absence of spaceflight, also would cause subjects to separate into presyncopal and non-presyncopal groups according to their sympathetic responses during tilt. We studied 20 subjects, including 10 veteran astronauts, on three occasions. On Days 1 (normovolemia) and 3 (hypovolemia), plasma volume, tilt tolerance and supine and standing plasma norepinephrine levels were measured. Forty hours prior to Day 3, subjects were given intravenous furosemide, followed by 36 hours of a 10MEq Na diet. Statistical comparisons were made between normovolemia and hypovolemia responses. This protocol reproduced landing day tilt test outcomes with 100% fidelity in the astronauts. Similarly to patterns reported after flight, non-presyncopal subjects had greater norepinephrine responses to tilt during hypovolemia compared to normovolemia (580 plus or minus 79 vs. 298 plus or minus 37 pg/ml, P less than 0.05), but presyncopal subjects had no increase (180 plus or minus 44 vs. 145 plus or minus 32 pg/ml, P=NS). This model can be used to predict astronauts who will become presyncopal on landing day, so that prospective, individualized countermeasures can be developed. Within patient populations, it can be used to study the interaction of volemic state and the sympathetic nervous system

Thirty Years After Michael E. Porter: What Do We Know About Business Exit?

Although a business exit is an important corporate change initiative, the buyer’s side seems to be more appealing to management researchers than the seller’s because acquisitions imply growth, i.e., success. Yet from an optimistic viewpoint, business exit can effectively create value for the selling company. In this paper we attempt to bring the relevance of the seller’s side back into our consciousness by asking: What do we know about business exit? We start our exploration with Porter (1976), focusing on literature that investigates the antecedents of, barriers to, and outcomes of business exit. We also include studies from related fields such as finance and economics.1 Through this research we determine three clusters of findings: factors promoting business exit, exit barriers, and exit outcomes. Overall, it is the intention of this paper to highlight the importance of business exit for research and practice. Knowing what we know about business exits and their high financial value we should bear in mind that exit need not mean failure but a new beginning for a corporation

A biologically plausible model of time-scale invariant interval timing

The temporal durations between events often exert a strong influence over behavior. The details of this influence have been extensively characterized in behavioral experiments in different animal species. A remarkable feature of the data collected in these experiments is that they are often time-scale invariant. This means that response measurements obtained under intervals of different durations coincide when plotted as functions of relative time. Here we describe a biologically plausible model of an interval timing device and show that it is consistent with time-scale invariant behavior over a substantial range of interval durations. The model consists of a set of bistable units that switch from one state to the other at random times. We first use an abstract formulation of the model to derive exact expressions for some key quantities and to demonstrate time-scale invariance for any range of interval durations. We then show how the model could be implemented in the nervous system through a generic and biologically plausible mechanism. In particular, we show that any system that can display noise-driven transitions from one stable state to another can be used to implement the timing device. Our work demonstrates that a biologically plausible model can qualitatively account for a large body of data and thus provides a link between the biology and behavior of interval timing

Conditional Knockout of NMDA Receptors in Dopamine Neurons Prevents Nicotine-Conditioned Place Preference

Nicotine from smoking tobacco produces one of the most common forms of addictive behavior and has major societal and health consequences. It is known that nicotine triggers tobacco addiction by activating nicotine acetylcholine receptors (nAChRs) in the midbrain dopaminergic reward system, primarily via the ventral tegmental area. Heterogeneity of cell populations in the region has made it difficult for pharmacology-based analyses to precisely assess the functional significance of glutamatergic inputs to dopamine neurons in nicotine addiction. By generating dopamine neuron-specific NR1 knockout mice using cre/loxP-mediated method, we demonstrate that genetic inactivation of the NMDA receptors in ventral tegmental area dopamine neurons selectively prevents nicotine-conditioned place preference. Interestingly, the mutant mice exhibit normal performances in the conditioned place aversion induced by aversive air puffs. Therefore, this selective effect on addictive drug-induced reinforcement behavior suggests that NMDA receptors in the dopamine neurons are critical for the development of nicotine addiction

Insights on the Neuromagnetic Representation of Temporal Asymmetry in Human Auditory Cortex.

Communication sounds are typically asymmetric in time and human listeners are highly sensitive to this short-term temporal asymmetry. Nevertheless, causal neurophysiological correlates of auditory perceptual asymmetry remain largely elusive to our current analyses and models. Auditory modelling and animal electrophysiological recordings suggest that perceptual asymmetry results from the presence of multiple time scales of temporal integration, central to the auditory periphery. To test this hypothesis we recorded auditory evoked fields (AEF) elicited by asymmetric sounds in humans. We found a strong correlation between perceived tonal salience of ramped and damped sinusoids and the AEFs, as quantified by the amplitude of the N100m dynamics. The N100m amplitude increased with stimulus half-life time, showing a maximum difference between the ramped and damped stimulus for a modulation half-life time of 4 ms which is greatly reduced at 0.5 ms and 32 ms. This behaviour of the N100m closely parallels psychophysical data in a manner that: i) longer half-life times are associated with a stronger tonal percept, and ii) perceptual differences between damped and ramped are maximal at 4 ms half-life time. Interestingly, differences in evoked fields were significantly stronger in the right hemisphere, indicating some degree of hemispheric specialisation. Furthermore, the N100m magnitude was successfully explained by a pitch perception model using multiple scales of temporal integration of auditory nerve activity patterns. This striking correlation between AEFs, perception, and model predictions suggests that the physiological mechanisms involved in the processing of pitch evoked by temporal asymmetric sounds are reflected in the N100m

Time Estimation Predicts Mathematical Intelligence

Background: Performing mental subtractions affects time (duration) estimates, and making time estimates disrupts mental subtractions. This interaction has been attributed to the concurrent involvement of time estimation and arithmetic with general intelligence and working memory. Given the extant evidence of a relationship between time and number, here we test the stronger hypothesis that time estimation correlates specifically with mathematical intelligence, and not with general intelligence or working-memory capacity. Methodology/Principal Findings: Participants performed a (prospective) time estimation experiment, completed several subtests of the WAIS intelligence test, and self-rated their mathematical skill. For five different durations, we found that time estimation correlated with both arithmetic ability and self-rated mathematical skill. Controlling for non-mathematical intelligence (including working memory capacity) did not change the results. Conversely, correlations between time estimation and non-mathematical intelligence either were nonsignificant, or disappeared after controlling for mathematical intelligence. Conclusions/Significance: We conclude that time estimation specifically predicts mathematical intelligence. On the basis of the relevant literature, we furthermore conclude that the relationship between time estimation and mathematical intelligence is likely due to a common reliance on spatial ability