Late Shocks Research Articles

Discounting of Future Rewards and Punishments in Rats.

Temporal reward discounting describes the decrease of value of a reward as a function of delay. Decision-making between future aversive outcomes is much less studied, and there is no clear decision pattern across studies; while some authors suggest that human and nonhuman animals prefer sooner over later painful shocks, others found the exact opposite. In a series of three experiments, Long-Evans rats chose between differently timed electric shocks and rewards in a T-maze. In experiment 1, rats chose between early and late painful shocks with identical, long reward delays; in experiment 2, they chose between early reward and early shocks, or late rewards and late shocks; in experiment 3, they chose between early and late rewards, with identical, short delays to the shock. We tested the predictions of two competing hypotheses: the aversive discounting theory assumes that future shocks are discounted, and, hence, less unpleasant than early shocks. The utility from anticipation theory implies that rats derive negative utility from waiting for the shock; late shocks should, hence, be more unpleasant than early shocks. We did not find unanimous evidence for either theory. Instead, our results are more consistent with the post hoc idea that shocks may have negative spill-over effects on reward values, the closer in time a shock is to a subsequent reward, the stronger the reward is devalued. Interestingly and consistent with our theory, we find that, depending on the temporal shock-reward contiguity, rats can be brought to prefer later over sooner rewards of identical magnitudes.

The ventricular fibrillation waveform in relation to shock success in early vs. late phases of out-of-hospital resuscitation

BackgroundThe amplitude spectrum area (AMSA) of the ventricular fibrillation (VF) waveform predicts shock success and clinical outcome after out-of-hospital cardiac arrest (OHCA). Recently, also AMSA-changes demonstrated prognostic value. Until now, most studies focused on early shocks, while many patients require prolonged resuscitations. We studied AMSA and its changes in relation to shock success, for both the early and later phase of resuscitation. MethodsPer-shock VF-waveform analysis of a prospective OHCA-cohort (Nijmegen, The Netherlands). The absolute AMSA and relative AMSA-changes (ΔAMSA) were calculated from three-second VF-segments prior to defibrillation. Shocks were categorised as early (#1–3) or late (#4–8). Shock success was defined as return of organised rhythm. ResultsShock success was 46% for early (131/286) and 52% for late shocks (85/162), p = 0.18. Early shock success varied from 23% to 70% with increasing quartiles of AMSA (p-trend<0.001). For late shocks, there also was an association with AMSA, with a narrower range in shock success from 43% to 68% (p-trend = 0.04). Higher values of ΔAMSA were associated with shock success in the early, but not in the later phase. ConclusionAMSA relates to shock success during the entire resuscitation, but associations were most apparent for early shocks. AMSA-changes were also associated with shock success, but only in the early phase of resuscitation. In an era of smart defibrillators, absolute AMSA and relative changes hold promise for studies on early guidance of resuscitation, whereas additional studies are warranted to further characterize shock prediction in the later phase.

Terminating spiral wave and spatiotemporal chaos in cardiac tissues by using late sodium current

Most Na+ channels open transiently upon depolarization of cardiac cell membrane and then are quickly inactivated. However, some Na+ channels remain active, which generate the late sodium current during the action potential plateau. So far, late sodium current has been regarded as a relevant contributor to arrhythmias and its inhibition can suppress re-entrant and multifocal ventricular fibrillation so that its inhibition may become a novel therapeutic strategy to treat cardiac arrhythmias in the future. Therefore, how to inhibit late sodium current has received special attention. Since both the late sodium current and defibrillation shocks can lead to the increase of action potential duration, the late sodium current can be used to terminate ventricular fibrillation. However, the suppression of spiral wave and spatiotemporal chaos in cardiac tissues via late sodium current has been neglected. In this paper, we use the model of human heart to study the suppression of spiral wave and spatiotemporal chaos in two-dimensional cardiac tissue by generating late sodium current. We suggest that such a control strategy to induce late sodium current. The slow inactivation gate of sodium channel is clamped to 0.7 while the threshold voltage of corresponding fast inactivation gate is real-timely modulated. We first reduce the threshold voltage from 71.55 mV to 50.55 mV within the time interval T1, and then increase it from 50.55 mV to 71.55 mV within the time interval T2. When the threshold voltage returns to 71.55 mV, the changes of the relevant inactivation gates of sodium channel go back to normal dynamic state. Numerical simulation results show that when the control parameters are properly chosen, the control-induced late sodium current can effectively suppress spiral wave and spatiotemporal chaos even if there are some cardiac cells with spontaneous late sodium current. The advantage of the control scheme is that the control-induced late sodium current is small. The control duration is short because the spiral wave and spatiotemporal chaos disappear mainly due to the conduction obstacle. In a few cases, the spatiotemporal chaos disappears through the transition from spiral wave to target wave. We hope that these results may provide a new strategy to treat heart disease.

Arrhythmias in Patients with Cardiac Implantable Electrical Devices after Implantation of a Left Ventricular Assist Device.

Utilization of continuous-flow left ventricular assist devices (CF-LVADs) for advanced heart failure is increasing, and the role of cardiac implantable electrical devices (CIED) is unclear. Prior studies of the incidence of arrhythmias and shocks are frequently limited by ascertainment. One hundred and seventy-eight patients were examined with a previous CIED who were implanted with a CF-LVAD. Medical history, medications, and CIED data from device interrogations were gathered. A cardiac surgery control group (n = 38) was obtained to control for surgical factors. Several clinically significant events increased after LVAD implantation: treated-zone ventricular arrhythmias (VA; p < 0.01), monitored-zone VA (p < 0.01), antitachycardia pacing (ATP)-terminated episodes (p < 0.01), and shocks (p = 0.01), although administered shocks later decreased (p < 0.01). Presence of a preimplant VA was associated with postoperative VA (odds ratio [OR]: 4.31; confidence interval [CI]: 1.5-12.3, p < 0.01). Relative to cardiac surgery, LVAD patients experienced more perioperative events (i.e., monitored VAs and shocks, p < 0.01 and p = 0.04). Neither implantable cardioverter defibrillator (ICD) shocks before implant nor early or late postimplant arrhythmias or shocks predicted survival (p = 0.07, p = 0.55, and p = 0.55). Our experience demonstrates time-dependent effects on clinically significant arrhythmias after LVAD implantation, including evidence that early LVAD-related arrhythmias may be caused by the unique arrhythmogenic effects of VAD implant.

Characterization and financial impact of implantable cardioverter-defibrillator patients without interventions 5 years after implantation

Implantable cardioverter defibrillators (ICD's) are increasingly used for primary and secondary prevention of sudden cardiac death. However, data on how many ICD patients indeed receive appropriate ICD therapy during long-term follow-up is scarce. The aim of our study was to determine the number of patients without appropriate ICD therapy 5 years after ICD implantation, to identify predicting factors, to assess the occurrence of late first ICD therapy and to quantify the financial impact of ICD therapy in a real-world setting. Prospective observational study. We prospectively enrolled 322 consecutive ICD patients. Baseline data were collected at implantation and patients were followed for a median of 7.3 years (IQR 5.8-9.2 years). Time to first appropriate ICD therapy (either antitachycardia pacing or cardioversion) was documented. Five years after implantation, 139 patients (43%) had not received appropriate ICD therapy. In multivariable analysis, a primary prevention indication and negative electrophysiological studies prior to ICD implantation were independent predictors of freedom from ICD therapy. Of the patients without ICD therapy, 5 years after implantation, 25% had experienced inappropriate ICD shocks. Two hundred and seven devices (1.5 devices per patient) were needed for the 139 patients without ICD intervention within 5 years, accounting for € 31,784 per patient. During an additional follow-up of 3 years, 12% of the patients with unused ICD received a late first appropriate ICD therapy. About half of the ICD patients receive appropriate ICD therapy within 5 years after implantation. Furthermore, there is a significant proportion of patients receiving late first shocks after five initially uneventful years.

A systematic description of shocks in gamma-ray bursts - I. Formulation

Since the suggestion of relativistic shocks as the origin of gamma-ray bursts (GRBs) in early 90's, the mathematical formulation of this process has stayed at phenomenological level. One of the reasons for the slow development of theoretical works in this domain has been the simple power-law behaviour of the afterglows hours or days after the prompt gamma-ray emission. Nowadays with the launch of the Swift satellite, gamma-ray bursts can be observed in multi-wavelength from a few tens of seconds after trigger onward. These observations have leaded to the discovery of features unexplainable by the simple formulation of the shocks and emission processes used up to now. But "devil is in details" and some of these features may be explained with a more detailed formulation of phenomena and without adhoc addition of new processes. Such a formulation is the goal of this work. We present a consistent formulation of the collision between two spherical relativistic shells. The model can be applied to both internal and external shocks. Notably, we propose two phenomenological models for the evolution of the emitting region during the collision. One of these models is more suitable for the internal shocks and the other for the external collisions. We calculate radiation flux, lags, and hardness ratios. One of our aims has been a formulation enough complex to include the essential processes, but enough simple such that the data can be directly compared with the theory to extract the value and evolution of physical quantities. To accomplish this goal, we also suggest a procedure for extracting parameters of the model from data. In a following paper we numerically calculate the evolution of some simulated models and compare their features with the properties of the observed gamma-ray bursts.(abbreviated)

The economy and the presidential vote: What leading indicators reveal well in advance

Everybody knows that “the economy” matters in presidential elections, but how can one incorporate economic information in an early forecasting equation? Our economic forecasting tool is the cumulative growth of leading indicators during a presidential term—weighting recent growth most heavily—which provides an early warning, as early as quarter 1 of the election year, about the Election Day economy. To control for other, non-economic factors, our model also includes presidential approval or trial-heat polls. In this paper we show how cumulative leading indicators measured early in the election year actually reveal as much about the final vote as cumulative income growth observed on the eve of the election. That is, voters respond at least as much to economic change that is predicted well in advance of elections as to economic surprises that are felt during the course of the campaign. Approval judgments incorporate these effects over the course of the election year. Very late economic shocks matter, to be sure, but they are not known until well after the campaign. The findings are informative about how the economy matters on Election Day, and have implications for our ability to forecast the outcome well in advance.

X-ray flares from late internal and late external shocks

We analyze several recently detected gamma-ray bursts (GRBs) with late X-ray flares in the context of late internal shock and late external shock models. We find that the X-ray flares in GRB 050421 and GRB 050502B originate from late internal shocks, while the main X-ray flares in GRB 050406 and GRB 050607 may arise from late external shocks. We also constrain the lower limit on the Lorentz factor of X-ray flares in the context of the late internal shock model.

The Fundamentals, the Polls, and the Presidential Vote

As the experience of 2000 shows, forecasting presidential elections is an inexact science. Everybody knows that “the economy” matters, but simple projection from economic conditions at the time of the forecast is not enough. And the most important economic shocks to the economy are the late shocks, which may arrive too late to be measured by the forecaster. Other events also impact, such as (in 2004) the Iraq war. Incorporating presidential approval into the model helps to control for “other” events that economic indicators ignore, but obviously only those that are observable by the time of the latest approval reading. They also don't reveal much about voters' comparative judgments of the two candidates. Of course one can forecast the presidential race from trial-heat polls available at the moment rather than trying to capture the fundamentals that will matter on Election Day. But the whole purpose of forecasting is to present information about the voters' future behavior that is not yet evident in the trialheat polls. Besides, early polls only tell us little about the final election outcome.

The snowball Earth hypothesis: testing the limits of global change

The gradual discovery that late Neoproterozoic ice sheets extended to sea level near the equator poses a palaeoenvironmental conundrum. Was the Earth's orbital obliquity &gt; 60° (making the tropics colder than the poles) for 4.0 billion years following the lunar‐forming impact, or did climate cool globally for some reason to the point at which runaway ice‐albedo feedback created a `snowball' Earth? The high‐obliquity hypothesis does not account for major features of the Neoproterozoic glacial record such as the abrupt onsets and terminations of discrete glacial events, their close association with large (&gt; 10‰) negative δ13C shifts in seawater proxies, the deposition of strange carbonate layers (`cap carbonates') globally during post‐glacial sea‐level rise, and the return of large sedimentary iron formations, after a 1.1 billion year hiatus, exclusively during glacial events. A snowball event, on the other hand, should begin and end abruptly, particularly at lower latitudes. It should last for millions of years, because outgassing must amass an intense greenhouse in order to overcome the ice albedo. A largely ice‐covered ocean should become anoxic and reduced iron should be widely transported in solution and precipitated as iron formation wherever oxygenic photosynthesis occurred, or upon deglaciation. The intense greenhouse ensures a transient post‐glacial regime of enhanced carbonate and silicate weathering, which should drive a flux of alkalinity that could quantitatively account for the world‐wide occurrence of cap carbonates. The resulting high rates of carbonate sedimentation, coupled with the kinetic isotope effect of transferring the CO2 burden to the ocean, should drive down the δ13C of seawater, as is observed. If cap carbonates are the `smoke' of a snowball Earth, what was the `gun'? In proposing the original Neoproterozoic snowball Earth hypothesis, Joe Kirschvink postulated that an unusual preponderance of land masses in the middle and low latitudes, consistent with palaeomagnetic evidence, set the stage for snowball events by raising the planetary albedo. Others had pointed out that silicate weathering would most likely be enhanced if many continents were in the tropics, resulting in lower atmospheric CO2 and a colder climate. Negative δ13C shifts of 10–20‰ precede glaciation in many regions, giving rise to speculation that the climate was destabilized by a growing dependency on greenhouse methane, stemming ultimately from the same unusual continental distribution. Given the existing palaeomagnetic, geochemical and geological evidence for late Neoproterozoic climatic shocks without parallel in the Phanerozoic, it seems inevitable that the history of life was impacted, perhaps profoundly so.

Can shocks timed to action potentials in low-gradient regions improve both internal and out-of-hospital defibrillation?

During the first minute of fibrillation, circulating wavefronts excite new fibrillation action potentials almost immediately following termination of the preceding action potential. The extension of refractoriness hypothesis states that a successful defibrillating shock must produce a uniform postshock refractoriness of a specific optimal duration throughout the ventricle, which blocks these wavefronts and terminates fibrillation. We hypothesized that, if shocks are appropriately timed early in the fibrillation action potential in low-voltage-gradient regions, postshock refractoriness will already be long and the shock need not be strong enough to further extend it. This will result in a lower defibrillation threshold (DFT). This hypothesis was tested in the isolated rabbit heart model. Shocks were synchronized to monophasic action potentials recorded from a low-intensity region. An up/down protocol was used. I 50 for early shocks was 17% lower than that for late shocks (31% decrease in E 50). Standard deviation of I 50 was reduced from 32% for late shocks to 18% for early shocks. Therefore, shock synchronization improves both DFT and inter-subject variability during early fibrillation. As fibrillation duration increases, action potential frequency decreases and periods of diastole occur. Because of these ischemic changes, it is uncertain whether shock timing can produce similar improvements in defibrillation under out-of-hospital conditions.

Pressure-induced retention of second polar body and suppression of first cleavage in rainbow trout: Production of all-triploids, all-tetraploids, and heterozygous and homozygous diploid gynogenetics

Retention of the second polar body in rainbow trout eggs was induced by 7000 psi early pressure shocks (applied 40 min after insemination) lasting 4 min. This resulted in all-triploid progenies after fertilization with functional sperm, and in high yields of heterozygous diploid gynogenetic fry after insemination with gamma-irradiated sperm. All-tetraploid progenies were produced by 7000 psi late pressure shocks (applied 5 h 50 min after insemination) lasting 4 min, if normal sperm had been used. With eggs activated by gamma-irradiated sperm, these shocks resulted in diploid gynogenetic embryos that were supposed to be homozygous at all their loci because obviously they result from the fusion of two mitotic products. This fact may explain their very low post-hatching survival, but the occurrence of residual chromosome fragments of paternal origin in their cells, demonstrated by an extensive karyological investigation, could also be responsible of the poor yields; such an observation suggests that we abandon the use of gamma irradiation for sperm inactivation. Finally, tetraploid hybrid embryos were produced with similar late pressure shocks applied after heterospecific inseminations.

Novel behaviour of the mitotic clock in Physarum.

ABSTRACT Surface plasmodia of the myxomycete, Physarum polycephalum were subjected to heat shocks at 38 °C for varying durations either in late G2, or at M + 4 h, and the excess delay to the next synchronous mitosis observed. Three-hour heat shocks applied in late G2 yielded mitotic excess delays which clustered at peaks of 4–5, 11–12 and 22–23 h. Hence plasmodia can skip part of a cycle, one full cycle, or even two full cycles, yet continue to count cycle times up to two cycles. This is one line of evidence that mitosis itself is not a necessary condition for timing the length of the mitotic cycle. In a large number of late G2 shocks, only a fraction of the nuclei divided at 4–5 h excess delay, and then went through their first full synchronous mitosis at 12 h excess delay. These partial mitoses also were observed for plasmodia which had their first full synchronous mitosis at 22–24 h excess delay. The fraction of nuclei which undergo partial mitosis is nearly independent of the mitotic interval occurring between the partial mitosis and the first full synchronous mitosis, indicating that nuclear:cytoplasmic ratio is unlikely to be the sole factor governing mitotic cycle length. The dependence of mitotic excess delay on: (1) the exact time at which heat shock began shortly before mitosis; (2) the condition of the culture from which a set of plasmodia were plated; (3) the average cycle length; (4) the occurrence of nucleolar breakdown; and (5) the extent of plasmodial death, is minimal. Six-hour heat shocks applied in late G2, also yielded rhythmical mitotic excess delay responses with peaks at 6–8, 14–16, and 26–27 h excess delay. Nine-hour heat shocks given in late G2 produced the greatest mean excess delays (17·5 h). Finally, plasmodia exposed to 12-h heat shocks in late G2, yielded mitotic excess delays with a mean of 10· 7 h, considerably less than either the 6–or 9–h heat shocks. In contrast, plasmodia given a 3–, 6– 9-, or 12–h heat shock at M+4 h showed only a monotonically increasing mitotic excess delay, which never exceeded one full cycle of delay. The above results are consistent with and predicted by the mitotic oscillator model in which the periodicity of the mitotic cycle is underlain by a continuous biochemical limit cycle oscillation, which drives mitosis but which continues to oscillate even when mitosis is suppressed.

Krakatão

ALTHOUGH I have not yet had the good fortune of reading Dr. Verbeek's “Krakatão,” yet in the review published in NATURE of October 22 (p. 601) there are one or two points I would like to draw attention to. In speaking of the earthquake of September, 1880, we are told that it may have facilitated the entrance of water by the Sunda fissure. If this were so, it certainly seems a strange thing that no less than three years should he necessary to heat the water before the explosion took place. I think that at present few geologists believe in water gaining access to the magma by fissures while we neglect percolation through porous rocks. It seems to me that the above earthquake was the result of rupture and extension of the magma-filled fissure towards the surface, in consequence of which the final outburst was put off for a short time by increasing the space for, and so lowering the tension of, the magma-filled fissure. By a careful study of the products of many volcanoes I have shown how the magma gradually dissolves or takes up within it water from the surrounding rocks, and as this is a slow process, the longer a volcano remains inactive, other things being equal, the more violent will be the subsequent eruption and the more vitreous will be the pumice owing to the rapid cooling of the magma froth in consequence of the large absorption of heat in converting the dissolved water into the gaseous state of steam, in the samé way that the temperature of seltzer water falls on allowing the gas to escape on removal of the cork. The above earthquake has its parallels in A.D. 63 at Vesuvius, those of 1536 and 1537 at Monte Nuovo, and in the late Ischian shocks.