Stress-facilitated LTD induces output plasticity through a synchronized-spikes and spontaneous unitary discharges the CA1 region of the hippocampus

Long-term potentiation (LTP) and long-term depression (LTD) of the excitatory synaptic inputs plasticity in the hippocampus is believed to underlie certain types of learning and memory. Especially, stressful experiences, well known to produce long-lasting strong memories of the event themselves, enable LTD by low frequency stimulation (LFS, 3 Hz) but block LTP induction by high frequency stimulation (HFS, 200 Hz). However, it is unknown whether stress-affected synaptic plasticity has an impact on the output plasticity. Thus, we have simultaneously studied the effects of stress on synaptic plasticity and neuronal output in the hippocampal CA1 region of anesthetized Wistar rats. Our results revealed that stress increased basal power spectrum of the evoked synchronized-spikes and enabled LTD induction by LFS. The induction of stress-facilitated LTD but not LFS induced persistent decreases of the power spectrum of the synchronized-spikes and the frequency of the spontaneous unitary discharges; However, HFS induced UP in non-stressed animals and increased the power spectrum of the synchronized-spikes, without affecting the frequency of the spontaneous unitary discharges, but HFS failed to induce UP in stressed animals without affecting the power spectrum of the synchronized-spikes and the frequency of the spontaneous unitary discharges. These observations that stress-facilitated LTD induces the output plasticity through the synchronized-spikes and spontaneous unitary discharges suggest that these types of stress-related plasticity may play significant roles in distribution, amplification and integration of encoded information to other brain structures under stressful conditions. (C) 2004 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.

The price of pain and the value of suffering.

Estimating the financial value of pain informs issues as diverse as the market price of analgesics, the cost-effectiveness of clinical treatments, compensation for injury, and the response to public hazards. Such valuations are assumed to reflect a stable trade-off between relief of discomfort and money. Here, using an auction-based health-market experiment, we show that the price people pay for relief of pain is strongly determined by the local context of the market, that is, by recent intensities of pain or immediately disposable income (but not overall wealth). The absence of a stable valuation metric suggests that the dynamic behavior of health markets is not predictable from the static behavior of individuals. We conclude that the results follow the dynamics of habit-formation models of economic theory, and thus, this study provides the first scientific basis for this type of preference modeling.

A simple diesel engine air-path model to predict the cylinder charge during transients: Strategies for reducing transient emissions spikes

Simple air-path models for modern (VGT/EGR equipped) diesel engines are in common use, and have been reported in the literature. This paper addresses some of the shortcomings of control-oriented models to allow better prediction of the cylinder charge properties. A fast response CO2 analyzer is used to validate the model by comparing the recorded and predicted CO2 concentrations in both the intake port and exhaust manifold of one of the cylinders. Data showing the recorded NOx emissions and exhaust gas opacity during a step change in engine load illustrate the spikes in both NOx and smoke seen during transient conditions. The predicted cylinder charge properties from the model are examined and compared with the measured NOx and opacity. Together, the emissions data and charge properties paint a consistent picture of the phenomena occurring during the transient. Alternative strategies for the fueling and cylinder charge during these load transients are investigated and discussed. Experimental results are presented showing that spikes in both NOx and smoke can be avoided at the expense of some loss in torque response. Even if the torque response must be maintained, it is demonstrated that it is still possible to eliminate spikes in NOx emissions for the transient situation being examined. Copyright © 2006 SAE International.

Changing the responses of cortical neurons from sub- to suprathreshold using single spikes in vivo.

Action Potential (APs) patterns of sensory cortex neurons encode a variety of stimulus features, but how can a neuron change the feature to which it responds? Here, we show that in vivo a spike-timing-dependent plasticity (STDP) protocol-consisting of pairing a postsynaptic AP with visually driven presynaptic inputs-modifies a neurons' AP-response in a bidirectional way that depends on the relative AP-timing during pairing. Whereas postsynaptic APs repeatedly following presynaptic activation can convert subthreshold into suprathreshold responses, APs repeatedly preceding presynaptic activation reduce AP responses to visual stimulation. These changes were paralleled by restructuring of the neurons response to surround stimulus locations and membrane-potential time-course. Computational simulations could reproduce the observed subthreshold voltage changes only when presynaptic temporal jitter was included. Together this shows that STDP rules can modify output patterns of sensory neurons and the timing of single-APs plays a crucial role in sensory coding and plasticity.DOI:http://dx.doi.org/10.7554/eLife.00012.001.

Statistical analysis of microscale gas flows and stock price changes

First, recent studies on the information preservation (IP) method, a particle approach for low-speed micro-scale gas flows, are reviewed. The IP method was validated for benchmark issues such as Couette, Poiseuille and Rayleigh flows, compared well with measured data for typical internal flows through micro-channels and external flows past micro flat plates, and combined with the Navier-Stokes equations to be a hybrid scheme for subsonic, rarefied gas flows. Second, the focus is moved to the microscopic characteristic of China stock market, particularly the price correlation between stock deals. A very interesting phenomenon was found that showed a reverse transition behaviour between two neighbouring price changes. This behaviour significantly differs from the transition rules for atomic and molecular energy levels, and it is very helpful to understand the essential difference between stock markets and nature.

How smokers may react to cigarette taxes and price increases in Brazil: data from a national survey

Background: Despite being the third largest tobacco producer in the world, Brazil has developed a comprehensive tobacco control policy that includes a broad restriction on both advertising and smoking in indoor public places, compulsory pictorial warning labels, and a menthol cigarette ban. However, tax and pricing policies have been developed slowly and only very recently were stronger measures implemented. This study investigated the expected responses of smokers to hypothetical price increases in Brazil.Methods: We analyzed smokers' responses to hypothetical future price increases according to sociodemographic characteristics and smoking conditions in a multistage sample of Brazilian current cigarette smokers aged >= 14 years (n = 500). Logistic regression analysis was used to examine the relationship between possible responses and different predictors.Results: in most subgroups investigated, smokers most frequently said they would react to a hypothetical price increase by taking up alternatives that might have a positive impact on health, i.e., they would try to stop smoking (52.3%) or smoke fewer cigarettes (46.8%). However, a considerable percentage responded that they would use alternatives that would reduce the effect of price increases, such as the same brand with lower cost (48.1%). After controlling for sex age group (14-19, 20-39, 40-59, and >= 60 years), schooling level (>= 9 versus <= 9 years), number of cigarettes per day (>20 versus <= 20), and stage of change for smoking cessation (precontemplation, contemplation, and preparation), lower levels of dependence were positively associated with the response I would try to stop smoking (odds ratio [OR], 2.19). Young age was associated with I would decrease the number of cigarettes (OR, 3.44). A low schooling level was strongly associated with all responses.Conclusions: Taxes and prices increases have great potential to stimulate cessation or reduction of cigarette consumption further among two important vulnerable populations of smokers in Brazil: young smokers and those of low educational level. the results from the present study also suggest that seeking illegal products may reduce the impact of increased taxes, but does not eliminate it.

Spikes, Synchrony, and Attentive Learning by Laminar Thalamocortical Circuits

This article develops the Synchronous Matching Adaptive Resonance Theory (SMART) neural model to explain how the brain may coordinate multiple levels of thalamocortical and corticocortical processing to rapidly learn, and stably remember, important information about a changing world. The model clarifies how bottom-up and top-down processes work together to realize this goal, notably how processes of learning, expectation, attention, resonance, and synchrony are coordinated. The model hereby clarifies, for the first time, how the following levels of brain organization coexist to realize cognitive processing properties that regulate fast learning and stable memory of brain representations: single cell properties, such as spiking dynamics, spike-timing-dependent plasticity (STDP), and acetylcholine modulation; detailed laminar thalamic and cortical circuit designs and their interactions; aggregate cell recordings, such as current-source densities and local field potentials; and single cell and large-scale inter-areal oscillations in the gamma and beta frequency domains. In particular, the model predicts how laminar circuits of multiple cortical areas interact with primary and higher-order specific thalamic nuclei and nonspecific thalamic nuclei to carry out attentive visual learning and information processing. The model simulates how synchronization of neuronal spiking occurs within and across brain regions, and triggers STDP. Matches between bottom-up adaptively filtered input patterns and learned top-down expectations cause gamma oscillations that support attention, resonance, and learning. Mismatches inhibit learning while causing beta oscillations during reset and hypothesis testing operations that are initiated in the deeper cortical layers. The generality of learned recognition codes is controlled by a vigilance process mediated by acetylcholine.

From Synapse to Self: Spikes, Synchrony, and Attentive Learning by Laminar Thalamocortical Circuits

How do our brains transform the "blooming buzzing confusion" of daily experience into a coherent sense of self that can learn and selectively attend to important information? How do local signals at multiple processing stages, none of which has a global view of brain dynamics or behavioral outcomes, trigger learning at multiple synaptic sites when appropriate, and prevent learning when inappropriate, to achieve useful behavioral goals in a continually changing world? How does the brain allow synaptic plasticity at a remarkably rapid rate, as anyone who has gone to an exciting movie is readily aware, yet also protect useful memories from catastrophic forgetting? A neural model provides a unified answer by explaining and quantitatively simulating data about single cell biophysics and neurophysiology, laminar neuroanatomy, aggregate cell recordings (current-source densities, local field potentials), large-scale oscillations (beta, gamma), and spike-timing dependent plasticity, and functionally linking them all to cognitive information processing requirements.

At what price? A cost-effectiveness analysis comparing trial of labour after previous caesarean versus elective repeat caesarean delivery

Background: Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland.Methods: Using a decision analytic model, a cost-effectiveness analysis (CEA) was performed where the measure of health gain was quality-adjusted life years (QALYs) over a six-week time horizon. A review of international literature was conducted to derive representative estimates of adverse maternal health outcomes following a trial of labour after caesarean (TOLAC) and ERCD. Delivery/procedure costs derived from primary data collection and combined both "bottom-up" and "top-down" costing estimations.Results: Maternal morbidities emerged in twice as many cases in the TOLAC group than the ERCD group. However, a TOLAC was found to be the most-effective method of delivery because it was substantially less expensive than ERCD ((sic)1,835.06 versus (sic)4,039.87 per women, respectively), and QALYs were modestly higher (0.84 versus 0.70). Our findings were supported by probabilistic sensitivity analysis.Conclusions: Clinicians need to be well informed of the benefits and risks of TOLAC among low risk women. Ideally, clinician-patient discourse would address differences in length of hospital stay and postpartum recovery time. While it is premature advocate a policy of TOLAC across maternity units, the results of the study prompt further analysis and repeat iterations, encouraging future studies to synthesis previous research and new and relevant evidence under a single comprehensive decision model.

The price of innovation: new estimates of drug development costs.

The research and development costs of 68 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms. These data were used to estimate the average pre-tax cost of new drug development. The costs of compounds abandoned during testing were linked to the costs of compounds that obtained marketing approval. The estimated average out-of-pocket cost per new drug is 403 million US dollars (2000 dollars). Capitalizing out-of-pocket costs to the point of marketing approval at a real discount rate of 11% yields a total pre-approval cost estimate of 802 million US dollars (2000 dollars). When compared to the results of an earlier study with a similar methodology, total capitalized costs were shown to have increased at an annual rate of 7.4% above general price inflation.

Paying the price for loss of light

Considers the Court of Appeal ruling in Forsyth-Grant v Allen on the principles to be applied in assessing damages for the loss of light. Outlines the method for calculating damages for loss of right to light, the type of amenity which will be included in calculations for loss of amenity and the process applied in this case for assessing damages arising from the loss of profits that would have been made by the owner of the right to light if they had negotiated to relax the covenant, with reference to case law. Notes the limits to damages available for hypothetical loss and the difference between this award of profits and an account of profits.