Multiple and plastic receptors mediate tonic GABAA receptor currents in the hippocampus

Persistent activation of GABAA receptors by extracellular GABA (tonic inhibition) plays a critical role in signal processing and network excitability in the brain. In hippocampal principal cells, tonic inhibition has been reported to be mediated by {alpha}5-subunit-containing GABAA receptors ({alpha}5GABAARs). Pharmacological or genetic disruption of these receptors improves cognitive performance, suggesting that tonic inhibition has an adverse effect on information processing. Here, we show that {alpha}5GABAARs contribute to tonic currents in pyramidal cells only when ambient GABA concentrations increase (as may occur during increased brain activity). At low ambient GABA concentrations, activation of {delta}-subunit-containing GABAA receptors predominates. In epileptic tissue, {alpha}5GABAARs are downregulated and no longer contribute to tonic currents under conditions of raised extracellular GABA concentrations. Under these conditions, however, the tonic current is greater in pyramidal cells from epileptic tissue than in pyramidal cells from nonepileptic tissue, implying substitution of {alpha}5GABAARs by other GABAA receptor subtypes. These results reveal multiple components of tonic GABAA receptor-mediated conductance that are activated by low GABA concentrations. The relative contribution of these components changes after the induction of epilepsy, implying an adaptive plasticity of the tonic current in the presence of spontaneous seizures

Perioperative infection prophylaxis and risk factor impact in colon surgery

Background: A prospective observational study was undertaken in 2,481 patients undergoing elective colon resection in 114 German centers to identify optimal drug and dosing modalities and risk factors for postoperative infection. Methods: Patients were pair matched using six risk factors and divided into 672 pairs (ceftriaxone vs, other cephalosporins, group A) and 400 pairs (ceftriaxone vs. penicillins, group B). End points were local and systemic postoperative infection and cost effectiveness. Results: Local infection rates were 6.0 versus 6.5% (group A) and 4.0 versus 10.5% (group B); systemic infection rates in groups A and B were 4.9 versus 6.3% and 3.3 versus 10.5%, respectively. Ceftriaxone was more effective than penicillins overall (6.8 vs. 17.8%, p < 0.001). Length of postoperative hospital stay was 16.2 versus 16.9 days (group A) and 15.8 versus 17.6 days (group B). Of the six risk factors, age and concomitant disease were significant for systemic infection, and blood loss, rectum resection and immunosuppressive therapy were significant for local infection. Penicillin was a risk factor compared to ceftriaxone (p < 0.0001). Ceftriaxone saved Q160.7 versus other cephalosporins and O416.2 versus penicillins. Conclusion: Clinical and microbiological efficacy are responsible for the cost effectiveness of ceftriaxone for perioperative prophylaxis in colorectal surgery. Copyright (C) 2000 S. Karger AG, Basel

Dynamic asset trees and Black Monday

The minimum spanning tree, based on the concept of ultrametricity, is constructed from the correlation matrix of stock returns. The dynamics of this asset tree can be characterised by its normalised length and the mean occupation layer, as measured from an appropriately chosen centre called the `central node'. We show how the tree length shrinks during a stock market crisis, Black Monday in this case, and how a strong reconfiguration takes place, resulting in topological shrinking of the tree.Comment: 6 pages, 3 eps figues. Elsevier style. Will appear in Physica A as part of the Bali conference proceedings, in pres

Statistical properties of short term price trends in high frequency stock market data

We investigated distributions of short term price trends for high frequency stock market data. A number of trends as a function of their lengths was measured. We found that such a distribution does not fit to results following from an uncorrelated stochastic process. We proposed a simple model with a memory that gives a qualitative agreement with real data.Comment: 10 pages, 9 figures, in ver. 2 one chapter adde

Spike-Timing Dependent Plasticity in Inhibitory Circuits

Inhibitory circuits in the brain rely on GABA-releasing interneurons. For long, inhibitory circuits were considered weakly plastic in the face of patterns of neuronal activity that trigger long-term changes in the synapses between excitatory principal cells. Recent studies however have shown that GABAergic circuits undergo various forms of long-term plasticity. For the purpose of this review, we identify three major long-term plasticity expression sites. The first locus is the glutamatergic synapses that excite GABAergic inhibitory cells and drive their activity. Such synapses, on many but not all inhibitory interneurons, exhibit long-term potentiation (LTP) and depression (LTD). Second, GABAergic synapses themselves can undergo changes in GABA release probability or postsynaptic GABA receptors. The third site of plasticity is in the postsynaptic anion gradient of GABAergic synapses; coincident firing of GABAergic axons and postsynaptic neurons can cause a long-lasting change in the reversal potential of GABAA receptors mediating fast inhibitory postsynaptic potentials. We review the recent literature on these forms of plasticity by asking how they may be triggered by specific patterns of pre- and postsynaptic action potentials, although very few studies have directly examined spike-timing dependent plasticity (STDP) protocols in inhibitory circuits. Plasticity of interneuron recruitment and of GABAergic signaling provides for a rich flexibility in inhibition that may be central to many aspects of brain function. We do not consider plasticity at glutamatergic synapses on Purkinje cells and other GABAergic principal cells

Analog modulation of mossy fiber transmission is uncoupled from changes in presynaptic Ca2+

Subthreshold somatic depolarization has been shown recently to modulate presynaptic neurotransmitter release in cortical neurons. To understand the mechanisms underlying this mode of signaling in the axons of dentate granule cells (hippocampal mossy fibers), we have combined two- photon Ca2+ imaging with dual-patch recordings from somata and giant boutons forming synapses on CA3 pyramidal cells. In intact axons, subthreshold depolarization propagates both orthodromically and antidromically, with an estimated length constant of 200-600 mu m depending on the signal waveform. Surprisingly, presynaptic depolarization sufficient to enhance glutamate release at mossy fiber-CA3 pyramidal cell synapses has no detectable effect on either basal Ca2+-dependent fluorescence or action-potential-evoked fluorescence transients in giant boutons. We further estimate that neurotransmitter release varies with presynaptic Ca2+ entry with a 2.5-power relationship and that depolarization-induced synaptic facilitation remains intact in the presence of high-affinity presynaptic Ca2+ buffers or after blockade of local Ca2+ stores. We conclude that depolarization-dependent modulation of transmission at these boutons does not rely on changes in presynaptic Ca2+

A retrospective cohort study of super-refractory status epilepticus in a tertiary neuro-ICU setting

PURPOSE: Over the last decade, the range of treatments available for the management of super-refractory status epilepticus (SRSE) has expanded. However, it is unclear whether this has had an impact on its high mortality and morbidity. The aim of this study was to investigate whether there has been a change in the outcome of SRSE over time in a neurological intensive care unit (ICU) within a tertiary centre. METHODS: Analysis of a retrospective cohort of 53 admissions from 45 patients to the neurological ICU at the National Hospital for Neurology and Neurosurgery, Queen Square, London, between January 2004 and September 2018. RESULTS: Significant reductions were observed in both duration of SRSE over time and in the time spent in ICU, suggesting that treatment quality has improved over time. A median of four antiseizure drugs (ASDs) were given prior to seizure resolution. In 23 % resolution of SRSE occurred following optimisation of current treatment rather than introduction of a new ASD. The mortality rate was very low at 11 % by 6 months; however, there was no indication of improvement in outcome as all surviving patients had a modified Rankin scale score of 3-5 upon discharge from ICU, classified as moderate-to-severe disability. CONCLUSION: Neither the survival rate nor the outcome score changed significantly over time, suggesting that changes in the treatment of SRSE have had no impact on patient outcome

Extensive study of nuclear uncertainties and their impact on the r-process nucleosynthesis in neutron star mergers

Theoretically predicted yields of elements created by the rapid neutron capture (r-) process carry potentially large uncertainties associated with incomplete knowledge of nuclear properties as well as approximative hydrodynamical modelling of the matter ejection processes. We present an in-depth study of the nuclear uncertainties by systematically varying theoretical nuclear input models that describe the experimentally unknown neutron-rich nuclei. This includes two frameworks for calculating the radiative neutron capture rates and six, four and four models for the nuclear masses, $\beta$-decay rates and fission properties, respectively. Our r-process nuclear network calculations are based on detailed hydrodynamical simulations of dynamically ejected material from NS-NS or NS-BH binary mergers plus the secular ejecta from BH-torus systems. The impact of nuclear uncertainties on the r-process abundance distribution and early radioactive heating rate is found to be modest (within a factor $\sim 20$ for individual $A>90$ nuclei and a factor 2 for the heating rate), however the impact on the late-time heating rate is more significant and depends strongly on the contribution from fission. We witness significantly larger sensitivity to the nuclear physics input if only a single trajectory is used compared to considering ensembles of $\sim$200-300 trajectories, and the quantitative effects of the nuclear uncertainties strongly depend on the adopted conditions for the individual trajectory. We use the predicted Th/U ratio to estimate the cosmochronometric age of six metal-poor stars to set a lower limit of the age of the Galaxy and find the impact of the nuclear uncertainties to be up to 2 Gyr.Comment: 26 pages, 22 figures, submitted to MNRA

Exploiting Resolution-based Representations for MaxSAT Solving

Most recent MaxSAT algorithms rely on a succession of calls to a SAT solver in order to find an optimal solution. In particular, several algorithms take advantage of the ability of SAT solvers to identify unsatisfiable subformulas. Usually, these MaxSAT algorithms perform better when small unsatisfiable subformulas are found early. However, this is not the case in many problem instances, since the whole formula is given to the SAT solver in each call. In this paper, we propose to partition the MaxSAT formula using a resolution-based graph representation. Partitions are then iteratively joined by using a proximity measure extracted from the graph representation of the formula. The algorithm ends when only one partition remains and the optimal solution is found. Experimental results show that this new approach further enhances a state of the art MaxSAT solver to optimally solve a larger set of industrial problem instances