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

Long-term potentiation in neurogliaform interneurons modulates excitation-inhibition balance in the temporoammonic pathway

Apical dendrites of pyramidal neurons integrate information from higher-order cortex and thalamus, and gate signalling and plasticity at proximal synapses. In the hippocampus, neurogliaform cells and other interneurons located within stratum lacunosum-moleculare mediate powerful inhibition of CA1 pyramidal neuron distal dendrites. Is the recruitment of such inhibition itself subject to use-dependent plasticity, and if so, what induction rules apply? Here we show that interneurons in mouse stratum lacunosum-moleculare exhibit Hebbian NMDA receptor-dependent long-term potentiation (LTP). Such plasticity can be induced by selective optogenetic stimulation of afferents in the temporoammonic pathway from the entorhinal cortex, but not by equivalent stimulation of afferents from the thalamic nucleus reuniens. We further show that theta-burst patterns of afferent firing induces LTP in neurogliaform interneurons identified using neuron-derived neurotrophic factor (Ndnf)-Cre mice. Theta-burst activity of entorhinal cortex afferents led to an increase in disynaptic feed-forward inhibition, but not monosynaptic excitation, of CA1 pyramidal neurons. Activity-dependent synaptic plasticity in stratum lacunosum-moleculare interneurons thus alters the excitation-inhibition balance at entorhinal cortex inputs to the apical dendrites of pyramidal neurons, implying a dynamic role for these interneurons in gating CA1 dendritic computations. Abstract figure legend Hebbian LTP of excitatory transmission onto interneurons located within hippocampal stratum lacunosum moleculare (SLM) can be induced by electrical stimulation protocols involving pairing of pre-and post-synaptic activity. Using Ndnf-Cre mice, we show that hippocampal neurogliaform (NGF) cells express this form of LTP. These cells receive glutamatergic afferents from both the nucleus reuniens of the thalamus and the entorhinal cortex (EC), but selective optogenetic activation of either set of fibers reveals LTP at EC inputs only. Using an optogenetic theta-burst stimulation (OptoTBS) protocol to stimulate EC fibers in a physiologically relevant way, we show that NGF interneuron LTP translates to an increase in disynaptic inhibition onto CA1 pyramidal cell distal dendrites. Monosynaptic EC-CA1 pyramidal cell inputs do not undergo equivalent potentiation, leading to a net decrease in the excitation/inhibition (E/I) ratio of this pathway

Activity clamp provides insights into paradoxical effects of the anti-seizure drug carbamazepine

A major challenge in experimental epilepsy research is to reconcile the effects of anti-epileptic drugs (AEDs) on individual neurons with their network-level actions. Highlighting this difficulty, it is unclear why carbamazepine (CBZ), a front-line AED with a known molecular mechanism, has been reported to increase epileptiform activity in several clinical and experimental studies. We confirmed in an in vitro mouse model (both sexes) that the frequency of interictal bursts increased following CBZ perfusion. To address the underlying mechanisms we developed a method, activity clamp, to distinguish the response of individual neurons from network-level actions of CBZ. We first recorded barrages of synaptic conductances from neurons during epileptiform activity, and then replayed them in pharmacologically isolated neurons under control conditions and in the presence of CBZ. CBZ consistently decreased the reliability of the second action potential in each burst of activity. Conventional current clamp recordings using excitatory ramp or square step current injections failed to reveal this effect. Network modelling showed that a CBZ-induced decrease of neuron recruitment during epileptic bursts can lead to an increase in burst frequency at the network level, by reducing the refractoriness of excitatory transmission. By combining activity clamp with computer simulations, the present study provides a potential explanation for the paradoxical effects of CBZ on epileptiform activity.SIGNIFICANCE STATEMENTThe effects of anti-epileptic drugs on individual neurons are difficult to separate from their network-level actions. Although carbamazepine has a known anti-epileptic mechanism, it has also been reported to paradoxically increase epileptiform activity in clinical and experimental studies. To investigate this paradox during realistic neuronal epileptiform activity we developed a method, activity clamp, to distinguish effects of carbamazepine on individual neurons from network-level actions. We demonstrate that carbamazepine consistently decreases the reliability of the second action potential in each burst of epileptiform activity. Network modelling shows that this effect on individual neuronal responses could explain the paradoxical effect of carbamazepine at the network level

The mass of odd-odd nuclei in microscopic mass models

Accurate estimates of the binding energy of nuclei far from stability that cannot be produced in the laboratory are crucial to our understanding of nuclear processes in astrophysical scenarios. Models based on energy density functionals have shown that they are capable of reproducing all known masses with root-mean-square error better than 800 keV, while retaining a firm microscopic foundation. However, it was recently pointed out in [M. Hukkanen et al., arXiv:2210.10674] that the recent BSkG1 model fails to account for a contribution to the binding energy that is specific to odd-odd nuclei, and which can be studied by using appropriate mass difference formulas. We analyse here the (lacking) performance of three recent microscopic mass models with respect to such formulas and examine possibilities to remedy this deficiency in the future.Comment: 6 pages, 2 figures; Contribution to the proceedings of INPC 2022, Cape Town, South Afric

Cost functions for pairwise data clustering

Cost functions for non-hierarchical pairwise clustering are introduced, in the probabilistic autoencoder framework, by the request of maximal average similarity between the input and the output of the autoencoder. The partition provided by these cost functions identifies clusters with dense connected regions in data space; differences and similarities with respect to a well known cost function for pairwise clustering are outlined.Comment: 5 pages, 4 figure

Time scales involved in market emergence

In addressing the question of the time scales characteristic for the market formation, we analyze high frequency tick-by-tick data from the NYSE and from the German market. By using returns on various time scales ranging from seconds or minutes up to two days, we compare magnitude of the largest eigenvalue of the correlation matrix for the same set of securities but for different time scales. For various sets of stocks of different capitalization (and the average trading frequency), we observe a significant elevation of the largest eigenvalue with increasing time scale. Our results from the correlation matrix study go in parallel with the so-called Epps effect. There is no unique explanation of this effect and it seems that many different factors play a role here. One of such factors is randomness in transaction moments for different stocks. Another interesting conclusion to be drawn from our results is that in the contemporary markets the emergence of significant correlations occurs on time scales much smaller than in the more distant history.Comment: 13 page

Preferencial growth: exact solution of the time dependent distributions

We consider a preferential growth model where particles are added one by one to the system consisting of clusters of particles. A new particle can either form a new cluster (with probability q) or join an already existing cluster with a probability proportional to the size thereof. We calculate exactly the probability \Pm_i(k,t) that the size of the i-th cluster at time t is k. We analyze the asymptotics, the scaling properties of the size distribution and of the mean size as well as the relation of our system to recent network models.Comment: 8 pages, 4 figure

Quantifying dynamics of the financial correlations

A novel application of the correlation matrix formalism to study dynamics of the financial evolution is presented. This formalism allows to quantify the memory effects as well as some potential repeatable intradaily structures in the financial time-series. The present study is based on the high-frequency Deutsche Aktienindex (DAX) data over the time-period between November 1997 and December 1999 and demonstrates a power of the method. In this way two significant new aspects of the DAX evolution are identified: (i) the memory effects turn out to be sizably shorter than what the standard autocorrelation function analysis seems to indicate and (ii) there exist short term repeatable structures in fluctuations that are governed by a distinct dynamics. The former of these results may provide an argument in favour of the market efficiency while the later one may indicate origin of the difficulty in reaching a Gaussian limit, expected from the central limit theorem, in the distribution of returns on longer time-horizons.Comment: 10 pages, 7 PostScript figures, talk presented by the first Author at the NATO ARW on Econophysics, Prague, February 8-10, 2001; to be published in proceedings (Physica A