983 research outputs found
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,
-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 for individual 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
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
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