Trimming of a Broken Migrated Biliary Metal Stent with the Nd:YAG Laser

Biliary metal stents are a permanent solution for bile duct stenosis. Complications can arise when the stent migrates, breaks or is overgrown by tumour. The following case demonstrates how a Nd:YAG laser can be used to solve these problems. A 93-year-old man presented with jaundice and fever. Two years earlier a 6-cm metal stent had been implanted into a postinflammatory stenosis of the common bile duct after recurrent cholangitis and repetitive plastic stenting. Duodenoscopy showed that the stent was broken. It had migrated about 3 cm into the duodenum, leading to kinking of the stent and breaking of the wires. The stent was also occluded. It was necessary to purge the common bile duct and to introduce a second stent. However, the only way to reach the papilla was through the broken wires. Placing a second stent this way was impossible. Thus we trimmed the stent with a Nd:YAG laser. The piece that had migrated into the duodenum was retrieved. Now the papilla could be reached. The rest of the metal stent was purged with NaCl 0.9%. A second metal stent was placed. Since an Nd:YAG laser is part of the equipment of most endoscopy units, it can be used to trim a broken or migrated biliary metal stent

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

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

GABAergic Interneurons in Seizures: Investigating Causality With Optogenetics

Seizures are complex pathological network events characterized by excessive and hypersynchronized activity of neurons, including a highly diverse population of GABAergic interneurons. Although the primary function of inhibitory interneurons under normal conditions is to restrain excitation in the brain, this system appears to fail intermittently, allowing runaway excitation. Recent developments in optogenetics, combined with genetic tools and advanced electrophysiological and imaging techniques, allow us for the first time to assess the causal roles of identified cell-types in network dynamics. While these methods have greatly increased our understanding of cortical microcircuits in epilepsy, the roles played by individual GABAergic cell-types in controlling ictogenesis remain incompletely resolved. Indeed, the ability of interneurons to suppress epileptic discharges varies across different subtypes, and an accumulating body of evidence paradoxically implicates some interneuron subtypes in the initiation and maintenance of epileptiform activity. Here, we bring together findings from this growing field and discuss what can be inferred regarding the causal role of different GABAergic cell-types in seizures

KCC2 overexpression prevents the paradoxical seizure-promoting action of somatic inhibition

Although cortical interneurons are apparently well-placed to suppress seizures, several recent reports have highlighted a paradoxical role of perisomatic-targeting parvalbumin-positive (PV+) interneurons in ictogenesis. Here, we use an acute in vivo model of focal cortical seizures in awake behaving mice, together with closed-loop optogenetic manipulation of PV+ interneurons, to investigate their function during seizures. We show that photo-depolarization of PV+ interneurons rapidly switches from an anti-ictal to a pro-ictal effect within a few seconds of seizure initiation. The pro-ictal effect of delayed photostimulation of PV+ interneurons was not shared with dendrite-targeting somatostatin-positive (SOM+) interneurons. We also show that this switch can be prevented by overexpression of the neuronal potassium-chloride co-transporter KCC2 in principal cortical neurons. These results suggest that strategies aimed at improving the ability of principal neurons to maintain a trans-membrane chloride gradient in the face of excessive network activity can prevent interneurons from contributing to seizure perpetuation

LISA Metrology System - Final Report

Gravitational Waves will open an entirely new window to the Universe, different from all other astronomy in that the gravitational waves will tell us about large-scale mass motions even in regions and at distances totally obscured to electromagnetic radiation. The most interesting sources are at low frequencies (mHz to Hz) inaccessible on ground due to seismic and other unavoidable disturbances. For these sources observation from space is the only option, and has been studied in detail for more than 20 years as the LISA concept. Consequently, The Gravitational Universe has been chosen as science theme for the L3 mission in ESA's Cosmic Vision program. The primary measurement in LISA and derived concepts is the observation of tiny (picometer) pathlength fluctuations between remote spacecraft using heterodyne laser interferometry. The interference of two laser beams, with MHz frequency difference, produces a MHz beat note that is converted to a photocurrent by a photodiode on the optical bench. The gravitational wave signal is encoded in the phase of this beat note. The next, and crucial, step is therefore to measure that phase with µcycle resolution in the presence of noise and other signals. This measurement is the purpose of the LISA metrology system and the subject of this report

StdpC: a modern dynamic clamp

With the advancement of computer technology many novel uses of dynamic clamp have become possible. We have added new features to our dynamic clamp software StdpC (“Spike timing-dependent plasticity Clamp”) allowing such new applications while conserving the ease of use and installation of the popular earlier Dynclamp 2/4 package. Here, we introduce the new features of a waveform generator, freely programmable Hodgkin–Huxley conductances, learning synapses, graphic data displays, and a powerful scripting mechanism and discuss examples of experiments using these features. In the first example we built and ‘voltage clamped’ a conductance based model cell from a passive resistor–capacitor (RC) circuit using the dynamic clamp software to generate the voltage-dependent currents. In the second example we coupled our new spike generator through a burst detection/burst generation mechanism in a phase-dependent way to a neuron in a central pattern generator and dissected the subtle interaction between neurons, which seems to implement an information transfer through intraburst spike patterns. In the third example, making use of the new plasticity mechanism for simulated synapses, we analyzed the effect of spike timing-dependent plasticity (STDP) on synchronization revealing considerable enhancement of the entrainment of a post-synaptic neuron by a periodic spike train. These examples illustrate that with modern dynamic clamp software like StdpC, the dynamic clamp has developed beyond the mere introduction of artificial synapses or ionic conductances into neurons to a universal research tool, which might well become a standard instrument of modern electrophysiology

Evolving networks with disadvantaged long-range connections

We consider a growing network, whose growth algorithm is based on the preferential attachment typical for scale-free constructions, but where the long-range bonds are disadvantaged. Thus, the probability to get connected to a site at distance $d$ is proportional to $d^{-\alpha}$, where $\alpha$ is a tunable parameter of the model. We show that the properties of the networks grown with $\alpha <1$ are close to those of the genuine scale-free construction, while for $\alpha >1$ the structure of the network is vastly different. Thus, in this regime, the node degree distribution is no more a power law, and it is well-represented by a stretched exponential. On the other hand, the small-world property of the growing networks is preserved at all values of $\alpha$.Comment: REVTeX, 6 pages, 5 figure