Modelling combined intravenous thrombolysis and mechanical thrombectomy in acute ischaemic stroke: Understanding the relationship between stent retriever configuration and clot lysis mechanisms

Background: Combined intravenous thrombolysis and mechanical thrombectomy (IVT-MT) is a common treatment in acute ischaemic stroke, however the interaction between IVT and MT from a physiological standpoint is poorly understood. In this pilot study, we conduct numerical simulations of combined IVT-MT with various idealised stent retriever configurations to evaluate performance in terms of complete recanalisation times and lysis patterns. Methods: A 3D patient-specific geometry of a terminal internal carotid artery with anterior and middle cerebral arteries is reconstructed, and a thrombus is artificially implanted in the MCA branch. Various idealised stent retriever configurations are implemented by varying stent diameter and stent placement, and a configuration without a stent retriever provides a baseline for comparison. A previously validated multi-level model of thrombolysis is used, which incorporates blood flow, drug transport, and fibrinolytic reactions within a fibrin thrombus. Results: Fastest total recanalisation was achieved in the thrombus without a stent retriever, with lysis times increasing with stent retriever diameter. Two mechanisms of clot lysis were established: axial and radial permeation. Axial permeation from the clot front was the primary mechanism of lysis in all configurations, as it facilitated increased protein binding with fibrin fibres. Introducing a stent retriever channel allowed for radial permeation, which occurred at the fluid-thrombus interface, although lysis was much slower in the radial direction because of weaker secondary velocities. Conclusions: Numerical models can be used to better understand the complex physiological relationship between IVT and MT. Two different mechanisms of lysis were established, providing a basis towards improving the efficacy of combined treatments

Computational simulations of thrombolytic therapy in acute ischaemic stroke

Ischaemic stroke can occur when an artery to the brain is blocked by a blood clot. The use of thrombolytic agents, such as tissue plasminogen activator (tPA), to dissolve the occluding clot is limited by the risk of intracerebral haemorrhage (ICH), a known side effect associated with tPA. We developed a computational thrombolysis model for a 3D patient-specific artery coupled with a compartmental model for temporal concentrations of tPA and lysis proteins during intravenous infusion of tPA, in order to evaluate the effects of tPA dose on the efficacy of thrombolytic therapy and the risk of ICH. The model was applied to a 3-mm-long fibrin clot with two different fibrin fibre radii in the middle cerebral artery (MCA) – a setting relevant to ischaemic stroke, and results for different tPA dose levels and fibrin fibre radii were compared. Our simulation results showed that clot lysis was accelerated at higher tPA doses at the expense of a substantial increase in the risk of ICH. It was also found that a fine clot with a smaller fibre radius dissolved much slowly than a coarse clot due to a slower tPA penetration into the clots

Finite Temperature Path Integral Method for Fermions and Bosons: a Grand Canonical Approach

The calculation of the density matrix for fermions and bosons in the Grand Canonical Ensemble allows an efficient way for the inclusion of fermionic and bosonic statistics at all temperatures. It is shown that in a Path Integral Formulation fermionic density matrix can be expressed via an integration over a novel representation of the universal temperature dependent functional. While several representations for the universal functional have already been developed, they are usually presented in a form inconvenient for computer calculations. In this work we discuss a new representation for the universal functional in terms of Hankel functions which is advantageous for computational applications. Temperature scaling for the universal functional and its derivatives are also introduced thus allowing an efficient rescaling rather then recalculation of the functional at different temperatures. A simple illustration of the method of calculation of density profiles in Grand Canonical ensemble is presented using a system of noninteracting electrons in a finite confining potential.Comment: 13 pages 3 figure

An intrinsic nonlinear scale governs oscillations in rapid fracture

When branching is suppressed, rapid cracks undergo a dynamic instability from a straight to an oscillatory path at a critical velocity $v_c$. In a systematic experimental study using a wide range of different brittle materials, we first show how the opening profiles of straight cracks scale with the size $\ell_{nl}$ of the nonlinear zone surrounding a crack's tip. We then show, for all materials tested, that $v_c$ is both a fixed fraction of the shear speed and, moreover, that the instability wavelength is proportional to $\ell_{nl}$. These findings directly verify recent theoretical predictions and suggest that the nonlinear zone is not passive, but rather is closely linked to rapid crack instabilities.Comment: 4 pages, 4 figures + supplementary informatio

Roughening kinetics of chemical vapor deposited copper films on Si(100)

3 pages, 3 figures.The roughening kinetics of copper films synthesized by low pressure chemical vapor deposition (LPCVD) on Si(100) substrates was investigated by scanning tunneling microscopy (STM). By applying the dynamic scaling theory to the STM images, a steady growth roughness exponent (alfa)=0.81 ± 0.05 and a dynamic growth roughness exponent (beta)=0.62 ± 0.09 were determined. The value of (alfa) is consistent with growth model predictions incorporating surface diffusion. The value of (beta), while higher than expected from these models, can be related to LPCVD processing conditions favoring growth instabilities.This work was partially supported by the CSICCONICET cooperation program and by a grant from the NASA New Jersey Space Grant Consortium.Peer reviewe

Simple eigenvalue-self-consistent Δ ¯ G W 0 .

We show that a rigid scissors-like GW self-consistency approach, labeled here Δ ¯ G W 0 , can be trivially implemented at zero additional cost for large scale one-shot G 0 W 0 calculations. The method significantly improves one-shot G 0 W 0 and for large systems is very accurate. Δ ¯ G W 0 is similar in spirit to evGW 0 where the self-consistency is only applied on the eigenvalues entering Green's function, while both W and the eigenvectors of Green's function are held fixed. Δ ¯ G W 0 further assumes that the shift of the eigenvalues is rigid scissors-like so that all occupied states are shifted by the same amount and analogously for all the unoccupied states. We show that this results in a trivial modification of the time-dependent G 0 W 0 self-energy, enabling an a posteriori self-consistency cycle. The method is applicable for our recent stochastic-GW approach, thereby enabling self-consistent calculations for giant systems with thousands of electrons. The accuracy of Δ ¯ G W 0 increases with the system size. For molecules, it is up to 0.4-0.5 eV away from coupled-cluster single double triple (CCSD(T)), but for tetracene and hexacene, it matches the ionization energies from both CCSD(T) and evGW 0 to better than 0.05 eV. For solids, as exemplified here by periodic supercells of semiconductors and insulators with 6192 valence electrons, the method matches evGW 0 quite well and both methods are in good agreement with the experiment

Family Belongingness Attenuates Entrapment and Buffers Its Association with Suicidal Ideation in a Sample of Dutch Sexual Minority Emerging Adults

Sexual minority emerging adults are more likely to engage in suicidal ideation than their heterosexual counterparts. Experiences of homophobic violence are associated with suicidal ideation. Yet, the specific mechanisms linking homophobic violence to suicidal ideation remain unclear. Entrapment and social belongingness were tested to determine their relevance for understanding the link between homophobic violence and suicidal ideation. A sample of sexual minority Dutch emerging adults (N = 675; ages 18–29, M = 21.93 years, SD = 3.20) were recruited through online platforms and flyers. Homophobic violence was expected to be positively associated with suicidal ideation and entrapment. The association between homophobic violence and suicidal ideation was expected to be indirectly linked through entrapment. We explored whether various sources of social belongingness moderated the path between entrapment and suicidal ideation and whether those sources of social belongingness moderated the indirect effect of homophobic violence on suicidal ideation through entrapment. Results showed that homophobic violence and entrapment were positively associated with suicidal ideation and that family belongingness was negatively associated with suicidal ideation. Homophobic violence and suicidal ideation were not indirectly linked through entrapment. The interaction effect between entrapment and family belongingness was significant, suggesting that, on average, the effect of entrapment on suicidal ideation decreased when family belongingness was high. These results suggest that family belongingness may reduce the association between entrapment and suicidal ideation while adjusting for homophonic violence. Reducing entrapment and improving family belongingness may be useful targets for programs aimed at preventing suicidal ideation among sexual minority emerging adults

Can Solid-Organ-Transplanted Patients Perform a Cycling Marathon? Trends in Kidney Function Parameters in Comparison With Healthy Subjects.

Abstract Background Few solid-organ–transplanted patients (TP) perform regular sport activity. Poor data are available on the safety of intense and prolonged physical exercise on this population. The aim of the study was to evaluate kidney function parameters in a group of TP in comparison with healthy volunteers (HV) involved in a long-distance road cycling race: length 130 km and total uphill gradient, 1871 m. Methods Nineteen TP were recruited: 10 renal, 8 liver, and 1 heart and compared with 35 HV. Renal function parameters, namely, creatinine, estimated glomerular filtration rate (eGFR), urea, uric acid, urine specific gravity, microalbuminuria, and proteinuria were collected and their values were compared the day before the race (T1), immediately after crossing the finish line (T2), and 18 to 24 hours after the competition (T3). Results No adverse events were recorded. At baseline, TP showed lower values of eGFR (69 ± 22 versus 87 ± 13 mL/min/1.73 m 2 ), lower urine specific gravity (1015 ± 4 versus 1019 ± 6), and higher microalbuminuria (56 ± 74 versus 8 ± 15) and proteinuria values (166 ± 99 versus 74 ± 44) (in mg/L). At T2 in both groups, renal function parameters showed the same trends: decline of eGFR (54 ± 19 versus 69 ± 15 mL/min/1.73 m 2 ) and rise in protein excretion. At T3, functional parameters returned to baseline, except for urine specific gravity values remaining stable in TP (1018 ± 6) and growing higher in HV (1028 ± 4). Conclusions Selected and well-trained organ-transplanted patients can perform an intensive exercise, displaying temporary modifications on kidney function parameters comparable to healthy subjects, despite differences related to baseline clinical conditions and pharmacological therapies