324 research outputs found

    Drift of scroll waves in thin layers caused by thickness features: asymptotic theory and numerical simulations

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    Copyright © 2015 American Physical SocietyA scroll wave in a very thin layer of excitable medium is similar to a spiral wave, but its behavior is affected by the layer geometry. We identify the effect of sharp variations of the layer thickness, which is separate from filament tension and curvature-induced drifts described earlier. We outline a two-step asymptotic theory describing this effect, including asymptotics in the layer thickness and calculation of the drift of so-perturbed spiral waves using response functions. As specific examples, we consider drift of scrolls along thickness steps, ridges, ditches, and disk-shaped thickness variations. Asymptotic predictions agree with numerical simulations.FWO-Flanders (Belgium)Engineering and Physical Sciences Research Council (EPSRC

    Filament tension and phase-locked drift of meandering scroll waves

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    Rotating scroll waves are self-organising patterns which are found in many oscillating or excitable systems. Here we show that quasi-periodic (meandering) scroll waves, which include the rotors that organise cardiac arrhythmias, exhibit filament tension when averaged over the meander cycle. With strong filament curvature or medium thickness gradients, however, scroll wave dynamics are governed by phase-locked drift instead of filament tension. Our results are validated in computational models of cycloidal meander and a cardiac tissue model with linear core.Comment: accepted for publication in Physical Review Letters (December 2017

    Measurement and structure of spiral wave response functions

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    The rotating spiral waves that emerge in diverse natural and man-made systems typically exhibit a particle-like behaviour since their adjoint critical eigenmodes (response functions) are often seen to be localised around the spiral core. We present a simple method to numerically compute response functions for circular-core and meandering spirals by recording their drift response to many elementary perturbations. Although our method is computationally more expensive than solving the adjoint system, our technique is fully parallellisable, does not suffer from memory limitations and can be applied to experiments. For a cardiac tissue model with the linear spiral core, we find that the response functions are localised near the turning points of the trajectory

    Prognostic value of 11C-methionine volume-based PET parameters in IDH wild type glioblastoma

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    PURPOSE: (11)C-Methionine ((11)C-MET) PET prognostication of isocitrate dehydrogenase (IDH) wild type glioblastomas is inadequate as conventional parameters such as standardized uptake value (SUV) do not adequately reflect tumor heterogeneity. We retrospectively evaluated whether volume-based parameters such as metabolic tumor volume (MTV) and total lesion methionine metabolism (TLMM) outperformed SUV for survival correlation in patients with IDH wild type glioblastomas. METHODS: Thirteen IDH wild type glioblastoma patients underwent preoperative (11)C-MET PET. Both SUV-based parameters and volume-based parameters were calculated for each lesion. Kaplan-Meier curves with log-rank testing and Cox regression analysis were used for correlation between PET parameters and overall survival. RESULTS: Median overall survival for the entire cohort was 393 days. MTV (HR 1.136, p = 0.007) and TLMM (HR 1.022, p = 0.030) were inversely correlated with overall survival. SUV-based (11)C-MET PET parameters did not show a correlation with survival. In a paired analysis with other clinical parameters including age and radiotherapy dose, MTV and TLMM were found to be independent factors. CONCLUSIONS: MTV and TLMM, and not SUV, significantly correlate with overall survival in patients with IDH wild type glioblastomas. The incorporation of volume-based (11)C-MET PET parameters may lead to a better outcome prediction for this heterogeneous patient population

    Diagnostic accuracy of positron emission tomography tracers for the differentiation of tumor progression from treatment-related changes in high-grade glioma:a systematic review and meta-analysis

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    Background: Post-treatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent response assessment in neuro-oncology (RANO) recommendations PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and meta-analysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: Pubmed, Web of Science and Embase were searched systematically. Study selection, data extraction and quality assessment were performed independently by two authors. Meta-analysis was performed using a bivariate random effects model when ≥ 5 studies were included. Results: 39 studies (11 tracers) were included in the systematic review. 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95%CI 72-92) and 84% (69-93), respectively. 18F-FET (7 studies, 172 lesions) demonstrated a sensitivity of 90% (81-95) and specificity of 85% (71-93). 11C-MET (8 studies, 151 lesions) sensitivity was 93% (80-98) and specificity was 82% (68-91). The number of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93-100% and 0-100% for 18F-FLT, 85-100% and 72-100% for 18F-FDOPA and 100% and 70-88% for 11C-CHO, respectively. Conclusion:18F-FET and 11C-MET, both amino-acid tracers, showed a comparable higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited, thus 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas

    Buckling of scroll waves

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    A scroll wave in a sufficiently thin layer of an excitable medium with negative filament tension can be stable nevertheless due to filament rigidity. Above a certain critical thickness of the medium, such scroll wave will have a tendency to deform into a buckled, precessing state. Experimentally this will be seen as meandering of the spiral wave on the surface, the amplitude of which grows with the thickness of the layer, until a break-up to scroll wave turbulence happens. We present a simplified theory for this phenomenon and illustrate it with numerical examples.Comment: 4 pages main text + 5 pages appendix, 4+2 figures and a movie, as accepted by Phys Rev Letters 2012/09/2

    No evidence for decreased D2/3 receptor availability and frontal hypoperfusion in subjects with compulsive pornography use

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    Pornographic addiction refers to an addiction model associated with compulsive and repeated use of pornographic material. Whether the use of pornography may indeed become addictive remains a matter of debate. The current study investigated whether compulsive pornography use (CPU) is accompanied by reduced D2/3 receptor availability in the striatum and frontal hypofunctionality. Male subjects between 18 and 50 years of age with and without CPU were recruited using online and newspaper advertisements. Questionnaires were used to the assess the severity of compulsive pornography use (CIUS) and symptoms of depression, impulsivity and sensation seeking. Dopaminergic imaging was performed using [11C]-raclopride PET. Striatal binding potentials (BPND) and regional frontal cerebral influx values (R1) of [11C]-raclopride were calculated. Arterial Spin Labeling (ASL) MRI was performed to assess regional cerebral blood flow. No group differences between striatal BPND's of [11C]-raclopride in subjects with (n = 15) and without (n = 10) CPU were detected. In CPU subjects, no correlation was found between the CIUS score and striatal BPND's. Cerebral R1 values in frontal brain regions and cerebral blood flow measurements did not differ between groups. The current study fails to provide imaging support for sharing similar neurobiological alterations as previously has been reported in other addictive modalities

    Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis

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    Leishmania parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive in vitro and ex vivo mapping of the signaling pathways upstream and downstream of antioxidant transcription factor [nuclear factor erythroid 2-related factor 2 (Nrf2)] in cutaneous leishmaniasis (CL), by combining functional assays in human and murine macrophages with a systems biology analysis of in situ (skin biopsies) CL patient samples. First, we show the PKR pathway controls the expression and activation of Nrf2 in Leishmania amazonensis infection in vitro. Nrf2 activation also required PI3K/Akt signaling and autophagy mechanisms. Nrf2- or PKR/Akt-deficient macrophages exhibited increased levels of ROS/RNS and reduced expression of Sod1 Nrf2-dependent gene and reduced parasite load. L. amazonensis counteracted the Nrf2 inhibitor Keap1 through the upregulation of p62 via PKR. This Nrf2/Keap1 observation was confirmed in situ in skin biopsies from Leishmania-infected patients. Next, we explored the ex vivo transcriptome in CL patients, as compared to healthy controls. We found the antioxidant response element/Nrf2 signaling pathway was significantly upregulated in CL, including downstream target p62. In silico enrichment analysis confirmed upstream signaling by interferon and PI3K/Akt, and validated our in vitro findings. Our integrated in vitro, ex vivo, and in silico approach establish Nrf2 as a central player in human cutaneous leishmaniasis and reveal Nrf2/PKR crosstalk and PI3K/Akt pathways as potential therapeutic targets
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