Phase locking below rate threshold in noisy model neurons

The property of a neuron to phase-lock to an oscillatory stimulus before adapting its spike rate to the stimulus frequency plays an important role for the auditory system. We investigate under which conditions neurons exhibit this phase locking below rate threshold. To this end, we simulate neurons employing the widely used leaky integrate-and-fire (LIF) model. Tuning parameters, we can arrange either an irregular spontaneous or a tonic spiking mode. When the neuron is stimulated in both modes, a significant rise of vector strength prior to a noticeable change of the spike rate can be observed. Combining analytic reasoning with numerical simulations, we trace this observation back to a modulation of interspike intervals, which itself requires spikes to be only loosely coupled. We test the limits of this conception by simulating an LIF model with threshold fatigue, which generates pronounced anticorrelations between subsequent interspike intervals. In addition we evaluate the LIF response for harmonic stimuli of various frequencies and discuss the extension to more complex stimuli. It seems that phase locking below rate threshold occurs generically for all zero mean stimuli. Finally, we discuss our findings in the context of stimulus detection

Motoneuron membrane potentials follow a time inhomogeneous jump diffusion process

Stochastic leaky integrate-and-fire models are popular due to their simplicity and statistical tractability. They have been widely applied to gain understanding of the underlying mechanisms for spike timing in neurons, and have served as building blocks for more elaborate models. Especially the Ornstein–Uhlenbeck process is popular to describe the stochastic fluctuations in the membrane potential of a neuron, but also other models like the square-root model or models with a non-linear drift are sometimes applied. Data that can be described by such models have to be stationary and thus, the simple models can only be applied over short time windows. However, experimental data show varying time constants, state dependent noise, a graded firing threshold and time-inhomogeneous input. In the present study we build a jump diffusion model that incorporates these features, and introduce a firing mechanism with a state dependent intensity. In addition, we suggest statistical methods to estimate all unknown quantities and apply these to analyze turtle motoneuron membrane potentials. Finally, simulated and real data are compared and discussed. We find that a square-root diffusion describes the data much better than an Ornstein–Uhlenbeck process with constant diffusion coefficient. Further, the membrane time constant decreases with increasing depolarization, as expected from the increase in synaptic conductance. The network activity, which the neuron is exposed to, can be reasonably estimated to be a threshold version of the nerve output from the network. Moreover, the spiking characteristics are well described by a Poisson spike train with an intensity depending exponentially on the membrane potential

Classification of coronary artery bifurcation lesions and treatments: Time for a consensus!

Background: Percutaneous coronary intervention (PCI) of coronary bifurcation lesions remains a subject of debate. Many studies have been published in this setting. They are often small scale and display methodological flaws and other shortcomings such as inaccurate designation of lesions, heterogeneity, and inadequate description of techniques implemented. Methods: The aim is to propose a consensus established by the European Bifurcation Club (EBC), on the definition and classification of bifurcation lesions and treatments implemented with the purpose of allowing comparisons between techniques in various anatomical and clinical settings. Results: A bifurcation lesion is a coronary artery narrowing occurring adjacent to, and/or involving, the origin of a significant side branch. The simple lesion classification proposed by Medina has been adopted. To analyze the outcomes of different techniques by intention to treat, it is necessary to clearly define which vessel is the distal main branch and which is (are) the side branche(s) and give each branch a distinct name. Each segment of the bifurcation has been named following the same pattern as the Medina classification. The classification of the techniques (MADS: Main, Across, Distal, Side) is based on the manner in which the first stent has been implanted. A visual presentation of PCI techniques and devices used should allow the development of a software describing quickly and accurately the procedure performed. Conclusion: The EBC proposes a new classification of bifurcation lesions and their treatments to permit accurate comparisons of well described techniques in homogeneous lesion groups. © 2008 Wiley-Liss, Inc

Wall shear stress estimated by 3D-QCA can predict cardiovascular events in lesions with borderline negative fractional flow reserve

Background and aims: There is some evidence of the implications of wall shear stress (WSS) derived from three-dimensional quantitative coronary angiography (3D-QCA) models in predicting adverse cardiovascular events. This study investigates the efficacy of 3D-QCA-derived WSS in detecting lesions with a borderline negative fractional flow reserve (FFR: 0.81–0.85) that progressed and caused events. Methods: In this retrospective cohort study, we identified 548 patients who had at least one lesion with an FFR 0.81–0.85 and complete follow-up data; 293 lesions (286 patients) with suitable angiographic characteristics were reconstructed using a dedicated 3D-QCA software and included in the analysis. In the reconstructed models blood flow simulation was performed and the value of 3D-QCA variables and WSS distribution in predicting events was examined. The primary endpoint of the study was the composite of cardiac death, target lesion related myocardial infarction or clinically indicated target lesion revascularization. Results: During a median follow-up of 49.4 months, 37 events were reported. Culprit lesions had a greater area stenosis [(AS), 66.1% (59.5–72.3) vs 54.8% (46.5–63.2), p<0.001], smaller minimum lumen area [(MLA), 1.66 mm2 (1.45–2.30) vs 2.10 mm2 (1.69–2.70), p=0.011] and higher maximum WSS [9.0 Pa (5.10–12.46) vs 5.0 Pa (3.37–7.54), p < 0.001] than those that remained quiescent. In multivariable analysis, AS [hazard ratio (HR): 1.06, 95% confidence interval (CI): 1.03–1.10, p=0.001] and maximum WSS (HR: 1.08, 95% CI: 1.02–1.14, p=0.012) were the only independent predictors of the primary endpoint. Lesions with an increased AS (≥58.6%) that were exposed to high WSS (≥7.69Pa) were more likely to progress and cause events (27.8%) than those with a low AS exposed to high WSS (7.4%) or those exposed to low WSS that had increased (12.8%) or low AS (2.7%, p<0.001). Conclusions: This study for the first time highlights the potential value of 3D-QCA-derived WSS in detecting, among lesions with a borderline negative FFR, those that cause cardiovascular events

Variability Measures of Positive Random Variables

During the stationary part of neuronal spiking response, the stimulus can be encoded in the firing rate, but also in the statistical structure of the interspike intervals. We propose and discuss two information-based measures of statistical dispersion of the interspike interval distribution, the entropy-based dispersion and Fisher information-based dispersion. The measures are compared with the frequently used concept of standard deviation. It is shown, that standard deviation is not well suited to quantify some aspects of dispersion that are often expected intuitively, such as the degree of randomness. The proposed dispersion measures are not entirely independent, although each describes the interspike intervals from a different point of view. The new methods are applied to common models of neuronal firing and to both simulated and experimental data

Predictive value of the QFR in detecting vulnerable plaques in non-flow limiting lesions: a combined analysis of the PROSPECT and IBIS-4 study

“This is a post-peer-review, pre-copyedit version of an article published in Int J Cardiovasc Imaging. The final authenticated version is available online at: https://doi.org/10.1007/s10554-020-01805-9”

Homemade oral supplement: a proposal for the nutritional recovery of children and adolescents with cancer

Objective The aim of this study was to evaluate the impact of homemade oral supplements on the nutritional recovery of patients with mild or severe malnutrition or at nutritional risk. Methods Eight recipes of homemade oral supplements containing 30% to 35% of the total energy expenditure were proposed. The patients with severe malnutrition (group B) received the oral supplement for 2 weeks and the others for 4 weeks (group A). Oral supplementation with homemade supplements was compared with oral supplementation with store-bought supplements, investigated earlier with a protocol with the same design. Results Homemade oral supplements contain much lower amounts of certain micronutrients but are five times cheaper than store-bought supplements. In group A, 88% of the patients taking homemade oral supplements and 84% of the patients taking store-bought supplements responded positively to supplementation. In group B, 22% of the patients taking homemade oral supplements and 25% of the patients taking store-bought supplements recovered. The difference was not significant. The impact of store-bought supplementation on the triceps skinfold thicknesses and arm circumferences of the patients in group A was greater than that obtained with homemade supplements. In group B, the effect on triceps skinfold thickness was not significant (p=0.16). Patients taking homemade or store-bought oral supplements presented similar protein and energy intakes and improvements in nutritional status. Only the body composition of patients in group A taking store-bought oral supplements was better. Conclusion The results obtained by this study suggest that the therapeutic use of homemade oral supplements is an alternative capable of promoting the nutritional recovery of cancer patients, especially those who cannot afford store-bought supplements.Objetivo Avaliar o impacto do suplemento oral artesanal na recuperação do estado nutricional de pacientes com desnutrição leve, grave e com risco nutricional. Métodos Propuseram-se oito receitas de suplementos visando ofertar entre 30,0% e 35,0% do gasto energético total. Os pacientes com desnutrição grave (grupo B) receberam o suplemento oral por duas semanas, e os demais pacientes (grupo A), por quatro semanas. Para a comparação dos resultados obtidos com o emprego do suplemento oral artesanal, foram utilizados dados referentes a um protocolo anterior, com o mesmo desenho, entretanto, com a utilização de suplemento oral industrializado. Resultados O suplemento oral artesanal fica muito aquém no que diz respeito a alguns micronutrientes, entretanto é cinco vezes mais barato do que a preparação com o suplemento oral industrializado. Os pacientes do grupo A com suplemento oral artesanal apresentaram 88,0% de resposta positiva na semana de avaliação, enquanto os com suplemento oral industrializado tiveram 84,0%. No grupo B, foram recuperados 22,0% dos pacientes com suplemento oral artesanal e 25,0% do grupo com suplemento oral industrializado, não apresentando, portanto, diferença significante. Comparando o impacto do industrializado com o do artesanal na prega cutânea tricipital e circunferência do braço, verificou-se que o suplemento oral industrializado no grupo A apresentou melhores resultados que o suplemento oral artesanal, e no grupo B, esse efeito observado na prega cutânea não foi significante (p=0,16). Os consumos de energia e de proteína, assim como a evolução nutricional, foram semelhantes entre suplemento oral industrializado e suplemento oral artesanal. Apenas a composição corpórea no grupo A com suplemento oral industrializado apresentou melhores resultados. Conclusão Os resultados apresentados neste estudo sugerem que o emprego da terapia com suplemento artesanal seja uma opção capaz de auxiliar na recuperação nutricional de pacientes oncológicos e uma opção para populações financeiramente desfavorecidas.Hospital Samaritano de São PauloInstituto Adriana GarófoloUniversidade Federal de São Paulo (UNIFESP) Departamento de Pediatria Instituto de Oncologia PediátricaUniversidade Federal de São Paulo (UNIFESP) Departamento de PediatriaUNIFESP, Depto. de Pediatria Instituto de Oncologia PediátricaUNIFESP, Depto. de PediatriaSciEL

Wall shear stress estimated by 3D-QCA can predict cardiovascular events in lesions with borderline negative fractional flow reserve

Background and aims: There is some evidence of the implications of wall shear stress (WSS) derived from three-dimensional quantitative coronary angiography (3D-QCA) models in predicting adverse cardiovascular events. This study investigates the efficacy of 3D-QCA-derived WSS in detecting lesions with a borderline negative fractional flow reserve (FFR: 0.81-0.85) that progressed and caused events.Methods: In this retrospective cohort study, we identified 548 patients who had at least one lesion with an FFR 0.81-0.85 and complete follow-up data; 293 lesions (286 patients) with suitable angiographic characteristics were reconstructed using a dedicated 3D-QCA software and included in the analysis. In the reconstructed models blood flow simulation was performed and the value of 3D-QCA variables and WSS distribution in predicting events was examined. The primary endpoint of the study was the composite of cardiac death, target lesion related myocardial infarction or clinically indicated target lesion revascularization.Results: During a median follow-up of 49.4 months, 37 events were reported. Culprit lesions had a greater area stenosis [(AS), 66.1% (59.5-72.3) vs 54.8% (46.5-63.2), p= 58.6%) that were exposed to high WSS (>= 7.69Pa) were more likely to progress and cause events (27.8%) than those with a low AS exposed to high WSS (7.4%) or those exposed to low WSS that had increased (12.8%) or low AS (2.7%, p<0.001).Conclusions: This study for the first time highlights the potential value of 3D-QCA-derived WSS in detecting, among lesions with a borderline negative FFR, those that cause cardiovascular events.Cardiovascular Aspects of Radiolog

The prevalence of stillbirths: a systematic review

BACKGROUND: Stillbirth rate is an important indicator of access to and quality of antenatal and delivery care. Obtaining overall estimates across various regions of the world is not straightforward due to variation in definitions, data collection methods and reporting. METHODS: We conducted a systematic review of a range of pregnancy-related conditions including stillbirths and performed meta-analysis of the subset of studies reporting stillbirth rates. We examined variation across rates and used meta-regression techniques to explain observed variation. RESULTS: We identified 389 articles on stillbirth prevalence among the 2580 included in the systematic review. We included 70 providing 80 data sets from 50 countries in the meta-analysis. Pooled prevalence rates show variation across various subgroup categories. Rates per 100 births are higher in studies conducted in less developed country settings as compared to more developed (1.17 versus 0.50), of inadequate quality as compared to adequate (1.12 versus 0.66), using sub-national sample as compared to national (1.38 versus 0.68), reporting all stillbirths as compared to late stillbirths (0.95 versus 0.63), published in non-English as compared to English (0.91 versus 0.59) and as journal articles as compared to non-journal (1.37 versus 0.67). The results of the meta-regression show the significance of two predictor variables – development status of the setting and study quality – on stillbirth prevalence. CONCLUSION: Stillbirth prevalence at the community level is typically less than 1% in more developed parts of the world and could exceed 3% in less developed regions. Regular reviews of stillbirth rates in appropriately designed and reported studies are useful in monitoring the adequacy of care. Systematic reviews of prevalence studies are helpful in explaining sources of variation across rates. Exploring these methodological issues will lead to improved standards for assessing the burden of reproductive ill-health