Investigating the integrate and fire model as the limit of a random discharge model: a stochastic analysis perspective

In the mean field integrate-and-fire model, the dynamics of a typical neuron within a large network is modeled as a diffusion-jump stochastic process whose jump takes place once the voltage reaches a threshold. In this work, the main goal is to establish the convergence relationship between the regularized process and the original one where in the regularized process, the jump mechanism is replaced by a Poisson dynamic, and jump intensity within the classically forbidden domain goes to infinity as the regularization parameter vanishes. On the macroscopic level, the Fokker-Planck equation for the process with random discharges (i.e. Poisson jumps) are defined on the whole space, while the equation for the limit process is on the half space. However, with the iteration scheme, the difficulty due to the domain differences has been greatly mitigated and the convergence for the stochastic process and the firing rates can be established. Moreover, we find a polynomial-order convergence for the distribution by a re-normalization argument in probability theory. Finally, by numerical experiments, we quantitatively explore the rate and the asymptotic behavior of the convergence for both linear and nonlinear models

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

A synchronization-capturing multi-scale solver to the noisy integrate-and-fire neuron networks

The noisy leaky integrate-and-fire (NLIF) model describes the voltage configurations of neuron networks with an interacting many-particles system at a microscopic level. When simulating neuron networks of large sizes, computing a coarse-grained mean-field Fokker-Planck equation solving the voltage densities of the networks at a macroscopic level practically serves as a feasible alternative in its high efficiency and credible accuracy. However, the macroscopic model fails to yield valid results of the networks when simulating considerably synchronous networks with active firing events. In this paper, we propose a multi-scale solver for the NLIF networks, which inherits the low cost of the macroscopic solver and the high reliability of the microscopic solver. For each temporal step, the multi-scale solver uses the macroscopic solver when the firing rate of the simulated network is low, while it switches to the microscopic solver when the firing rate tends to blow up. Moreover, the macroscopic and microscopic solvers are integrated with a high-precision switching algorithm to ensure the accuracy of the multi-scale solver. The validity of the multi-scale solver is analyzed from two perspectives: firstly, we provide practically sufficient conditions that guarantee the mean-field approximation of the macroscopic model and present rigorous numerical analysis on simulation errors when coupling the two solvers; secondly, the numerical performance of the multi-scale solver is validated through simulating several large neuron networks, including networks with either instantaneous or periodic input currents which prompt active firing events over a period of time.Comment: 25 Pages, 18 Figure

BEAR1, a bHLH transcription factor, controls seedling growth by regulating gibberellins biosynthesis in rice

The genetic pathways of rice seedling growth have a major impact on seedling emergence from soil and development. In this study, we identified a new bHLH transcription factor, BEAR1, from rice RNAi mutant library. Both the BEAR1-RNAi and bear1 CRISPR mutants had accelerated seedling growth. Histological section of leaves showed accelerated development of lacuna and vascular bundles in bear1 mutant. GUS staining revealed that BEAR1 was highly expressed in coleoptiles and leaves at seedling stage. Expression analysis of gibberellin (GA) biosynthesis and metabolic genes and content determination of active GAs indicated that the expression of GA biosynthesis genes, especially OsKS4 and OsCPS2, were upregulated and the GAs content were significantly increased in bear1, which correlated with the seedling phenotype of bear1 mutant. Molecular and biochemical assays revealed that BEAR1 directly binds to the promoter of OsKS4, thereby repressing its expression. Haplotypes analysis showed clear differentiation in indica and japonica rice varieties, and a strong correlation with seedling height. These findings provide novel insights into the regulation of seedling growth in rice

Spatial and temporal variation of nearshore significant wave height in the Three Gorges Reservoir, China

The study of wave characteristic changes is critical for understanding the role of wave erosion in the shoreline erosion of reservoirs and its subsequent impact on environmental pollution. This study utilizes RBRvirtuoso D-wave-pressure-based wave gauges to make in situ observations of the nearshore significant wave height (SWH) in the Three Gorges Reservoir. The differential and impact factors affecting the SWH under varying water levels, in the main and tributary streams, and shoreline sections are analyzed. This research also investigates the alteration of the frequency distribution of the SWH. The findings indicate that the average SWH increases as the water level increases, reaching 1.2 cm, 1.5 cm, and 1.9 cm for water levels of 150 m, 165 m, and 175 m, respectively, with a SWH frequency distribution curve that becomes increasingly smooth. The average SWH in the mainstream is 2.9 times larger than that in the tributaries, with the former having a smoother frequency distribution curve. The average SWHs in different shoreline sections are inconsistent at the same water level, with the Badong (downstream) section near the Three Gorges Dam exhibiting a significantly higher average SWH than the Zhongxian (midstream) section further from the dam. When shipping activities intensify, there is often a marked increase in the magnitude of the SWH. The SWH in narrower reservoir sections is significantly greater than that in wider sections, with average measurements of 2.2 cm and 1.4 cm, respectively. Fluctuations of the water level, shipping activities, and other factors in the Three Gorges Reservoir have a significant impact on the alteration of the nearshore SWH, and changes in the SWH from low to high water levels may result in changes in both the spatial and temporal patterns of shoreline erosion. These alterations can, in turn, affect sediment and nutrient transport, potentially exacerbating environmental pollution issues

CYP2D6*4 allele polymorphism increases the risk of Parkinson's disease: evidence from meta-analysis.

BACKGROUND: Many epidemiological studies have been conducted to explore the association between a single CYP2D6 gene polymorphism and Parkinson's disease (PD) susceptibility. However, the results remain controversial. OBJECTIVES: To clarify the effects of a single CYP2D6 gene polymorphism on the risk of PD, a meta-analysis of all available studies relating to CYP2D6*4 polymorphism and the risk of PD was conducted. METHODS: A comprehensive literature search of PubMed, EMBASE, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2013 was conducted. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated. Meta-regression, Galbraith plots, subgroup analysis, sensitivity analysis, and publication bias analysis were also performed. RESULTS: Twenty-two separate comparisons consisting of 2,629 patients and 3,601 controls were included in our meta-analysis. The pooled analyses showed a significant association between CYP2D6*4G/A polymorphism and PD risk in all of the comparisons (A vs. G allele: OR = 1.28, 95% CI = 1.14-1.43, P = 0.001; AA vs. GG: OR = 1.43, 95% CI = 1.06-1.93, P = 0.018; AG vs. GG: OR = 1.22, 95% CI = 1.06-1.40, P = 0.006; AG+AA vs. GG: OR = 1.26, 95% CI = 1.10-1.44, P = 0.001; AA vs. AG+GG: OR = 1.37, 95% CI = 1.02-1.83, P = 0.036). In subgroup analysis stratified by ethnicity, significant associations were also demonstrated in Caucasians but not in Asians. No significant association was found in subgroup analysis stratified by age of onset or disease form. CONCLUSIONS: We concluded that the CYP2D6*4G/A polymorphism denotes an increased genetic susceptibility to PD in the overall population, especially in Caucasians. Further large and well-designed studies are needed to confirm this association

Funnel plot analysis and Egger’s test to detect publication bias in different contrast models.

<p>Each point represents a separate study for the indicated association. a Funnel plot and Egger’s test for contrast A vs. G; b Funnel plot and Egger’s test for contrast AA vs. GG; c Funnel plot and Egger’s test for contrast AG vs. GG; d Funnel plot and Egger’s test for contrast AG+AA vs. GG; e Funnel plot and Egger’s test for contrast AA vs. GG+AG.</p

Flow diagram for the selection of articles for inclusion in the meta-analysis.

<p>Flow diagram for the selection of articles for inclusion in the meta-analysis.</p