Synaptic Heterogeneity and Stimulus-induced Modulation of Depression in Central Synapses

Short-term plasticity is a pervasive feature of synapses. Synapses exhibit many forms of plasticity operating over a range of time scales. We develop an optimization method that allows rapid characterization of synapses with multiple time scales of facilitation and depression. Investigation of paired neurons that are postsynaptic to the same identified interneuron in the buccal ganglion of Aplysia reveals that the responses of the two neurons differ in the magnitude of synaptic depression. Also, for single neurons, prolonged stimulation of the presynaptic neuron causes stimulus-induced increases in the early phase of synaptic depression. These observations can be described by a model that incorporates two availability factors, e.g., depletable vesicle pools or desensitizing receptor populations, with different time courses of recovery, and a single facilitation component. This model accurately predicts the responses to novel stimuli. The source of synaptic heterogeneity is identified with variations in the relative sizes of the two availability factors, and the stimulus-induced decrement in the early synaptic response is explained by a slowing of the recovery rate of one of the availability factors. The synaptic heterogeneity and stimulus-induced modifications in synaptic depression observed here emphasize that synaptic efficacy depends on both the individual properties of synapses and their past history

Using a Hybrid Agent-based and Equation Based Model to Test School Closure Policies During a Measles Outbreak

Background In order to be prepared for an infectious disease outbreak it is important to know what interventions will or will not have an impact on reducing the outbreak. While some interventions might have a greater effect in mitigating an outbreak, others might only have a minor effect but all interventions will have a cost in implementation. Estimating the effectiveness of an intervention can be done using computational modelling. In particular, comparing the results of model runs with an intervention in place to control runs where no interventions were used can help to determine what interventions will have the greatest effect on an outbreak. Methods To test the effects of a school closure policy on the spread of an infectious disease (in this case measles) we run simulations closing schools based on either the proximity of the town to the initial outbreak or the centrality of the town within the network of towns in the simulation. To do this we use a hybrid model that combines an agent-based model with an equation-based model. In our analysis, we use three measures to compare the effects of different intervention strategies: the total number of model runs leading to an outbreak, the total number of infected agents, and the geographic spread of outbreaks. Results Our results show that closing down the schools in the town where an outbreak begins and the town with the highest in degree centrality provides the largest reduction in percent of runs leading to an outbreak as well as a reduction in the geographic spread of the outbreak compared to only closing down the town where the outbreak begins. Although closing down schools in the town with the closest proximity to the town where the outbreak begins also provides a reduction in the chance of an outbreak, we do not find the reduction to be as large as when the schools in the high in degree centrality town are closed. Conclusions Thus we believe that focusing on high in degree centrality towns during an outbreak is important in reducing the overall size of an outbreak

Validating and Testing an Agent-Based Model for the Spread of COVID-19 in Ireland

Agent-based models can be used to better understand the impacts of lifting restrictions or implementing interventions during a pandemic. However, agent-based models are computationally expensive, and running a model of a large population can result in a simulation taking too long to run for the model to be a useful analysis tool during a public health crisis. To reduce computing time and power while running a detailed agent-based model for the spread of COVID-19 in the Republic of Ireland, we introduce a scaling factor that equates 1 agent to 100 people in the population. We present the results from model validation and show that the scaling factor increases the variability in the model output, but the average model results are similar in scaled and un-scaled models of the same population, and the scaled model is able to accurately simulate the number of cases per day in Ireland during the autumn of 2020. We then test the usability of the model by using the model to explore the likely impacts of increasing community mixing when schools reopen after summer holidays

Clustering Neural Spike Trains with Transient Responses

The detection of transient responses, i.e. nonstationarities, that arise in a varying and small fraction of the total number of neural spike trains recorded from chronically implanted multielectrode grids becomes increasingly difficult as the number of electrodes grows. This paper presents a novel application of an unsupervised neural network for clustering neural spike trains with transient responses. This network is constructed by incorporating projective clustering into an adaptive resonance type neural network (ART) architecture resulting in a PART neural network. Since comparisons are made between inputs and learned patterns using only a subset of the total number of available dimensions, PART neural networks are ideally suited to the detection of transients. We show that PART neural networks are an effective tool for clustering neural spike trains that is easily implemented, computationally inexpensive, and well suited for detecting neural responses to dynamic environmental stimuli

Age Specific Models to Capture the Change in Risk Factor Contribution by Age to Short Term Primary Ischemic Stroke Risk

Age is one of the most important risk factors when it comes to stroke risk prediction. However, including age as a risk factor in a stroke prediction model can give rise to a number of difficulties. Age often dominates the risk score, and also not all risk factors contribute proportionally to stroke risk by age. In this study we investigate a number of common stroke risk factors, using Framingham heart study data from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center to determine if they appear to contribute proportionally by age to a stroke risk score. As we find evidence that there is some non-proportionality by age, we then create a set of logistic regression risk models that each predict the 5 year stroke risk for a different age group. The age group models are shown to be better calibrated when compared to a model for all ages that includes age as a risk factor. This suggests that to get better predictions for stroke risk it may be necessary to consider alternative methods for including age in stroke risk prediction models that account for the non-proportionality of the other risk factors as age changes

A review of risk concepts and models for predicting the risk of primary stroke

Predicting an individual\u27s risk of primary stroke is an important tool that can help to lower the burden of stroke for both the individual and society. There are a number of risk models and risk scores in existence but no review or classification designed to help the reader better understand how models differ and the reasoning behind these differences. In this paper we review the existing literature on primary stroke risk prediction models. From our literature review we identify key similarities and differences in the existing models. We find that models can differ in a number of ways, including the event type, the type of analysis, the model type and the time horizon. Based on these similarities and differences we have created a set of questions and a system to help answer those questions that modelers and readers alike can use to help classify and better understand the existing models as well as help to make necessary decisions when creating a new model

Determining the Proportionality of Ischemic Stroke Risk Factors to Age

While age is an important risk factor, there are some disadvantages to including it in a stroke risk model: age can dominate the risk score and lead to over-or under-predictions in some age groups. There is evidence to suggest that some of these disadvantages are due to the non-proportionality of other risk factors with age, eg, risk factors contribute differently to stroke risk based on an individual’s age. In this paper, we present a framework to test if risk factors are proportional with age. We then apply the framework to a set of risk factors using Framingham heart study data from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center to determine if we can find evidence of non-proportionality. Using our framework, we find that a number of risk factors (diastolic blood pressure, total cholesterol, BMI, sex, high blood pressure treatment) may be non-proportional to age. This suggests that testing for the proportionality of risk factors with age should be something that is considered in stroke risk prediction modelling and traditional modelling methods may need to be adjusted to capture this non-proportionality

Understanding the assumptions of an SEIR compartmental model using agentization and a complexity hierarchy

Equation-based and agent-based models are popular methods in understanding disease dynamics. Although there are many types of equation-based models, the most common is the SIR compartmental model that assumes homogeneous mixing and populations. One way to understand the effects of these assumptions is by agentization. Equation-based models can be agentized by creating a simple agent-based model that replicates the results of the equationbased model, then by adding complexity to these agentized models it is possible to break the assumptions of homogeneous mixing and populations and test how breaking these assumptions results in different outputs. We report a set of experiments comparing the outputs of an SEIR model and a set of agent-based models of varying levels of complexity, using as a case study a measles outbreak in a town in Ireland. We define and use a six level complexity hierarchy for agent-based models to create a set of progressively more complex variants of an agentized SEIR model for the spread of infectious disease. We then compare the results of the agentbased model at each level of complexity with results of the SEIR model to determine when the agentization breaks. Our analysis shows this occurs on the fourth step of complexity, when scheduled movements are added into the model. When agents networks and behaviours are complex the peak of the outbreak is shifted to the right and is lower than in the SEIR model suggesting that heterogeneous populations and mixing patterns lead to slower outbreaks compared homogeneous populations and mixing patterns