A Regulatory Circuit Controlling the Dynamics of NFκB cRel Transitions B Cells from Proliferation to Plasma Cell Differentiation.

Humoral immunity depends on efficient activation of B cells and their subsequent differentiation into antibody-secreting cells (ASCs). The transcription factor NFκB cRel is critical for B cell proliferation, but incorporating its known regulatory interactions into a mathematical model of the ASC differentiation circuit prevented ASC generation in simulations. Indeed, experimental ectopic cRel expression blocked ASC differentiation by inhibiting the transcription factor Blimp1, and in wild-type (WT) cells cRel was dynamically repressed during ASC differentiation by Blimp1 binding the Rel locus. Including this bi-stable circuit of mutual cRel-Blimp1 antagonism into a multi-scale model revealed that dynamic repression of cRel controls the switch from B cell proliferation to ASC generation phases and hence the respective cell population dynamics. Our studies provide a mechanistic explanation of how dysregulation of this bi-stable circuit might result in pathologic B cell population phenotypes and thus offer new avenues for diagnostic stratification and treatment.

Dynamics of cell-type transition mediated by epigenetic modifications.

Maintaining tissue homeostasis requires appropriate regulation of stem cell differentiation. The Waddington landscape posits that gene circuits in a cell form a potential landscape of different cell types, wherein cells follow attractors of the probability landscape to develop into distinct cell types. However, how adult stem cells achieve a delicate balance between self-renewal and differentiation remains unclear. We propose that random inheritance of epigenetic states plays a pivotal role in stem cell differentiation and present a hybrid model of stem cell differentiation induced by epigenetic modifications. Our comprehensive model integrates gene regulation networks, epigenetic state inheritance, and cell regeneration, encompassing multi-scale dynamics ranging from transcription regulation to cell population. Through model simulations, we demonstrate that random inheritance of epigenetic states during cell divisions can spontaneously induce cell differentiation, dedifferentiation, and transdifferentiation. Furthermore, we investigate the influences of interfering with epigenetic modifications and introducing additional transcription factors on the probabilities of dedifferentiation and transdifferentiation, revealing the underlying mechanism of cell reprogramming. This in silico model provides valuable insights into the intricate mechanism governing stem cell differentiation and cell reprogramming and offers a promising path to enhance the field of regenerative medicine.

[Progress in the analysis of hemolysis and coagulation models for interventional micro-axial flow blood pumps].

Interventional micro-axial flow blood pump is widely used as an effective treatment for patients with cardiogenic shock. Hemolysis and coagulation are vital concerns in the clinical application of interventional micro-axial flow pumps. This paper reviewed hemolysis and coagulation models for micro-axial flow blood pumps. Firstly, the structural characteristics of commercial interventional micro-axial flow blood pumps and issues related to clinical applications were introduced. Then the basic mechanisms of hemolysis and coagulation were used to study the factors affecting erythrocyte damage and platelet activation in interventional micro-axial flow blood pumps, focusing on the current models of hemolysis and coagulation on different scales (macroscopic, mesoscopic, and microscopic). Since models at different scales have different perspectives on the study of hemolysis and coagulation, a comprehensive analysis combined with multi-scale models is required to fully consider the influence of complex factors of interventional pumps on hemolysis and coagulation.

Multi-scale model of lumen formation via inverse membrane blebbing mechanism during sprouting angiogenesis process.

Cancer is one of the leading causes of mortality and morbidity among people worldwide. Cancer appears as solid tumors in many cases. Angiogenesis is the growth of blood vessels from the existing vasculature and is one of the imperative processes in tumor growth. Another vital phenomenon for formation and functionality of this vasculature network is lumen formation. The results of recent studies indicate the importance of blood pressure in this mechanism. Computational modeling can study these processes in different scales. Hence, wide varieties of these models have been proposed during recent years. In this research, a multi-scale model is developed for the angiogenesis process. In the extracellular scale, the growth factor concentration is calculated via the reaction diffusion equation. At the cellular scale, growth, migration, and the adhesion of endothelial cells are modeled by the Potts cellular model. At the intra-cellular scale by considering biochemical signals, a Boolean network model describes migration, division, or apoptosis of endothelial cells. A stochastic model developed for lumen formation via inverse membrane blebbing mechanism. A CFD simulation was also used to investigate the role of pulsated blood pressure in the inverse membrane blebbing mechanism. The lumen formation model shows stochastic behavior in blebs expansion and lumen expansion. Comparing the stochastic model's results with the CFD simulation also shows the vital role of pressure pulse and the topology of the blebs in bleb retraction.

Optimal Interruption of P. vivax Malaria Transmission Using Mass Drug Administration.

Plasmodium vivax is the most geographically widespread malaria-causing parasite resulting in significant associated global morbidity and mortality. One of the factors driving this widespread phenomenon is the ability of the parasites to remain dormant in the liver. Known as 'hypnozoites', they reside in the liver following an initial exposure, before activating later to cause further infections, referred to as 'relapses'. As around 79-96% of infections are attributed to relapses from activating hypnozoites, we expect it will be highly impactful to apply treatment to target the hypnozoite reservoir (i.e. the collection of dormant parasites) to eliminate P. vivax. Treatment with radical cure, for example tafenoquine or primaquine, to target the hypnozoite reservoir is a potential tool to control and/or eliminate P. vivax. We have developed a deterministic multiscale mathematical model as a system of integro-differential equations that captures the complex dynamics of P. vivax hypnozoites and the effect of hypnozoite relapse on disease transmission. Here, we use our multiscale model to study the anticipated effect of radical cure treatment administered via a mass drug administration (MDA) program. We implement multiple rounds of MDA with a fixed interval between rounds, starting from different steady-state disease prevalences. We then construct an optimisation model with three different objective functions motivated on a public health basis to obtain the optimal MDA interval. We also incorporate mosquito seasonality in our model to study its effect on the optimal treatment regime. We find that the effect of MDA interventions is temporary and depends on the pre-intervention disease prevalence (and choice of model parameters) as well as the number of MDA rounds under consideration. The optimal interval between MDA rounds also depends on the objective (combinations of expected intervention outcomes). We find radical cure alone may not be enough to lead to P. vivax elimination under our mathematical model (and choice of model parameters) since the prevalence of infection eventually returns to pre-MDA levels.

Computational Modeling to Determine the Effect of Phenotypic Heterogeneity in Tumors on the Collective Tumor-Immune Interactions.

Tumor immunotherapy aims to maintain or enhance the killing capability of CD8+ T cells to clear tumor cells. The tumor-immune interactions affect the function of CD8+ T cells. However, the effect of phenotype heterogeneity of a tumor mass on the collective tumor-immune interactions is insufficiently investigated. We developed the cellular-level computational model based on the principle of cellular Potts model to solve the case mentioned above. We considered how asymmetric division and glucose distribution jointly regulated the transient changes in the proportion of proliferating/quiescent tumor cells in a solid tumor mass. The evolution of a tumor mass in contact with T cells was explored and validated by comparing it with previous studies. Our modeling exhibited that proliferating/quiescent tumor cells, exhibiting distinct anti-apoptotic and suppressive behaviors, redistributed within the domain accompanied by the evolution of a tumor mass. Collectively, a tumor mass prone to a quiescent state weakened the collective suppressive functions of a tumor mass on cytotoxic T cells and triggered a decline of apoptosis of tumor cells. Although quiescent tumor cells did not sufficiently do their inhibitory functions, the possibility of long-term survival was improved due to their interior location within a mass. Overall, the proposed model provides a useful framework to investigate collective-targeted strategies for improving the efficiency of immunotherapy.

Controlling Multiple COVID-19 Epidemic Waves: An Insight from a Multi-scale Model Linking the Behaviour Change Dynamics to the Disease Transmission Dynamics.

COVID-19 epidemics exhibited multiple waves regionally and globally since 2020. It is important to understand the insight and underlying mechanisms of the multiple waves of COVID-19 epidemics in order to design more efficient non-pharmaceutical interventions (NPIs) and vaccination strategies to prevent future waves. We propose a multi-scale model by linking the behaviour change dynamics to the disease transmission dynamics to investigate the effect of behaviour dynamics on COVID-19 epidemics using game theory. The proposed multi-scale models are calibrated and key parameters related to disease transmission dynamics and behavioural dynamics with/without vaccination are estimated based on COVID-19 epidemic data (daily reported cases and cumulative deaths) and vaccination data. Our modeling results demonstrate that the feedback loop between behaviour changes and COVID-19 transmission dynamics plays an essential role in inducing multiple epidemic waves. We find that the long period of high-prevalence or persistent deterioration of COVID-19 epidemics could drive almost all of the population to change their behaviours and maintain the altered behaviours. However, the effect of behaviour changes fades out gradually along the progress of epidemics. This suggests that it is essential to have not only persistent, but also effective behaviour changes in order to avoid subsequent epidemic waves. In addition, our model also suggests the importance to maintain the effective altered behaviours during the initial stage of vaccination, and to counteract relaxation of NPIs, it requires quick and massive vaccination to avoid future epidemic waves.

Sensitivity Analysis in an Immuno-Epidemiological Vector-Host Model.

Sensitivity Analysis (SA) is a useful tool to measure the impact of changes in model parameters on the infection dynamics, particularly to quantify the expected efficacy of disease control strategies. SA has only been applied to epidemic models at the population level, ignoring the effect of within-host virus-with-immune-system interactions on the disease spread. Connecting the scales from individual to population can help inform drug and vaccine development. Thus the value of understanding the impact of immunological parameters on epidemiological quantities. Here we consider an age-since-infection structured vector-host model, in which epidemiological parameters are formulated as functions of within-host virus and antibody densities, governed by an ODE system. We then use SA for these immuno-epidemiological models to investigate the impact of immunological parameters on population-level disease dynamics such as basic reproduction number, final size of the epidemic or the infectiousness at different phases of an outbreak. As a case study, we consider Rift Valley Fever Disease utilizing parameter estimations from prior studies. SA indicates that [Formula: see text] increase in within-host pathogen growth rate can lead up to [Formula: see text] increase in [Formula: see text] up to [Formula: see text] increase in steady-state infected host abundance, and up to [Formula: see text] increase in infectiousness of hosts when the reproduction number [Formula: see text] is larger than one. These significant increases in population-scale disease quantities suggest that control strategies that reduce the within-host pathogen growth can be important in reducing disease prevalence.

Computational analysis of the hemodynamic characteristics under interaction influence of ß-blocker and LVAD.

BACKGROUND: Hemodynamic characteristics of the interaction influence among support level and model of LVAD, and coupling ß-blocker has not been reported. METHODS: In this study, the effect of support level and model of LVAD on cardiovascular hemodynamic characteristics is investigated. In addition, the effect of ß-blocker on unloading with LVAD is analyzed to elucidate the mechanism of LVAD coupling ß-blocker. A multi-scale model from cell level to system level is proposed. Moreover, LVAD coupling ß-blocker has been researching to explain the hemodynamics of cardiovascular system. RESULTS: Myocardial force was decreased along with the increase of support level of LVAD, and co-pulse mode was the lowest among the three support modes. Additionally, the ß-blocker combined with LVAD significantly reduced the left ventricular volume compared with LVAD support without ß-blocker. However, the left ventricular pressure under both cases has no significant difference. External work of right ventricular was increased along with the growth of support level of only LVAD. The LVAD under co-pulse mode achieved the lowest right-ventricular EW among the three support modes. CONCLUSIONS: Co-pulse mode with ß-blocker could be an optimal strategy for promoting cardiac structure and function recovery.

Multi-scale modeling of APC and [Formula: see text]-catenin regulation in the human colonic crypt.

Stem cell renewal and differentiation in the human colonic crypt are linked to the [Formula: see text]-catenin pathway. The spatial balance of Wnt factors in proliferative cells within the crypt maintain an appropriate level of cellular reproduction needed for normal crypt homeostasis. Mutational events at the gene level are responsible for deregulating the balance of Wnt factors along the crypt, causing an overpopulation of proliferative cells, a loss of structure of the crypt domain, and the initiation of colorectal carcinomas. We formulate a PDE model describing cell movement and reproduction in a static crypt domain. We consider a single cell population whose proliferative capabilities are determined by stemness, a quantity defined by intracellular levels of adenomatous polyposis coli (APC) scaffold protein and [Formula: see text]-catenin. We fit APC regulation parameters to biological data that describe normal protein gradients in the crypt. We also fit cell movement and protein flux parameters to normal crypt characteristics such as renewal time, total cell count, and proportion of proliferating cells. The model is used to investigate abnormal crypt dynamics when subjected to a diminished APC gradient, a scenario synonymous to mutations in the APC gene. We find that a 25% decrease in APC synthesis leads to a fraction of 0.88 proliferative, which is reflective of normal-appearing FAP crypts. A 50% drop in APC activity yields a fully proliferative crypt showing a doubling of the level of stemness, which characterizes the initial stages of colorectal cancer development. A sensitivity analysis of APC regulation parameters shows the perturbation of factors that is required to restore crypt dynamics to normal in the case of APC mutations.

A theoretical analysis of anatomical and functional intestinal slow wave re-entry.

Intestinal bioelectrical slow waves are a key regulator of intestinal motility. Peripheral pacemakers, ectopic initiations and sustained periods of re-entrant activities have all been experimentally observed to be important factors in setting the frequency of intestinal slow waves, but the tissue-level mechanisms underpinning these activities are unclear. This theoretical analysis aimed to define the initiation, maintenance, and termination criteria of two classes of intestinal re-entrant activities: anatomical re-entry and functional re-entry. Anatomical re-entry was modeled in a three-dimensional (3D) cylindrical model, and functional rotor was modeled in a 2D rectangle model. A single-pulse stimulus was used to invoke an anatomical re-entry and a prolonged refractory block was used to invoke the rotor. In both cases, the simulated re-entrant activities operated at frequencies above the baseline entrainment frequency. The anatomical re-entry simulation results demonstrated that a temporary functional refractory block would be required to initiate the re-entrant activity in a single direction around the cylindrical model. The rotor could be terminated by a single-pulse stimulus delivered around the core of the rotor. In conclusion, the simulation results provide the following new insights into the mechanisms of intestinal re-entry: (i) anatomical re-entry is only maintained within a specific range of velocities, outside of which the re-entrant activities become either an ectopic activity or simultaneous activations of the intestinal wall; (ii) a maintained rotor entrained slow waves faster in the antegrade direction than in the retrograde direction. Simulations are shown to be a valuable tool for achieving novel insights into the mechanisms of intestinal slow wave dysrhythmia.

Mechanism for multiplicity of steady states with distinct cell concentration in continuous culture of mammalian cells.

Continuous culture for the production of biopharmaceutical proteins offers the possibility of steady state operations and thus more consistent product quality and increased productivity. Under some conditions, multiplicity of steady states has been observed in continuous cultures of mammalian cells, wherein with the same dilution rate and feed nutrient composition, steady states with very different cell and product concentrations may be reached. At those different steady states, cells may exhibit a high glycolysis flux with high lactate production and low cell concentration, or a low glycolysis flux with low lactate and high cell concentration. These different steady states, with different cell concentration, also have different productivity. Developing a mechanistic understanding of the occurrence of steady state multiplicity and devising a strategy to steer the culture toward the desired steady state is critical. We establish a multi-scale kinetic model that integrates a mechanistic intracellular metabolic model and cell growth model in a continuous bioreactor. We show that steady state multiplicity exists in a range of dilution rate in continuous culture as a result of the bistable behavior in glycolysis. The insights from the model were used to devise strategies to guide the culture to the desired steady state in the multiple steady state region. The model provides a guideline principle in the design of continuous culture processes of mammalian cells.

Myocardial ischemia simulation based on a multi-scale heart electrophysiology model.

BACKGROUND: Myocardial ischemia, caused by insufficient myocardial blood supply, is a leading cause of human death worldwide. Therefore, it is crucial to prioritize the prevention and treatment of this condition. Mathematical modeling is a powerful technique for studying heart diseases. OBJECTIVE: The aim of this study was to discuss the quantitative relationship between extracellular potassium concentration and the degree of myocardial ischemia directly related to it. METHODS: A human cardiac electrophysiological multiscale model was developed to calculate action potentials of all cells simultaneously, enhancing efficiency over traditional reaction-diffusion models. RESULTS: Contrary to the commonly held view that myocardial ischemia is caused by an increase in extracellular potassium concentration, our simulation results indicate that level 1 ischemia is associated with a decrease in extracellular potassium concentration. CONCLUSION: This unusual finding provides a new perspective on the mechanisms underlying myocardial ischemia and has the potential to lead to the development of new diagnostic and treatment strategies.

Optimal control of a multi-scale HIV-opioid model.

In this study, we apply optimal control theory to an immuno-epidemiological model of HIV and opioid epidemics. For the multi-scale model, we used four controls: treating the opioid use, reducing HIV risk behaviour among opioid users, entry inhibiting antiviral therapy, and antiviral therapy which blocks the viral production. Two population-level controls are combined with two within-host-level controls. We prove the existence and uniqueness of an optimal control quadruple. Comparing the two population-level controls, we find that reducing the HIV risk of opioid users has a stronger impact on the population who is both HIV-infected and opioid-dependent than treating the opioid disorder. The within-host-level antiviral treatment has an effect not only on the co-affected population but also on the HIV-only infected population. Our findings suggest that the most effective strategy for managing the HIV and opioid epidemics is combining all controls at both within-host and between-host scales.

Outdoor heat stress assessment using an integrated multi-scale numerical weather prediction system: A case study of a heatwave in Montreal.

More frequent and severe extreme weather events such as heatwaves are among the most serious challenges to society in coping with the changing climate. To evaluate the impacts of the heatwave on large-scale urban areas, a multi-scale weather forecasting system is designed by integrating different resolutions of the Canadian urbanized version of the Global Environmental Multiscale (GEM) Numerical Weather Prediction (NWP) model, cascading from 10 km to 2.5 km, and 250 m. The multi-scale model is implemented in Montreal, Canada, for modeling the 2018 heatwave. Simulation results are well-validated against measurement data, including Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery and ten weather stations in the city. The Universal Thermal Climate Index (UTCI) map was calculated to identify vulnerable regions in the city against the heatwave. Land-use types in hotspots and coldspots are analyzed to find dominant factors in the formation of hot and cold areas. It is found that natural landscapes such as vegetation, trees, and water bodies are the dominant features of most coldspots. On the other hand, roads, parking lots, less tree covers, and industrial activities are the common land use features in the hotspots. A weak correlation is found between heat-related death locations and the outdoor UTCI map, implying that the assessment of an outdoor heatwave may not address overheated buildings and communities. This paper shows the importance of built environments - their properties and occupants' socio-demographic factors in the study of heat-related mortalities in cities.

Multiaxial Fatigue Analysis of Jacket-Type Offshore Wind Turbine Based on Multi-Scale Finite Element Model.

The fatigue damage of a local joint is the key factor accounting for the structural failure of a jacket-type offshore wind turbine. Meanwhile, the structure experiences a complex multiaxial stress state under wind and wave random loading. This paper aims to develop a multi-scale modeling method for a jacket-type offshore wind turbine, in which local joints of the jacket are modeled in a detail by using solid elements, and other components are modeled via the common beam element. Considering the multiaxial stress state of the local joint, multi-axial fatigue damage analysis based on the multiaxial S-N curve is performed using equivalent Mises and Lemaitre methods. The uniaxial fatigue damage data of the jacket model calculated using the multi-scale finite element model are compared with those of the conventional beam model. The results show that the tubular joint of jacket leg and brace connections can be modeled using the multi-scale method, since the uniaxial fatigue damage degree can reach a 15% difference. The comparison of uniaxial and multiaxial fatigue results obtained using the multi-scale finite element model shows that the difference can be about 15% larger. It is suggested that the multi-scale finite element model should be used for better accuracy in the multiaxial fatigue analysis of the jacket-type offshore wind turbine under wind and wave random loading.

Effects of abnormal vertebral arteries and the circle of Willis on vertebrobasilar dolichoectasia: A multi-scale simulation study.

BACKGROUND: Vertebrobasilar dolichoectasia is a rare cerebrovascular disease characterized by obvious extension, dilation and tortuosity of vertebrobasilar artery, and its pathophysiological mechanism is not clear. This study focused on local hemodynamic changes in basilar arteries with typical vertebrobasilar dolichoectasia, together with unbalanced vertebral arteries and abnormal structures of the circle of Willis, through multi-scale modeling. METHODS: Three-dimensional models of 3 types of vertebrobasilar arteries were constructed from magnetic resonance images. The first type has no vertebrobasilar dolichoectasia, the second type has vertebrobasilar dolichoectasia and balanced vertebral arteries, and the third type has vertebrobasilar dolichoectasia and unbalanced vertebral arteries. A lumped parameter model of the circle of Willis was established and coupled to these three-dimensional models. FINDINGS: The results showed that unbalanced bilateral vertebral arteries, especially single vertebral artery deletion mutation, might associate with higher wall shear stress on anterior wall of basilar artery in patients with vertebrobasilar dolichoectasia. And unbalanced bilateral vertebral arteries would increase the blood pressure in basilar artery. Meanwhile, missing communicating arteries in the circle of Willis, especially bilateral posterior communicating arteries absences, would significantly increase blood pressure in basilar artery. The unilateral absence of posterior communicating arteries would increase differences in blood flow between the left and right posterior cerebral arteries. INTERPRETATION: This study provided a multi-scale modeling method and some preliminary results for helping understand the role of hemodynamics in occurrence and development of vertebrobasilar dolichoectasia.

Multi-Scale Model for the Aging Performance of Particle-Filled Polymer Composites.

In this study, we developed a novel multi-scale model to predict the aging performance of particle-filled polymer composites (PFPCs) under thermo-oxidative aging conditions. To investigate the aging behavior, high-temperature accelerated aging tests were conducted in combination with macroscopic and microscopic characterization. At the microscopic level, the crosslinking density of the polymer matrix is calculated using the closed-loop chain reaction of polymer oxidation. In addition, the theory of polymer physics was used to determine the relationship between crosslinking density and elastic modulus. Relationships between elastic modulus and dewetting strain were analyzed at the macroscopic level. Based on the observations and analyses, a multi-scale model was developed to predict the aging performance of PFPCs. The predicted results show good agreement with the test results, which verifies the reliability of the model.

A new synergistic model for simulating exercise incorporating control mechanisms at cellular and organ scales.

The physiological response of the cardio-vascular system (CVS) to physical activity is of great importance to those working in sporting research and has profound consequences for the health and well-being of people. Coronary vasodilation and the physiological mechanisms involved in exercise have frequently been the focus of numerical models for simulating exercise. This is partly achieved using the time-varying-elastance (TVE) theory, which prescribes the pressure-volume relationship of the ventricle as a periodic function of time, tuned using empirical data. The empirical foundations of the TVE method however, and its suitability for CVS modelling are frequently questioned. To overcome this challenge, we adopt a different synergistic approach in which a model for the microscale heart muscle (myofibers) activity is embedded within a macro organ-scale CVS model. We developed such a synergistic model by including the coronary flow and various control mechanisms at the circulation level through feedback and feedforward means, and at the microscale (contractile) through the regulation of ATP availability and myofiber force depending on exercise intensity or heart rate. The coronary flow produced by the model displays the well-known 2-phase character of the flow, which is preserved under exercise. The model is tested by simulating reactive hyperemia, which is a transient occlusion of the coronary flow, successfully reproducing the additional coronary flow following the block removal. On-transient exercise results reveal a rise in both cardiac output and mean ventricle pressure as expected. The stroke volume increases initially, but then declines during the latter period of HR rise, corresponding with one of the main physiological responses to exercise. The pressure-volume loop expands during exercise, as systolic pressure rises. The Myocardial oxygen demand increases during exercise and the coronary blood supply increases in response, causing an excess of oxygen supply to the heart. Off-transient exercise recovery is largely a reverse of this response, although the behaviour is slightly more varied, with sudden spikes in coronary resistance. Different levels of fitness and exercise intensity are tested and reveal that the stroke volume rises until a level of myocardial oxygen demand is reached at which point it declines. This level of demand is independent of fitness or exercise intensity. An advantage of our model is demonstrated in the correspondence between the micro and organ scale mechanics so that cellular pathologies can be traced from exercise performance with relatively little computational or experimental expense.

Correlation of viral loads in disease transmission could affect early estimates of the reproduction number.

Early estimates of the transmission properties of a newly emerged pathogen are critical to an effective public health response, and are often based on limited outbreak data. Here, we use simulations to investigate how correlations between the viral load of cases in transmission chains can affect estimates of these fundamental transmission properties. Our computational model simulates a disease transmission mechanism in which the viral load of the infector at the time of transmission influences the infectiousness of the infectee. These correlations in transmission pairs produce a population-level convergence process during which the distributions of initial viral loads in each subsequent generation converge to a steady state. We find that outbreaks arising from index cases with low initial viral loads give rise to early estimates of transmission properties that could be misleading. These findings demonstrate the potential for transmission mechanisms to affect estimates of the transmission properties of newly emerged viruses in ways that could be operationally significant to a public health response.