Automated Data-Driven Discovery of Material Models Based on Symbolic Regression: A Case Study on the Human Brain Cortex.

We introduce a data-driven framework to automatically identify interpretable and physically meaningful hyperelastic constitutive models from sparse data. Leveraging symbolic regression, our approach generates elegant hyperelastic models that achieve accurate data fitting with parsimonious mathematic formulas, while strictly adhering to hyperelasticity constraints such as polyconvexity/ellipticity. Our investigation spans three distinct hyperelastic models-invariant-based, principal stretch-based, and normal strain-based-and highlights the versatility of symbolic regression. We validate our new approach using synthetic data from five classic hyperelastic models and experimental data from the human brain cortex to demonstrate algorithmic efficacy. Our results suggest that our symbolic regression algorithms robustly discover accurate models with succinct mathematic expressions in invariant-based, stretch-based, and strain-based scenarios. Strikingly, the strain-based model exhibits superior accuracy, while both stretch-based and strain-based models effectively capture the nonlinearity and tension-compression asymmetry inherent to the human brain tissue. Polyconvexity/ellipticity assessment affirm the rigorous adherence to convexity requirements both within and beyond the training regime. However, the stretch-based models raise concerns regarding potential convexity loss under large deformations. The evaluation of predictive capabilities demonstrates remarkable interpolation capabilities for all three models and acceptable extrapolation performance for stretch-based and strain-based models. Finally, robustness tests on noise-embedded data underscore the reliability of our symbolic regression algorithms. Our study confirms the applicability and accuracy of symbolic regression in the automated discovery of isotropic hyperelastic models for the human brain and gives rise to a wide variety of applications in other soft matter systems. STATEMENT OF SIGNIFICANCE: Our research introduces a pioneering data-driven framework that revolutionizes the automated identification of hyperelastic constitutive models, particularly in the context of soft matter systems such as the human brain. By harnessing the power of symbolic regression, we have unlocked the ability to distill intricate physical phenomena into elegant and interpretable mathematical expressions. Our approach not only ensures accurate fitting to sparse data but also upholds crucial hyperelasticity constraints, including polyconvexity, essential for maintaining physical relevance.

Sex-specific cardiovascular risk factors in the UK Biobank.

The lack of sex-specific cardiovascular disease criteria contributes to the underdiagnosis of women compared to that of men. For more than half a century, the Framingham Risk Score has been the gold standard to estimate an individual's risk of developing cardiovascular disease based on the age, sex, cholesterol levels, blood pressure, diabetes status, and the smoking status. Now, machine learning can offer a much more nuanced insight into predicting the risk of cardiovascular diseases. The UK Biobank is a large database that includes traditional risk factors and tests related to the cardiovascular system: magnetic resonance imaging, pulse wave analysis, electrocardiograms, and carotid ultrasounds. Here, we leverage 20,542 datasets from the UK Biobank to build more accurate cardiovascular risk models than the Framingham Risk Score and quantify the underdiagnosis of women compared to that of men. Strikingly, for a first-degree atrioventricular block and dilated cardiomyopathy, two conditions with non-sex-specific diagnostic criteria, our study shows that women are under-diagnosed 2× and 1.4× more than men. Similarly, our results demonstrate the need for sex-specific criteria in essential primary hypertension and hypertrophic cardiomyopathy. Our feature importance analysis reveals that out of the top 10 features across three sexes and four disease categories, traditional Framingham factors made up between 40% and 50%; electrocardiogram, 30%-33%; pulse wave analysis, 13%-23%; and magnetic resonance imaging and carotid ultrasound, 0%-10%. Improving the Framingham Risk Score by leveraging big data and machine learning allows us to incorporate a wider range of biomedical data and prediction features, enhance personalization and accuracy, and continuously integrate new data and knowledge, with the ultimate goal to improve accurate prediction, early detection, and early intervention in cardiovascular disease management. Our analysis pipeline and trained classifiers are freely available at https://github.com/LivingMatterLab/CardiovascularDiseaseClassification.

Minimal Design of the Elephant Trunk as an Active Filament.

One of the key problems in active materials is the control of shape through actuation. A fascinating example of such control is the elephant trunk, a long, muscular, and extremely dexterous organ with multiple vital functions. The elephant trunk is an object of fascination for biologists, physicists, and children alike. Its versatility relies on the intricate interplay of multiple unique physical mechanisms and biological design principles. Here, we explore these principles using the theory of active filaments and build, theoretically, computationally, and experimentally, a minimal model that explains and accomplishes some of the spectacular features of the elephant trunk.

Panel stacking is a threat to consensus statement validity.

Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.

Benchmarking physics-informed frameworks for data-driven hyperelasticity.

Data-driven methods have changed the way we understand and model materials. However, while providing unmatched flexibility, these methods have limitations such as reduced capacity to extrapolate, overfitting, and violation of physics constraints. Recently, frameworks that automatically satisfy these requirements have been proposed. Here we review, extend, and compare three promising data-driven methods: Constitutive Artificial Neural Networks (CANN), Input Convex Neural Networks (ICNN), and Neural Ordinary Differential Equations (NODE). Our formulation expands the strain energy potentials in terms of sums of convex non-decreasing functions of invariants and linear combinations of these. The expansion of the energy is shared across all three methods and guarantees the automatic satisfaction of objectivity, material symmetries, and polyconvexity, essential within the context of hyperelasticity. To benchmark the methods, we train them against rubber and skin stress-strain data. All three approaches capture the data almost perfectly, without overfitting, and have some capacity to extrapolate. This is in contrast to unconstrained neural networks which fail to make physically meaningful predictions outside the training range. Interestingly, the methods find different energy functions even though the prediction on the stress data is nearly identical. The most notable differences are observed in the second derivatives, which could impact performance of numerical solvers. On the rich data used in these benchmarks, the models show the anticipated trade-off between number of parameters and accuracy. Overall, CANN, ICNN and NODE retain the flexibility and accuracy of other data-driven methods without compromising on the physics. These methods are ideal options to model arbitrary hyperelastic material behavior.

Automated model discovery for muscle using constitutive recurrent neural networks.

The stiffness of soft biological tissues not only depends on the applied deformation, but also on the deformation rate. To model this type of behavior, traditional approaches select a specific time-dependent constitutive model and fit its parameters to experimental data. Instead, a new trend now suggests a machine-learning based approach that simultaneously discovers both the best model and best parameters to explain given data. Recent studies have shown that feed-forward constitutive neural networks can robustly discover constitutive models and parameters for hyperelastic materials. However, feed-forward architectures fail to capture the history dependence of viscoelastic soft tissues. Here we combine a feed-forward constitutive neural network for the hyperelastic response and a recurrent neural network for the viscous response inspired by the theory of quasi-linear viscoelasticity. Our novel rheologically-informed network architecture discovers the time-independent initial stress using the feed-forward network and the time-dependent relaxation using the recurrent network. We train and test our combined network using unconfined compression relaxation experiments of passive skeletal muscle and compare our discovered model to a neo Hookean standard linear solid, to an advanced mechanics-based model, and to a vanilla recurrent neural network with no mechanics knowledge. We demonstrate that, for limited experimental data, our new constitutive recurrent neural network discovers models and parameters that satisfy basic physical principles and generalize well to unseen data. We discover a Mooney-Rivlin type two-term initial stored energy function that is linear in the first invariant I1 and quadratic in the second invariant I2 with stiffness parameters of 0.60 kPa and 0.55 kPa. We also discover a Prony-series type relaxation function with time constants of 0.362s, 2.54s, and 52.0s with coefficients of 0.89, 0.05, and 0.03. Our newly discovered model outperforms both the neo Hookean standard linear solid and the vanilla recurrent neural network in terms of prediction accuracy on unseen data. Our results suggest that constitutive recurrent neural networks can autonomously discover both model and parameters that best explain experimental data of soft viscoelastic tissues. Our source code, data, and examples are available at https://github.com/LivingMatterLab.

Validating MRI-Derived Myocardial Stiffness Estimates Using In Vitro Synthetic Heart Models.

Impaired cardiac filling in response to increased passive myocardial stiffness contributes to the pathophysiology of heart failure. By leveraging cardiac MRI data and ventricular pressure measurements, we can estimate in vivo passive myocardial stiffness using personalized inverse finite element models. While it is well-known that this approach is subject to uncertainties, only few studies quantify the accuracy of these stiffness estimates. This lack of validation is, at least in part, due to the absence of ground truth in vivo passive myocardial stiffness values. Here, using 3D printing, we created soft, homogenous, isotropic, hyperelastic heart phantoms of varying geometry and stiffness and simulate diastolic filling by incorporating the phantoms into an MRI-compatible left ventricular inflation system. We estimate phantom stiffness from MRI and pressure data using inverse finite element analyses based on a Neo-Hookean model. We demonstrate that our identified softest and stiffest values of 215.7 and 512.3 kPa agree well with the ground truth of 226.2 and 526.4 kPa. Overall, our estimated stiffnesses revealed a good agreement with the ground truth ([Formula: see text] error) across all models. Our results suggest that MRI-driven computational constitutive modeling can accurately estimate synthetic heart material stiffnesses in the range of 200-500 kPa.

Automated model discovery for human brain using Constitutive Artificial Neural Networks.

The brain is our softest and most vulnerable organ, and understanding its physics is a challenging but significant task. Throughout the past decade, numerous competing models have emerged to characterize its response to mechanical loading. However, selecting the best constitutive model remains a heuristic process that strongly depends on user experience and personal preference. Here we challenge the conventional wisdom to first select a constitutive model and then fit its parameters to data. Instead, we propose a new strategy that simultaneously discovers both model and parameters. We integrate more than a century of knowledge in thermodynamics and state-of-the-art machine learning to build a Constitutive Artificial Neural Network that enables automated model discovery. Our design paradigm is to reverse engineer the network from a set of functional building blocks that are, by design, a generalization of popular constitutive models, including the neo Hookean, Blatz Ko, Mooney Rivlin, Demiray, Gent, and Holzapfel models. By constraining input, output, activation functions, and architecture, our network a priori satisfies thermodynamic consistency, objectivity, symmetry, and polyconvexity. We demonstrate that-out of more than 4000 models-our network autonomously discovers the model and parameters that best characterize the behavior of human gray and white matter under tension, compression, and shear. Importantly, our network weights translate naturally into physically meaningful parameters, such as shear moduli of 1.82kPa, 0.88kPa, 0.94kPa, and 0.54kPa for the cortex, basal ganglia, corona radiata, and corpus callosum. Our results suggest that Constitutive Artificial Neural Networks have the potential to induce a paradigm shift in soft tissue modeling, from user-defined model selection to automated model discovery. Our source code, data, and examples are available at https://github.com/LivingMatterLab/CANN. STATEMENT OF SIGNIFICANCE: Human brain is ultrasoft, difficult to test, and challenging to model. Numerous competing constitutive models exist, but selecting the best model remains a matter of personal preference. Here we automate the process of model selection. We formulate the problem of autonomous model discovery as a neural network and capitalize on the powerful optimizers in deep learning. However, rather than using a conventional neural network, we reverse engineer our own Constitutive Artificial Neural Network from a set of modular building blocks, which we rationalize from common constitutive models. When trained with tension, compression, and shear experiments of gray and white matter, our network simultaneously discovers both model and parameters that describes the data better than any existing invariant-based model. Our network could induce a paradigm shift from user-defined model selection to automated model discovery.

Mechanics of axon growth and damage: A systematic review of computational models.

Normal axon development depends on the action of mechanical forces both generated within the cytoskeleton and outside the cell, but forces of large magnitude or rate cause damage instead. Computational models aid scientists in studying the role of mechanical forces in axon growth and damage. These studies use simulations to evaluate how different sources of force generation within the cytoskeleton interact with each other to regulate axon elongation and retraction. Furthermore, mathematical models can help optimize externally applied tension to promote axon growth without causing damage. Finally, scientists also use simulations of axon damage to investigate how forces are distributed among different components of the axon and how the tissue surrounding an axon influences its susceptibility to injury. In this review, we discuss how computational studies complement experimental studies in the areas of axon growth, regeneration, and damage.

Image-based axon model highlights heterogeneity in initiation of damage.

Head injury simulations predict the occurrence of traumatic brain injury by placing a threshold on the calculated strains for axon tracts within the brain. However, a current roadblock to accurate injury prediction is the selection of an appropriate axon damage threshold. While several computational studies have used models of the axon cytoskeleton to investigate damage initiation, these models all employ an idealized, homogeneous axonal geometry. This homogeneous geometry with regularly spaced microtubules, evenly distributed throughout the model, overestimates axon strength because, in reality, the axon cytoskeleton is heterogeneous. In the heterogeneous cytoskeleton, the weakest cross section determines the initiation of failure, but these weak spots are not present in a homogeneous model. Addressing one source of heterogeneity in the axon cytoskeleton, we present a new semiautomated image analysis pipeline for using serial-section transmission electron micrographs to reconstruct the microtubule geometry of an axon. The image analysis procedure locates microtubules within the images, traces them throughout the image stack, and reconstructs the microtubule structure as a finite element mesh. We demonstrate the image analysis approach using a C. elegans touch receptor neuron due to the availability of high-quality serial-section transmission electron micrograph data sets. The results of the analysis highlight the heterogeneity of the microtubule structure in the spatial variation of both microtubule number and length. Simulations comparing this image-based geometry with homogeneous geometries show that structural heterogeneity in the image-based model creates significant spatial variation in deformation. The homogeneous geometries, on the other hand, deform more uniformly. Since no single homogeneous model can replicate the mechanical behavior of the image-based model, our results argue that heterogeneity in axon microtubule geometry should be considered in determining accurate axon failure thresholds.

Correlating the microstructural architecture and macrostructural behaviour of the brain.

The computational simulation of pathological conditions and surgical procedures, for example the removal of cancerous tissue, can contribute crucially to the future of medicine. Especially for brain surgery, these methods can be important, as the ultra-soft tissue controls vital functions of the body. However, the microstructural interactions and their effects on macroscopic material properties remain incompletely understood. Therefore, we investigated the mechanical behaviour of brain tissue under three different deformation modes, axial tension, compression, and semi-confined compression, in different anatomical regions, and for varying axon orientation. In addition, we characterised the underlying microstructure in terms of myelin, cells, glial cells and neuron area fraction, and density. The correlation of these quantities with the material parameters of the anisotropic Ogden model reveals a decrease in shear modulus with increasing myelin area fraction. Strikingly, the tensile shear modulus correlates positively with cell and neuronal area fraction (Spearman's correlation coefficient of rs=0.40 and rs=0.33), whereas the compressive shear modulus decreases with increasing glial cell area (rs=-0.33). Our study finds that tissue non-linearity significantly depends on the myelin area fraction (rs=0.47), cell density (rs=0.41) and glial cell area (rs=0.49). Our results provide an important step towards understanding the micromechanical load transfer that leads to the non-linear macromechanical behaviour of the brain. STATEMENT OF SIGNIFICANCE: Within this article, we investigate the mechanical behaviour of brain tissue under three different deformation modes, in different anatomical regions, and for varying axon orientation. Further, we characterise the underlying microstructure in terms of various constituents. The correlation of these quantities with the material parameters of the anisotropic Ogden model reveals a decrease in shear modulus with increasing myelin area fraction. Strikingly, the tensile shear modulus correlates positively with cell and neuronal area fraction, whereas the compressive shear modulus decreases with increasing glial cell area. Our study finds that tissue non-linearity significantly depends on the myelin area fraction, cell density, and glial cell area. Our results provide an important step towards understanding the micromechanical load transfer that leads to the non-linear macromechanical behaviour of the brain.

Sex Matters: A Comprehensive Comparison of Female and Male Hearts.

Cardiovascular disease in women remains under-diagnosed and under-treated. Recent studies suggest that this is caused, at least in part, by the lack of sex-specific diagnostic criteria. While it is widely recognized that the female heart is smaller than the male heart, it has long been ignored that it also has a different microstructural architecture. This has severe implications on a multitude of cardiac parameters. Here, we systematically review and compare geometric, functional, and structural parameters of female and male hearts, both in the healthy population and in athletes. Our study finds that, compared to the male heart, the female heart has a larger ejection fraction and beats at a faster rate but generates a smaller cardiac output. It has a lower blood pressure but produces universally larger contractile strains. Critically, allometric scaling, e.g., by lean body mass, reduces but does not completely eliminate the sex differences between female and male hearts. Our results suggest that the sex differences in cardiac form and function are too complex to be ignored: the female heart is not just a small version of the male heart. When using similar diagnostic criteria for female and male hearts, cardiac disease in women is frequently overlooked by routine exams, and it is diagnosed later and with more severe symptoms than in men. Clearly, there is an urgent need to better understand the female heart and design sex-specific diagnostic criteria that will allow us to diagnose cardiac disease in women equally as early, robustly, and reliably as in men. Systematic Review Registration: https://livingmatter.stanford.edu/.

How viscous is the beating heart?: Insights from a computational study.

Understanding tissue rheology is critical to accurately model the human heart. While the elastic properties of cardiac tissue have been extensively studied, its viscous properties remain an issue of ongoing debate. Here we adopt a viscoelastic version of the classical Holzapfel Ogden model to study the viscous timescales of human cardiac tissue. We perform a series of simulations and explore stress-relaxation curves, pressure-volume loops, strain profiles, and ventricular wall strains for varying viscosity parameters. We show that the time window for model calibration strongly influences the parameter identification. Using a four-chamber human heart model, we observe that, during the physiologically relevant time scales of the cardiac cycle, viscous relaxation has a negligible effect on the overall behavior of the heart. While viscosity could have important consequences in pathological conditions with compromised contraction or relaxation properties, we conclude that, for simulations within the physiological range of a human heart beat, we can reasonably approximate the human heart as hyperelastic.

Growth and remodeling in the pulmonary autograft: Computational evaluation using kinematic growth models and constrained mixture theory.

Computational investigations of how soft tissues grow and remodel are gaining more and more interest and several growth and remodeling theories have been developed. Roughly, two main groups of theories for soft tissues can be distinguished: kinematic-based growth theory and theories based on constrained mixture theory. Our goal was to apply these two theories on the same experimental data. Within the experiment, a pulmonary artery was exposed to systemic conditions. The change in diameter was followed-up over time. A mechanical and microstructural analysis of native pulmonary artery and pulmonary autograft was conducted. Whereas the kinematic-based growth theory is able to accurately capture the growth of the tissue, it does not account for the mechanobiological processes causing this growth. The constrained mixture theory takes into account the mechanobiological processes including removal, deposition and adaptation of all structural constituents, allowing us to simulate a changing microstructure and mechanical behavior.

Sex Differences in Drug-Induced Arrhythmogenesis.

The electrical activity in the heart varies significantly between men and women and results in a sex-specific response to drugs. Recent evidence suggests that women are more than twice as likely as men to develop drug-induced arrhythmia with potentially fatal consequences. Yet, the sex-specific differences in drug-induced arrhythmogenesis remain poorly understood. Here we integrate multiscale modeling and machine learning to gain mechanistic insight into the sex-specific origin of drug-induced cardiac arrhythmia at differing drug concentrations. To quantify critical drug concentrations in male and female hearts, we identify the most important ion channels that trigger male and female arrhythmogenesis, and create and train a sex-specific multi-fidelity arrhythmogenic risk classifier. Our study reveals that sex differences in ion channel activity, tissue conductivity, and heart dimensions trigger longer QT-intervals in women than in men. We quantify the critical drug concentration for dofetilide, a high risk drug, to be seven times lower for women than for men. Our results emphasize the importance of including sex as an independent biological variable in risk assessment during drug development. Acknowledging and understanding sex differences in drug safety evaluation is critical when developing novel therapeutic treatments on a personalized basis. The general trends of this study have significant implications on the development of safe and efficacious new drugs and the prescription of existing drugs in combination with other drugs.

Effects of B.1.1.7 and B.1.351 on COVID-19 Dynamics: A Campus Reopening Study.

The timing and sequence of safe campus reopening has remained the most controversial topic in higher education since the outbreak of the COVID-19 pandemic. By the end of March 2020, almost all colleges and universities in the United States had transitioned to an all online education and many institutions have not yet fully reopened to date. For a residential campus like Stanford University, the major challenge of reopening is to estimate the number of incoming infectious students at the first day of class. Here we learn the number of incoming infectious students using Bayesian inference and perform a series of retrospective and projective simulations to quantify the risk of campus reopening. We create a physics-based probabilistic model to infer the local reproduction dynamics for each state and adopt a network SEIR model to simulate the return of all undergraduates, broken down by their year of enrollment and state of origin. From these returning student populations, we predict the outbreak dynamics throughout the spring, summer, fall, and winter quarters using the inferred reproduction dynamics of Santa Clara County. We compare three different scenarios: the true outbreak dynamics under the wild-type SARS-CoV-2, and the hypothetical outbreak dynamics under the new COVID-19 variants B.1.1.7 and B.1.351 with 56% and 50% increased transmissibility. Our study reveals that even small changes in transmissibility can have an enormous impact on the overall case numbers. With no additional countermeasures, during the most affected quarter, the fall of 2020, there would have been 203 cases under baseline reproduction, compared to 4727 and 4256 cases for the B.1.1.7 and B.1.351 variants. Our results suggest that population mixing presents an increased risk for local outbreaks, especially with new and more infectious variants emerging across the globe. Tight outbreak control through mandatory quarantine and test-trace-isolate strategies will be critical in successfully managing these local outbreak dynamics.

Bayesian Physics-Based Modeling of Tau Propagation in Alzheimer's Disease.

Amyloid-ß and hyperphosphorylated tau protein are known drivers of neuropathology in Alzheimer's disease. Tau in particular spreads in the brains of patients following a spatiotemporal pattern that is highly sterotypical and correlated with subsequent neurodegeneration. Novel medical imaging techniques can now visualize the distribution of tau in the brain in vivo, allowing for new insights to the dynamics of this biomarker. Here we personalize a network diffusion model with global spreading and local production terms to longitudinal tau positron emission tomography data of 76 subjects from the Alzheimer's Disease Neuroimaging Initiative. We use Bayesian inference with a hierarchical prior structure to infer means and credible intervals for our model parameters on group and subject levels. Our results show that the group average protein production rate for amyloid positive subjects is significantly higher with 0.019±0.27/yr, than that for amyloid negative subjects with -0.143±0.21/yr (p = 0.0075). These results support the hypothesis that amyloid pathology drives tau pathology. The calibrated model could serve as a valuable clinical tool to identify optimal time points for follow-up scans and predict the timeline of disease progression.

Multiscale modeling meets machine learning: What can we learn?

Machine learning is increasingly recognized as a promising technology in the biological, biomedical, and behavioral sciences. There can be no argument that this technique is incredibly successful in image recognition with immediate applications in diagnostics including electrophysiology, radiology, or pathology, where we have access to massive amounts of annotated data. However, machine learning often performs poorly in prognosis, especially when dealing with sparse data. This is a field where classical physics-based simulation seems to remain irreplaceable. In this review, we identify areas in the biomedical sciences where machine learning and multiscale modeling can mutually benefit from one another: Machine learning can integrate physics-based knowledge in the form of governing equations, boundary conditions, or constraints to manage ill-posted problems and robustly handle sparse and noisy data; multiscale modeling can integrate machine learning to create surrogate models, identify system dynamics and parameters, analyze sensitivities, and quantify uncertainty to bridge the scales and understand the emergence of function. With a view towards applications in the life sciences, we discuss the state of the art of combining machine learning and multiscale modeling, identify applications and opportunities, raise open questions, and address potential challenges and limitations. We anticipate that it will stimulate discussion within the community of computational mechanics and reach out to other disciplines including mathematics, statistics, computer science, artificial intelligence, biomedicine, systems biology, and precision medicine to join forces towards creating robust and efficient models for biological systems.

Global and local mobility as a barometer for COVID-19 dynamics.

The spreading of infectious diseases including COVID-19 depends on human interactions. In an environment where behavioral patterns and physical contacts are constantly evolving according to new governmental regulations, measuring these interactions is a major challenge. Mobility has emerged as an indicator for human activity and, implicitly, for human interactions. Here, we study the coupling between mobility and COVID-19 dynamics and show that variations in global air traffic and local driving mobility can be used to stratify different disease phases. For ten European countries, our study shows a maximal correlation between driving mobility and disease dynamics with a time lag of [Formula: see text] days. Our findings suggest that trends in local mobility allow us to forecast the outbreak dynamics of COVID-19 for a window of two weeks and adjust local control strategies in real time.

Are college campuses superspreaders? A data-driven modeling study.

The COVID-19 pandemic continues to present enormous challenges for colleges and universities and strategies for save reopening remain a topic of ongoing debate. Many institutions that reopened cautiously in the fall experienced a massive wave of infections and colleges were soon declared as the new hotspots of the pandemic. However, the precise effects of college outbreaks on their immediate neighborhood remain largely unknown. Here we show that the first two weeks of instruction present a high-risk period for campus outbreaks and that these outbreaks tend to spread into the neighboring communities. By integrating a classical mathematical epidemiology model and Bayesian learning, we learned the dynamic reproduction number for 30 colleges from their daily case reports. Of these 30 institutions, 14 displayed a spike of infections within the first two weeks of class, with peak seven-day incidences well above 1,000 per 100,000, an order of magnitude larger than the nation-wide peaks of 70 and 150 during the first and second waves of the pandemic. While most colleges were able to rapidly reduce the number of new infections, many failed to control the spread of the virus beyond their own campus: Within only two weeks, 17 campus outbreaks translated directly into peaks of infection within their home counties. These findings suggests that college campuses are at risk to develop an extreme incidence of COVID-19 and become superspreaders for neighboring communities. We anticipate that tight test-trace-quarantine strategies, flexible transition to online instruction, and-most importantly-compliance with local regulations will be critical to ensure a safe campus reopening after the winter break.