Caleb Luke Mayer

All Publications

• Efficient assessment of real-world dynamics of circadian rhythms in heart rate and body temperature from wearable data JOURNAL OF THE ROYAL SOCIETY INTERFACE Kim, D., Mayer, C., Lee, M. P., Choi, S., Tewari, M., Forger, D. B. 2023; 20 (205): 20230030

  Abstract

  Laboratory studies have made unprecedented progress in understanding circadian physiology. Quantifying circadian rhythms outside of laboratory settings is necessary to translate these findings into real-world clinical practice. Wearables have been considered promising way to measure these rhythms. However, their limited validation remains an open problem. One major barrier to implementing large-scale validation studies is the lack of reliable and efficient methods for circadian assessment from wearable data. Here, we propose an approximation-based least-squares method to extract underlying circadian rhythms from wearable measurements. Its computational cost is ∼ 300-fold lower than that of previous work, enabling its implementation in smartphones with low computing power. We test it on two large-scale real-world wearable datasets: [Formula: see text] of body temperature data from cancer patients and ∼ 184 000 days of heart rate and activity data collected from the 'Social Rhythms' mobile application. This shows successful extraction of real-world dynamics of circadian rhythms. We also identify a reasonable harmonic model to analyse wearable data. Lastly, we show our method has broad applicability in circadian studies by embedding it into a Kalman filter that infers the state space of the molecular clocks in tissues. Our approach facilitates the translation of scientific advances in circadian fields into actual improvements in health.

  View details for DOI 10.1098/rsif.2023.0030

  View details for Web of Science ID 001052853500005

  View details for PubMedID 37608712

  View details for PubMedCentralID PMC10445022

• Impact of Light Schedules and Model Parameters on the Circadian Outcomes of Individuals JOURNAL OF BIOLOGICAL RHYTHMS Mayer, C., Walch, O., Forger, D. B., Hannay, K. 2023; 38 (4): 379-391

  Abstract

  Key differences exist between individuals in terms of certain circadian-related parameters, such as intrinsic period and sensitivity to light. These variations can differentially impact circadian timing, leading to challenges in accurately implementing time-sensitive interventions. In this work, we parse out these effects by investigating the impact of parameters from a macroscopic model of human circadian rhythms on phase and amplitude outputs. Using in silico light data designed to mimic commonly studied schedules, we assess the impact of parameter variations on model outputs to gain insight into the different effects of these schedules. We show that parameter sensitivity is heavily modulated by the lighting routine that a person follows, with darkness and shift work schedules being the most sensitive. We develop a framework to measure overall sensitivity levels of the given light schedule and furthermore decompose the overall sensitivity into individual parameter contributions. Finally, we measure the ability of the model to extract parameters given light schedules with noise and show that key parameters like the circadian period can typically be recovered given known light history. This can inform future work on determining the key parameters to consider when personalizing a model and the lighting protocols to use when assessing interindividual variability.

  View details for DOI 10.1177/07487304231176936

  View details for Web of Science ID 001011927000001

  View details for PubMedID 37350312

• Consumer-grade wearables identify changes in multiple physiological systems during COVID-19 disease progression CELL REPORTS MEDICINE Mayer, C., Tyler, J., Fang, Y., Flora, C., Frank, E., Tewari, M., Choi, S., Sen, S., Forger, D. B. 2022; 3 (4): 100601

  Abstract

  Consumer-grade wearables are needed to track disease, especially in the ongoing pandemic, as they can monitor patients in real time. We show that decomposing heart rate from low-cost wearable technologies into signals from different systems can give a multidimensional description of physiological changes due to COVID-19 infection. We find that the separate physiological features of basal heart rate, heart rate response to physical activity, circadian variation in heart rate, and autocorrelation of heart rate are significantly altered and can classify symptomatic versus healthy periods. Increased heart rate and autocorrelation begin at symptom onset, while the heart rate response to activity increases soon after symptom onset and increases more in individuals exhibiting cough. Symptom onset is associated with a blunting of circadian variation in heart rate, as measured by the uncertainty in the phase estimate. This work establishes an innovative data analytic approach to monitor disease progression remotely using consumer-grade wearables.

  View details for DOI 10.1016/j.xcrm.2022.100601

  View details for Web of Science ID 000838714200007

  View details for PubMedID 35480626

  View details for PubMedCentralID PMC9017023

• Distinct Circadian Assessments From Wearable Data Reveal Social Distancing Promoted Internal Desynchrony Between Circadian Markers FRONTIERS IN DIGITAL HEALTH Huang, Y., Mayer, C., Walch, O. J., Bowman, C., Sen, S., Goldstein, C., Tyler, J., Forger, D. B. 2021; 3: 727504

  Abstract

  Mobile measures of human circadian rhythms (CR) are needed in the age of chronotherapy. Two wearable measures of CR have recently been validated: one that uses heart rate to extract circadian rhythms that originate in the sinoatrial node of the heart, and another that uses activity to predict the laboratory gold standard and central circadian pacemaker marker, dim light melatonin onset (DLMO). We first find that the heart rate markers of normal real-world individuals align with laboratory DLMO measurements when we account for heart rate phase error. Next, we expand upon previous work that has examined sleep patterns or chronotypes during the COVID-19 lockdown by studying the effects of social distancing on circadian rhythms. In particular, using data collected from the Social Rhythms app, a mobile application where individuals upload their wearable data and receive reports on their circadian rhythms, we compared the two circadian phase estimates before and after social distancing. Interestingly, we found that the lockdown had different effects on the two ambulatory measurements. Before the lockdown, the two measures aligned, as predicted by laboratory data. After the lockdown, when circadian timekeeping signals were blunted, these measures diverged in 70% of subjects (with circadian rhythms in heart rate, or CRHR, becoming delayed). Thus, while either approach can measure circadian rhythms, both are needed to understand internal desynchrony. We also argue that interventions may be needed in future lockdowns to better align separate circadian rhythms in the body.

  View details for DOI 10.3389/fdgth.2021.727504

  View details for Web of Science ID 001030182300001

  View details for PubMedID 34870267

  View details for PubMedCentralID PMC8634937

• Predicting circadian phase across populations: a comparison of mathematical models and wearable devices SLEEP Huang, Y., Mayer, C., Cheng, P., Siddula, A., Burgess, H. J., Drake, C., Goldstein, C., Walch, O., Forger, D. B. 2021; 44 (10)

  Abstract

  From smart work scheduling to optimal drug timing, there is enormous potential in translating circadian rhythms research results for precision medicine in the real world. However, the pursuit of such effort requires the ability to accurately estimate circadian phase outside of the laboratory. One approach is to predict circadian phase noninvasively using light and activity measurements and mathematical models of the human circadian clock. Most mathematical models take light as an input and predict the effect of light on the human circadian system. However, consumer-grade wearables that are already owned by millions of individuals record activity instead of light, which prompts an evaluation of the accuracy of predicting circadian phase using motion alone. Here, we evaluate the ability of four different models of the human circadian clock to estimate circadian phase from data acquired by wrist-worn wearable devices. Multiple datasets across populations with varying degrees of circadian disruption were used for generalizability. Though the models we test yield similar predictions, analysis of data from 27 shift workers with high levels of circadian disruption shows that activity, which is recorded in almost every wearable device, is better at predicting circadian phase than measured light levels from wrist-worn devices when processed by mathematical models. In those living under normal living conditions, circadian phase can typically be predicted to within 1 h, even with data from a widely available commercial device (the Apple Watch). These results show that circadian phase can be predicted using existing data passively collected by millions of individuals with comparable accuracy to much more invasive and expensive methods.

  View details for DOI 10.1093/sleep/zsab126

  View details for Web of Science ID 000713786500018

  View details for PubMedID 34013347

  View details for PubMedCentralID PMC8503830

• High-frequency temperature monitoring for early detection of febrile adverse events in patients with cancer CANCER CELL Flora, C., Tyler, J., Mayer, C., Warner, D. E., Khan, S. N., Gupta, V., Lindstrom, R., Mazzoli, A., Rozwadowski, M., Braun, T. M., Ghosh, M., Forger, D. B., Choi, S., Tewari, M. 2021; 39 (9): 1167-1168

  View details for DOI 10.1016/j.ccell.2021.07.019

  View details for Web of Science ID 000695626600002

  View details for PubMedID 34388378

  View details for PubMedCentralID PMC8982843

• TRAVELING WAVE SOLUTIONS FOR A CANCER STEM CELL INVASION MODEL DISCRETE AND CONTINUOUS DYNAMICAL SYSTEMS-SERIES B Mayer, C., Stachura, E. 2021; 26 (9): 5067-5093

  View details for DOI 10.3934/dcdsb.2020333

  View details for Web of Science ID 000652031300020

• A method for characterizing daily physiology from widely used wearables CELL REPORTS METHODS Bowman, C., Huang, Y., Walch, O. J., Fang, Y., Frank, E., Tyler, J., Mayer, C., Stockbridge, C., Goldstein, C., Sen, S., Forger, D. B. 2021; 1 (4)

  Abstract

  Millions of wearable-device users record their heart rate (HR) and activity. We introduce a statistical method to extract and track six key physiological parameters from these data, including an underlying circadian rhythm in HR (CRHR), the direct effects of activity, and the effects of meals, posture, and stress through hormones like cortisol. We test our method on over 130,000 days of real-world data from medical interns on rotating shifts, showing that CRHR dynamics are distinct from those of sleep-wake or physical activity patterns and vary greatly among individuals. Our method also estimates a personalized phase-response curve of CRHR to activity for each individual, representing a passive and personalized determination of how human circadian timekeeping continually changes due to real-world stimuli. We implement our method in the "Social Rhythms" iPhone and Android app, which anonymously collects data from wearable-device users and provides analysis based on our method.

  View details for DOI 10.1016/j.crmeth.2021.100058

  View details for Web of Science ID 000907613200007

  View details for PubMedID 34568865

  View details for PubMedCentralID PMC8462795

• Monitoring Beliefs and Physiological Measures Using Wearable Sensors and Smartphone Technology Among Students at Risk of COVID-19: Protocol for a mHealth Study JMIR RESEARCH PROTOCOLS Cislo, C., Clingan, C., Gilley, K., Rozwadowski, M., Gainsburg, I., Bradley, C., Barabas, J., Sandford, E., Olesnavich, M., Tyler, J., Mayer, C., DeMoss, M., Flora, C., Forger, D. B., Cunningham, J., Tewari, M., Choi, S. 2021; 10 (6)

  Abstract

  The COVID-19 pandemic has impacted lives significantly and greatly affected an already vulnerable population, college students, in relation to mental health and public safety. Social distancing and isolation have brought about challenges to student's mental health. Mobile health apps and wearable sensors may help to monitor students at risk for COVID-19 and support their mental well-being.Through the use of a wearable sensor and smartphone-based survey completion, this study aimed to monitor students at risk for COVID-19.We conducted a prospective study of students, undergraduate and graduate, at a public university in the Midwest. Students were instructed to download the Fitbit, Social Rhythms, and Roadmap 2.0 apps onto their personal mobile devices (Android or iOS). Subjects consented to provide up to 10 saliva samples during the study period. Surveys were administered through the Roadmap 2.0 app at five timepoints - at baseline, 1-month later, 2-months later, 3-months later, and at study completion. The surveys gathered information regarding demographics, COVID-19 diagnoses and symptoms, and mental health resilience, with the aim of documenting the impact of COVID-19 on the college student population.This study enrolled 2,158 college students between September 2020 and January 2021. Subjects are currently being followed on-study for one academic year. Data collection and analysis are ongoing.This study examined student health and well-being during the COVID-19 pandemic. It also assessed the feasibility of wearable sensor use and survey completion in a college student population, which may inform the role of our mobile health tools on student health and well-being. Finally, using wearable sensor data, biospecimen collection, and self-reported COVID-19 diagnosis, our results may provide key data towards the development of a model for the early prediction and detection of COVID-19.ClinicalTrials.gov NCT04766788.

  View details for DOI 10.2196/29561

  View details for Web of Science ID 000669565700019

  View details for PubMedID 34115607

  View details for PubMedCentralID PMC8386373

• Monitoring Health Care Workers at Risk for COVID-19 Using Wearable Sensors and Smartphone Technology: Protocol for an Observational mHealth Study JMIR RESEARCH PROTOCOLS Clingan, C. A., Dittakavi, M., Rozwadowski, M., Gilley, K. N., Cislo, C. R., Barabas, J., Sandford, E., Olesnavich, M., Flora, C., Tyler, J., Mayer, C., Stoneman, E., Braun, T., Forger, D. B., Tewari, M., Choi, S. 2021; 10 (5): e29562

  Abstract

  Health care workers (HCWs) have been working on the front lines of the COVID-19 pandemic with high risks of viral exposure, infection, and transmission. Standard COVID-19 testing is insufficient to protect HCWs from these risks and prevent the spread of disease. Continuous monitoring of physiological data with wearable sensors, self-monitoring of symptoms, and asymptomatic COVID-19 testing may aid in the early detection of COVID-19 in HCWs and may help reduce further transmission among HCWs, patients, and families.By using wearable sensors, smartphone-based symptom logging, and biospecimens, this project aims to assist HCWs in self-monitoring COVID-19.We conducted a prospective, longitudinal study of HCWs at a single institution. The study duration was 1 year, wherein participants were instructed on the continuous use of two wearable sensors (Fitbit Charge 3 smartwatch and TempTraq temperature patches) for up to 30 days. Participants consented to provide biospecimens (ie, nasal swabs, saliva swabs, and blood) for up to 1 year from study entry. Using a smartphone app called Roadmap 2.0, participants entered a daily mood score, submitted daily COVID-19 symptoms, and completed demographic and health-related quality of life surveys at study entry and 30 days later. Semistructured qualitative interviews were also conducted at the end of the 30-day period, following completion of daily mood and symptoms reporting as well as continuous wearable sensor use.A total of 226 HCWs were enrolled between April 28 and December 7, 2020. The last participant completed the 30-day study procedures on January 16, 2021. Data collection will continue through January 2023, and data analyses are ongoing.Using wearable sensors, smartphone-based symptom logging and survey completion, and biospecimen collections, this study will potentially provide data on the prevalence of COVID-19 infection among HCWs at a single institution. The study will also assess the feasibility of leveraging wearable sensors and self-monitoring of symptoms in an HCW population.ClinicalTrials.gov NCT04756869; https://clinicaltrials.gov/ct2/show/NCT04756869.DERR1-10.2196/29562.

  View details for DOI 10.2196/29562

  View details for Web of Science ID 000658257400021

  View details for PubMedID 33945497

  View details for PubMedCentralID PMC8117956

• Predicting circadian misalignment with wearable technology: validation of wrist-worn actigraphy and photometry in night shift workers SLEEP Cheng, P., Walch, O., Huang, Y., Mayer, C., Sagong, C., Castelan, A., Burgess, H. J., Roth, T., Forger, D. B., Drake, C. L. 2021; 44 (2)

  Abstract

  A critical barrier to successful treatment of circadian misalignment in shift workers is determining circadian phase in a clinical or field setting. Light and movement data collected passively from wrist actigraphy can generate predictions of circadian phase via mathematical models; however, these models have largely been tested in non-shift working adults. This study tested the feasibility and accuracy of actigraphy in predicting dim light melatonin onset (DLMO) in fixed night shift workers.A sample of 45 night shift workers wore wrist actigraphs before completing DLMO in the laboratory (17.0 days ± 10.3 SD). DLMO was assessed via 24 hourly saliva samples in dim light (<10 lux). Data from actigraphy were provided as input to a mathematical model to generate predictions of circadian phase. Agreement was assessed and compared to average sleep timing on non-workdays as a proxy of DLMO. Model code and an open-source prototype assessment tool are available (www.predictDLMO.com).Model predictions of DLMO showed good concordance with in-lab DLMO, with Lin's concordance coefficient of 0.70, which was twice as high as agreement using average sleep timing as a proxy of DLMO. The absolute mean error of the predictions was 2.88 h, with 76% and 91% of the predictions falling with 2 and 4 h, respectively.This study is the first to demonstrate the use of wrist actigraphy-based estimates of circadian phase as a clinically useful and valid alternative to in-lab measurement of DLMO in fixed night shift workers. Future research should explore how additional predictors may impact accuracy.

  View details for DOI 10.1093/sleep/zsaa180

  View details for Web of Science ID 000649380000021

  View details for PubMedID 32918087

  View details for PubMedCentralID PMC8240654