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Automated exposure notification for COVID-19

Summary

Private Automated Contact Tracing (PACT) was a collaborative team and effort formed during the beginning of the Coronavirus Disease 2019 (COVID-19) pandemic. PACT's mission was to enhance contact tracing in pandemic response by designing exposure-detection functions in personal digital communication devices that have maximal public health utility while preserving privacy. This report explains and discusses the use of automated exposure notification during the COVID-19 pandemic and to provide some recommendations for those who may try to design and deploy similar technologies in future pandemics.
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Summary

Private Automated Contact Tracing (PACT) was a collaborative team and effort formed during the beginning of the Coronavirus Disease 2019 (COVID-19) pandemic. PACT's mission was to enhance contact tracing in pandemic response by designing exposure-detection functions in personal digital communication devices that have maximal public health utility while preserving privacy...

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Development and validation of the public-facing SimAEN web application

Summary

During a pandemic such as COVID-19, non-pharmaceutical interventions (NPIs) can help protect public health; however, it is not always clear which actions will have the greatest positive impact, or what the trade-offs are between different options. Exposure Notification (EN) was introduced as a prevention measure during the COVID-19 pandemic to supplement traditional contact tracing activities. To predict the estimated impacts of EN, a model for "simulation of automated exposure notification" (SimAEN) was developed by researchers at MIT Lincoln Laboratory (MIT LL) with CDC funding [2]. The model was published through an accessible web interface, available for use by the general public at https://SimAEN.philab.cdc.gov/.
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Summary

During a pandemic such as COVID-19, non-pharmaceutical interventions (NPIs) can help protect public health; however, it is not always clear which actions will have the greatest positive impact, or what the trade-offs are between different options. Exposure Notification (EN) was introduced as a prevention measure during the COVID-19 pandemic to...

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Fun as a strategic advantage: applying lessons in engagement from commercial games to military logistics training

Summary

Digital games offer many elements to augment traditional classroom lectures and reading assignments. They enable players to explore concepts through repeat play in a low-risk environment, and allow players to integrate feedback given during gameplay and evaluate their own performance. Commercial games leverage a number of features to engage players and hold their attention. But do those engagement-improving methods have a place in instructional environments with a captive and motivated audience? Our experience building a logistics supply chain training game for the Marine Corps University suggests that yes; applying lessons in engagement from commercial games can both help improve player experience with the learning environment, and potentially improve learning outcomes.
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Summary

Digital games offer many elements to augment traditional classroom lectures and reading assignments. They enable players to explore concepts through repeat play in a low-risk environment, and allow players to integrate feedback given during gameplay and evaluate their own performance. Commercial games leverage a number of features to engage players...

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Toward improving EN adoption: Bridging the gap between stated intention and actual use

Summary

As the COVID-19 pandemic swept the globe in the spring of 2020, technologists looked to enlist technology to assist public health authorities (PHAs) and help stem the tide of infections. As part of this technology push, experts in health care, cryptography, and other related fields developed the Private Automated Contact Tracing (PACT) protocol and related projects to assist the public health objective of slowing the spread of SARS-CoV-2 through digital contact tracing. The joint Google and Apple deployed protocol (Google-Apple Exposure Notifications, also known as GAEN or EN), which became the de facto standard in the U.S., employs the same features as detailed by PACT. The protocol leverages smartphone Bluetooth communications to alert users of potential contact with those carrying the COVID-19 virus in a way that preserves the privacy of both the known-infected individual, and the users receiving the alert. Contact tracing and subsequent personal precautions are more effective at reducing disease spread when more of the population participates, but there are known difficulties with the adoption of novel technology. In order to help the U.S. Centers for Disease Control and Prevention (CDC) and U.S. state-level public health teams address these difficulties, a team of staff from MIT's Lincoln Laboratory (MIT LL) and Computer Science and Artificial Intelligence Laboratory (MIT CSAIL) focused on studying user perception and information needs.
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Summary

As the COVID-19 pandemic swept the globe in the spring of 2020, technologists looked to enlist technology to assist public health authorities (PHAs) and help stem the tide of infections. As part of this technology push, experts in health care, cryptography, and other related fields developed the Private Automated Contact...

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Detection of COVID-19 using multimodal data from a wearable device: results from the first TemPredict Study

Summary

Early detection of diseases such as COVID-19 could be a critical tool in reducing disease transmission by helping individuals recognize when they should self-isolate, seek testing, and obtain early medical intervention. Consumer wearable devices that continuously measure physiological metrics hold promise as tools for early illness detection. We gathered daily questionnaire data and physiological data using a consumer wearable (Oura Ring) from 63,153 participants, of whom 704 self-reported possible COVID-19 disease. We selected 73 of these 704 participants with reliable confirmation of COVID-19 by PCR testing and high-quality physiological data for algorithm training to identify onset of COVID-19 using machine learning classification. The algorithm identified COVID-19 an average of 2.75 days before participants sought diagnostic testing with a sensitivity of 82% and specificity of 63%. The receiving operating characteristic (ROC) area under the curve (AUC) was 0.819 (95% CI [0.809, 0.830]). Including continuous temperature yielded an AUC 4.9% higher than without this feature. For further validation, we obtained SARS CoV-2 antibody in a subset of participants and identified 10 additional participants who self-reported COVID-19 disease with antibody confirmation. The algorithm had an overall ROC AUC of 0.819 (95% CI [0.809, 0.830]), with a sensitivity of 90% and specificity of 80% in these additional participants. Finally, we observed substantial variation in accuracy based on age and biological sex. Findings highlight the importance of including temperature assessment, using continuous physiological features for alignment, and including diverse populations in algorithm development to optimize accuracy in COVID-19 detection from wearables.
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Summary

Early detection of diseases such as COVID-19 could be a critical tool in reducing disease transmission by helping individuals recognize when they should self-isolate, seek testing, and obtain early medical intervention. Consumer wearable devices that continuously measure physiological metrics hold promise as tools for early illness detection. We gathered daily...

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Detecting pathogen exposure during the non-symptomatic incubation period using physiological data: proof of concept in non-human primates

Summary

Background and Objectives: Early warning of bacterial and viral infection, prior to the development of overt clinical symptoms, allows not only for improved patient care and outcomes but also enables faster implementation of public health measures (patient isolation and contact tracing). Our primary objectives in this effort are 3-fold. First, we seek to determine the upper limits of early warning detection through physiological measurements. Second, we investigate whether the detected physiological response is specific to the pathogen. Third, we explore the feasibility of extending early warning detection with wearable devices. Research Methods: For the first objective, we developed a supervised random forest algorithm to detect pathogen exposure in the asymptomatic period prior to overt symptoms (fever). We used high-resolution physiological telemetry data (aortic blood pressure, intrathoracic pressure, electrocardiograms, and core temperature) from non-human primate animal models exposed to two viral pathogens: Ebola and Marburg (N = 20). Second, to determine reusability across different pathogens, we evaluated our algorithm against three independent physiological datasets from non-human primate models (N = 13) exposed to three different pathogens: Lassa and Nipah viruses and Y. pestis. For the third objective, we evaluated performance degradation when the algorithm was restricted to features derived from electrocardiogram (ECG) waveforms to emulate data from a non-invasive wearable device. Results: First, our cross-validated random forest classifier provides a mean early warning of 51 ± 12 h, with an area under the receiver-operating characteristic curve (AUC) of 0.93 ± 0.01. Second, our algorithm achieved comparable performance when applied to datasets from different pathogen exposures – a mean early warning of 51 ± 14 h and AUC of 0.95 ± 0.01. Last, with a degraded feature set derived solely from ECG, we observed minimal degradation – a mean early warning of 46 ± 14 h and AUC of 0.91 ± 0.001. Conclusion: Under controlled experimental conditions, physiological measurements can provide over 2 days of early warning with high AUC. Deviations in physiological signals following exposure to a pathogen are due to the underlying host’s immunological response and are not specific to the pathogen. Pre-symptomatic detection is strong even when features are limited to ECG-derivatives, suggesting that this approach may translate to non-invasive wearable devices.
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Summary

Background and Objectives: Early warning of bacterial and viral infection, prior to the development of overt clinical symptoms, allows not only for improved patient care and outcomes but also enables faster implementation of public health measures (patient isolation and contact tracing). Our primary objectives in this effort are 3-fold. First...

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Geographic source estimation using airborne plant environmental DNA in dust

Summary

Information obtained from the analysis of dust, particularly biological particles such as pollen, plant parts, and fungal spores, has great utility in forensic geolocation. As an alternative to manual microscopic analysis of dust components, we developed a pipeline that utilizes the airborne plant environmental DNA (eDNA) in settled dust to estimate geographic origin. Metabarcoding of settled airborne eDNA was used to identify plant species whose geographic distributions were then derived from occurrence records in the USGS Biodiversity in Service of Our Nation (BISON) database. The distributions for all plant species identified in a sample were used to generate a probabilistic estimate of the sample source. With settled dust collected at four U.S. sites over a 15-month period, we demonstrated positive regional geolocation (within 600 km2 of the collection point) with 47.6% (20 of 42) of the samples analyzed. Attribution accuracy and resolution was dependent on the number of plant species identified in a dust sample, which was greatly affected by the season of collection. In dust samples that yielded a minimum of 20 identified plant species, positive regional attribution was achieved with 66.7% (16 of 24 samples). For broader demonstration, citizen-collected dust samples collected from 31 diverse U.S. sites were analyzed, and trace plant eDNA provided relevant regional attribution information on provenance in 32.2% of samples. This showed that analysis of airborne plant eDNA in settled dust can provide an accurate estimate regional provenance within the U.S., and relevant forensic information, for a substantial fraction of samples analyzed.
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Summary

Information obtained from the analysis of dust, particularly biological particles such as pollen, plant parts, and fungal spores, has great utility in forensic geolocation. As an alternative to manual microscopic analysis of dust components, we developed a pipeline that utilizes the airborne plant environmental DNA (eDNA) in settled dust to...

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Geographic source estimation using airborne plant environmental DNA in dust

Summary

Information obtained from the analysis of dust, particularly biological particles such as pollen, plant parts, and fungal spores, has great utility in forensic geolocation. As an alternative to manual microscopic analysis, we developed a pipeline that utilizes the environmental DNA (eDNA) from plants in dust samples to estimate previous sample location(s). The species of plant-derived eDNA within dust samples were identified using metabarcoding and their geographic distributions were then derived from occurrence records in the USGS Biodiversity in Service of Our Nation (BISON) database. The distributions for all plant species identified in a sample were used to generate a probabilistic estimate of the sample source. With settled dust collected at four U.S. sites over a 15-month period, we demonstrated positive regional geolocation (within 600 km2 of the collection point) with 47.6% (20 of 42) of the samples analyzed. Attribution accuracy and resolution was dependent on the number of plant species identified in a dust sample, which was greatly affected by the season of collection. In dust samples that yielded a minimum of 20 identified plant species, positive regional attribution improved to 66.7% (16 of 24 samples). Using dust samples collected from 31 different U.S. sites, trace plant eDNA provided relevant regional attribution information on provenance in 32.2%. This demonstrated that analysis of plant eDNA in dust can provide an accurate estimate regional provenance within the U.S., and relevant forensic information, for a substantial fraction of samples analyzed.
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Summary

Information obtained from the analysis of dust, particularly biological particles such as pollen, plant parts, and fungal spores, has great utility in forensic geolocation. As an alternative to manual microscopic analysis, we developed a pipeline that utilizes the environmental DNA (eDNA) from plants in dust samples to estimate previous sample...

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Image processing pipeline for liver fibrosis classification using ultrasound shear wave elastography

Published in:
Ultrasound in Med. & Biol., Vol. 46, No. 10, October 2020, pp. 2667-2676.

Summary

The purpose of this study was to develop an automated method for classifying liver fibrosis stage >=F2 based on ultrasound shear wave elastography (SWE) and to assess the system's performance in comparison with a reference manual approach. The reference approach consists of manually selecting a region of interest from each of eight or more SWE images, computing the mean tissue stiffness within each of the regions of interest and computing a resulting stiffness value as the median of the means. The 527-subject database consisted of 5526 SWE images and pathologist-scored biopsies, with data collected from a single system at a single site. The automated method integrates three modules that assess SWE image quality, select a region of interest from each SWE measurement and perform machine learning-based, multi-image SWE classification for fibrosis stage >=F2. Several classification methods were developed and tested using fivefold cross-validation with training, validation and test sets partitioned by subject. Performance metrics were area under receiver operating characteristic curve (AUROC), specificity at 95% sensitivity and number of SWE images required. The final automated method yielded an AUROC of 0.93 (95% confidence interval: 0.90-0.94) versus 0.69 (95% confidence interval: 0.65-0.72) for the reference method, 71% specificity with 95% sensitivity versus 5% and four images per decision versus eight or more. In conclusion, the automated method reported in this study significantly improved the accuracy for >=F2 classification of SWE measurements as well as reduced the number of measurements needed, which has the potential to reduce clinical workflow.
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Summary

The purpose of this study was to develop an automated method for classifying liver fibrosis stage >=F2 based on ultrasound shear wave elastography (SWE) and to assess the system's performance in comparison with a reference manual approach. The reference approach consists of manually selecting a region of interest from each...

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COVID-19: famotidine, histamine, mast cells, and mechanisms [eprint]

Summary

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We explore several plausible avenues of activity including antiviral and host-mediated actions. We propose that the principal famotidine mechanism of action for COVID-19 involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release.
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Summary

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain...

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