Interpretable Deep Learning for the Remote Characterisation of Ambulation in Multiple Sclerosis using Smartphones

The emergence of digital technologies such as smartphones in healthcare applications have demonstrated the possibility of developing rich, continuous, and objective measures of multiple sclerosis (MS) disability that can be administered remotely and out-of-clinic. In this work, deep convolutional neural networks (DCNN) applied to smartphone inertial sensor data were shown to better distinguish healthy from MS participant ambulation, compared to standard Support Vector Machine (SVM) feature-based methodologies. To overcome the typical limitations associated with remotely generated health data, such as low subject numbers, sparsity, and heterogeneous data, a transfer learning (TL) model from similar large open-source datasets was proposed. Our TL framework utilised the ambulatory information learned on Human Activity Recognition (HAR) tasks collected from similar smartphone-based sensor data. A lack of transparency of "black-box" deep networks remains one of the largest stumbling blocks to the wider acceptance of deep learning for clinical applications. Ensuing work therefore aimed to visualise DCNN decisions attributed by relevance heatmaps using Layer-Wise Relevance Propagation (LRP). Through the LRP framework, the patterns captured from smartphone-based inertial sensor data that were reflective of those who are healthy versus persons with MS (PwMS) could begin to be established and understood. Interpretations suggested that cadence-based measures, gait speed, and ambulation-related signal perturbations were distinct characteristics that distinguished MS disability from healthy participants. Robust and interpretable outcomes, generated from high-frequency out-of-clinic assessments, could greatly augment the current in-clinic assessment picture for PwMS, to inform better disease management techniques, and enable the development of better therapeutic interventions

Schools are open during the coronavirus outbreak but should I voluntarily keep my kids home anyway, if I can? We asked 5 experts

We asked five experts to answer the question: schools are staying open but should I voluntarily keep my kids home anyway, if I can

Self-supervised learning for human activity recognition using 700,000 person-days of wearable data

Accurate physical activity monitoring is essential to understand the impact of physical activity on one's physical health and overall well-being. However, advances in human activity recognition algorithms have been constrained by the limited availability of large labelled datasets. This study aims to leverage recent advances in self-supervised learning to exploit the large-scale UK Biobank accelerometer dataset-a 700,000 person-days unlabelled dataset-in order to build models with vastly improved generalisability and accuracy. Our resulting models consistently outperform strong baselines across eight benchmark datasets, with an F1 relative improvement of 2.5-130.9% (median 24.4%). More importantly, in contrast to previous reports, our results generalise across external datasets, cohorts, living environments, and sensor devices. Our open-sourced pre-trained models will be valuable in domains with limited labelled data or where good sampling coverage (across devices, populations, and activities) is hard to achieve

2D-WinSpatt-Net: a dual spatial self-attention Vision Transformer boosts classification of tetanus severity for patients wearing ECG sensors in low- and middle-income countries

Tetanus is a life-threatening bacterial infection that is often prevalent in low- and middle-income countries (LMIC), Vietnam included. Tetanus affects the nervous system, leading to muscle stiffness and spasms. Moreover, severe tetanus is associated with autonomic nervous system (ANS) dysfunction. To ensure early detection and effective management of ANS dysfunction, patients require continuous monitoring of vital signs using bedside monitors. Wearable electrocardiogram (ECG) sensors offer a more cost-effective and user-friendly alternative to bedside monitors. Machine learning-based ECG analysis can be a valuable resource for classifying tetanus severity; however, using existing ECG signal analysis is excessively time-consuming. Due to the fixed-sized kernel filters used in traditional convolutional neural networks (CNNs), they are limited in their ability to capture global context information. In this work, we propose a 2D-WinSpatt-Net, which is a novel Vision Transformer that contains both local spatial window self-attention and global spatial self-attention mechanisms. The 2D-WinSpatt-Net boosts the classification of tetanus severity in intensive-care settings for LMIC using wearable ECG sensors. The time series imaging—continuous wavelet transforms—is transformed from a one-dimensional ECG signal and input to the proposed 2D-WinSpatt-Net. In the classification of tetanus severity levels, 2D-WinSpatt-Net surpasses state-of-the-art methods in terms of performance and accuracy. It achieves remarkable results with an F1 score of 0.88 ± 0.00, precision of 0.92 ± 0.02, recall of 0.85 ± 0.01, specificity of 0.96 ± 0.01, accuracy of 0.93 ± 0.02 and AUC of 0.90 ± 0.00

Personalized Longitudinal Assessment of Multiple Sclerosis Using Smartphones

Personalized longitudinal disease assessment is central to quickly diagnosing, appropriately managing, and optimally adapting the therapeutic strategy of multiple sclerosis (MS). It is also important for identifying the idiosyncratic subject-specific disease profiles. Here, we design a novel longitudinal model to map individual disease trajectories in an automated way using sensor data that may contain missing values. First, we collect digital measurements related to gait and balance, and upper extremity functions using sensor-based assessments administered on a smartphone. Next, we treat missing data via imputation. We then discover potential markers of MS by employing a generalized estimation equation. Subsequently, parameters learned from multiple training datasets are ensembled to form a simple, unified longitudinal predictive model to forecast MS over time in previously unseen people with MS. To mitigate potential underestimation for individuals with severe disease scores, the final model incorporates additional subject-specific fine-tuning using data from the first day. The results show that the proposed model is promising to achieve personalized longitudinal MS assessment; they also suggest that features related to gait and balance as well as upper extremity function, remotely collected from sensor-based assessments, may be useful digital markers for predicting MS over time

Self-supervised machine learning to characterise step counts from wrist-worn accelerometers in the UK Biobank

Purpose: Step count is an intuitive measure of physical activity frequently quantified in health-related studies; however, accurate step counting is difficult in the free-living environment, with error routinely above 20% in wrist-worn devices against camera-annotated ground truth. This study aims to describe the development and validation of step count derived from a wrist-worn accelerometer and assess its association with cardiovascular and all-cause mortality in a large prospective cohort. Methods: We developed and externally validated a self-supervised machine learning step detection model, trained on an open-source and step-annotated free-living dataset. 39 individuals will free-living ground-truth annotated step counts were used for model development. An open-source dataset with 30 individuals was used for external validation. Epidemiological analysis was performed using 75,263 UK Biobank participants without prevalent cardiovascular disease (CVD) or cancer. Cox regression was used to test the association of daily step count with fatal CVD and all-cause mortality after adjustment for potential confounders. Results: The algorithm substantially outperformed reference models (free-living mean absolute percent error of 12.5%, versus 65-231%). Our data indicate an inverse dose-response association, where taking 6,430-8,277 daily steps was associated with 37% [25-48%] and 28% [20-35%] lower risk of fatal CVD and all-cause mortality up to seven years later, compared to those taking fewer steps each day. Conclusions: We have developed an open and transparent method that markedly improves the measurement of steps in large-scale wrist-worn accelerometer datasets. The application of this method demonstrated expected associations with CVD and all-cause mortality, indicating excellent face validity. This reinforces public health messaging for increasing physical activity and can help lay the groundwork for the inclusion of target step counts in future public health guidelines

Digital health technologies and machine learning augment patient reported outcomes to remotely characterise rheumatoid arthritis

Digital measures of health status captured during daily life could greatly augment current in-clinic assessments for rheumatoid arthritis (RA), to enable better assessment of disease progression and impact. This work presents results from weaRAble-PRO, a 14-day observational study, which aimed to investigate how digital health technologies (DHT), such as smartphones and wearables, could augment patient reported outcomes (PRO) to determine RA status and severity in a study of 30 moderate-to-severe RA patients, compared to 30 matched healthy controls (HC). Sensor-based measures of health status, mobility, dexterity, fatigue, and other RA specific symptoms were extracted from daily iPhone guided tests (GT), as well as actigraphy and heart rate sensor data, which was passively recorded from patients’ Apple smartwatch continuously over the study duration. We subsequently developed a machine learning (ML) framework to distinguish RA status and to estimate RA severity. It was found that daily wearable sensor-outcomes robustly distinguished RA from HC participants (F1, 0.807). Furthermore, by day 7 of the study (half-way), a sufficient volume of data had been collected to reliably capture the characteristics of RA participants. In addition, we observed that the detection of RA severity levels could be improved by augmenting standard patient reported outcomes with sensor-based features (F1, 0.833) in comparison to using PRO assessments alone (F1, 0.759), and that the combination of modalities could reliability measure continuous RA severity, as determined by the clinician-assessed RAPID-3 score at baseline (r2, 0.692; RMSE, 1.33). The ability to measure the impact of the disease during daily life—through objective and remote digital outcomes—paves the way forward to enable the development of more patient-centric and personalised measurements for use in RA clinical trials

Digital health technologies and machine learning augment patient reported outcomes to remotely characterise rheumatoid arthritis

Digital measures of health status captured during daily life could greatly augment current in-clinic assessments for rheumatoid arthritis (RA), to enable better assessment of disease progression and impact. This work presents results from weaRAble-PRO, a 14-day observational study, which aimed to investigate how digital health technologies (DHT), such as smartphones and wearables, could augment patient reported outcomes (PRO) to determine RA status and severity in a study of 30 moderate-to-severe RA patients, compared to 30 matched healthy controls (HC). Sensor-based measures of health status, mobility, dexterity, fatigue, and other RA specific symptoms were extracted from daily iPhone guided tests (GT), as well as actigraphy and heart rate sensor data, which was passively recorded from patients’ Apple smartwatch continuously over the study duration. We subsequently developed a machine learning (ML) framework to distinguish RA status and to estimate RA severity. It was found that daily wearable sensor-outcomes robustly distinguished RA from HC participants (F1, 0.807). Furthermore, by day 7 of the study (half-way), a sufficient volume of data had been collected to reliably capture the characteristics of RA participants. In addition, we observed that the detection of RA severity levels could be improved by augmenting standard patient reported outcomes with sensor-based features (F1, 0.833) in comparison to using PRO assessments alone (F1, 0.759), and that the combination of modalities could reliability measure continuous RA severity, as determined by the clinician-assessed RAPID-3 score at baseline (r2, 0.692; RMSE, 1.33). The ability to measure the impact of disease during daily life—through objective and remote digital outcomes—paves the way forward to enable the development of more patient-centric and personalised measurements for use in RA clinical trials

Non-canonical inflammasome activation mediates the adjuvanticity of nanoparticles

The non-canonical inflammasome sensor caspase-11 and gasdermin D (GSDMD) drive inflammation and pyroptosis, a type of immunogenic cell death that favors cell-mediated immunity (CMI) in cancer, infection, and autoimmunity. Here we show that caspase-11 and GSDMD are required for CD8+ and Th1 responses induced by nanoparticulate vaccine adjuvants. We demonstrate that nanoparticle-induced reactive oxygen species (ROS) are size dependent and essential for CMI, and we identify 50- to 60-nm nanoparticles as optimal inducers of ROS, GSDMD activation, and Th1 and CD8+ responses. We reveal a division of labor for IL-1 and IL-18, where IL-1 supports Th1 and IL-18 promotes CD8+ responses. Exploiting size as a key attribute, we demonstrate that biodegradable poly-lactic co-glycolic acid nanoparticles are potent CMI-inducing adjuvants. Our work implicates ROS and the non-canonical inflammasome in the mode of action of polymeric nanoparticulate adjuvants and establishes adjuvant size as a key design principle for vaccines against cancer and intracellular pathogens