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Health acoustic sounds such as coughs and breaths are known to contain useful health signals with significant potential for monitoring health and disease, yet are underexplored in the medical machine learning community. The existing deep learning systems for health acoustics are often narrowly trained and evaluated on a single task, which is limited by data and may hinder generalization to other tasks. To mitigate these gaps, we develop HeAR, a scalable self-supervised learning-based deep learning system using masked autoencoders trained on a large dataset of 313 million two-second long audio clips. Through linear probes, we establish HeAR as a state-of-the-art health audio embedding model on a benchmark of 33 health acoustic tasks across 6 datasets. By introducing this work, we hope to enable and accelerate further health acoustics research., Comment: 4 tables, 4 figures, 6 supplementary tables, 3 supplementary figures

In this work, we present an approach, which we call Embeddings for Language/Image-aligned X-Rays, or ELIXR, that leverages a language-aligned image encoder combined or grafted onto a fixed LLM, PaLM 2, to perform a broad range of chest X-ray tasks. We train this lightweight adapter architecture using images paired with corresponding free-text radiology reports from the MIMIC-CXR dataset. ELIXR achieved state-of-the-art performance on zero-shot chest X-ray (CXR) classification (mean AUC of 0.850 across 13 findings), data-efficient CXR classification (mean AUCs of 0.893 and 0.898 across five findings (atelectasis, cardiomegaly, consolidation, pleural effusion, and pulmonary edema) for 1% (~2,200 images) and 10% (~22,000 images) training data), and semantic search (0.76 normalized discounted cumulative gain (NDCG) across nineteen queries, including perfect retrieval on twelve of them). Compared to existing data-efficient methods including supervised contrastive learning (SupCon), ELIXR required two orders of magnitude less data to reach similar performance. ELIXR also showed promise on CXR vision-language tasks, demonstrating overall accuracies of 58.7% and 62.5% on visual question answering and report quality assurance tasks, respectively. These results suggest that ELIXR is a robust and versatile approach to CXR AI.

Cardiovascular diseases (CVDs) are responsible for a large proportion of premature deaths in low- and middle-income countries. Early CVD detection and intervention is critical in these populations, yet many existing CVD risk scores require a physical examination or lab measurements, which can be challenging in such health systems due to limited accessibility. Here we investigated the potential to use photoplethysmography (PPG), a sensing technology available on most smartphones that can potentially enable large-scale screening at low cost, for CVD risk prediction. We developed a deep learning PPG-based CVD risk score (DLS) to predict the probability of having major adverse cardiovascular events (MACE: non-fatal myocardial infarction, stroke, and cardiovascular death) within ten years, given only age, sex, smoking status and PPG as predictors. We compared the DLS with the office-based refit-WHO score, which adopts the shared predictors from WHO and Globorisk scores (age, sex, smoking status, height, weight and systolic blood pressure) but refitted on the UK Biobank (UKB) cohort. In UKB cohort, DLS's C-statistic (71.1%, 95% CI 69.9-72.4) was non-inferior to office-based refit-WHO score (70.9%, 95% CI 69.7-72.2; non-inferiority margin of 2.5%, p<0.01). The calibration of the DLS was satisfactory, with a 1.8% mean absolute calibration error. Adding DLS features to the office-based score increased the C-statistic by 1.0% (95% CI 0.6-1.4). DLS predicts ten-year MACE risk comparable with the office-based refit-WHO score. It provides a proof-of-concept and suggests the potential of a PPG-based approach strategies for community-based primary prevention in resource-limited regions., Comment: main: 24 pages (3 tables, 2 figures, 42 references), supplementary: 25 pages (9 tables, 4 figures, 11 references)

Chronic kidney disease (CKD) represents a slowly progressive disorder that can eventually require renal replacement therapy (RRT) including dialysis or renal transplantation. Early identification of patients who will require RRT (as much as 1 year in advance) improves patient outcomes, for example by allowing higher-quality vascular access for dialysis. Therefore, early recognition of the need for RRT by care teams is key to successfully managing the disease. Unfortunately, there is currently no commonly used predictive tool for RRT initiation. In this work, we present a machine learning model that dynamically identifies CKD patients at risk of requiring RRT up to one year in advance using only claims data. To evaluate the model, we studied approximately 3 million Medicare beneficiaries for which we made over 8 million predictions. We showed that the model can identify at risk patients with over 90% sensitivity and specificity. Although additional work is required before this approach is ready for clinical use, this study provides a basis for a screening tool to identify patients at risk within a time window that enables early proactive interventions intended to improve RRT outcomes., Comment: This preprint has not undergone peer review or any post-submission improvements or corrections. Submitted to the Applications of Medical AI (AMAI) at MICCAI 2022

External eye photos were recently shown to reveal signs of diabetic retinal disease and elevated HbA1c. In this paper, we evaluate if external eye photos contain information about additional systemic medical conditions. We developed a deep learning system (DLS) that takes external eye photos as input and predicts multiple systemic parameters, such as those related to the liver (albumin, AST); kidney (eGFR estimated using the race-free 2021 CKD-EPI creatinine equation, the urine ACR); bone & mineral (calcium); thyroid (TSH); and blood count (Hgb, WBC, platelets). Development leveraged 151,237 images from 49,015 patients with diabetes undergoing diabetic eye screening in 11 sites across Los Angeles county, CA. Evaluation focused on 9 pre-specified systemic parameters and leveraged 3 validation sets (A, B, C) spanning 28,869 patients with and without diabetes undergoing eye screening in 3 independent sites in Los Angeles County, CA, and the greater Atlanta area, GA. We compared against baseline models incorporating available clinicodemographic variables (e.g. age, sex, race/ethnicity, years with diabetes). Relative to the baseline, the DLS achieved statistically significant superior performance at detecting AST>36, calcium<8.6, eGFR<60, Hgb<11, platelets<150, ACR>=300, and WBC<4 on validation set A (a patient population similar to the development sets), where the AUC of DLS exceeded that of the baseline by 5.2-19.4%. On validation sets B and C, with substantial patient population differences compared to the development sets, the DLS outperformed the baseline for ACR>=300 and Hgb<11 by 7.3-13.2%. Our findings provide further evidence that external eye photos contain important biomarkers of systemic health spanning multiple organ systems. Further work is needed to investigate whether and how these biomarkers can be translated into clinical impact.

Machine learning systems show significant promise for forecasting patient adverse events via risk scores. However, these risk scores implicitly encode assumptions about future interventions that the patient is likely to receive, based on the intervention policy present in the training data. Without this important context, predictions from such systems are less interpretable for clinicians. We propose a joint model of intervention policy and adverse event risk as a means to explicitly communicate the model's assumptions about future interventions. We develop such an intervention policy model on MIMIC-III, a real world de-identified ICU dataset, and discuss some use cases that highlight the utility of this approach. We show how combining typical risk scores, such as the likelihood of mortality, with future intervention probability scores leads to more interpretable clinical predictions., Comment: Accepted by DSHealth on KDD 2022

Literature on machine learning for multiple sclerosis has primarily focused on the use of neuroimaging data such as magnetic resonance imaging and clinical laboratory tests for disease identification. However, studies have shown that these modalities are not consistent with disease activity such as symptoms or disease progression. Furthermore, the cost of collecting data from these modalities is high, leading to scarce evaluations. In this work, we used multi-dimensional, affordable, physical and smartphone-based performance outcome measures (POM) in conjunction with demographic data to predict multiple sclerosis disease progression. We performed a rigorous benchmarking exercise on two datasets and present results across 13 clinically actionable prediction endpoints and 6 machine learning models. To the best of our knowledge, our results are the first to show that it is possible to predict disease progression using POMs and demographic data in the context of both clinical trials and smartphone-base studies by using two datasets. Moreover, we investigate our models to understand the impact of different POMs and demographics on model performance through feature ablation studies. We also show that model performance is similar across different demographic subgroups (based on age and sex). To enable this work, we developed an end-to-end reusable pre-processing and machine learning framework which allows quicker experimentation over disparate MS datasets.

Fetal ultrasounds are an essential part of prenatal care and can be used to estimate gestational age (GA). Accurate GA assessment is important for providing appropriate prenatal care throughout pregnancy and identifying complications such as fetal growth disorders. Since derivation of GA from manual fetal biometry measurements (head, abdomen, femur) are operator-dependent and time-consuming, there have been a number of research efforts focused on using artificial intelligence (AI) models to estimate GA using standard biometry images, but there is still room to improve the accuracy and reliability of these AI systems for widescale adoption. To improve GA estimates, without significant change to provider workflows, we leverage AI to interpret standard plane ultrasound images as well as 'fly-to' ultrasound videos, which are 5-10s videos automatically recorded as part of the standard of care before the still image is captured. We developed and validated three AI models: an image model using standard plane images, a video model using fly-to videos, and an ensemble model (combining both image and video). All three were statistically superior to standard fetal biometry-based GA estimates derived by expert sonographers, the ensemble model has the lowest mean absolute error (MAE) compared to the clinical standard fetal biometry (mean difference: -1.51 $\pm$ 3.96 days, 95% CI [-1.9, -1.1]) on a test set that consisted of 404 participants. We showed that our models outperform standard biometry by a more substantial margin on fetuses that were small for GA. Our AI models have the potential to empower trained operators to estimate GA with higher accuracy while reducing the amount of time required and user variability in measurement acquisition.

Despite considerable progress in maternal healthcare, maternal and perinatal deaths remain high in low-to-middle income countries. Fetal ultrasound is an important component of antenatal care, but shortage of adequately trained healthcare workers has limited its adoption. We developed and validated an artificial intelligence (AI) system that uses novice-acquired "blind sweep" ultrasound videos to estimate gestational age (GA) and fetal malpresentation. We further addressed obstacles that may be encountered in low-resourced settings. Using a simplified sweep protocol with real-time AI feedback on sweep quality, we have demonstrated the generalization of model performance to minimally trained novice ultrasound operators using low cost ultrasound devices with on-device AI integration. The GA model was non-inferior to standard fetal biometry estimates with as few as two sweeps, and the fetal malpresentation model had high AUC-ROCs across operators and devices. Our AI models have the potential to assist in upleveling the capabilities of lightly trained ultrasound operators in low resource settings.

Diagnosing and mitigating changes in model fairness under distribution shift is an important component of the safe deployment of machine learning in healthcare settings. Importantly, the success of any mitigation strategy strongly depends on the structure of the shift. Despite this, there has been little discussion of how to empirically assess the structure of a distribution shift that one is encountering in practice. In this work, we adopt a causal framing to motivate conditional independence tests as a key tool for characterizing distribution shifts. Using our approach in two medical applications, we show that this knowledge can help diagnose failures of fairness transfer, including cases where real-world shifts are more complex than is often assumed in the literature. Based on these results, we discuss potential remedies at each step of the machine learning pipeline.

Tuberculosis (TB) is a top-10 cause of death worldwide. Though the WHO recommends chest radiographs (CXRs) for TB screening, the limited availability of CXR interpretation is a barrier. We trained a deep learning system (DLS) to detect active pulmonary TB using CXRs from 9 countries across Africa, Asia, and Europe, and utilized large-scale CXR pretraining, attention pooling, and noisy student semi-supervised learning. Evaluation was on (1) a combined test set spanning China, India, US, and Zambia, and (2) an independent mining population in South Africa. Given WHO targets of 90% sensitivity and 70% specificity, the DLS's operating point was prespecified to favor sensitivity over specificity. On the combined test set, the DLS's ROC curve was above all 9 India-based radiologists, with an AUC of 0.90 (95%CI 0.87-0.92). The DLS's sensitivity (88%) was higher than the India-based radiologists (75% mean sensitivity), p<0.001 for superiority; and its specificity (79%) was non-inferior to the radiologists (84% mean specificity), p=0.004. Similar trends were observed within HIV positive and sputum smear positive sub-groups, and in the South Africa test set. We found that 5 US-based radiologists (where TB isn't endemic) were more sensitive and less specific than the India-based radiologists (where TB is endemic). The DLS also remained non-inferior to the US-based radiologists. In simulations, using the DLS as a prioritization tool for confirmatory testing reduced the cost per positive case detected by 40-80% compared to using confirmatory testing alone. To conclude, our DLS generalized to 5 countries, and merits prospective evaluation to assist cost-effective screening efforts in radiologist-limited settings. Operating point flexibility may permit customization of the DLS to account for site-specific factors such as TB prevalence, demographics, clinical resources, and customary practice patterns.

Hyperkalemia is a potentially life-threatening condition that can lead to fatal arrhythmias. Early identification of high risk patients can inform clinical care to mitigate the risk. While hyperkalemia is often a complication of acute kidney injury (AKI), it also occurs in the absence of AKI. We developed predictive models to identify intensive care unit (ICU) patients at risk of developing hyperkalemia by using the Medical Information Mart for Intensive Care (MIMIC) and the eICU Collaborative Research Database (eICU-CRD). Our methodology focused on building multiple models, optimizing for interpretability through model selection, and simulating various clinical scenarios. In order to determine if our models perform accurately on patients with and without AKI, we evaluated the following clinical cases: (i) predicting hyperkalemia after AKI within 14 days of ICU admission, (ii) predicting hyperkalemia within 14 days of ICU admission regardless of AKI status, and compared different lead times for (i) and (ii). Both clinical scenarios were modeled using logistic regression (LR), random forest (RF), and XGBoost. Using observations from the first day in the ICU, our models were able to predict hyperkalemia with an AUC of (i) 0.79, 0.81, 0.81 and (ii) 0.81, 0.85, 0.85 for LR, RF, and XGBoost respectively. We found that 4 out of the top 5 features were consistent across the models. AKI stage was significant in the models that included all patients with or without AKI, but not in the models which only included patients with AKI. This suggests that while AKI is important for hyperkalemia, the specific stage of AKI may not be as important. Our findings require further investigation and confirmation., Comment: 6 pages, 3 figures, 3 tables

ML models often exhibit unexpectedly poor behavior when they are deployed in real-world domains. We identify underspecification as a key reason for these failures. An ML pipeline is underspecified when it can return many predictors with equivalently strong held-out performance in the training domain. Underspecification is common in modern ML pipelines, such as those based on deep learning. Predictors returned by underspecified pipelines are often treated as equivalent based on their training domain performance, but we show here that such predictors can behave very differently in deployment domains. This ambiguity can lead to instability and poor model behavior in practice, and is a distinct failure mode from previously identified issues arising from structural mismatch between training and deployment domains. We show that this problem appears in a wide variety of practical ML pipelines, using examples from computer vision, medical imaging, natural language processing, clinical risk prediction based on electronic health records, and medical genomics. Our results show the need to explicitly account for underspecification in modeling pipelines that are intended for real-world deployment in any domain., Comment: Updates: Updated statistical analysis in Section 6; Additional citations

Given an equilateral triangle with $a$ the square of its side length and a point in its plane with $b$, $c$, $d$ the squares of the distances from the point to the vertices of the triangle, it can be computed that $a$, $b$, $c$, $d$ satisfy $3(a^2+b^2+c^2+d^2)=(a+b+c+d)^2$. This paper derives properties of quadruples of nonnegative integers $(a,\, b,\, c,\, d)$, called triangle quadruples, satisfying this equation. It is easy to verify that the operation generating $(a,\, b,\, c,\, a+b+c-d)$ from $(a,\, b,\, c,\, d)$ preserves this feature and that it and analogous ones for the other elements can be represented by four matrices. We examine in detail the triangle group, the group with these operations as generators, and completely classify the orbits of quadruples with respect to the triangle group action. We also compute the number of triangle quadruples generated after a certain number of operations and approximate the number of quadruples bounded by characteristics such as the maximal element. Finally, we prove that the triangle group is a hyperbolic Coxeter group and derive information about the elements of triangle quadruples by invoking Lie groups. We also generalize the problem to higher dimensions.

Define a body A to be able to hide behind a body B if the orthogonal projection of B contains a translation of the corresponding orthogonal projection of A in every direction. In two dimensions, it is easy to observe that there exist two objects such that one can hide behind another and have a larger area than the other. It was recently shown that similar examples exist in higher dimensions as well. However, the highest possible volume ratio for such bodies is still undetermined. We investigated two three-dimensional examples, one involving a tetrahedron and a ball and the other involving a tetrahedron and an inverted tetrahedron. We calculate the highest volume ratio known up to this date, 1.16, which is generated by our second example., Comment: 11 pages, 7 figures

For n >= 2 a construction is given for a large family of compact convex sets K and L in n-dimensional Euclidean space such that the orthogonal projection L_u onto the subspace u^\perp contains a translate of the corresponding projection K_u for every direction u, while the volumes of K and L satisfy V_n(K) > V_n(L). It is subsequently shown that, if the orthogonal projection L_u onto the subspace u^\perp contains a translate of K_u for every direction u, then the set (n/(n-1))L contains a translate of K. If follows that V_n(K) <= (n/(n-1))^n V_n(L). In particular, we derive a universal constant bound V_n(K) <= 2.942 V_n(L), independent of the dimension n of the ambient space. Related results are obtained for projections onto subspaces of some fixed intermediate co-dimension. Open questions and conjectures are also posed., Comment: 19 pages, 3 figures