The classical view of emotion hypothesizes that certain emotion categories have a specific autonomic nervous system (ANS) "fingerprint" that is distinct from other categories. Substantial ANS variation within a category is presumed to be epiphenomenal. The theory of constructed emotion hypothesizes that an emotion category is a population of context-specific, highly variable instances that need not share an ANS fingerprint. Instead, ANS variation within a category is a meaningful part of the nature of emotion. We present a meta-analysis of 202 studies measuring ANS reactivity during lab-based inductions of emotion in nonclinical samples of adults, using a random effects, multilevel meta-analysis and multivariate pattern classification analysis to test our hypotheses. We found increases in mean effect size for 59.4% of ANS variables across emotion categories, but the pattern of effect sizes did not clearly distinguish 1 emotion category from another. We also observed significant variation within emotion categories; heterogeneity accounted for a moderate to substantial percentage (i.e., I2 ≥ 30%) of variability in 54% of these effect sizes. Experimental moderators epiphenomenal to emotion, such as induction type (e.g., films vs. imagery), did not explain a large portion of the variability. Correction for publication bias reduced estimated effect sizes even further, increasing heterogeneity of effect sizes for certain emotion categories. These findings, when considered in the broader empirical literature, are more consistent with population thinking and other principles from evolutionary biology found within the theory of constructed emotion, and offer insights for developing new hypotheses to understand the nature of emotion. (PsycINFO Database Record

Background There is notable heterogeneity in the clinical presentation of patients with COPD. To characterize this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from the COPDGene Study. Methods We applied a clustering method, k-means, to data from 10,192 smokers in the COPDGene Study. After splitting the sample into a training and validation set, we evaluated three sets of input features across a range of k (user-specified number of clusters). Stable solutions were tested for association with four COPD-related measures and five genetic variants previously associated with COPD at genome-wide significance. The results were confirmed in the validation set. Findings We identified four clusters that can be characterized as 1) relatively resistant smokers (i.e. no/mild obstruction and minimal emphysema despite heavy smoking), 2) mild upper zone emphysema predominant, 3) airway disease predominant, and 4) severe emphysema. All clusters are strongly associated with COPD-related clinical characteristics, including exacerbations and dyspnea (p<0.001). We found strong genetic associations between the mild upper zone emphysema group and rs1980057 near HHIP, and between the severe emphysema group and rs8034191 in the chromosome 15q region (p<0.001). All significant associations were replicated at p<0.05 in the validation sample (12/12 associations with clinical measures and 2/2 genetic associations). Interpretation Cluster analysis identifies four subgroups of smokers that show robust associations with clinical characteristics of COPD and known COPD-associated genetic variants.

One of the most common smoking-related diseases, chronic obstructive pulmonary disease (COPD), results from a dysregulated, multi-tissue inflammatory response to cigarette smoke. We hypothesized that systemic inflammatory signals in genome-wide blood gene expression can identify clinically important COPD-related disease subtypes, and we leveraged pre-existing gene interaction networks to guide unsupervised clustering of blood microarray expression data. Using network-informed non-negative matrix factorization, we analyzed genome-wide blood gene expression from 229 former smokers in the ECLIPSE Study, and we identified novel, clinically relevant molecular subtypes of COPD. These network-informed clusters were more stable and more strongly associated with measures of lung structure and function than clusters derived from a network-naïve approach, and they were associated with subtype-specific enrichment for inflammatory and protein catabolic pathways. These clusters were successfully reproduced in an independent sample of 135 smokers from the COPDGene Study.

Cardiac abnormalities are a leading cause of death and their early diagnosis are of importance for providing timely interventions. The goal of 2020 PhysioNet/CinC challenge was to develop algorithms to diagnose multiple cardiac abnormalities using 12-lead ECG data. In this work, we develop a wide and deep transformer neural network to classify each 12-lead ECG sequence into 27 cardiac abnormality classes. Our approach combines handcrafted ECG features, which were determined to be important by a random forest model, and discriminative feature representations that are automatically learned from a transformer neural network. Our entry to the 2020 Phys-ioNet/CinC challenge placed 1 st out of 41 official ranking teams (team name = prna). Using the official generalized weighted accuracy metric for evaluation, we achieved a validation score of 0.587 and top score of 0.533 on the full held-out test set.

Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.

Heterogeneous patient populations, complex pharmacology and low recruitment rates in the Intensive Care Unit (ICU) have led to the failure of many clinical trials. Recently, machine learning (ML) emerged as a new technology to process and identify big data relationships, enabling a new era in clinical trial design. In this study, we designed a ML model for predictively stratifying acute respiratory distress syndrome (ARDS) patients, ultimately reducing the required number of patients by increasing statistical power through cohort homogeneity. From the Philips eICU Research Institute (eRI) database, no less than 51,555 ARDS patients were extracted. We defined three subpopulations by outcome: (1) rapid death, (2) spontaneous recovery, and (3) long-stay patients. A retrospective univariate analysis identified highly predictive variables for each outcome. All 220 variables were used to determine the most accurate and generalizable model to predict long-stay patients. Multiclass gradient boosting was identified as the best-performing ML model. Whereas alterations in pH, bicarbonate or lactate proved to be strong predictors for rapid death in the univariate analysis, only the multivariate ML model was able to reliably differentiate the disease course of the long-stay outcome population (AUC of 0.77). We demonstrate the feasibility of prospective patient stratification using ML algorithms in the by far largest ARDS cohort reported to date. Our algorithm can identify patients with sufficiently long ARDS episodes to allow time for patients to respond to therapy, increasing statistical power. Further, early enrollment alerts may increase recruitment rate.

We introduce a novel Bayesian nonparametric model that uses the concept of disease trajectories for disease subtype identification. Although our model is general, we demonstrate that by treating fractions of tissue patterns derived from medical images as compositional data, our model can be applied to study distinct progression trends between population subgroups. Specifically, we apply our algorithm to quantitative emphysema measurements obtained from chest CT scans in the COPDGene Study and show several distinct progression patterns. As emphysema is one of the major components of chronic obstructive pulmonary disease (COPD), the third leading cause of death in the United States [1], an improved definition of emphysema and COPD subtypes is of great interest. We investigate several models with our algorithm, and show that one with age, pack years (a measure of cigarette exposure), and smoking status as predictors gives the best compromise between estimated predictive performance and model complexity. This model identified nine subtypes which showed significant associations to seven single nucleotide polymorphisms (SNPs) known to associate with COPD. Additionally, this model gives better predictive accuracy than multiple, multivariate ordinary least squares regression as demonstrated in a five-fold cross validation analysis. We view our subtyping algorithm as a contribution that can be applied to bridge the gap between CT-level assessment of tissue composition to population-level analysis of compositional trends that vary between disease subtypes.

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