Prediction of infectious disease epidemics via weighted density ensembles

Accurate and reliable predictions of infectious disease dynamics can be valuable to public health organizations that plan interventions to decrease or prevent disease transmission. A great variety of models have been developed for this task, using different model structures, covariates, and targets for prediction. Experience has shown that the performance of these models varies; some tend to do better or worse in different seasons or at different points within a season. Ensemble methods combine multiple models to obtain a single prediction that leverages the strengths of each model. We considered a range of ensemble methods that each form a predictive density for a target of interest as a weighted sum of the predictive densities from component models. In the simplest case, equal weight is assigned to each component model; in the most complex case, the weights vary with the region, prediction target, week of the season when the predictions are made, a measure of component model uncertainty, and recent observations of disease incidence. We applied these methods to predict measures of influenza season timing and severity in the United States, both at the national and regional levels, using three component models. We trained the models on retrospective predictions from 14 seasons (1997/1998 - 2010/2011) and evaluated each model's prospective, out-of-sample performance in the five subsequent influenza seasons. In this test phase, the ensemble methods showed overall performance that was similar to the best of the component models, but offered more consistent performance across seasons than the component models. Ensemble methods offer the potential to deliver more reliable predictions to public health decision makers.Comment: 20 pages, 6 figure

Physical Activity Classification with Conditional Random Fields

In this thesis we develop methods for classifying physical activity using accelerometer recordings. We cast this as a problem of classification in time series with moderate to high dimensional observations at each time point. Specifically, we observe a vector of summary statistics of the accelerometer signal at each point in time, and we wish to use these observations to estimate the type and intensity of physical activity the individual engaged in as it changes over time. Our methods are based on Conditional Random Fields, which allow us to capture temporal dependence in an individual’s physical activity type without requiring us to model the distribution of the observed features at each point in time. We develop three novel estimation strategies for Conditional Random Fields, evaluate their performance on classification tasks through simulation studies and demonstrate their use in applications with real physical activity data sets

Evaluating epidemic forecasts in an interval format

For practical reasons, many forecasts of case, hospitalization and death counts in the context of the current COVID-19 pandemic are issued in the form of central predictive intervals at various levels. This is also the case for the forecasts collected in the COVID-19 Forecast Hub (https://covid19forecasthub.org/). Forecast evaluation metrics like the logarithmic score, which has been applied in several infectious disease forecasting challenges, are then not available as they require full predictive distributions. This article provides an overview of how established methods for the evaluation of quantile and interval forecasts can be applied to epidemic forecasts in this format. Specifically, we discuss the computation and interpretation of the weighted interval score, which is a proper score that approximates the continuous ranked probability score. It can be interpreted as a generalization of the absolute error to probabilistic forecasts and allows for a decomposition into a measure of sharpness and penalties for over- and underprediction

Comparison of combination methods to create calibrated ensemble forecasts for seasonal influenza in the U.S.

The characteristics of influenza seasons vary substantially from year to year, posing challenges for public health preparation and response. Influenza forecasting is used to inform seasonal outbreak response, which can in turn potentially reduce the impact of an epidemic. The United States Centers for Disease Control and Prevention, in collaboration with external researchers, has run an annual prospective influenza forecasting exercise, known as the FluSight challenge. Uniting theoretical results from the forecasting literature with domain-specific forecasts from influenza outbreaks, we applied parametric forecast combination methods that simultaneously optimize model weights and calibrate the ensemble via a beta transformation and made adjustments to the methods to reduce their complexity. We used the beta-transformed linear pool, the finite beta mixture model, and their equal weight adaptations to produce ensemble forecasts retrospectively for the 2016/2017, 2017/2018, and 2018/2019 influenza seasons in the U.S. We compared their performance to methods that were used in the FluSight challenge to produce the FluSight Network ensemble, namely the equally weighted linear pool and the linear pool. Ensemble forecasts produced from methods with a beta transformation were shown to outperform those from the equally weighted linear pool and the linear pool for all week-ahead targets across in the test seasons based on average log scores. We observed improvements in overall accuracy despite the beta-transformed linear pool or beta mixture methods\u27 modest under-prediction across all targets and seasons. Combination techniques that explicitly adjust for known calibration issues in linear pooling should be considered to improve probabilistic scores in outbreak settings

The Zoltar forecast archive, a tool to standardize and store interdisciplinary prediction research

Forecasting has emerged as an important component of informed, data-driven decision-making in a wide array of felds. We introduce a new data model for probabilistic predictions that encompasses a wide range of forecasting settings. This framework clearly defnes the constituent parts of a probabilistic forecast and proposes one approach for representing these data elements. The data model is implemented in Zoltar, a new software application that stores forecasts using the data model and provides standardized API access to the data. In one real-time case study, an instance of the Zoltar web application was used to store, provide access to, and evaluate real-time forecast data on the order of 108 rows, provided by over 40 international research teams from academia and industry making forecasts of the COVID-19 outbreak in the US. Tools and data infrastructure for probabilistic forecasts, such as those introduced here, will play an increasingly important role in ensuring that future forecasting research adheres to a strict set of rigorous and reproducible standards

Exercise Training Prevents the Perivascular Adipose Tissue-induced Aortic Dysfunction with Metabolic Syndrome

The aim of the study was to determine the effects of exercise training on improving the thoracic perivascularadipose tissue (tPVAT) phenotype (inflammation, oxidative stress, and proteasome function) in metabolic syn-drome and its subsequent actions on aortic function.Methods:Lean and obese (model of metabolic syndrome) Zucker rats (n=8/group) underwent 8-weeks ofcontrol conditions or treadmill exercise (70% of max speed, 1 h/day, 5 days/week). At the end of the inter-vention, the tPVAT was removed and conditioned media was made. The cleaned aorta was attached to a forcetransducer to assess endothelium-dependent and independent dilation in the presence or absence of tPVAT-conditioned media. tPVAT gene expression, inflammatory /oxidative phenotype, and proteasome function wereassessed.Results:The mainfindings were that Ex induced: (1) a beige-like, anti-inflammatory tPVAT phenotype; (2) agreater abundance of•NO in tPVAT; (3) a reduction in tPVAT oxidant production; and (4) an improved tPVATproteasome function. Regarding aortic function, endothelium-dependent dilation was greater in exercised leanand obese groups vs. controls (p \u3c 0.05). Lean control tPVAT improved aortic relaxation, whereas obese controltPVAT decreased aortic relaxation. In contrast, the obese Ex-tPVAT increased aortic dilation, whereas the leanEx-tPVAT did not affect aortic dilation.Conclusion:Overall, exercise had the most dramatic impact on the obese tPVAT reflecting a change towards anenvironment with less oxidant load, less inflammation and improved proteasome function. Such beneficialchanges to the tPVAT micro-environment with exercise likely played a significant role in mediating the im-provement in aortic function in metabolic syndrome following 8 weeks of exercise

Evaluation of a clinical decision support strategy to increase seasonal influenza vaccination among hospitalized children before inpatient discharge

Importance: Hospitalized children are at increased risk of influenza-related complications, yet influenza vaccine coverage remains low among this group. Evidence-based strategies about vaccination of vulnerable children during all health care visits are especially important during the COVID-19 pandemic. Objective: To design and evaluate a clinical decision support (CDS) strategy to increase the proportion of eligible hospitalized children who receive a seasonal influenza vaccine prior to inpatient discharge. Design, Setting, and Participants: This quality improvement study was conducted among children eligible for the seasonal influenza vaccine who were hospitalized in a tertiary pediatric health system providing care to more than half a million patients annually in 3 hospitals. The study used a sequential crossover design from control to intervention and compared hospitalizations in the intervention group (2019-2020 season with the use of an intervention order set) with concurrent controls (2019-2020 season without use of an intervention order set) and historical controls (2018-2019 season with use of an order set that underwent intervention during the 2019-2020 season). Interventions: A CDS intervention was developed through a user-centered design process, including (1) placing a default influenza vaccine order into admission order sets for eligible patients, (2) a script to offer the vaccine using a presumptive strategy, and (3) just-in-time education for clinicians addressing vaccine eligibility in the influenza order group with links to further reference material. The intervention was rolled out in a stepwise fashion during the 2019-2020 influenza season. Main Outcomes and Measures: Proportion of eligible hospitalizations in which 1 or more influenza vaccines were administered prior to discharge. Results: Among 17 740 hospitalizations (9295 boys [52%]), the mean (SD) age was 8.0 (6.0) years, and the patients were predominantly Black (n = 8943 [50%]) or White (n = 7559 [43%]) and mostly had public insurance (n = 11 274 [64%]). There were 10 997 hospitalizations eligible for the influenza vaccine in the 2019-2020 season. Of these, 5449 (50%) were in the intervention group, and 5548 (50%) were concurrent controls. There were 6743 eligible hospitalizations in 2018-2019 that served as historical controls. Vaccine administration rates were 31% (n = 1676) in the intervention group, 19% (n = 1051) in concurrent controls, and 14% (n = 912) in historical controls (P \u3c .001). In adjusted analyses, the odds of receiving the influenza vaccine were 3.25 (95% CI, 2.94-3.59) times higher in the intervention group and 1.28 (95% CI, 1.15-1.42) times higher in concurrent controls than in historical controls. Conclusions and Relevance: This quality improvement study suggests that user-centered CDS may be associated with significantly improved influenza vaccination rates among hospitalized children. Stepwise implementation of CDS interventions was a practical method that was used to increase quality improvement rigor through comparison with historical and concurrent controls

Quantitative Evidence for the Effects of Multiple Drivers on Continental-Scale Amphibian Declines

Since amphibian declines were first proposed as a global phenomenon over a quarter century ago, the conservation community has made little progress in halting or reversing these trends. The early search for a “smoking gun” was replaced with the expectation that declines are caused by multiple drivers. While field observations and experiments have identified factors leading to increased local extinction risk, evidence for effects of these drivers is lacking at large spatial scales. Here, we use observations of 389 time-series of 83 species and complexes from 61 study areas across North America to test the effects of 4 of the major hypothesized drivers of declines. While we find that local amphibian populations are being lost from metapopulations at an average rate of 3.79% per year, these declines are not related to any particular threat at the continental scale; likewise the effect of each stressor is variable at regional scales. This result - that exposure to threats varies spatially, and populations vary in their response - provides little generality in the development of conservation strategies. Greater emphasis on local solutions to this globally shared phenomenon is needed

Quantitative Evidence for the Effects of Multiple Drivers on Continental-Scale Amphibian Declines

Since amphibian declines were first proposed as a global phenomenon over a quarter century ago, the conservation community has made little progress in halting or reversing these trends. The early search for a “smoking gun” was replaced with the expectation that declines are caused by multiple drivers. While field observations and experiments have identified factors leading to increased local extinction risk, evidence for effects of these drivers is lacking at large spatial scales. Here, we use observations of 389 time-series of 83 species and complexes from 61 study areas across North America to test the effects of 4 of the major hypothesized drivers of declines. While we find that local amphibian populations are being lost from metapopulations at an average rate of 3.79% per year, these declines are not related to any particular threat at the continental scale; likewise the effect of each stressor is variable at regional scales. This result - that exposure to threats varies spatially, and populations vary in their response - provides little generality in the development of conservation strategies. Greater emphasis on local solutions to this globally shared phenomenon is needed