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Public services collect massive volumes of data to fulfill their missions. These data fuel the generation of regional, national, and international statistics across various sectors. However, their immense potential remains largely untapped due to strict and legitimate privacy regulations. In this context, Lomas is a novel open-source platform designed to realize the full potential of the data held by public administrations. It enables authorized users, such as approved researchers and government analysts, to execute algorithms on confidential datasets without directly accessing the data. The Lomas platform is designed to operate within a trusted computing environment, such as governmental IT infrastructure. Authorized users access the platform remotely to submit their algorithms for execution on private datasets. Lomas executes these algorithms without revealing the data to the user and returns the results protected by Differential Privacy, a framework that introduces controlled noise to the results, rendering any attempt to extract identifiable information unreliable. Differential Privacy allows for the mathematical quantification and control of the risk of disclosure while allowing for a complete transparency regarding how data is protected and utilized. The contributions of this project will significantly transform how data held by public services are used, unlocking valuable insights from previously inaccessible data. Lomas empowers research, informing policy development, e.g., public health interventions, and driving innovation across sectors, all while upholding the highest data confidentiality standards.

Since the beginning of the COVID-19 pandemic, many dashboards have emerged as useful tools to monitor the evolution of the pandemic, inform the public, and assist governments in decision making. Our goal is to develop a globally applicable method, integrated in a twice daily updated dashboard that provides an estimate of the trend in the evolution of the number of cases and deaths from reported data of more than 200 countries and territories, as well as a seven-day forecast. One of the significant difficulties to manage a quickly propagating epidemic is that the details of the dynamic needed to forecast its evolution are obscured by the delays in the identification of cases and deaths and by irregular reporting. Our forecasting methodology substantially relies on estimating the underlying trend in the observed time series using robust seasonal trend decomposition techniques. This allows us to obtain forecasts with simple, yet effective extrapolation methods in linear or log scale. We present the results of an assessment of our forecasting methodology and discuss its application to the production of global and regional risk maps.

Identifying individuals who are at high risk of cancer due to inherited germline mutations is critical for effective implementation of personalized prevention strategies. Most existing models to identify these individuals focus on specific syndromes by including family and personal history for a small number of cancers. Recent evidence from multi-gene panel testing has shown that many syndromes once thought to be distinct are overlapping, motivating the development of models that incorporate family history information on several cancers and predict mutations for more comprehensive panels of genes. Once such class of models are Mendelian risk prediction models, which use family history information and Mendelian laws of inheritance to estimate the probability of carrying genetic mutations, as well as future risk of developing associated cancers. To flexibly model the complexity of many cancer-mutation associations, we present a new software tool called PanelPRO, a R package that extends the previously developed BayesMendel R package to user-selected lists of susceptibility genes and associated cancers. The model identifies individuals at an increased risk of carrying cancer susceptibility gene mutations and predicts future risk of developing hereditary cancers associated with those genes. Additional functionalities adjust for prophylactic interventions, known genetic testing results, and risk modifiers such as race and ancestry. The package comes with a customizable database with default parameter values estimated from published studies. The PanelPRO package is open-source and provides a fast and flexible back-end for multi-gene, multi-cancer risk modeling with pedigree data. The software enables the identification of high-risk individuals, which will have an impact on personalized prevention strategies for cancer and individualized decision making about genetic testing.

There is increasing focus on whether air pollution originating from different sources has different health implications. In particular, recent evidence suggests that fine particulate matter (PM2.5) with chemical tracers suggesting coal combustion origins is especially harmful. Augmenting this knowledge with estimates from causal inference methods to identify the health impacts of PM2.5 derived from specific point sources of coal combustion would be an important step towards informing specific, targeted interventions. We investigated the effect of high-exposure to coal combustion emissions from 783 coal-fired power generating units on ischemic heart disease (IHD) hospitalizations in over 19 million Medicare beneficiaries residing at 21,351 ZIP codes in the eastern United States. We used InMAP, a newly-developed, reduced-complexity air quality model to classify each ZIP code as either a high-exposed or control location. Our health outcomes analysis uses a causal inference method - propensity score matching - to adjust for potential confounders of the relationship between exposure and IHD. We fit separate Poisson regression models to the matched data in each geographic region to estimate the incidence rate ratio for IHD comparing high-exposed to control locations. High exposure to coal power plant emissions and IHD were positively associated in the Northeast (IRR = 1.08, 95% CI = 1.06, 1.09) and the Southeast (IRR = 1.06, 95% CI = 1.04, 1.08). No significant association was found in the Industrial Midwest (IRR = 1.02, 95% CI = 1.00, 1.04), likely the result of small exposure contrasts between high-exposed and control ZIP codes in that region. This study provides targeted evidence of the association between emissions from specific coal power plants and IHD hospitalizations among Medicare beneficiaries., Comment: 26 pages, 14 figures

Emission control technologies installed on power plants are a key feature of many air pollution regulations in the US. While such regulations are predicated on the presumed relationships between emissions, ambient air pollution, and human health, many of these relationships have never been empirically verified. The goal of this paper is to develop new statistical methods to quantify these relationships. We frame this problem as one of mediation analysis to evaluate the extent to which the effect of a particular control technology on ambient pollution is mediated through causal effects on power plant emissions. Since power plants emit various compounds that contribute to ambient pollution, we develop new methods for multiple intermediate variables that are measured contemporaneously, may interact with one another, and may exhibit joint mediating effects. Specifically, we propose new methods leveraging two related frameworks for causal inference in the presence of mediating variables: principal stratification and causal mediation analysis. We define principal effects based on multiple mediators, and also introduce a new decomposition of the total effect of an intervention on ambient pollution into the natural direct effect and natural indirect effects for all combinations of mediators. Both approaches are anchored to the same observed-data models, which we specify with Bayesian nonparametric techniques. We provide assumptions for estimating principal causal effects, then augment these with an additional assumption required for causal mediation analysis. The two analyses, interpreted in tandem, provide the first empirical investigation of the presumed causal pathways that motivate important air quality regulatory policies.

Pollutant emissions from coal-burning power plants have been deemed to adversely impact ambient air quality and public health conditions. Despite the noticeable reduction in emissions and the improvement of air quality since the Clean Air Act (CAA) became the law, the public-health benefits from changes in emissions have not been widely evaluated yet. In terms of the chain of accountability (HEI Accountability Working Group, 2003), the link between pollutant emissions from the power plants (SO2) and public health conditions (respiratory diseases) accounting for changes in ambient air quality (PM2.5) is unknown. We provide the first assessment of the longitudinal effect of specific pollutant emission (SO2) on public health outcomes that is mediated through changes in the ambient air quality. It is of particular interest to examine the extent to which the effect that is mediated through changes in local ambient air quality differs from year to year. In this paper, we propose a Bayesian approach to estimate novel causal estimands: time-varying mediation effects in the presence of mediators and responses measured every year. We replace the commonly invoked sequential ignorability assumption with a new set of assumptions which are sufficient to identify the distributions of the natural indirect and direct effects in this setting.

Researchers are often faced with evaluating the effect of a policy or program that was simultaneously initiated across an entire population of units at a single point in time, and its effects over the targeted population can manifest at any time period afterwards. In the presence of data measured over time, Bayesian time series models have been used to impute what would have happened after the policy was initiated, had the policy not taken place, in order to estimate causal effects. However, the considerations regarding the definition of the target estimands, the underlying assumptions, the plausibility of such assumptions, and the choice of an appropriate model have not been thoroughly investigated. In this paper, we establish useful estimands for the evaluation of large-scale policies. We discuss that imputation of missing potential outcomes relies on an assumption which, even though untestable, can be partially evaluated using observed data. We illustrate an approach to evaluate this key causal assumption and facilitate model elicitation based on data from the time interval before policy initiation and using classic statistical techniques. As an illustration, we study the Hospital Readmissions Reduction Program (HRRP), a US federal intervention aiming to improve health outcomes for patients with pneumonia, acute myocardial infraction, or congestive failure admitted to a hospital. We evaluate the effect of the HRRP on population mortality among the elderly across the US and in four geographic subregions, and at different time windows. We find that the HRRP increased mortality from pneumonia and acute myocardial infraction across at least one geographical region and time horizon, and is likely to have had a detrimental effect on public health.

Fine particulate matter (PM$_{2.5}$) is one of the criteria air pollutants regulated by the Environmental Protection Agency in the United States. There is strong evidence that ambient exposure to (PM$_{2.5}$) increases risk of mortality and hospitalization. Large scale epidemiological studies on the health effects of PM$_{2.5}$ provide the necessary evidence base for lowering the safety standards and inform regulatory policy. However, ambient monitors of PM$_{2.5}$ (as well as monitors for other pollutants) are sparsely located across the U.S., and therefore studies based only on the levels of PM$_{2.5}$ measured from the monitors would inevitably exclude large amounts of the population. One approach to resolving this issue has been developing models to predict local PM$_{2.5}$, NO$_2$, and ozone based on satellite, meteorological, and land use data. This process typically relies developing a prediction model that relies on large amounts of input data and is highly computationally intensive to predict levels of air pollution in unmonitored areas. We have developed a flexible R package that allows for environmental health researchers to design and train spatio-temporal models capable of predicting multiple pollutants, including PM$_{2.5}$. We utilize H2O, an open source big data platform, to achieve both performance and scalability when used in conjunction with cloud or cluster computing systems.

We propose a new approach for estimating causal effects when the exposure is measured with error and confounding adjustment is performed via a generalized propensity score (GPS). Using validation data, we propose a regression calibration (RC)-based adjustment for a continuous error-prone exposure combined with GPS to adjust for confounding (RC-GPS). The outcome analysis is conducted after transforming the corrected continuous exposure into a categorical exposure. We consider confounding adjustment in the context of GPS subclassification, inverse probability treatment weighting (IPTW) and matching. In simulations with varying degrees of exposure error and confounding bias, RC-GPS eliminates bias from exposure error and confounding compared to standard approaches that rely on the error-prone exposure. We applied RC-GPS to a rich data platform to estimate the causal effect of long-term exposure to fine particles ($PM_{2.5}$) on mortality in New England for the period from 2000 to 2012. The main study consists of $2,202$ zip codes covered by $217,660$ 1km $\times$ 1km grid cells with yearly mortality rates, yearly $PM_{2.5}$ averages estimated from a spatio-temporal model (error-prone exposure) and several potential confounders. The internal validation study includes a subset of 83 1km $\times$ 1km grid cells within 75 zip codes from the main study with error-free yearly $PM_{2.5}$ exposures obtained from monitor stations. Under assumptions of non-interference and weak unconfoundedness, using matching we found that exposure to moderate levels of $PM_{2.5}$ ($8 <$ $PM_{2.5}$ $\leq 10\ {\rm \mu g/m^3}$) causes a $2.8\%$ ($95\%$ CI: $0.6\%, 3.6\%$) increase in all-cause mortality compared to low exposure ($PM_{2.5}$ $\leq 8\ {\rm \mu g/m^3}$).

Propensity score matching is a common tool for adjusting for observed confounding in observational studies, but is known to have limitations in the presence of unmeasured confounding. In many settings, researchers are confronted with spatially-indexed data where the relative locations of the observational units may serve as a useful proxy for unmeasured confounding that varies according to a spatial pattern. We develop a new method, termed Distance Adjusted Propensity Score Matching (DAPSm) that incorporates information on units' spatial proximity into a propensity score matching procedure. We show that DAPSm can adjust for both observed and some forms of unobserved confounding and evaluate its performance relative to several other reasonable alternatives for incorporating spatial information into propensity score adjustment. The method is motivated by and applied to a comparative effectiveness investigation of power plant emission reduction technologies designed to reduce population exposure to ambient ozone pollution. Ultimately, DAPSm provides a framework for augmenting a "standard" propensity score analysis with information on spatial proximity and provides a transparent and principled way to assess the relative trade offs of prioritizing observed confounding adjustment versus spatial proximity adjustment., Comment: 31 pages

In some estimation problems, especially in applications dealing with information theory, signal processing and biology, theory provides us with additional information allowing us to restrict the parameter space to a finite number of points. In this case, we speak of discrete parameter models. Even though the problem is quite old and has interesting connections with testing and model selection, asymptotic theory for these models has hardly ever been studied. Therefore, we discuss consistency, asymptotic distribution theory, information inequalities and their relations with efficiency and superefficiency for a general class of $m$-estimators., Comment: Published in at http://dx.doi.org/10.1214/11-STS371 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org)

We study the error in quadrature rules on a compact manifold. As in the Koksma-Hlawka inequality, we consider a discrepancy of the sampling points and a generalized variation of the function. In particular, we give sharp quantitative estimates for quadrature rules of functions in Sobolev classes.