An Introduction to G Methods

Robins' generalized methods (g methods) provide consistent estimates of contrasts (e.g. differences, ratios) of potential outcomes under a less restrictive set of identification conditions than do standard regression methods (e.g. linear, logistic, Cox regression). Uptake of g methods by epidemiologists has been hampered by limitations in understanding both conceptual and technical details. We present a simple worked example that illustrates basic concepts, while minimizing technical complications

WOODSTOCC: Extracting Latent Parallelism from a DNA Sequence Aligner on a GPU

An exponential increase in the speed of DNA sequencing over the past decade has driven demand for fast, space-efficient algorithms to process the resultant data. The first step in processing is alignment of many short DNA sequences, or reads, against a large reference sequence. This work presents WOODSTOCC, an implementation of short-read alignment designed for Graphics Processing Unit (GPU) architectures. WOODSTOCC translates a novel CPU implementation of gapped short-read alignment, which has guaranteed optimal and complete results, to the GPU. Our implementation combines an irregular trie search with dynamic programming to expose regularly structured parallelism. We first describe this implementation, then discuss its port to the GPU. WOODSTOCC’s GPU port exploits three generally useful techniques for extracting regular parallelism from irregular computations: dynamic thread mapping with a worklist, kernel stage decoupling, and kernel slicing. We discuss the performance impact of these techniques and suggest further opportunities for improvement

A hybrid Bayesian hierarchical model combining cohort and case–control studies for meta-analysis of diagnostic tests: Accounting for partial verification bias

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented

On the Use of High-Frequency Surface Wave Oceanographic Research Radars as Bistatic Single-Frequency Oblique Ionospheric Sounders

We demonstrate that bistatic reception of high-frequency oceanographic radars can be used as single-frequency oblique ionospheric sounders. We develop methods that are agnostic of the software-defined radio system to estimate the group range from the bistatic observations. The group range observations are used to estimate the virtual height and equivalent vertical frequency at the midpoint of the oblique propagation path. Uncertainty estimates of the virtual height and equivalent vertical frequency are presented. We apply this analysis to observations collected from two experiments run at two locations in different years, but utilizing similar software-defined radio data collection systems. In the first experiment, 10 d of data were collected in March 2016 at a site located in Maryland, USA, while the second experiment collected 20 d of data in October 2020 at a site located in South Carolina, USA. In both experiments, three Coastal Oceanographic Dynamics and Applications Radars (CODARs) located along the Virginia and North Carolina coast of the US were bistatically observed at 4.53718 MHz. The virtual height and equivalent virtual frequency were estimated in both experiments and compared with contemporaneous observations from a vertical incident digisonde-ionosonde at Wallops Island, VA, USA. We find good agreement between the oblique CODAR-derived and WP937 digisonde virtual heights. Variations in the virtual height from the CODAR observations and the digisonde are found to be nearly in phase with each other. We conclude from this investigation that observations of oceanographic radar can be used as single-frequency oblique incidence sounders. We discuss applications with respect to investigations of traveling ionospheric disturbances, studies of day-to-day ionospheric variability, and using these observations in data assimilation

Marginal structural cox models with case-cohort sampling

A common objective of biomedical cohort studies is assessing the effect of a time-varying treatment or exposure on a survival time. In the presence of time-varying confounders, marginal structural models fit using inverse probability weighting can be employed to obtain a consistent and asymptotically normal estimator of the causal effect of a time-varying treatment. This article considers estimation of parameters in the semiparametric marginal structural Cox model (MSCM) from a case-cohort study. Case-cohort sampling entails assembling covariate histories only for cases and a random subcohort, which can be cost effective, particularly in large cohort studies with low outcome rates. Following Cole et al. (2012), we consider estimating the causal hazard ratio from a MSCM by maximizing a weighted-pseudo-partial-likelihood. The estimator is shown to be consistent and asymptotically normal under certain regularity conditions. Finite sample performance of the proposed estimator is evaluated in a simulation study. In the corresponding supplementary document, computation of the estimator using standard survival analysis software is presented

Sensitivity analysis for an unobserved moderator in RCT-to-target-population generalization of treatment effects

In the presence of treatment effect heterogeneity, the average treatment effect (ATE) in a randomized controlled trial (RCT) may differ from the average effect of the same treatment if applied to a target population of interest. If all treatment effect moderators are observed in the RCT and in a dataset representing the target population, then we can obtain an estimate for the target population ATE by adjusting for the difference in the distribution of the moderators between the two samples. This paper considers sensitivity analyses for two situations: (1) where we cannot adjust for a specific moderator $V$ observed in the RCT because we do not observe it in the target population; and (2) where we are concerned that the treatment effect may be moderated by factors not observed even in the RCT, which we represent as a composite moderator $U$. In both situations, the outcome is not observed in the target population. For situation (1), we offer three sensitivity analysis methods based on (i) an outcome model, (ii) full weighting adjustment and (iii) partial weighting combined with an outcome model. For situation (2), we offer two sensitivity analyses based on (iv) a bias formula and (v) partial weighting combined with a bias formula. We apply methods (i) and (iii) to an example where the interest is to generalize from a smoking cessation RCT conducted with participants of alcohol/illicit drug use treatment programs to the target population of people who seek treatment for alcohol/illicit drug use in the US who are also cigarette smokers. In this case a treatment effect moderator is observed in the RCT but not in the target population dataset