The New England Journal of Statistics in Data Science

Background: Generalized estimating equations (GEE) and mixed-model repeated measures (MMRM) can handle longitudinal continuous outcomes when modeling the mean with time included categorically. Due to small sample sizes in rare diseases, a compound symmetry (CS) covariance pattern is sometimes adopted. In this setting, there is scant literature in the rare disease community that provide practical advice about the use of both methods based on real datasets from trials conducted in rare diseases, including when to use the sandwich variance estimator with or without a bias correction.

Cell boundary information is crucial for analyzing cell behaviors from time-lapse microscopy videos. Existing supervised cell segmentation tools, such as ImageJ, require tuning various parameters and rely on restrictive assumptions about the shape of the objects. While recent supervised segmentation tools based on convolutional neural networks enhance accuracy, they depend on high-quality labeled images, making them unsuitable for segmenting new types of objects not in the database. We developed a novel unsupervised cell segmentation algorithm based on fast Gaussian processes for noisy microscopy images without the need for parameter tuning or restrictive assumptions about the shape of the object. We derived robust thresholding criteria adaptive for heterogeneous images containing distinct brightness at different parts to separate objects from the background, and employed watershed segmentation to distinguish touching cell objects. Both simulated studies and real-data analysis of large microscopy images demonstrate the scalability and accuracy of our approach compared with the alternatives.

We study local change point detection in variance using generalized likelihood ratio tests. Building on [24], we utilize the multiplier bootstrap to approximate the unknown, non-asymptotic distribution of the test statistic and introduce a multiplicative bias correction that improves upon the existing additive version. This proposed correction offers a clearer interpretation of the bootstrap estimators while significantly reducing computational costs. Simulation results demonstrate that our method performs comparably to the original approach. We apply it to the growth rates of U.S. inflation, industrial production, and Bitcoin returns.

Observations of groundwater pollutants, such as arsenic or Perfluorooctane sulfonate (PFOS), are riddled with left censoring. These measurements have an impact on the health and lifestyle of the populace. Left censoring of these spatially correlated observations is usually addressed by applying Gaussian processes (GPs), which have theoretical advantages. However, this comes with a challenging computational complexity of $\mathcal{O}({n^{3}})$, impractical for large datasets. Additionally, a sizable proportion of the left-censored data creates further bottlenecks since the likelihood computation now involves an intractable high-dimensional integral of the multivariate Gaussian density. In this article, we tackle these two problems simultaneously by approximating the GP with a Gaussian Markov random field (GMRF) approach that exploits an explicit link between a GP with Matérn correlation function and a GMRF using stochastic partial differential equations (SPDEs). We introduce a GMRF-based measurement error into the model, which alleviates the likelihood computation for the censored data, drastically improving the computational speed while maintaining admirable accuracy. Our approach demonstrates robustness and substantial computational scalability compared to state-of-the-art methods for censored spatial responses across various simulation settings. Finally, the fit of this fully Bayesian model to the concentration of PFOS in groundwater available at 24,959 sites across California, where 46.62% responses are censored, produces prediction surface and uncertainty quantification in real-time, thereby substantiating the applicability and scalability of the proposed method. Code for implementation is made available via GitHub.