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Jens M. Tarp

Publications and source records attributed to Jens M. Tarp.

5 recordsLinked to original sources

Estimation of treatment effects in presence of differential use of post-randomization concomitant medication with time-to-event outcomes

In placebo-controlled randomized trials, the post-randomization use of concomitant medications may be higher in the placebo arm than in the treatment arm. This may dilute the full benefits of the randomized drug as estimated by the intention-to-treat analysis. We focus on cardiovascular outcomes trials in type-2 diabetes patients of glucose-lowering treatments where patients in the placebo arm are more likely to add other glucose-lowering agents with established cardio-protective properties. As a supplement to the intention-to-treat analysis, we propose a class of estimands within a causal framework that isolates the specific impact of the treatment being studied from that of concomitant treatment use. These estimands are defined under time-dependent treatment interventions to balance exposure to additional medications across intervention arms. We advocate for specific stochastic interventions to achieve this balance while minimizing positivity violations, which arise when certain treatment combinations or characteristics are not sufficiently represented in the data. We employ targeted minimum loss-based estimation (TMLE) to optimize the estimation procedure for our estimands while allowing for flexible adjustments for time-dependent covariates from follow-up visits. Finally, we demonstrate the application of the methods through a simulation study and a real-world example from the LEADER cardiovascular outcomes trial, which assessed cardiovascular risk for liraglutide versus placebo.

stat.ME

concrete: Targeted Estimation of Survival and Competing Risks in Continuous Time

This article introduces the R package concrete, which implements a recently developed targeted maximum likelihood estimator (TMLE) for the cause-specific absolute risks of time-to-event outcomes measured in continuous time. Cross-validated Super Learner machine learning ensembles are used to estimate propensity scores and conditional cause-specific hazards, which are then targeted to produce robust and efficient plug-in estimates of the effects of static or dynamic interventions on a binary treatment given at baseline quantified as risk differences or risk ratios. Influence curve-based asymptotic inference is provided for TMLE estimates and simultaneous confidence bands can be computed for target estimands spanning multiple multiple times or events. In this paper we review the one-step continuous-time TMLE methodology as it is situated in an overarching causal inference workflow, describe its implementation, and demonstrate the use of the package on the PBC dataset.

stat.CO

Short Term Blood Glucose Prediction based on Continuous Glucose Monitoring Data

Continuous Glucose Monitoring (CGM) has enabled important opportunities for diabetes management. This study explores the use of CGM data as input for digital decision support tools. We investigate how Recurrent Neural Networks (RNNs) can be used for Short Term Blood Glucose (STBG) prediction and compare the RNNs to conventional time-series forecasting using Autoregressive Integrated Moving Average (ARIMA). A prediction horizon up to 90 min into the future is considered. In this context, we evaluate both population-based and patient-specific RNNs and contrast them to patient-specific ARIMA models and a simple baseline predicting future observations as the last observed. We find that the population-based RNN model is the best performing model across the considered prediction horizons without the need of patient-specific data. This demonstrates the potential of RNNs for STBG prediction in diabetes patients towards detecting/mitigating severe events in the STBG, in particular hypoglycemic events. However, further studies are needed in regards to the robustness and practical use of the investigated STBG prediction models.

eess.SP

Rotation-limited growth of three dimensional body-centered cubic crystals

According to classical grain growth laws, grain growth is driven by the minimization of surface energy and will continue until a single grain prevails. These laws do not take into account the lattice anisotropy and the details of the microscopic rearrangement of mass between grains. Here we consider coarsening of body-centered cubic polycrystalline materials in three dimensions using the phase field crystal model. We observe as function of the quenching depth, a cross over between a state where grain rotation halts and the growth stagnates and a state where grains coarsen rapidly by coalescence through rotation and alignment of the lattices of neighboring grains. We show that the grain rotation per volume change of a grain follows a power law with an exponent of $-1.25$. The scaling exponent is consistent with theoretical considerations based on the conservation of dislocations.

cond-mat.mtrl-sci

Intermittent dislocation density fluctuations in crystal plasticity from a phase-field crystal model

Plastic deformation mediated by collective dislocation dynamics is investigated in the two-dimensional phase-field crystal model of sheared single crystals. We find that intermittent fluctuations in the dislocation population number accompany bursts in the plastic strain-rate fluctuations. Dislocation number fluctuations exhibit a power-law spectral density $1/f^2$ at high frequencies $f$. The probability distribution of number fluctuations becomes bimodal at low driving rates corresponding to a scenario where low density of defects alternate at irregular times with high population of defects. We propose a simple stochastic model of dislocation reaction kinetics that is able to capture these statistical properties of the dislocation density fluctuations as a function of shear rate.

cond-mat.mtrl-sci