Regression models using parametric pseudo-observations.

Pseudo-observations based on the nonparametric Kaplan-Meier estimator of the survival function have been proposed as an alternative to the widely used Cox model for analyzing censored time-to-event data. Using a spline-based estimator of the survival has some potential benefits over the nonparametric approach in terms of less variability. We propose to define pseudo-observations based on a flexible parametric estimator and use these for analysis in regression models to estimate parameters related to the cumulative risk. We report the results of a simulation study that compares the empirical standard errors of estimates based on parametric and nonparametric pseudo-observations in various settings. Our simulations show that in some situations there is a substantial gain in terms of reduced variability using the proposed parametric pseudo-observations compared with the nonparametric pseudo-observations. The gain can be measured as a reduction of the empirical standard error by up to about one third; corresponding to an additional 125% larger sample size. We illustrate the use of the proposed method in a brief data example.

Development and validation of deep learning based embryo selection across multiple days of transfer.

This work describes the development and validation of a fully automated deep learning model, iDAScore v2.0, for the evaluation of human embryos incubated for 2, 3, and 5 or more days. We trained and evaluated the model on an extensive and diverse dataset including 181,428 embryos from 22 IVF clinics across the world. To discriminate the transferred embryos with known outcome, we show areas under the receiver operating curve ranging from 0.621 to 0.707 depending on the day of transfer. Predictive performance increased over time and showed a strong correlation with morphokinetic parameters. The model's performance is equivalent to the KIDScore D3 model on day 3 embryos while it significantly surpasses the performance of KIDScore D5 v3 on day 5+ embryos. This model provides an analysis of time-lapse sequences without the need for user input, and provides a reliable method for ranking embryos for their likelihood of implantation, at both cleavage and blastocyst stages. This greatly improves embryo grading consistency and saves time compared to traditional embryo evaluation methods.

Perfusion Changes in Acute Stroke Treated with Theophylline as an Add-on to Thrombolysis : A Randomized Clinical Trial Subgroup Analysis.

PURPOSE: Theophylline has been suggested to have a neuroprotective effect in ischemic stroke; however, results from animal stroke models and clinical trials in humans are controversial. The aim of this study was to assess the effect of theophylline on the cerebral perfusion with multiparametric magnetic resonance imaging (MRI). METHODS: The relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) in the infarct core, penumbra, and unaffected tissue were measured using multi-parametric MRI at baseline and 3­h follow-up in patients treated with theophylline or placebo as an add-on to thrombolytic therapy. RESULTS: No significant differences in mean rCBF, rCBV, and rMTT was found in the penumbra and unaffected tissue between the theophylline group and the control group between baseline and 3­h follow-up. In the infarct core, mean rCBV increased on average by 0.05 in the theophylline group and decreased by 0.14 in the control group (p < 0.04). Mean rCBF and mean rMTT in the infarct core were similar between the two treatment groups. CONCLUSION: The results indicate that theophylline does not change the perfusion in potentially salvageable penumbral tissue but only affects the rCBV in the infarct core. In contrast to the penumbra, the infarct core is unlikely to be salvageable, which might explain why theophylline failed in clinical trials.