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Women are at increased risk of bone loss during the menopausal transition; in fact, nearly 50\% of women's lifetime bone loss occurs during this time. The longitudinal relationships between estradiol (E2) and follicle-stimulating hormone (FSH), two hormones that change have characteristic changes during the menopausal transition, and bone health outcomes are complex. However, in addition to level and rate of change in E2 and FSH, variability in these hormones across the menopausal transition may be an important predictor of bone health, but this question has yet to be well explored. We introduce a joint model that characterizes individual mean estradiol (E2) trajectories and the individual residual variances and links these variances to bone health trajectories. In our application, we found that higher FSH variability was associated with declines in bone mineral density (BMD) before menopause, but this association was moderated over time after the menopausal transition. Additionally, higher mean E2, but not E2 variability, was associated with slower decreases in during the menopausal transition. We also include a simulation study that shows that naive two-stage methods often fail to propagate uncertainty in the individual-level variance estimates, resulting in estimation bias and invalid interval coverage

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Forecast combination involves using multiple forecasts to create a single, more accurate prediction. Recently, feature-based forecasting has been employed to either select the most appropriate forecasting models or to learn the weights of their convex combination. In this paper, we present a multi-task learning methodology that simultaneously addresses both problems. This approach is implemented through a deep neural network with two branches: the regression branch, which learns the weights of various forecasting methods by minimizing the error of combined forecasts, and the classification branch, which selects forecasting methods with an emphasis on their diversity. To generate training labels for the classification task, we introduce an optimization-driven approach that identifies the most appropriate methods for a given time series. The proposed approach elicits the essential role of diversity in feature-based forecasting and highlights the interplay between model combination and model selection when learning forecasting ensembles. Experimental results on a large set of series from the M4 competition dataset show that our proposal enhances point forecast accuracy compared to state-of-the-art methods.

We present the OGAN algorithm for automatic requirement falsification of cyber-physical systems. System inputs and output are represented as piecewise constant signals over time while requirements are expressed in signal temporal logic. OGAN can find inputs that are counterexamples for the safety of a system revealing design, software, or hardware defects before the system is taken into operation. The OGAN algorithm works by training a generative machine learning model to produce such counterexamples. It executes tests atomically and does not require any previous model of the system under test. We evaluate OGAN using the ARCH-COMP benchmark problems, and the experimental results show that generative models are a viable method for requirement falsification. OGAN can be applied to new systems with little effort, has few requirements for the system under test, and exhibits state-of-the-art CPS falsification efficiency and effectiveness.

In generalized regression models the effect of continuous covariates is commonly assumed to be linear. This assumption, however, may be too restrictive in applications and may lead to biased effect estimates and decreased predictive ability. While a multitude of alternatives for the flexible modeling of continuous covariates have been proposed, methods that provide guidance for choosing a suitable functional form are still limited. To address this issue, we propose a detection algorithm that evaluates several approaches for modeling continuous covariates and guides practitioners to choose the most appropriate alternative. The algorithm utilizes a unified framework for tree-structured modeling which makes the results easily interpretable. We assessed the performance of the algorithm by conducting a simulation study. To illustrate the proposed algorithm, we analyzed data of patients suffering from chronic kidney disease.

Muscle volume is a useful quantitative biomarker in sports, but also for the follow-up of degenerative musculo-skelletal diseases. In addition to volume, other shape biomarkers can be extracted by segmenting the muscles of interest from medical images. Manual segmentation is still today the gold standard for such measurements despite being very time-consuming. We propose a method for automatic segmentation of 18 muscles of the lower limb on 3D Magnetic Resonance Images to assist such morphometric analysis. By their nature, the tissue of different muscles is undistinguishable when observed in MR Images. Thus, muscle segmentation algorithms cannot rely on appearance but only on contour cues. However, such contours are hard to detect and their thickness varies across subjects. To cope with the above challenges, we propose a segmentation approach based on a hybrid architecture, combining convolutional and visual transformer blocks. We investigate for the first time the behaviour of such hybrid architectures in the context of muscle segmentation for shape analysis. Considering the consistent anatomical muscle configuration, we rely on transformer blocks to capture the longrange relations between the muscles. To further exploit the anatomical priors, a second contribution of this work consists in adding a regularisation loss based on an adjacency matrix of plausible muscle neighbourhoods estimated from the training data. Our experimental results on a unique database of elite athletes show it is possible to train complex hybrid models from a relatively small database of large volumes, while the anatomical prior regularisation favours better predictions.

While methods for measuring and correcting differential performance in risk prediction models have proliferated in recent years, most existing techniques can only be used to assess fairness across relatively large subgroups. The purpose of algorithmic fairness efforts is often to redress discrimination against groups that are both marginalized and small, so this sample size limitation often prevents existing techniques from accomplishing their main aim. We take a three-pronged approach to address the problem of quantifying fairness with small subgroups. First, we propose new estimands built on the "counterfactual fairness" framework that leverage information across groups. Second, we estimate these quantities using a larger volume of data than existing techniques. Finally, we propose a novel data borrowing approach to incorporate "external data" that lacks outcomes and predictions but contains covariate and group membership information. This less stringent requirement on the external data allows for more possibilities for external data sources. We demonstrate practical application of our estimators to a risk prediction model used by a major Midwestern health system during the COVID-19 pandemic.

We systematically study a wide variety of generative models spanning semantically-diverse image datasets to understand and improve the feature extractors and metrics used to evaluate them. Using best practices in psychophysics, we measure human perception of image realism for generated samples by conducting the largest experiment evaluating generative models to date, and find that no existing metric strongly correlates with human evaluations. Comparing to 17 modern metrics for evaluating the overall performance, fidelity, diversity, rarity, and memorization of generative models, we find that the state-of-the-art perceptual realism of diffusion models as judged by humans is not reflected in commonly reported metrics such as FID. This discrepancy is not explained by diversity in generated samples, though one cause is over-reliance on Inception-V3. We address these flaws through a study of alternative self-supervised feature extractors, find that the semantic information encoded by individual networks strongly depends on their training procedure, and show that DINOv2-ViT-L/14 allows for much richer evaluation of generative models. Next, we investigate data memorization, and find that generative models do memorize training examples on simple, smaller datasets like CIFAR10, but not necessarily on more complex datasets like ImageNet. However, our experiments show that current metrics do not properly detect memorization: none in the literature is able to separate memorization from other phenomena such as underfitting or mode shrinkage. To facilitate further development of generative models and their evaluation we release all generated image datasets, human evaluation data, and a modular library to compute 17 common metrics for 9 different encoders at //github.com/layer6ai-labs/dgm-eval.

Contraction in Wasserstein 1-distance with explicit rates is established for generalized Hamiltonian Monte Carlo with stochastic gradients under possibly nonconvex conditions. The algorithms considered include splitting schemes of kinetic Langevin diffusion. As consequence, quantitative Gaussian concentration bounds are provided for empirical averages. Convergence in Wasserstein 2-distance, total variation and relative entropy are also given, together with numerical bias estimates.

Threshold selection is a fundamental problem in any threshold-based extreme value analysis. While models are asymptotically motivated, selecting an appropriate threshold for finite samples can be difficult through standard methods. Inference can also be highly sensitive to the choice of threshold. Too low a threshold choice leads to bias in the fit of the extreme value model, while too high a choice leads to unnecessary additional uncertainty in the estimation of model parameters. In this paper, we develop a novel methodology for automated threshold selection that directly tackles this bias-variance trade-off. We also develop a method to account for the uncertainty in this threshold choice and propagate this uncertainty through to high quantile inference. Through a simulation study, we demonstrate the effectiveness of our method for threshold selection and subsequent extreme quantile estimation. We apply our method to the well-known, troublesome example of the River Nidd dataset.

Ensemble forecasts and their combination are explored from the perspective of a probability space. Manipulating ensemble forecasts as discrete probability distributions, multi-model ensembles (MMEs) are reformulated as barycenters of these distributions. Barycenters are defined with respect to a given distance. The barycenter with respect to the L2-distance is shown to be equivalent to the pooling method. Then, the barycenter-based approach is extended to a different distance with interesting properties in the distribution space: the Wasserstein distance. Another interesting feature of the barycenter approach is the possibility to give different weights to the ensembles and so to naturally build weighted MME. As a proof of concept, the L2- and the Wasserstein-barycenters are applied to combine two models from the S2S database, namely the European Centre Medium-Range Weather Forecasts (ECMWF) and the National Centers for Environmental Prediction (NCEP) models. The performance of the two (weighted-) MMEs are evaluated for the prediction of weekly 2m-temperature over Europe for seven winters. The weights given to the models in the barycenters are optimized with respect to two metrics, the CRPS and the proportion of skilful forecasts. These weights have an important impact on the skill of the two barycenter-based MMEs. Although the ECMWF model has an overall better performance than NCEP, the barycenter-ensembles are generally able to outperform both. However, the best MME method, but also the weights, are dependent on the metric. These results constitute a promising first implementation of this methodology before moving to combination of more models.

In this article, we introduce mixture representations for likelihood ratio ordered distributions. Essentially, the ratio of two probability densities, or mass functions, is monotone if and only if one can be expressed as a mixture of one-sided truncations of the other. To illustrate the practical value of the mixture representations, we address the problem of density estimation for likelihood ratio ordered distributions. In particular, we propose a nonparametric Bayesian solution which takes advantage of the mixture representations. The prior distribution is constructed from Dirichlet process mixtures and has large support on the space of pairs of densities satisfying the monotone ratio constraint. Posterior consistency holds under reasonable conditions on the prior specification and the true unknown densities. To our knowledge, this is the first posterior consistency result in the literature on order constrained inference. With a simple modification to the prior distribution, we can test the equality of two distributions against the alternative of likelihood ratio ordering. We develop a Markov chain Monte Carlo algorithm for posterior inference and demonstrate the method in a biomedical application.

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