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Statistics is sometimes described as the science of reasoning under uncertainty. Statistical models provide one view of this uncertainty, but what is frequently neglected is the invisible portion of uncertainty: that assumed not to exist once a model has been fitted to some data. Systematic errors, i.e. bias, in data relative to some model and inferential goal can seriously undermine research conclusions, and qualitative and quantitative techniques have been created across several disciplines to quantify and generally appraise such potential biases. Perhaps best known are so-called risk of bias assessment instruments used to investigate the likely quality of randomised controlled trials in medical research. However, the logic of assessing the risks caused by various types of systematic error to statistical arguments applies far more widely. This logic applies even when statistical adjustment strategies for potential biases are used, as these frequently make assumptions (e.g. data missing at random) that can never be guaranteed in finite samples. Mounting concern about such situations can be seen in the increasing calls for greater consideration of biases caused by nonprobability sampling in descriptive inference (i.e. survey sampling), and the statistical generalisability of in-sample causal effect estimates in causal inference; both of which relate to the consideration of model-based and wider uncertainty when presenting research conclusions from models. Given that model-based adjustments are never perfect, we argue that qualitative risk of bias reporting frameworks for both descriptive and causal inferential arguments should be further developed and made mandatory by journals and funders. It is only through clear statements of the limits to statistical arguments that consumers of research can fully judge their value for any specific application.

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Introduction: The amount of data generated by original research is growing exponentially. Publicly releasing them is recommended to comply with the Open Science principles. However, data collected from human participants cannot be released as-is without raising privacy concerns. Fully synthetic data represent a promising answer to this challenge. This approach is explored by the French Centre de Recherche en {\'E}pid{\'e}miologie et Sant{\'e} des Populations in the form of a synthetic data generation framework based on Classification and Regression Trees and an original distance-based filtering. The goal of this work was to develop a refined version of this framework and to assess its risk-utility profile with empirical and formal tools, including novel ones developed for the purpose of this evaluation.Materials and Methods: Our synthesis framework consists of four successive steps, each of which is designed to prevent specific risks of disclosure. We assessed its performance by applying two or more of these steps to a rich epidemiological dataset. Privacy and utility metrics were computed for each of the resulting synthetic datasets, which were further assessed using machine learning approaches.Results: Computed metrics showed a satisfactory level of protection against attribute disclosure attacks for each synthetic dataset, especially when the full framework was used. Membership disclosure attacks were formally prevented without significantly altering the data. Machine learning approaches showed a low risk of success for simulated singling out and linkability attacks. Distributional and inferential similarity with the original data were high with all datasets.Discussion: This work showed the technical feasibility of generating publicly releasable synthetic data using a multi-step framework. Formal and empirical tools specifically developed for this demonstration are a valuable contribution to this field. Further research should focus on the extension and validation of these tools, in an effort to specify the intrinsic qualities of alternative data synthesis methods.Conclusion: By successfully assessing the quality of data produced using a novel multi-step synthetic data generation framework, we showed the technical and conceptual soundness of the Open-CESP initiative, which seems ripe for full-scale implementation.

While well-established methods for time-to-event data are available when the proportional hazards assumption holds, there is no consensus on the best inferential approach under non-proportional hazards (NPH). However, a wide range of parametric and non-parametric methods for testing and estimation in this scenario have been proposed. To provide recommendations on the statistical analysis of clinical trials where non proportional hazards are expected, we conducted a comprehensive simulation study under different scenarios of non-proportional hazards, including delayed onset of treatment effect, crossing hazard curves, subgroups with different treatment effect and changing hazards after disease progression. We assessed type I error rate control, power and confidence interval coverage, where applicable, for a wide range of methods including weighted log-rank tests, the MaxCombo test, summary measures such as the restricted mean survival time (RMST), average hazard ratios, and milestone survival probabilities as well as accelerated failure time regression models. We found a trade-off between interpretability and power when choosing an analysis strategy under NPH scenarios. While analysis methods based on weighted logrank tests typically were favorable in terms of power, they do not provide an easily interpretable treatment effect estimate. Also, depending on the weight function, they test a narrow null hypothesis of equal hazard functions and rejection of this null hypothesis may not allow for a direct conclusion of treatment benefit in terms of the survival function. In contrast, non-parametric procedures based on well interpretable measures as the RMST difference had lower power in most scenarios. Model based methods based on specific survival distributions had larger power, however often gave biased estimates and lower than nominal confidence interval coverage.

Large language models based on self-attention mechanisms have achieved astonishing performances not only in natural language itself, but also in a variety of tasks of different nature. However, regarding processing language, our human brain may not operate using the same principle. Then, a debate is established on the connection between brain computation and artificial self-supervision adopted in large language models. One of most influential hypothesis in brain computation is the predictive coding framework, which proposes to minimize the prediction error by local learning. However, the role of predictive coding and the associated credit assignment in language processing remains unknown. Here, we propose a mean-field learning model within the predictive coding framework, assuming that the synaptic weight of each connection follows a spike and slab distribution, and only the distribution, rather than specific weights, is trained. This meta predictive learning is successfully validated on classifying handwritten digits where pixels are input to the network in sequence, and moreover on the toy and real language corpus. Our model reveals that most of the connections become deterministic after learning, while the output connections have a higher level of variability. The performance of the resulting network ensemble changes continuously with data load, further improving with more training data, in analogy with the emergent behavior of large language models. Therefore, our model provides a starting point to investigate the connection among brain computation, next-token prediction and general intelligence.

Evaluating environmental variables that vary stochastically is the principal topic for designing better environmental management and restoration schemes. Both the upper and lower estimates of these variables, such as water quality indices and flood and drought water levels, are important and should be consistently evaluated within a unified mathematical framework. We propose a novel pair of Orlicz regrets to consistently bound the statistics of random variables both from below and above. Here, consistency indicates that the upper and lower bounds are evaluated with common coefficients and parameter values being different from some of the risk measures proposed thus far. Orlicz regrets can flexibly evaluate the statistics of random variables based on their tail behavior. The explicit linkage between Orlicz regrets and divergence risk measures was exploited to better comprehend them. We obtain sufficient conditions to pose the Orlicz regrets as well as divergence risk measures, and further provide gradient descent-type numerical algorithms to compute them. Finally, we apply the proposed mathematical framework to the statistical evaluation of 31-year water quality data as key environmental indicators in a Japanese river environment.

In clinical trials of longitudinal continuous outcomes, reference based imputation (RBI) has commonly been applied to handle missing outcome data in settings where the estimand incorporates the effects of intercurrent events, e.g. treatment discontinuation. RBI was originally developed in the multiple imputation framework, however recently conditional mean imputation (CMI) combined with the jackknife estimator of the standard error was proposed as a way to obtain deterministic treatment effect estimates and correct frequentist inference. For both multiple and CMI, a mixed model for repeated measures (MMRM) is often used for the imputation model, but this can be computationally intensive to fit to multiple data sets (e.g. the jackknife samples) and lead to convergence issues with complex MMRM models with many parameters. Therefore, a step-wise approach based on sequential linear regression (SLR) of the outcomes at each visit was developed for the imputation model in the multiple imputation framework, but similar developments in the CMI framework are lacking. In this article, we fill this gap in the literature by proposing a SLR approach to implement RBI in the CMI framework, and justify its validity using theoretical results and simulations. We also illustrate our proposal on a real data application.

Electrical circuits are present in a variety of technologies, making their design an important part of computer aided engineering. The growing number of tunable parameters that affect the final design leads to a need for new approaches of quantifying their impact. Machine learning may play a key role in this regard, however current approaches often make suboptimal use of existing knowledge about the system at hand. In terms of circuits, their description via modified nodal analysis is well-understood. This particular formulation leads to systems of differential-algebraic equations (DAEs) which bring with them a number of peculiarities, e.g. hidden constraints that the solution needs to fulfill. We aim to use the recently introduced dissection concept for DAEs that can decouple a given system into ordinary differential equations, only depending on differential variables, and purely algebraic equations that describe the relations between differential and algebraic variables. The idea then is to only learn the differential variables and reconstruct the algebraic ones using the relations from the decoupling. This approach guarantees that the algebraic constraints are fulfilled up to the accuracy of the nonlinear system solver, which represents the main benefit highlighted in this article.

While the test-negative design (TND), which is routinely used for monitoring seasonal flu vaccine effectiveness (VE), has recently become integral to COVID-19 vaccine surveillance, it is susceptible to selection bias due to outcome-dependent sampling. Some studies have addressed the identifiability and estimation of causal parameters under the TND, but efficiency bounds for nonparametric estimators of the target parameter under the unconfoundedness assumption have not yet been investigated. We propose a one-step doubly robust and locally efficient estimator called TNDDR (TND doubly robust), which utilizes sample splitting and can incorporate machine learning techniques to estimate the nuisance functions. We derive the efficient influence function (EIF) for the marginal expectation of the outcome under a vaccination intervention, explore the von Mises expansion, and establish the conditions for $\sqrt{n}-$consistency, asymptotic normality and double robustness of TNDDR. The proposed TNDDR is supported by both theoretical and empirical justifications, and we apply it to estimate COVID-19 VE in an administrative dataset of community-dwelling older people (aged $\geq 60$y) in the province of Qu\'ebec, Canada.

The emergence of complex structures in the systems governed by a simple set of rules is among the most fascinating aspects of Nature. The particularly powerful and versatile model suitable for investigating this phenomenon is provided by cellular automata, with the Game of Life being one of the most prominent examples. However, this simplified model can be too limiting in providing a tool for modelling real systems. To address this, we introduce and study an extended version of the Game of Life, with the dynamical process governing the rule selection at each step. We show that the introduced modification significantly alters the behaviour of the game. We also demonstrate that the choice of the synchronization policy can be used to control the trade-off between the stability and the growth in the system.

The goal of explainable Artificial Intelligence (XAI) is to generate human-interpretable explanations, but there are no computationally precise theories of how humans interpret AI generated explanations. The lack of theory means that validation of XAI must be done empirically, on a case-by-case basis, which prevents systematic theory-building in XAI. We propose a psychological theory of how humans draw conclusions from saliency maps, the most common form of XAI explanation, which for the first time allows for precise prediction of explainee inference conditioned on explanation. Our theory posits that absent explanation humans expect the AI to make similar decisions to themselves, and that they interpret an explanation by comparison to the explanations they themselves would give. Comparison is formalized via Shepard's universal law of generalization in a similarity space, a classic theory from cognitive science. A pre-registered user study on AI image classifications with saliency map explanations demonstrate that our theory quantitatively matches participants' predictions of the AI.

This paper does not describe a working system. Instead, it presents a single idea about representation which allows advances made by several different groups to be combined into an imaginary system called GLOM. The advances include transformers, neural fields, contrastive representation learning, distillation and capsules. GLOM answers the question: How can a neural network with a fixed architecture parse an image into a part-whole hierarchy which has a different structure for each image? The idea is simply to use islands of identical vectors to represent the nodes in the parse tree. If GLOM can be made to work, it should significantly improve the interpretability of the representations produced by transformer-like systems when applied to vision or language

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