In many instances, a subject can experience both a nonterminal and terminal event where the terminal event (e.g., death) censors the nonterminal event (e.g., relapse) but not vice versa. Typically, the two events are correlated. This situation has been termed semicompeting risks (e.g., Fine, Jiang, and Chappell, 2001, Biometrika 88, 907-939; Wang, 2003, Journal of the Royal Statistical Society, Series B 65, 257-273), and analysis has been based on a joint survival function of two event times over the positive quadrant but with observation restricted to the upper wedge. Implicitly, this approach entertains the idea of latent failure times and leads to discussion of a marginal distribution of the nonterminal event that is not grounded in reality. We argue that, similar to models for competing risks, latent failure times should generally be avoided in modeling such data. We note that semicompeting risks have more classically been described as an illness-death model and this formulation avoids any reference to latent times. We consider an illness-death model with shared frailty, which in its most restrictive form is identical to the semicompeting risks model that has been proposed and analyzed, but that allows for many generalizations and the simple incorporation of covariates. Nonparametric maximum likelihood estimation is used for inference and resulting estimates for the correlation parameter are compared with other proposed approaches. Asymptotic properties, simulations studies, and application to a randomized clinical trial in nasopharyngeal cancer evaluate and illustrate the methods. A simple and fast algorithm is developed for its numerical implementation.

In a contemporary clinical-practice registry study, the risk of death associated with PCI with everolimus-eluting stents was similar to that associated with CABG. PCI was associated with a higher risk of myocardial infarction (among patients with incomplete revascularization) and repeat revascularization but a lower risk of stroke. (Funded by Abbott Vascular.).

SUMMARY Chatterjee et al. (2011) established the consistency of the maximum likelihood estimator in the β-model for undirected random graphs when the number of vertices goes to infinity. By approximating the inverse of the Fisher information matrix, we obtain its asymptotic normality under mild conditions. Simulation studies and a data example illustrate the theoretical results.Some key words: β-model; Central limit theorem; Fisher information matrix.

Prion disease is a unique category of illness, affecting both animals and humans, in which the underlying pathogenesis is related to a conformational change of a normal, self-protein called PrPC (C for cellular) to a pathological and infectious conformer known as PrPSc (Sc for scrapie). Bovine spongiform encephalopathy (BSE), a prion disease believed to have arisen from feeding cattle with prion contaminated meat and bone meal products, crossed the species barrier to infect humans. Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment. Previously, we have demonstrated we could prevent transmission of prions in a proportion of susceptible mice with a mucosal vaccine. In the current study, white-tailed deer were orally inoculated with attenuated Salmonella expressing PrP, while control deer were orally inoculated with vehicle attenuated Salmonella. Once a mucosal response was established, the vaccinated animals were boosted orally and locally by application of polymerized recombinant PrP onto the tonsils and rectal mucosa. The vaccinated and control animals were then challenged orally with CWD-infected brain homogenate. Three years post CWD oral challenge all control deer developed clinical CWD (median survival 602 days), while among the vaccinated there was a significant prolongation of the incubation period (median survival 909 days; p=0.012 by Weibull regression analysis) and one deer has remained CWD free both clinically and by RAMALT and tonsil biopsies. This negative vaccinate has the highest titers of IgA in saliva and systemic IgG against PrP. Western blots showed that immunoglobulins from this vaccinate react to PrPCWD. We document the first partially successful vaccination for a prion disease in a species naturally at risk.

Objective: To evaluate the performance of transvaginal ultrasonography (TVS) in diagnosis of deep infiltrating endometriosis (DIE).Methods: We retrospectively analyzed 198 patients with pathological diagnosis of DIE in our hospital from January 2017 to December 2019 and assessed the performances of pre-operative TVS diagnosis of DIE with regarding to sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV), using the pathological diagnosis as the ground truth. We also characterized the ultrasonographic features of the DIE lesions.Results: Among all the 198 cases, 170 cases were uterosacral ligament (USL) involvement, SE: 96.47% and SP: 85.71%; 79 cases were intestinal involvement, SE: 94.94% and SP: 94.96%; 57 cases were vaginal rectal septum (VRS) involvement, SE: 73.68% and SP: 94.33%; 20 cases were vaginal involvement, SE: 50% and SP: 97.21%; three cases were bladder involvement, SE: 66.7% and SP: 100%; nine cases were ureter involvement, SE: 55.56% and SP: 100%; and 10 cases were broad ligament involvement, SE: 10% and SP: 100%.Conclusion: TVS showed high accuracy in diagnosing DIE.