Evidence for the presence of β-subunit of hexosaminidase in a case of Sandhoff disease using a blotting technique

Hexosaminidases, lysosomal enzymes whose deficiency is responsible for several genetic disorders, exist as two major forms: form A, containing two types of subunits alpha and beta; and form B, containing only beta subunits. We have used a technique involving successively electrophoresis of denatured proteins, transfer (blotting) onto nitrocellulose, and labelling by appropriate antibodies raised against the dissociated forms of hexosaminidases A and B. This technique allows the detection of alpha and beta subunits in crude extracts of normal tissues. The presence of beta chains was demonstrated in the liver of a fetus affected with Sandhoff's disease, deficient in functional hexosaminidases A and B.     

On the estimation of average treatment effects with right-censored time to event outcome and competing risks

We are interested in the estimation of average treatment effects based on right-censored data of an observational study. We focus on causal inference of differences between t-year absolute event risks in a situation with competing risks. We derive doubly robust estimation equations and implement estimators for the nuisance parameters based on working regression models for the outcome, censoring, and treatment distribution conditional on auxiliary baseline covariates. We use the functional delta method to show that these estimators are regular asymptotically linear estimators and estimate their variances based on estimates of their influence functions. In empirical studies, we assess the robustness of the estimators and the coverage of confidence intervals. The methods are further illustrated using data from a Danish registry study.