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The clinical presentation of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, varies widely across patients, making it challenging to determine if potential therapeutics slow progression. We sought to determine whether there were common patterns of disease progression that could aid in the design and analysis of clinical trials. We developed an approach based on a mixture of Gaussian processes to identify clusters of patients sharing similar disease progression patterns, modeling their average trajectories and the variability in each cluster. We show that ALS progression is frequently nonlinear, with periods of stable disease preceded or followed by rapid decline. We also show that our approach can be extended to Alzheimer’s and Parkinson’s diseases. Our results advance the characterization of disease progression of ALS and provide a flexible modeling approach that can be applied to other progressive diseases.

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Iatrogenic injury to the maxillary sinus membrane is a common complication during direct sinus lift procedures. The most common cause is perforation of the Schneiderian membrane using a tungsten-carbide round bur no.6. We propose a safe technique in which an acrylic stone trimmer is used to create a window in the maxillary antrum thereby minimizing the risk of injury to the delicate sinus membrane.