We report a biomarker-based non-endoscopic method for detecting Barrett’s esophagus (BE), based on detecting methylated DNAs retrieved via a swallowable balloon-based esophageal sampling device. BE is the precursor of, and a major recognized risk factor for, developing esophageal adenocarcinoma (EAC). Endoscopy, the current standard for BE detection, is not cost-effective for population screening. We performed genome-wide screening to ascertain regions targeted for recurrent aberrant cytosine methylation in BE, identifying high-frequency methylation within the CCNA1 locus. We tested CCNA1 DNA methylation as a BE biomarker in cytology brushings of the distal esophagus from 173 individuals with or without BE. CCNA1 DNA methylation demonstrated an area under the curve (AUC)=0.95 for discriminating BE-related metaplasia and neoplasia cases versus normal individuals, performing identically to methylation of VIM DNA, an established BE biomarker. When combined, the resulting two biomarker panel was 95% sensitive and 91% specific. These results were replicated in an independent validation cohort of 149 individuals, who were assayed using the same cutoff values for test positivity established in the training population. To progress toward non-endoscopic esophageal screening, we engineered a well-tolerated, swallowable, encapsulated balloon device able to selectively sample the distal esophagus within 5 minutes. In balloon samples from 86 individuals, tests of CCNA1 plus VIM DNA methylation detected BE metaplasia with 90.3% sensitivity and 91.7% specificity. Combining the balloon sampling device with molecular assays of CCNA1 plus VIM DNA methylation enables an efficient, well-tolerated, sensitive, and specific method of screening at-risk populations for BE.

One of the properties of interest in the analysis of networks is global communicability, i.e., how easy or difficult it is, generally, to reach nodes from other nodes by following edges. Different global communicability measures provide quantitative assessments of this property, emphasizing different aspects of the problem. This paper investigates the sensitivity of global measures of communicability to local changes. In particular, for directed, weighted networks, we study how different global measures of communicability change when the weight of a single edge is changed; or, in the unweighted case, when an edge is added or removed. The measures we study include the total network communicability, based on the matrix exponential of the adjacency matrix, and the Perron network communicability, defined in terms of the Perron root of the adjacency matrix and the associated left and right eigenvectors. Finding what local changes lead to the largest changes in global communicability has many potential applications, including assessing the resilience of a system to failure or attack, guidance for incremental system improvements, and studying the sensitivity of global communicability measures to errors in the network connection data.

We describe a computational method for parameter estimation in linear regression, that is capable of simultaneously producing sparse estimates and dealing with outliers and heavy-tailed error distributions. The method used is based on the image restoration method proposed in [G. Huang, A. Lanza, S. Morigi, L. Reichel, and F. Sgallari, Majorization-minimization generalized Krylov subspace methods for pq optimization applied to image restoration, BIT Numer. Math., 57 (2017), pp. 351-378]. It can be applied to problems of arbitrary size. The choice of certain parameters is discussed. Results obtained for simulated and real data are presented.

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