DP-EM: Differentially Private Expectation Maximization

The iterative nature of the expectation maximization (EM) algorithm presents a challenge for privacy-preserving estimation, as each iteration increases the amount of noise needed. We propose a practical private EM algorithm that overcomes this challenge using two innovations: (1) a novel moment perturbation formulation for differentially private EM (DP-EM), and (2) the use of two recently developed composition methods to bound the privacy “cost” of multiple EM iterations: the moments accountant (MA) and zero-mean concentrated differential privacy (zCDP). Both MA and zCDP bound the moment generating function of the privacy loss random variable and achieve a refined tail bound, which effectively decrease the amount of additive noise. We present empirical results showing the benefits of our approach, as well as similar performance between these two composition methods in the DP-EM setting for Gaussian mixture models. Our approach can be readily extended to many iterative learning algorithms, opening up various exciting future directions

MELCOR analyses of severe accident scenarios in Oconee, a B&W PWR plant

This paper presents the results and insights gained from MELCOR analyses of two severe accident scenarios, a Loss of Coolant Accident (LOCA) and a Station Blackout (TMLB) in Oconee, a Babcock & Wilcox (B&W) designed PWR with a large dry containment, and comparisons with Source Term Code Package (STCP) calculations of the same sequences. Results include predicted timing of key events, thermal-hydraulic response in the reactor coolant system and containment, and environmental releases of fission products. The paper also explores the impact of varying concrete type, vessel failure temperature, and break location on the accident progression, containment pressurization, and environmental releases of radionuclides

Membrane Hsp70 — a novel target for the isolation of circulating tumor cells after epithelial-to-mesenchymal transition

The presence of circulating tumor cells (CTCs) in the peripheral blood is a pre-requisite for progression, invasion, and metastatic spread of cancer. Consequently, the enumeration and molecular characterization of CTCs from the peripheral blood of patients with solid tumors before, during and after treatment serves as a valuable tool for categorizing disease, evaluating prognosis and for predicting and monitoring therapeutic responsiveness. Many of the techniques for isolating CTCs are based on the expression of epithelial cell surface adhesion molecule (EpCAM, CD326) on tumor cells. However, the transition of adherent epithelial cells to migratory mesenchymal cells (epithelial-to-mesenchymal transition, EMT)—an essential element of the metastatic process—is frequently associated with a loss of expression of epithelial cell markers, including EpCAM. A highly relevant proportion of mesenchymal CTCs cannot therefore be isolated using techniques that are based on the “capture” of cells expressing EpCAM. Herein, we provide evidence that a monoclonal antibody (mAb) directed against a membrane-bound form of Hsp70 (mHsp70)—cmHsp70.1—can be used for the isolation of viable CTCs from peripheral blood of tumor patients of different entities in a more quantitative manner. In contrast to EpCAM, the expression of mHsp70 remains stably upregulated on migratory, mesenchymal CTCs, metastases and cells that have been triggered to undergo EMT. Therefore, we propose that approaches for isolating CTCs based on the capture of cells that express mHsp70 using the cmHsp70.1 mAb are superior to those based on EpCAM expression

Classifying the precancers: A metadata approach

BACKGROUND: During carcinogenesis, precancers are the morphologically identifiable lesions that precede invasive cancers. In theory, the successful treatment of precancers would result in the eradication of most human cancers. Despite the importance of these lesions, there has been no effort to list and classify all of the precancers. The purpose of this study is to describe the first comprehensive taxonomy and classification of the precancers. As a novel approach to disease classification, terms and classes were annotated with metadata (data that describes the data) so that the classification could be used to link precancer terms to data elements in other biological databases. METHODS: Terms in the UMLS (Unified Medical Language System) related to precancers were extracted. Extracted terms were reviewed and additional terms added. Each precancer was assigned one of six general classes. The entire classification was assembled as an XML (eXtensible Mark-up Language) file. A Perl script converted the XML file into a browser-viewable HTML (HyperText Mark-up Language) file. RESULTS: The classification contained 4700 precancer terms, 568 distinct precancer concepts and six precancer classes: 1) Acquired microscopic precancers; 2) acquired large lesions with microscopic atypia; 3) Precursor lesions occurring with inherited hyperplastic syndromes that progress to cancer; 4) Acquired diffuse hyperplasias and diffuse metaplasias; 5) Currently unclassified entities; and 6) Superclass and modifiers. CONCLUSION: This work represents the first attempt to create a comprehensive listing of the precancers, the first attempt to classify precancers by their biological properties and the first attempt to create a pathologic classification of precancers using standard metadata (XML). The classification is placed in the public domain, and comment is invited by the authors, who are prepared to curate and modify the classification

Acute effects of nicotine on visual search tasks in young adult smokers

Rationale Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. Objectives We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. Methods In experiment 1 smokers and non-smokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. Results In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and refixations on all letters in the display. Conclusions Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to refixate previously seen letters, suggesting an improvement in working memory

Visual hallucinations associated with varenicline: a case report

<p>Abstract</p> <p>Introduction</p> <p>Varenicline is widely used for smoking cessation. It has shown efficacy over placebo and bupropion in manufacturer-sponsored trials. Those with mental illness were excluded from these trials. There are case reports of exacerbation of mental illness and development of psychiatric symptoms with varenicline use.</p> <p>Case presentation</p> <p>A 61-year-old male Caucasian being treated for post-traumatic stress disorder, depression not otherwise specified and alcohol dependence, was prescribed varenicline while he was in a post-traumatic stress disorder/alcohol dual diagnosis treatment program. He developed visual hallucinations, which became worse with titration of the medication. These symptoms resolved upon discontinuation of varenicline.</p> <p>Conclusion</p> <p>Patients with mental illness have a higher incidence of nicotine dependence, and attempts should be made for smoking cessation. Varenicline has not been widely tested in this population. There are reports of exacerbation of mental illness, and probable causation of psychiatric symptoms in the mentally ill. Providers should be aware of this possibility and advise their patients appropriately.</p

Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B

Background: We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner