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Lee, Sandra

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Lee

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Sandra

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Lee, Sandra

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    Using Collaborative Simulation Modeling to Develop a Web-Based Tool to Support Policy-Level Decision Making About Breast Cancer Screening Initiation Age
    (2017) Burnside, Elizabeth S.; Lee, Sandra; Bennette, Carrie; Near, Aimee M.; Alagoz, Oguzhan; Huang, Hui; van den Broek, Jeroen J.; Kim, Joo Yeon; Ergun, Mehmet A.; van Ravesteyn, Nicolien T.; Stout, Natasha; de Koning, Harry J.; Mandelblatt, Jeanne S.
    Background: There are no publicly available tools designed specifically to assist policy makers to make informed decisions about the optimal ages of breast cancer screening initiation for different populations of US women. Objective: To use three established simulation models to develop a web-based tool called Mammo OUTPuT. Methods: The simulation models use the 1970 US birth cohort and common parameters for incidence, digital screening performance, and treatment effects. Outcomes include breast cancers diagnosed, breast cancer deaths averted, breast cancer mortality reduction, false-positive mammograms, benign biopsies, and overdiagnosis. The Mammo OUTPuT tool displays these outcomes for combinations of age at screening initiation (every year from 40 to 49), annual versus biennial interval, lifetime versus 10-year horizon, and breast density, compared to waiting to start biennial screening at age 50 and continuing to 74. The tool was piloted by decision makers (n = 16) who completed surveys. Results: The tool demonstrates that benefits in the 40s increase linearly with earlier initiation age, without a specific threshold age. Likewise, the harms of screening increase monotonically with earlier ages of initiation in the 40s. The tool also shows users how the balance of benefits and harms varies with breast density. Surveys revealed that 100% of users (16/16) liked the appearance of the site; 94% (15/16) found the tool helpful; and 94% (15/16) would recommend the tool to a colleague. Conclusions: This tool synthesizes a representative subset of the most current CISNET (Cancer Intervention and Surveillance Modeling Network) simulation model outcomes to provide policy makers with quantitative data on the benefits and harms of screening women in the 40s. Ultimate decisions will depend on program goals, the population served, and informed judgments about the weight of benefits and harms.
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    Gene methylation biomarkers in sputum as a classifier for lung cancer risk
    (Impact Journals LLC, 2017) Leng, Shuguang; Wu, Guodong; Klinge, Donna M.; Thomas, Cynthia L.; Casas, Elia; Picchi, Maria A.; Stidley, Christine A.; Lee, Sandra; Aisner, Seena; Siegfried, Jill M.; Ramalingam, Suresh; Khuri, Fadlo R.; Karp, Daniel D.; Belinsky, Steven A.
    CT screening for lung cancer reduces mortality, but will cost Medicare ∼2 billion dollars due in part to high false positive rates. Molecular biomarkers could augment current risk stratification used to select smokers for screening. Gene methylation in sputum reflects lung field cancerization that remains in lung cancer patients post-resection. This population was used in conjunction with cancer-free smokers to evaluate classification accuracy of a validated eight-gene methylation panel in sputum for cancer risk. Sputum from resected lung cancer patients (n=487) and smokers from Lovelace (n=1380) and PLuSS (n=718) cohorts was studied for methylation of an 8-gene panel. Area under a receiver operating characteristic curve was calculated to assess the prediction performance in logistic regressions with different sets of variables. The prevalence for methylation of all genes was significantly increased in the ECOG-ACRIN patients compared to cancer-free smokers as evident by elevated odds ratios that ranged from 1.6 to 8.9. The gene methylation panel showed lung cancer prediction accuracy of 82–86% and with addition of clinical variables improved to 87–90%. With sensitivity at 95%, specificity increased from 25% to 54% comparing clinical variables alone to their inclusion with methylation. The addition of methylation biomarkers to clinical variables would reduce false positive screens by ruling out one-third of smokers eligible for CT screening and could increase cancer detection rates through expanding risk assessment criteria.
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    Acute Schistosoma mansoni Infection Increases Susceptibility to Systemic SHIV Clade C Infection in Rhesus Macaques after Mucosal Virus Exposure
    (Public Library of Science, 2008) Chenine, Agnès-Laurence; Shai-Kobiler, Ela; Steele, Lisa N.; Ong, Helena; Augostini, Peter; Song, Ruijiang; Lee, Sandra; Autissier, Patrick; Ruprecht, Ruth Margrit; Secor, W. Evan
    Background: Individuals living in sub-Saharan Africa represent 10% of the world's population but almost 2/3 of all HIV-1/AIDS cases. The disproportionate HIV-1 infection rates in this region may be linked to helminthic parasite infections that affect many individuals in the developing world. However, the hypothesis that parasite infection increases an individual's susceptibility to HIV-1 has never been prospectively tested in a relevant in vivo model. Methodology/Principal Findings: We measured whether pre-existing infection of rhesus monkeys with a parasitic worm would facilitate systemic infection after mucosal AIDS virus exposure. Two groups of animals, one consisting of normal monkeys and the other harboring Schistosoma mansoni, were challenged intrarectally with decreasing doses of R5-tropic clade C simian-human immunodeficiency virus (SHIV-C). Systemic infection occurred in parasitized monkeys at viral doses that remained sub-infectious in normal hosts. In fact, the 50% animal infectious (AID50) SHIV-C dose was 17-fold lower in parasitized animals compared to controls (P<0.001). Coinfected animals also had significantly higher peak viral RNA loads than controls (P<0.001), as well as increased viral replication in CD4+ central memory cells (P = 0.03). Conclusions/Significance: Our data provide the first direct evidence that acute schistosomiasis significantly increases the risk of de novo AIDS virus acquisition, and the magnitude of the effect suggests that control of helminth infections may be a useful public health intervention to help decrease the spread of HIV-1.