Alien Registration- Quinn, Ilene B. (Millinocket, Penobscot County)

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Comparison of the Transmembrane Mucins MUC1 and MUC16 in Epithelial Barrier Function

Membrane-anchored mucins are present in the apical surface glycocalyx of mucosal epithelial cells, each mucosal epithelium having at least two of the mucins. The mucins have been ascribed barrier functions, but direct comparisons of their functions within the same epithelium have not been done. In an epithelial cell line that expresses the membrane-anchored mucins, MUC1 and MUC16, the mucins were independently and stably knocked down using shRNA. Barrier functions tested included dye penetrance, bacterial adherence and invasion, transepithelial resistance, tight junction formation, and apical surface size. Knockdown of MUC16 decreased all barrier functions tested, causing increased dye penetrance and bacterial invasion, decreased transepithelial resistance, surprisingly, disruption of tight junctions, and greater apical surface cell area. Knockdown of MUC1 did not decrease barrier function, in fact, barrier to dye penetrance and bacterial invasion increased significantly. These data suggest that barrier functions of membrane-anchored mucins vary in the context of other membrane mucins, and MUC16 provides a major barrier when present

Rethinking Peer Review: Detecting and Addressing Medical Malpractice Claims Risk

A medical center department chair has just been notified that a physician in his department, Dr. G, is being sued for the fifth time in seven years. The CEO of co-defendant hospital wants the chair to solve Dr. G\u27s claims problems. At the chair\u27s request, the hospital peer review committee evaluates Dr. G\u27s malpractice cases. While committee members note some minor concerns in the cases, they conclude that in each circumstance he has met the standard of care. They cannot identify any specific technical or educational need, nor can they supply justification for a disciplinary action. The chair is in a vexing situation. Is Dr. G. the victim of bad luck, or is something more systematic at work? Is there some failure or deficiency other than technical incompetence which is making this physician vulnerable to malpractice suits? If so, is it remediable? In this Article, we analyze the ability of peer review to recognize and reduce physicians\u27 risk of medical malpractice claims. Critics argue that peer review neither consistently identifies substandard physicians, nor ensures their removal, while it unfairly targets colleagues for reasons such as economic competition. They suggest that the solution may be to modify statutes governing privilege and immunity, or to increase penalties for healthcare institutions that violate reporting statutes. Critics\u27 concerns may be misplaced. We will argue that peer review is not deficient in its basic conception, but rather aspects of its design and implementation which often do not directly link it to an institution\u27s risk management activities. We assert that peer review can effectively identify a physician\u27s risk of generating a disproportionate share of medical malpractice claims ex ante, and present a sample methodology which allows peer review to more effectively help physicians address that risk. Part I of this Article discusses the background and authority for peer review. Part II outlines common criticisms of peer review and discusses shortcomings in these analyses. Part III describes background medical malpractice research and introduces the Patient Advocacy Reporting System ( PARSSM ) program for peer review. In Part IV we conclude with a discussion of programmatic elements which, if incorporated into the legal framework for peer review, may allow peer review committees to systematically evaluate, monitor, and, potentially reduce physicians\u27 medical malpractice claims risk

Noncontact position measurement system using optical sensors

Optical and computational components are combined to form a high precision, six degree-of-freedom, single-sided, noncontact position measurement system. Reflective optical targets are provided on a target object whose position is to be sensed. Light beams are directed toward the optical targets, producing reflected beams. Electrical signals are produced indicating the points of intersection of the reflected beams and the position-sensitive detectors. The position sensitive detectors may be lateral-effect photodiodes. The signals are transformed to provide measurements of translation along and rotation around three nonparallel axes which define the space in which the target object moves.Board of Regents, University of Texas Syste

Cognitive Function, Physical Performance, Health, and Disease: Norms From the Georgia Centenarian Study

This study provides, for the first time, normative data on cognitive functioning and physical performance, health and health behaviors, and diseases from a population-based sample of 244 centenarians and near-centenarians (M age = 100.5 years, range 98–108, 84.8% women, 21.3% African American) from the Georgia Centenarian Study. Data are presented by the four key dimensions of gender, race, residence, and educational attainment. Results illustrate the profound range of functioning in this age group and indicate considerable differences as a function of each dimension. Bivariate models generally suggest that cognitive functioning and physical performance is higher for men than women; whites than African Americans; community than facility residents; and those with more than high school education than those with less than high school education. Multivariate models elaborate that differences in educational attainment generally account for the largest proportion of variance in cognitive functioning and residential status generally accounts for the largest proportion of variance in physical performance measures. Addition of health variables seldom increases variance accounted for in each domain beyond these four dimensions

Hostility, Race, and Glucose Metabolism in Nondiabetic Individuals

OBJECTIVE— The present study was designed to determine whether hostility is differentially related to measures of glucose metabolism in African-Americans and Caucasians. RESEARCH DESIGN AND METHODS— The relationship of hostility, as measured by a subset of the Cook-Medley hostility scale (CMHOST) inventory items, to various parameters of glucose metabolism were examined in a young, healthy sample of male and female African-American and Caucasian volunteers. Fasting blood samples were collected during an inpatient admission, at which time the CMHOST was also administered. RESULTS— In the entire sample, the CMHOST was found to be significantly correlated with fasting glucose and insulin sensitivity, as measured by the homeostatic model assessment (HOMA). However, the relationship of hostility to these parameters of glucose metabolism was different in African-American and Caucasian subjects. Hostility was significantly related to fasting glucose in African-Americans and to insulin sensitivity and fasting insulin in Caucasian subjects. The relationship of hostility to insulin sensitivity and fasting insulin was partially dependent on BMI in Caucasians, but the relationship of hostility to fasting glucose was unrelated to BMI in African-Americans. CONCLUSIONS— Our data suggest that the relationship of hostility to measures of glucose metabolism is mediated differently in these two ethnic groups. Therefore, hostility seems to be part of a constellation of risk-related behaviors related to BMI in Caucasians but independently related to fasting glucose in African-Americans

Diabetes mellitus in centenarians

OBJECTIVES: Describe prevalence of diabetes mellitus among centenarians. DESIGN: Cross-sectional, population-based. SETTING: 44 counties in northern Georgia. PARTICIPANTS: 244 centenarians (aged 98-108, 15.8% men, 20.5% African-American, 38.0% community-dwelling) from the Georgia Centenarian Study (2001-2009). MEASUREMENTS: Nonfasting blood samples assessed HbA(1c) and relevant clinical parameters. Demographic, diagnosis, and diabetes complications covariates were assessed. RESULTS: 12.5% of centenarians were known to have diabetes. Diabetes was more prevalent among African-Americans (27.7%) than Whites (8.6%, p=.0002). There were no differences between men (16.7%) and women (11.7%, p=.414), centenarians living in the community (10.2%) or facilities (13.9%, p=.540). Diabetes was more prevalent among overweight/obese (23.1%) than non-overweight (7.1%, p=.002) centenarians. Anemia (78.6% versus 48.3%, p=.004) and hypertension (79.3% versus 58.6%, p=.041) were more prevalent among centenarians with diabetes than without and centenarians with diabetes took more nonhypoglycemic medications(8.6 versus 7.0, p=.023). No centenarians with hemoglobin A1c < 6.5% had random serum glucose levels above 200 mg/dl. Diabetes was not associated with 12 month all-cause mortality, visual impairment, amputations, cardiovascular disease or neuropathy. 37% of centenarians reported onset before age 80 (survivors), 47% between 80 and 97 years (delayers) and 15% age 98 or older (escapers). CONCLUSION: Diabetes is a risk factor for cardiovascular disease and mortality, but is seen in persons who live into very old age. Aside from higher rates of anemia and use of more medications, few clinical correlates of diabetes were observed in centenarians

Suppression of Toll-like Receptor-Mediated Innate Immune Responses at the Ocular Surface by the Membrane-associated Mucins MUC1 and MUC16

Membrane-associated mucins (MAMs) expressed on the ocular surface epithelium form a dense glycocalyx, which is hypothesized to protect the cornea and conjunctiva from external insult. In this study, the hypothesis that the MAMs MUC1 and MUC16, expressed on the apical surface of the corneal epithelium, suppress Toll-like receptor (TLR)-mediated innate immune responses was tested. Using an in vitro model of corneal epithelial cells that are cultured to express MAMs, we show that reduced expression of either MUC1 or MUC16 correlates with increased message and secreted protein levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α following exposure of cells to the TLR2 and TLR5 agonists, heat killed Listeria monocytogenes and flagellin, respectively. Since mice express MUC1 (but not MUC16) in the corneal epithelium, a Muc1-/- mouse model was used to extend in vitro findings. Indeed, IL-6 and TNF-α message levels were increased in the corneal epithelium of Muc1-/- mice, in comparison to wild type mice, following exposure of enucleated eyes to the TLR2 and TLR5 agonists. Our results suggest that the MAMs MUC1 and MUC16 contribute to the maintenance of immune homeostasis at the ocular surface by limiting TLR-mediated innate immune responses