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Elizabeth Burns

Publications and source records attributed to Elizabeth Burns.

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CENP-A is required for accurate chromosome segregation and sustained kinetochore association of BubR1.

CENP-A is an evolutionarily conserved, centromere-specific variant of histone H3 that is thought to play a central role in directing kinetochore assembly and in centromere function. Here, we have analyzed the consequences of disrupting the CENP-A gene in the chicken DT40 cell line. In CENP-A-depleted cells, kinetochore protein assembly is impaired, as indicated by mislocalization of the inner kinetochore proteins CENP-I, CENP-H, and CENP-C as well as the outer components Nuf2/Hec1, Mad2, and CENP-E. However, BubR1 and the inner centromere protein INCENP are efficiently recruited to kinetochores. Following CENP-A depletion, chromosomes are deficient in proper congression on the mitotic spindle and there is a transient delay in prometaphase. CENP-A-depleted cells further proceed through anaphase and cytokinesis with unequal chromosome segregation, suggesting that some kinetochore function remains following substantial depletion of CENP-A. We furthermore demonstrate that CENP-A-depleted cells exhibit a specific defect in maintaining kinetochore localization of the checkpoint protein BubR1 under conditions of checkpoint activation. Our data thus point to a specific role for CENP-A in assembly of kinetochores competent in the maintenance of mitotic checkpoint signaling.

Animals↗

Complications in surgical patients.

HYPOTHESIS: Complications are common in hospitalized surgical patients. Provider error contributes to a significant proportion of these complications. DESIGN: Surgical patients were concurrently observed for the development of explicit complications. All complications were reviewed by the attending surgeon and other members of the service and evaluated for the severity of sequelae (major or minor) and for whether the complication resulted from medical error (avoidable) or not. SETTING: University teaching hospital with a level I trauma designation. PATIENTS: All inpatients (operative or nonoperative) from 4 different surgical services: general surgery, combined general surgery and trauma, vascular surgery, and cardiothoracic surgery. MAIN OUTCOME MEASURES: Total complication rate (number of complications divided by the number of patients) and the number of patients with complications. Complications were separated into those with major or minor sequelae and the proportion of each type that were due to medical error (avoidable). Rates of complications in a recent Institute of Medicine report were used as a criterion standard. RESULTS: The data for the respective groups (general surgery, vascular surgery, combined general surgery and trauma, and cardiothoracic surgery) are as follows. The number of patients was 1363, 978, 914, and 1403; number of complications, 413, 409, 295, and 378; total complication rate, 30.3%, 42.4%, 32.3%, and 26.9%; minor complication rate, 13.3%, 19.9%, 13.5%, and 13.0% (percentage of minor complications that were avoidable, 37.4%, 59.0%, 51.2%, and 49.5%); major complication rate, 16.2%, 21.1%, 18.1%, and 12.9% (percentage of major complications that were avoidable, 53.4%, 60.7%, 38.8%, and 38.7%); and mortality rate, 1.83%, 3.33%, 2.28%, and 3.34% (percentage of mortality that was avoidable, 28.0%, 44.1%, 19.0%, and 25.0%). CONCLUSIONS: Despite mortality rates that compare favorably with national benchmarks, a prospective examination of surgical patients reveals complication rates that are 2 to 4 times higher than those identified in an Institute of Medicine report. Almost half of these adverse events were judged contemporaneously by peers to be due to provider error (avoidable). Errors in care contributed to 38 (30%) of 128 deaths. Recognition that provider error contributes significantly to adverse events presents significant opportunities for improving patient outcomes.

Cardiac Surgical Procedures↗