Browsing by Author "Yan, Yan"

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    Development and external validation of the KIIDS-TBI tool for managing children with mild traumatic brain injury and intracranial injuries
    (Wiley, 2021-12) Greenberg, Jacob K.; Ahluwalia, Ranbir; Hill, Madelyn; Johnson, Gabbie; Hale, Andrew T.; Belal, Ahmed; Baygani, Shawyon; Olsen, Margaret A.; Foraker, Randi E.; Carpenter, Carpenter; Yan, Yan; Ackerman, Laurie; Noje, Corina; Jackson, Eric; Burns, Erin; Sayama, Christina M.; Selden, Nathan R.; Vachhrajani, Shobhan; Shannon, Chevis N.; Kuppermann, Nathan; Limbrick, David D., Jr.; Neurological Surgery, School of Medicine
    Background Clinical decision support (CDS) may improve the postneuroimaging management of children with mild traumatic brain injuries (mTBI) and intracranial injuries. While the CHIIDA score has been proposed for this purpose, a more sensitive risk model may have broader use. Consequently, this study's objectives were to: (1) develop a new risk model with improved sensitivity compared to the CHIIDA model and (2) externally validate the new model and CHIIDA model in a multicenter data set. Methods We analyzed children ≤18 years old with mTBI and intracranial injuries included in the PECARN head injury data set (2004–2006). We used binary recursive partitioning to predict the composite outcome of neurosurgical intervention, intubation for > 24 h due to TBI, or death due to TBI. The new model was externally validated in a separate data set that included children treated at any one of six centers from 2006 to 2019. Results Based on 839 patients from the PECARN data set, a new risk model, the KIIDS-TBI model, was developed that incorporated imaging (e.g., midline shift) and clinical (e.g., Glasgow Coma Scale score) findings. Based on the model-predicted probability of the composite outcome, three cutoffs were evaluated to classify patients as “high risk” for level of care decisions. In the external validation data set consisting of 1,630 patients, the most conservative cutoff (i.e., any predictor present) identified 119 of 119 children with the composite outcome (sensitivity = 100%), but had the lowest specificity (26.3%). The other two decision-making cutoffs had worse sensitivity (94.1%–96.6%) but improved specificity (67.4%–81.3%). The CHIIDA model lacked the most conservative cutoff and otherwise showed the same or slightly worse performance compared to the other two cutoffs. Conclusions The KIIDS-TBI model has high sensitivity and moderate specificity for risk stratifying children with mTBI and intracranial injuries. Use of this CDS tool may help improve the safe, resource-efficient management of this important patient population.
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    The effect of adverse housing and neighborhood conditions on the development of diabetes mellitus among middle-aged African Americans
    (Oxford University Press, 2007-08-15) Schootman, Mario; Andresen, Elena M.; Wolinsky, Fredric D.; Malmstrom, Theodore K.; Miller, J. Philip; Yan, Yan; Miller, Douglas K.; Department of Medicine, IU School of Medicine
    The authors examined the associations of observed neighborhood (block face) and housing conditions with the incidence of diabetes by using data from 644 subjects in the African-American Health Study (St. Louis area, Missouri). They also investigated five mediating pathways (health behavior, psychosocial, health status, access to medical care, and sociodemographic characteristics) if significant associations were identified. The external appearance of the block the subjects lived on and housing conditions were rated as excellent, good, fair, or poor. Subjects reported about neighborhood desirability. Self-reported diabetes was obtained at baseline and 3 years later. Of 644 subjects without self-reported diabetes, 10.3% reported having diabetes at the 3-year follow-up. Every housing condition rated as fair-poor was associated with an increased risk of diabetes, with odds ratios ranging from 2.53 (95% confidence interval: 1.47, 4.34 for physical condition inside the building) to 1.78 (95% confidence interval: 1.03, 3.07 for cleanliness inside the building) in unadjusted analyses. No association was found between any of the block face conditions or perceived neighborhood conditions and incident diabetes. The odds ratios for the five housing conditions were unaffected when adjusted for the mediating pathways. Poor housing conditions appear to be an independent contributor to the risk of incident diabetes in urban, middle-aged African Americans.
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    Neighborhood conditions, diabetes, and risk of lower-body functional limitations among middle-aged African Americans: A cohort study
    (BMC, 2010-05-27) Schootman, Mario; Andresen, Elena M.; Wolinsky, Fredric D.; Miller, J. Philip; Yan, Yan; Miller, Douglas K.; Medicine, School of Medicine
    Background The relationship between presence of diabetes and adverse neighborhood and housing conditions and their effect on functional decline is unclear. We examined the association of adverse neighborhood (block face) and housing conditions with incidence of lower-body functional limitations among persons with and those without diabetes using a prospective population-based cohort study of 563 African Americans 49-65 years of age at their 2000-2001 baseline interviews. Methods Participants were randomly sampled African Americans living in the St. Louis area (response rate: 76%). Physician-diagnosed diabetes was self reported at baseline interview. Lower-body functional limitations were self reported based on the Nagi physical performance scale at baseline and the three-year follow-up interviews. The external appearance of the block the respondent lived on and five housing conditions were rated by study interviewers. All analyses were done using propensity score methods to control for confounders. Results 109 (19.4%) of subjects experienced incident lower-body functional limitations at three-year follow-up. In adjusted analysis, persons with diabetes who lived on block faces rated as fair-poor on each of the five conditions had higher odds (7.79 [95% confidence interval: 1.36-37.55] to 144.6 [95% confidence interval: 4.45-775.53]) of developing lower-body functional limitations than the referent group of persons without diabetes who lived on block faces rated as good-excellent. At least 80 percent of incident lower-body functional limitations was attributable to the interaction between block face conditions and diabetes status. Conclusions Adverse neighborhood conditions appear to exacerbate the detrimental effects on lower-body functioning associated with diabetes.
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    RAD50 Is Required for Efficient Initiation of Resection and Recombinational Repair at Random, y-Induced Double-Strand Break Ends
    (PLOS, 2009-09-18) Westmoreland, Jim; Ma, Wenjian; Yan, Yan; Van Hulle, Kelly; Malkova, Anna; Resnick, Michael A.; Biology, School of Science
    Resection of DNA double-strand break (DSB) ends is generally considered a critical determinant in pathways of DSB repair and genome stability. Unlike for enzymatically induced site-specific DSBs, little is known about processing of random “dirty-ended” DSBs created by DNA damaging agents such as ionizing radiation. Here we present a novel system for monitoring early events in the repair of random DSBs, based on our finding that single-strand tails generated by resection at the ends of large molecules in budding yeast decreases mobility during pulsed field gel electrophoresis (PFGE). We utilized this “PFGE-shift” to follow the fate of both ends of linear molecules generated by a single random DSB in circular chromosomes. Within 10 min after γ-irradiation of G2/M arrested WT cells, there is a near-synchronous PFGE-shift of the linearized circular molecules, corresponding to resection of a few hundred bases. Resection at the radiation-induced DSBs continues so that by the time of significant repair of DSBs at 1 hr there is about 1–2 kb resection per DSB end. The PFGE-shift is comparable in WT and recombination-defective rad52 and rad51 strains but somewhat delayed in exo1 mutants. However, in rad50 and mre11 null mutants the initiation and generation of resected ends at radiation-induced DSB ends is greatly reduced in G2/M. Thus, the Rad50/Mre11/Xrs2 complex is responsible for rapid processing of most damaged ends into substrates that subsequently undergo recombinational repair. A similar requirement was found for RAD50 in asynchronously growing cells. Among the few molecules exhibiting shift in the rad50 mutant, the residual resection is consistent with resection at only one of the DSB ends. Surprisingly, within 1 hr after irradiation, double-length linear molecules are detected in the WT and rad50, but not in rad52, strains that are likely due to crossovers that are largely resection- and RAD50-independent.