PubMed · 14126987
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S LIEBE. 1963. [REGIONAL ENTERITIS].. https://pubmed.ncbi.nlm.nih.gov/14126987/
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During erythroid differentiation and maturation, it is critical that the 3 components of hemoglobin, alpha-globin, beta-globin, and heme, are made in proper stoichiometry to form stable hemoglobin. Heme-regulated translation mediated by the heme-regulated inhibitor kinase (HRI) provides one major mechanism that ensures balanced synthesis of globins and heme. HRI phosphorylates the alpha-subunit of eukaryotic translational initiation factor 2 (eLF2alpha) in heme deficiency, thereby inhibiting protein synthesis globally. In this manner, HRI serves as a feedback inhibitor of globin synthesis by sensing the intracellular concentration of heme through its heme-binding domains. HRI is essential not only for the translational regulation of globins, but also for the survival of erythroid precursors in iron deficiency. Recently, the protective function of HRI has also been demonstrated in murine models of erythropoietic protoporphyria and beta-thalassemia. In these 3 anemias, HRI is essential in determining red blood cell size, number, and hemoglobin content per cell. Translational regulation by HRI is critical to reduce excess synthesis of globin proteins or heme under nonoptimal disease states, and thus reduces the severity of these diseases. The protective role of HRI may be more common among red cell disorders.
A new test for the detection of publication bias in meta-analysis with sparse binary data is proposed. The test statistic is based on observed and expected cell frequencies, and the variance of the observed cell frequencies. These quantities are utilized in a rank correlation test. Type I error rate and power of the test are evaluated in simulations; results are compared to those of two other commonly used test procedures. Sample sizes were generated according to findings in a survey of eight German medical journals. Simulation results indicate that, in contrast to existing test procedures, the new test holds the prescribed significance level when data are sparse. However, the power of all tests is low in many situations of practical importance.
This study set out to determine whether there is a center effect on anemia management in hemodialysis patients. The US Renal Data System and Medicare standard analysis files were analyzed. Between-center variation and within-facility correlations in hematocrit values were examined in two separate data sets (years 2000 and 2001) and compared with simulated samples that were composed of random values that assumed no center effect. Mixed-effect models were used to adjust for multiple factors and quantify the within-facility correlation in hematocrit values. Expected hematocrit values were compared in patients who underwent dialysis at poor and superior performing facilities with fixed characteristics including epoetin alpha dosing. There was a wider center variation in hematocrit for the actual versus simulated data and a coefficient of variation of 4.1% for the former versus 1.7% for the latter, in both years. The within-facility correlation for hematocrit was 0.053 (95% confidence interval 0.050 to 0.056; P < 0.001) in 2000 with similar values in 2001 but no within-facility correlation in the simulated data. The impact of these findings was demonstrated with a difference in expected hematocrit for a patient who was treated with fixed-dosage epoetin alpha in the poorest versus best performing units (mean difference in expected hematocrit 3.06; 95% confidence interval 3.03 to 3.09; P < 0.001). Key attributes of a center effect on anemia management in hemodialysis have been identified. The presence of a center effect suggests that there are facility-specific processes that influence performance in dialysis anemia management and are independent of commonly titrated inputs, such as dosing of erythropoietic agents.