Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication.

RationaleWe recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest.ObjectivesWe now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients.MethodsWe conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test.Measurements and main resultsUrinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]).ConclusionsUrinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962)

Review of The Plains of North America and Their Inhabitants

Lieutenant Colonel Richard Irving Dodge wrote with the easy style of an experienced raconteur, drawing on twenty years of first-hand experience on the Plains. Most of his numerous anecdotes, however, date from the late 1860s and early 1870s. During this period he met an English promoter who encouraged Dodge to write the book. First published in 1876 it quickly went through two editions in England and two in the United States, all substantially edited. The present version, with only errors of spelling and punctuation corrected, is based on an unedited manuscript by Dodge and presents the work as he had envisioned it. Wayne R. Kime meticulously documents variations in the different editions and provides explanatory notes, an informative introduction, and useful commentary

Chipped stone artifacts

Archaeological site records from the Harvard Peabody Archaeological Photographic Collection

Artifacts from SR 12-5, figure number 39 - P. M. 59 No. 2

Archaeological site records from the Harvard Peabody Archaeological Photographic Collection

Chipped stone tools with Fremont culture components

Archaeological site records from the Harvard Peabody Archaeological Photographic Collection

Artifacts from 6-6, figure 40

Archaeological site records from the Harvard Peabody Archaeological Photographic Collection