Increasing the Discovery Space in Astrophysics - A Collation of Six Submitted White Papers

We write in response to the call from the 2020 Decadal Survey to submit white papers illustrating the most pressing scientific questions in astrophysics for the coming decade. We propose exploration as the central question for the Decadal Committee's discussions.The history of astronomy shows that paradigm changing discoveries are not driven by well formulated scientific questions, based on the knowledge of the time. They were instead the result of the increase in discovery space fostered by new telescopes and instruments. An additional tool for increasing the discovery space is provided by the analysis and mining of the increasingly larger amount of archival data available to astronomers. Revolutionary observing facilities, and the state of the art astronomy archives needed to support these facilities, will open up the universe to new discovery. Here we focus on exploration for compact objects and multi messenger science. This white paper includes science examples of the power of the discovery approach, encompassing all the areas of astrophysics covered by the 2020 Decadal Survey

Increasing the Discovery Space in Astrophysics - A Collation of Six Submitted White Papers

We write in response to the call from the 2020 Decadal Survey to submit white papers illustrating the most pressing scientific questions in astrophysics for the coming decade. We propose exploration as the central question for the Decadal Committee's discussions. The history of astronomy shows that paradigm changing discoveries are not driven by well formulated scientific questions, based on the knowledge of the time. They were instead the result of the increase in discovery space fostered by new telescopes and instruments. An additional tool for increasing the discovery space is provided by the analysis and mining of the increasingly larger amount of archival data available to astronomers. Revolutionary observing facilities, and the state of the art astronomy archives needed to support these facilities, will open up the universe to new discovery. Here we focus on exploration for compact objects and multi messenger science. This white paper includes science examples of the power of the discovery approach, encompassing all the areas of astrophysics covered by the 2020 Decadal Survey

Clinical use of the urine biomarker [TIMP-2] × [IGFBP7] for acute kidney injury risk assessment

Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.</p

Association of Peak Changes in Plasma Cystatin C and Creatinine With Death After Cardiac Operations

BackgroundAcute kidney injury is a risk factor for death in cardiac surgical patients. Plasma cystatin C and creatinine have different temporal profiles in the postoperative setting, but the associations of simultaneous changes in both filtration markers compared with change in only one marker with prognosis after hospital discharge are not well described.MethodsThis is a longitudinal study of 1,199 high-risk adult cardiac surgical patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium who survived hospitalization. We examined in-hospital peak changes of cystatin C and creatinine in the 3 days after cardiac operations. We evaluated associations of these filtration markers with death, adjusting for demographics, operative characteristics, medical comorbidities, preoperative estimated glomerular filtration rate, preoperative urinary albumin-to-creatinine ratio, and site.ResultsDuring the first 3 days of hospitalization, nearly twice as many patients had a 25% or higher rise in creatinine (30%) compared with a 25% or higher peak rise in cystatin C (15%). The risk of death was higher in those with elevations in cystatin C (adjusted hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.4 to 2.37) or creatinine (adjusted HR, 1.90; 95% CI, 1.32 to 2.72) compared with patients who experienced a postoperative decrease in either filtration marker. Patients who had simultaneous elevations of 25% or higher in cystatin C and creatinine were at similar adjusted risk for 3-year mortality (HR, 1.79; 95% CI, 1.03 to 3.1) as those with a 25% or higher increase in cystatin C alone (HR, 2.2; 95% CI, 1.09 to 4.47).ConclusionsElevations in creatinine postoperatively are more common than elevations in cystatin C. However, elevations in cystatin C appeared to be associated with a higher risk of death after hospital discharge

Serum Cystatin C– Versus Creatinine-Based Definitions of Acute Kidney Injury Following Cardiac Surgery: A Prospective Cohort Study

BACKGROUND: The primary aim of this study was to compare the sensitivity and rapidity of AKI detection by cystatin C relative to creatinine following cardiac surgery. STUDY DESIGN: Prospective cohort study SETTINGS AND PARTICIPANTS: 1,150 high-risk, adult cardiac surgery patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium. PREDICTOR: Changes in serum creatinine and cystatin C OUTCOME: Post-surgical incidence of AKI MEASUREMENTS: Serum creatinine and cystatin C were measured at the preoperative visit and daily on postoperative days 1–5. To allow comparisons between changes in creatinine and cystatin C, AKI endpoints were defined by the relative increases in each marker from baseline (25, 50 and 100%) and the incidence of AKI was compared based upon each marker. Secondary aims were to compare clinical outcomes among patients defined as having AKI by cystatin C and/or creatinine. RESULTS: Overall, serum creatinine detected more cases of AKI than cystatin C: 35% developed a ≥25% increase in serum creatinine, whereas only 23% had ≥25% increase in cystatin C (p < 0.001). Creatinine also had higher proportions meeting the 50% (14% and 8%, p<0.001) and 100% (4% and 2%, p=0.005) thresholds for AKI diagnosis. Clinical outcomes were generally not statistically different for AKI cases detected by creatinine or cystatin C. However, for each AKI threshold, patients with AKI confirmed by both markers had significantly higher risk of the combined mortality/dialysis outcome compared with patients with AKI detected by creatinine alone (p=0.002). LIMITATIONS: There were few adverse clinical outcomes, limiting our ability to detect differences in outcomes between subgroups of patients based upon their definitions of AKI. CONCLUSION: In this large multicenter study, we found that cystatin C was less sensitive for AKI detection compared with creatinine. However, confirmation by cystatin C appeared to identify a subset of AKI patients with substantially higher risk of adverse outcomes

Clinical Use of the Urine Biomarker [TIMP-2]&nbsp;× [IGFBP7] for&nbsp;Acute Kidney Injury Risk Assessment

Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2]&nbsp;× [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI