Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.

BackgroundEnrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors.MethodsIn a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies.Measurements and main resultsAn admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor.ConclusionsThresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials

Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis.

PURPOSE: Exposures to ambient air pollutants may prime the lung enhancing risk of acute respiratory distress syndrome (ARDS) in sepsis. Our objective was to determine the association of short-, medium-, and long-term pollutant exposures and ARDS risk in critically ill sepsis patients. METHODS: We analyzed a prospective cohort of 1858 critically ill patients with sepsis, and estimated short- (3 days), medium- (6 weeks), and long- (5 years) term exposures to ozone, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 μm (PM2.5), and PM < 10 μm (PM10) using weighted averages of daily levels from monitors within 50 km of subjects residences. Subjects were followed for 6 days for ARDS by the Berlin Criteria. The association between each pollutant and ARDS was determined using multivariable logistic regression adjusting for preselected confounders. In 764 subjects, we measured plasma concentrations of inflammatory proteins at presentation and tested for an association between pollutant exposure and protein concentration via linear regression. RESULTS: ARDS developed in 754 (41%) subjects. Short- and long-term exposures to SO2, NO2, and PM2.5 were associated with ARDS risk (SO2: odds ratio (OR) for the comparison of the 75-25th long-term exposure percentile 1.43 (95% confidence interval (CI) 1.16, 1.77); p < 0.01; NO2: 1.36 (1.06, 1.74); p = 0.04, PM2.5: 1.21 (1.04, 1.41); p = 0.03). Long-term exposures to these three pollutants were also associated with plasma interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor-1 concentrations. CONCLUSION: Short and long-term exposures to ambient SO2, PM2.5, and NO2 are associated with increased ARDS risk in sepsis, representing potentially modifiable environmental risk factors for sepsis-associated ARDS

Auto-Balanced Wavelength Modulated Zeeman Spectroscopy for Oxygen Detection

An effective method for continuously measuring oxygen would be beneficial in various areas of research, including medical diagnostics, molecular biotechnology, industrial production monitoring, environmental analysis, and food packaging [1]. We previously demonstrated the development and testing of a balanced Zeeman spectroscopy method utilizing wavelength modulation for selective detection of paramagnetic molecules. We compared our wavelength-modulated Zeeman spectroscopy (WM-ZS) system to wavelength-modulated Faraday rotation spectroscopy (WM-FRS) and determined a 1.5x improvement in minimum detectable limit. In this report, we describe continued testing of our WM-ZS system. We motivate testing our WM-ZS system with the goal of optimizing our measurements for long term operation by improving thermal management of the coil and minimizing drift with the implementation of dual-modulation balanced WM-ZS detection. From our results using the Nirvana autobalanced photodetector, we conclude that, with optimized parameters, the Nirvana effectively cancels common mode noise and minimizes drift without needing additional modulation of the magnetic field. We then investigate implementation of a miniaturized WM-ZS detection system with the goal of improving the sensitivity of an existing sensor for continuous in-airway monitoring of oxygen based on wavelength modulation spectroscopy (WMS). We present design considerations and discuss initial findings

As if: Utopian desire and the imagination of history in nineteenth-century America

Accounts of the development of historical consciousness in nineteenth-century America have overlooked the significant role played by utopian imaginaries, particularly during the antebellum period. As If: Utopian Desire and the Imagination of History in Nineteenth-Century America addresses this omission with two propositions. First, I argue that in contrast to literary history\u27s focus on Edward Bellamy\u27s 1888 Looking Backward as the origin point for American utopian fiction, it is instead literature of the antebellum period that initiates this development in American letters. Second, in response to a critical tendency to mark history and utopianism as contradictory discourses, I demonstrate the role utopianism plays in aiding and expanding historiographical thought. Four case studies develop these assertions in the context of specific historiographical problems. Chapter One examining Cooper\u27s The Crater reveals the pressures that new developments in the hard sciences placed on humanistic accounts of time and history. Chapter Two on Martin R. Delany\u27s Blake confronts the inbuilt resistance of American historical narratives to the possibility of a slave-led revolution. Chapter Three focusing on Emily Dickinson\u27s poetry speaks to the insufficiencies of Christian millennialism in providing a coherent and satisfying account of historical experience. The final chapter on Edward Bellamy\u27s Looking Backward addresses the relationship between antebellum and turn-of-the-century utopian writing and explores the novel\u27s struggle to represent radical historical change. In sum, these chapters demonstrate how, in the wake of the waning influence of the historical novel, utopianism offered writers a grammar for grappling with historiographical problems raised by new epistemologies (especially in hard sciences), race and revolution, shifting religious paradigms, and American imperialism. Utopian literary conventions provided ways for author to engage what I call the subjunctive aspects of these historiographical problems—desire, conjecture, ineffability, futurity, and loss—as the professional discipline of history became increasingly positivist and thus less capacious in its approach. In utilizing utopia as an analytic category, this project reclaims the undervalued critical lens of utopia, which like optics such as trauma and melancholy, offers an alternative approach to representing historical experience and theorizing historical expression

As if: Utopian desire and the imagination of history in nineteenth-century America

Accounts of the development of historical consciousness in nineteenth-century America have overlooked the significant role played by utopian imaginaries, particularly during the antebellum period. As If: Utopian Desire and the Imagination of History in Nineteenth-Century America addresses this omission with two propositions. First, I argue that in contrast to literary history\u27s focus on Edward Bellamy\u27s 1888 Looking Backward as the origin point for American utopian fiction, it is instead literature of the antebellum period that initiates this development in American letters. Second, in response to a critical tendency to mark history and utopianism as contradictory discourses, I demonstrate the role utopianism plays in aiding and expanding historiographical thought. Four case studies develop these assertions in the context of specific historiographical problems. Chapter One examining Cooper\u27s The Crater reveals the pressures that new developments in the hard sciences placed on humanistic accounts of time and history. Chapter Two on Martin R. Delany\u27s Blake confronts the inbuilt resistance of American historical narratives to the possibility of a slave-led revolution. Chapter Three focusing on Emily Dickinson\u27s poetry speaks to the insufficiencies of Christian millennialism in providing a coherent and satisfying account of historical experience. The final chapter on Edward Bellamy\u27s Looking Backward addresses the relationship between antebellum and turn-of-the-century utopian writing and explores the novel\u27s struggle to represent radical historical change. In sum, these chapters demonstrate how, in the wake of the waning influence of the historical novel, utopianism offered writers a grammar for grappling with historiographical problems raised by new epistemologies (especially in hard sciences), race and revolution, shifting religious paradigms, and American imperialism. Utopian literary conventions provided ways for author to engage what I call the subjunctive aspects of these historiographical problems—desire, conjecture, ineffability, futurity, and loss—as the professional discipline of history became increasingly positivist and thus less capacious in its approach. In utilizing utopia as an analytic category, this project reclaims the undervalued critical lens of utopia, which like optics such as trauma and melancholy, offers an alternative approach to representing historical experience and theorizing historical expression