Degradation of Spacesuit Fabrics in Low Earth Orbit

Six samples of pristine and dust-abraded outer layer spacesuit fabrics were included in the Materials International Space Station Experiment-7, in which they were exposed to the wake-side low Earth orbit environment on the International Space Station (ISS) for 18 months in order to determine whether abrasion by lunar dust increases radiation degradation. The fabric samples were characterized using optical microscopy, optical spectroscopy, field emission scanning electron microscopy, atomic force microscopy, and tensile testing before and after exposure on the ISS. Comparison of pre- and post-flight characterizations showed that the environment darkened and reddened all six fabrics, increasing their integrated solar absorptance by 7 to 38 percent. There was a decrease in the ultimate tensile strength and elongation to failure of lunar dust abraded Apollo spacesuit fibers by a factor of four and an increase in the elastic modulus by a factor of two

Functional Modulation of Cardiac Form through Regionally Confined Cell Shape Changes

Developing organs acquire a specific three-dimensional form that ensures their normal function. Cardiac function, for example, depends upon properly shaped chambers that emerge from a primitive heart tube. The cellular mechanisms that control chamber shape are not yet understood. Here, we demonstrate that chamber morphology develops via changes in cell morphology, and we determine key regulatory influences on this process. Focusing on the development of the ventricular chamber in zebrafish, we show that cardiomyocyte cell shape changes underlie the formation of characteristic chamber curvatures. In particular, cardiomyocyte elongation occurs within a confined area that forms the ventricular outer curvature. Because cardiac contractility and blood flow begin before chambers emerge, cardiac function has the potential to influence chamber curvature formation. Employing zebrafish mutants with functional deficiencies, we find that blood flow and contractility independently regulate cell shape changes in the emerging ventricle. Reduction of circulation limits the extent of cardiomyocyte elongation; in contrast, disruption of sarcomere formation releases limitations on cardiomyocyte dimensions. Thus, the acquisition of normal cardiomyocyte morphology requires a balance between extrinsic and intrinsic physical forces. Together, these data establish regionally confined cell shape change as a cellular mechanism for chamber emergence and as a link in the relationship between form and function during organ morphogenesis

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Retrospective review of vancomycin-induced nephrotoxicity in patients with leukemia

Background The occurrence of nephrotoxicity with vancomycin is approximately 17%, but can increase to 35% when combined with other nephrotoxic agents. Patients with hematologic malignancies may be at greater risk for vancomycin-induced nephrotoxicity due to nephrotoxic chemotherapy and tumor lysis syndrome. Objective The primary objective of this study was to determine the occurrence of nephrotoxicity in adult patients with leukemia receiving vancomycin. Methods A retrospective review approved by the Institutional Review Board was conducted on adult patients with leukemia who received at least one dose of vancomycin during hospital admission between 1 January 2009 and 30 April 2009. Results Forty patients had an occurrence of nephrotoxicity (16%) while 210 patients did not have an occurrence of nephrotoxicity. In multivariate analysis, variables significantly associated with development of nephrotoxicity included active disease status (odds ratio, 4.38 [95% CI 1.1–29.4], p = 0.0291), concomitant intravenous acyclovir administration (odds ratio, 3.83 [95% CI, 1.6–8.9]; p = 0.0022), and concomitant amphotericin administration (odds ratio, 4.26 [95% CI, 1.9–9.4]; p = 0.0004). Conclusion The occurrence of nephrotoxicity in patients with leukemia treated with vancomycin was 16% in our study, similar to previously published reports. Active disease status and concomitant use of intravenous acyclovir and amphotericin were identified as significant risk factors for development of nephrotoxicity. The presence of risk factors for vancomycin nephrotoxicity should be evaluated prior to initiation of therapy to determine appropriateness of use. </jats:sec