Protecting the Health of Astronauts: Enhancing Occupational Health Monitoring and Surveillance for Former NASA Astronauts to Understand Long-Term Outcomes of Spaceflight-Related Exposures

The astronaut community is unique, and may be disproportionately exposed to occupational hazards not commonly seen in other communities. The extent to which the demands of the astronaut occupation and exposure to spaceflight-related hazards affect the health of the astronaut population over the life course is not completely known. A better understanding of the individual, population, and mission impacts of astronaut occupational exposures is critical to providing clinical care, targeting occupational surveillance efforts, and planning for future space exploration. The ability to characterize the risk of latent health conditions is a significant component of this understanding. Provision of health screening services to active and former astronauts ensures individual, mission, and community health and safety. Currently, the NASA-Johnson Space Center (JSC) Flight Medicine Clinic (FMC) provides extensive medical monitoring to active astronauts throughout their careers. Upon retirement, astronauts may voluntarily return to the JSC FMC for an annual preventive exam. However, current retiree monitoring includes only selected screening tests, representing an opportunity for augmentation. The potential long-term health effects of spaceflight demand an expanded framework of testing for former astronauts. The need is two-fold: screening tests widely recommended for other aging populations are necessary to rule out conditions resulting from the natural aging process (e.g., colonoscopy, mammography); and expanded monitoring will increase NASA's ability to better characterize conditions resulting from astronaut occupational exposures. To meet this need, NASA has begun an extensive exploration of the overall approach, cost, and policy implications of e an Astronaut Occupational Health program to include expanded medical monitoring of former NASA astronauts. Increasing the breadth of monitoring services will ultimately enrich the existing evidence base of occupational health risks to astronauts. Such an expansion would therefore improve the understanding of the health of the astronaut population as a whole, and the ability to identify, mitigate, and manage such risks in preparation for deep space exploration missions

Managing the entanglement: complexity leadership in public sector systems

Complexity in public sector systems requires leaders to balance the administrative practices necessary to be aligned and efficient in the management of routine challenges and the adaptive practices required to respond to dynamic circumstances. Conventional notions of leadership in the field of public administration do not fully explain the role of leadership in balancing the entanglement of formal, top-down, administrative functions and informal, emergent, adaptive functions within public sector settings with different levels of complexity. Drawing on and extending existing complexity leadership constructs, this article explores how leadership is enacted over the duration of six urban regeneration projects representing high, medium, and low levels of project complexity. The article suggests that greater attention needs to be paid to the tensions inherent in enabling leadership if actors are to cope with the complex, collaborative, cross-boundary, adaptive work in which they are increasingly engage

Public Administration and Complexity – or how to teach things we can’t predict?

Introduction to the special issue ‘Teaching Complexity

Guest editorial: Complexity as a model for social innovation and social entrepreneurship: is there order in the chaos?

The complexity sciences are subject to increasing policy interest from governments and international organisations as a means for fostering both social innovation and social entrepreneurship. However, there remains little conceptual clarity in how theories, concepts and ideas can be used consistently and productively. This article reviews the application of the complexity sciences in social innovation and social entrepreneurship scholarship overall and considers its implications for both fields. We outline how social innovation and social entrepreneurship can be conceptualised as complex processes, set within complex environments, tackling complex goals, and present a suitably revised model of the social innovation lifecycle. Based on this review - and the articles contributed to this special issue of Social Enterprise Journal – we argue that a complexity-informed perspective can contribute to scholarship and practice in three ways: as a rhetorical device, as an analytical framework for empirical analysis, and as a basis for developing new tools and methods for social innovation and social entrepreneurship. In this way academics can play a crucial role in helping policymakers and practitioners interested in the complexity sciences walk a line between fatalism and overstatement

Managing the complexity of outcomes: a new approach to performance measurement and management

Governments, philanthropic agencies and public sector organisations have given increasing primacy to outcomes across their operations in recent years, particularly within the domain of performance management. We argue that societal outcomes challenge public agencies to respond to four specific forms of complexity - compositional, experiential, dynamic and governance complexities - which taken together confound the conceptual basis of traditional performance management systems. We adopt this understanding of complexity in a constructive capacity to consider the design parameters of a complexity-appropriate performance management system. We conclude that two theoretical transitions are necessary in a complexity-appropriate performance management approach: a shift from principal-agent theory to stewardship theory, and from technical to social management control theory. We explore the characteristics which such a model of performance management might take in practice, and conclude by outlining a research agenda to explore the potential applications of this new approach

Jowett’s Thucydides: A corpus-based analysis of translation as political intervention

Thucydides’ History of the Peloponnesian War is a key text in the classical Greek canon and an important source of insights into the structures and tensions at the heart of ancient Athenian democracy. Consequently, modern interpretations of his analysis have repeatedly played a major role in shaping debates on the viability and desirability of democratic rule. This paper aims to build on previous discussion of Benjamin Jowett's 1881 translation of Thucydides by applying a comparative corpus-based methodology to explore how this translator's own personal politics shaped his re-presentation of this text. The analysis reveals a striking emphasis on the position and activity of democratic leaders throughout Jowett’s version, strongly consistent with the ideology of leadership that he developed during his career as Master of Balliol College, Oxford

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Structure, function and diversity of the healthy human microbiome

Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

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