Flight Planning and Procedures

The National Aeronautics and Space Administration (NASA) was founded in 1958 by President Eisenhower as a civilian lead United States federal agency designed to advance the science of space. Over the years, NASA has grown with a vision to "reach for new heights and reveal the unknown for the benefit of humankind" (About NASA). Mercury, Gemini, Apollo, Skylab, and Space Shuttle are just a few of the programs that NASA has led to advance our understanding of the universe. Each of the eleven main NASA space centers located across the United States plays a unique role in accomplishing that vision. Since 1961, Johnson Space Center (JSC) has led the effort for manned spaceflight missions. JSC has a mission to "provide and apply the preeminent capabilities to develop, operate, and integrate human exploration missions spanning commercial, academic, international, and US government partners" (Co-op Orientation). To do that, JSC is currently focused on two main programs, Orion and the International Space Station (ISS). Orion is the exploration vehicle that will take astronauts to Mars; a vessel comparable to the Apollo capsule. The International Space Station (ISS) is a space research facility designed to expand our knowledge of science in microgravity. The first piece of the ISS was launched in November of 1998 and has been in a continuous low earth orbit ever since. Recently, two sub-programs have been developed to resupply the ISS. The Commercial Cargo program is currently flying cargo and payloads to the ISS; the Commercial Crew program will begin flying astronauts to the ISS in a few years

Human Lipoxygenase Pathway Gene Variation and Association with Markers of Subclinical Atherosclerosis in the Diabetes Heart Study

Aims. Genes of the 5-lipoxygenase pathway are compelling candidates for atherosclerosis. We hypothesize that polymorphisms in ALOX12, ALOX15, ALOX5, and ALOX5AP genes are associated with subclinical atherosclerosis in multiple vascular beds. Methods. Families with two or more siblings with type 2 diabetes and their nondiabetic siblings were studied as part of the Diabetes Heart Study (DHS). European American diabetic (n = 828) and nondiabetic (n = 170) siblings were genotyped for SNPs in the ALOX12, ALOX15, ALOX5, and ALOX5AP genes. Subclinical measures of atherosclerosis (IMT, coronary (CorCP), carotid (CarCP) and aortic (AorCP) calcified plaque) were obtained. Results. Associations were observed between ALOX12 with CorCP, ALOX5 with CorCP, AorCP, and IMT, and ALOX5AP with CorCP and CarCP, independent of known epidemiologic risk factors. Further, lipoxygenase pathway SNPs that were associated with measures of atherosclerosis were associated with markers of inflammation (CRP, ICAM-1) and calcification (MGP). Conclusions. Polymorphisms within ALOX12, ALOX5, and ALOX5AP are genetically associated with subclinical atherosclerosis and with biomarkers of disease in families with type 2 diabetes. These results suggest that variants in lipoxygenase pathway genes may have pleiotropic effects on multiple components that determine risk of cardiovascular disease

Looking for interaction: quantitative measurement of research utilization by Dutch local health officials

Background: In the Netherlands, local authorities are required by law to develop local health memoranda, based on epidemiological analyses. The purpose of this study was to assess the actual use of these epidemiological reports by municipal health officials and associated factors that affect this use.Method: Based on a conceptual framework, we designed a questionnaire in which we operationalized instrumental, conceptual, and symbolic use, the interaction between researchers and local health officials, and four clusters of barriers in this interaction process. We conducted an internet survey among 155 Dutch local health officials representing 35% of all Dutch municipalities. By means of multiple regression analyses, we gained insight into the related factors for each of the three types of research utilization.Results: The results show that local health officials use epidemiological research more often in a conceptual than an instrumental or symbolic way. This can be explained by the complexity of the local policy process which is often linked to policies in other areas, and the various policy actors involved. Conceptual use was statistically associated with a presentation given by the epidemiologist during the policy process, the presence of obstructions regarding the report's accessibility, and the local official's personal belief systems and interests originating from different professional values and responsibilities. Instrumental and symbolic use increased with the involvement of local officials in the research process.Conclusions: The results of this study provide a partial solution to understanding and influencing research utilization. The quantitative approach underpins earlier qualitative findings on this topic. The outcomes suggest that RPHS epidemiologists can use different strategies to improve research utilization. 'Blurring the boundaries', and the enhancement of interfaces between epidemiologists and local health officials, like direct interactions into each other's work processes, is expected to create better possibilities for optimizing research use

Precision Medicine in Diabetes: A Consensus Report From the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

The convergence of advances in medical science, human biology, data science, and technology has enabled the generation of new insights into the phenotype known as "diabetes." Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence, and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field, and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment), and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e., monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realize its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site.R01 HD094150/HD/NICHD NIH HHS/United States DP3 DK111906/DK/NIDDK NIH HHS/United States U01 DK105535/DK/NIDDK NIH HHS/United States R01 DK104942/DK/NIDDK NIH HHS/United States U54 DK118612/DK/NIDDK NIH HHS/United States R21 AI142483/AI/NIAID NIH HHS/United States R01 DK122586/DK/NIDDK NIH HHS/United States P30 DK026687/DK/NIDDK NIH HHS/United States WT_/Wellcome Trust/United Kingdom R01 DK052431/DK/NIDDK NIH HHS/United States UL1 TR001873/TR/NCATS NIH HHS/United States R01 DK104351/DK/NIDDK NIH HHS/United Statesaccepted version, submitted versio

The ASCEND-ND trial: study design and participant characteristics

Background: Anaemia is common in chronic kidney disease (CKD), and assessment of the risks and benefits of new therapies is important. Methods: The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3–5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8–10 g/dL, or receiving ESAs with screening Hb of 8–12 g/dL. Participants were randomised to daprodustat or darbepoetin alfa (1:1) in an open- label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28 to 52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials. Results: Overall, 3872 patients were randomised from 39 countries (median age 67 years, 56% female; 56% White, 27% Asian, and 10% Black). Median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and eGFR was 18 mL/min/1.73 m2. Among randomised patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin– angiotensin system blockers, 55% were taking statin and 49% oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials. Conclusion: ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis

Adhesion molecules, endothelin-1 and lung function in seven population-based cohorts

Endothelial function is abnormal in chronic obstructive pulmonary disease (COPD); whether endothelial dysfunction causes COPD is unknown

Collagen-Like Proteins in Pathogenic E. coli Strains

The genome sequences of enterohaemorrhagic E. coli O157:H7 strains show multiple open-reading frames with collagen-like sequences that are absent from the common laboratory strain K-12. These putative collagens are included in prophages embedded in O157:H7 genomes. These prophages carry numerous genes related to strain virulence and have been shown to be inducible and capable of disseminating virulence factors by horizontal gene transfer. We have cloned two collagen-like proteins from E. coli O157:H7 into a laboratory strain and analysed the structure and conformation of the recombinant proteins and several of their constituting domains by a variety of spectroscopic, biophysical, and electron microscopy techniques. We show that these molecules exhibit many of the characteristics of vertebrate collagens, including trimer formation and the presence of a collagen triple helical domain. They also contain a C-terminal trimerization domain, and a trimeric α-helical coiled-coil domain with an unusual amino acid sequence almost completely lacking leucine, valine or isoleucine residues. Intriguingly, these molecules show high thermal stability, with the collagen domain being more stable than those of vertebrate fibrillar collagens, which are much longer and post-translationally modified. Under the electron microscope, collagen-like proteins from E. coli O157:H7 show a dumbbell shape, with two globular domains joined by a hinged stalk. This morphology is consistent with their likely role as trimeric phage side-tail proteins that participate in the attachment of phage particles to E. coli target cells, either directly or through assembly with other phage tail proteins. Thus, collagen-like proteins in enterohaemorrhagic E. coli genomes may have a direct role in the dissemination of virulence-related genes through infection of harmless strains by induced bacteriophages

The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe