Layered Metals Fabrication Technology Development for Support of Lunar Exploration at NASA/MSFC

NASA's human exploration initiative poses great opportunity and risk for missions to the Moon and beyond. In support of these missions, engineers and scientists at the Marshall Space Flight Center are developing technologies for ground-based and in-situ fabrication capabilities utilizing provisioned and locally-refined materials. Development efforts are pushing state-of-the art fabrication technologies to support habitat structure development, tools and mechanical part fabrication, as well as repair and replacement of ground support and space mission hardware such as life support items, launch vehicle components and crew exercise equipment. This paper addresses current fabrication technologies relative to meeting targeted capabilities, near term advancement goals, and process certification of fabrication methods

The Yellowstone Hotspot, Greater Yellowstone Ecosystem, and Human Geography

Active geologic processes associated with the Yellowstone hotspot are fundamental in shaping the landscapes of the greater Yellowstone ecosystem (GYE), a high volcanic plateau flanked by a crescent of still higher mountainous terrain. The processes associated with the Yellowstone hotspot are volcanism, faulting, and uplift and are observed in the geology at the surface. We attribute the driving forces responsible for the northeastward progression of these processes to a thermal plume rising through the Earth’s mantle into the base of the southwest-moving North American plate. This progression began 16 million years ago (Ma) near the Nevada-Oregon border and arrived at Yellowstone about 2 Ma. Before arrival of the hotspot, an older landscape existed, particularly mountains created during the Laramide orogeny about 70–50 Ma and volcanic terrain formed by Absaroka andesitic volcanism mostly between 50–45 Ma. These landscapes were more muted than the present, hotspot-modified landscape because the Laramide-age mountains had worn down and an erosion surface of low relief had developed on the Absaroka volcanic terrain. The Yellowstone Plateau was built by hotspot volcanism of rhyolitic lavas and caldera-forming rhyolite tuffs (ignimbrites). Streams eroding back into the edges of this plateau have created scenic waterfalls and canyons such as the Grand Canyon of the Yellowstone and Lewis Canyon. Rhyolite is poor in plant nutrients and forms sandy, well-drained soils that support the monotonous, fire-adapted lodgepole pine forests of the Yellowstone Plateau. Non-rhyolitic rocks surround this plateau and sustain more varied vegetation, including spruce, fir, and whitebark pine forests broken by grassy meadows. Heat from the hotspot rises upward and drives Yellowstone’s famed geysers, hot springs, and mudpots. These thermal waters are home to specialized, primitive ecosystems, rich in algae and bacteria. The rock alteration associated with hydrothermal systems creates the bright colors of Yellowstone’s Grand Canyon. Basin-and-range-style faulting has accompanied migration of the hotspot to Yellowstone and formed the linear mountains and valleys that occur north and south of the hotspot track, which is the present-day eastern Snake River Plain. High rates of basin-and-range faulting occurred adjacent to the migrating Yellowstone hotspot, creating distinctive landscapes within the GYE such as the Teton Range/Jackson Hole, with characteristic rugged, forested ranges and adjacent flat-floored grassy valleys. The difference in altitude between the mountains and valleys provides a topographic gradient in which vegetation maturation advances with altitude; animal-migration patterns also follow this trend. The valleys provide natural meadows, agricultural land, town sites, and corridors for roads. Uplift of the GYE by as much as 1 km (3,000 ft) during the last 5 million years has resulted in ongoing erosion of deep, steep-walled valleys. Many prominent ecological characteristics of Yellowstone derive from this hotspot-induced uplift, including the moderate- to high- altitude terrain and associated cool temperatures and deep snowfall. Modern and Pleistocene climate and associated vegetation patterns strongly relate to the topography created by the hotspot and its track along the eastern Snake River Plain. Winter air masses from the moist northern Pacific Ocean traverse the topographic low of the Snake River Plain to where orographic rise onto the Yellowstone Plateau and adjacent mountains produces deep snow. A winter precipitation shadow forms on the lee (eastern) sides of the GYE. During Pleistocene glacial times, this moisture conduit provided by the hotspot-track-produced ice-age glaciers that covered the core of the present GYE. These glaciers sculpted bedrock and produced glacial moraines that are both forested and unforested, sand and gravel of ice-marginal streams and outwash gravels that are commonly covered with sagebrush-grassland, and silty lake sediments that are commonly covered by lush grassland such as Hayden Valley. The effects of the Yellowstone hotspot also profoundly shaped the human history in the GYE. Uplift associated with the hotspot elevates the GYE to form the Continental Divide, and streams drain radially outward like spokes from a hub. Inhabitants of the GYE 12,000–10,000 years ago, as well as more recent inhabitants, followed the seasonal green-up of plants and migrating animals up into the mountain areas. During European immigration, people settled around Yellowstone in the lower parts of the drainages and established roads, irrigation systems, and cultural associations. The core Yellowstone highland is too harsh for agriculture and inhospitable to people in the winter. Beyond this core, urban and rural communities exist in valleys and are separated by upland areas. The partitioning inhibits any physical connection of communities, which in turn complicates pursuit of common interests across the whole GYE. Settlements thus geographically isolated evolved as diverse, independent communities

Percutaneous coronary intervention versus medical therapy in patients with angina and grey-zone fractional flow reserve values: a randomised clinical trial

Introduction: There is conflicting evidence regarding the benefits of percutaneous coronary intervention (PCI) in patients with grey zone fractional flow reserve (GZFFR artery) values (0.75–0.80). The prevalence of ischaemia is unknown. We wished to define the prevalence of ischaemia in GZFFR artery and assess whether PCI is superior to optimal medical therapy (OMT) for angina control. Methods: We enrolled 104 patients with angina with 1:1 randomisation to PCI or OMT. The artery was interrogated with a Doppler flow/pressure wire. Patients underwent Magnetic Resonance Imaging (MRI) with follow-up at 3 and 12 months. The primary outcome was angina status at 3 months using the Seattle Angina Questionnaire (SAQ). Results: 104 patients (age 60±9 years), 79 (76%) males and 79 (76%) Left Anterior Descending (LAD) stenoses were randomised. Coronary physiology and SAQ were similar. Of 98 patients with stress perfusion MRI data, 17 (17%) had abnormal perfusion (≥2 segments with ≥25% ischaemia or ≥1 segment with ≥50% ischaemia) in the target GZFFR artery. Of 89 patients with invasive physiology data, 26 (28%) had coronary flow velocity reserve <2.0 in the target GZFFR artery. After 3 months of follow-up, compared with patients treated with OMT only, patients treated by PCI and OMT had greater improvements in SAQ angina frequency (21 (28) vs 10 (23); p=0.026) and quality of life (24 (26) vs 11 (24); p=0.008) though these differences were no longer significant at 12 months. Conclusions: Non-invasive evidence of major ischaemia is uncommon in patients with GZFFR artery. Compared with OMT alone, patients randomised to undergo PCI reported improved symptoms after 3 months but these differences were no longer significant after 12 months

Reframing Kurtz’s Painting: Colonial Legacies and Minority Rights in Ethnically Divided Societies

Minority rights constitute some of the most normatively and economically important human rights. Although the political science and legal literatures have proffered a number of constitutional and institutional design solutions to address the protection of minority rights, these solutions are characterized by a noticeable neglect of, and lack of sensitivity to, historical processes. This Article addresses that gap in the literature by developing a causal argument that explains diverging practices of minority rights protections as functions of colonial governments’ variegated institutional practices with respect to particular ethnic groups. Specifically, this Article argues that in instances where colonial governments politicize and institutionalize ethnic hegemony in the pre-independence period, an institutional legacy is created that leads to lower levels of minority rights protections. Conversely, a uniform treatment and depoliticization of ethnicity prior to independence ultimately minimizes ethnic cleavages post-independence and consequently causes higher levels of minority rights protections. Through a highly structured comparative historical analysis of Botswana and Ghana, this Article builds on a new and exciting research agenda that focuses on the role of long-term historio-structural and institutional influences on human rights performance and makes important empirical contributions by eschewing traditional methodologies that focus on single case studies that are largely descriptive in their analyses. Ultimately, this Article highlights both the strength of a historical approach to understanding current variations in minority rights protections and the varied institutional responses within a specific colonial government

Rationale and design of the Coronary Microvascular Angina Cardiac Magnetic Resonance imaging (CorCMR) diagnostic study: the CorMicA CMR sub-study

Introduction: Angina with no obstructive coronary artery disease (ANOCA) is a common syndrome with unmet clinical needs. Microvascular and vasospastic angina are relevant but may not be diagnosed without measuring coronary vascular function. The relationship between cardiovascular magnetic resonance (CMR)-derived myocardial blood flow (MBF) and reference invasive coronary function tests is uncertain. We hypothesise that multiparametric CMR assessment will be clinically useful in the ANOCA diagnostic pathway. Methods/analysis: The Stratified Medical Therapy Using Invasive Coronary Function Testing In Angina (CorMicA) trial is a prospective, blinded, randomised, sham-controlled study comparing two management approaches in patients with ANOCA. We aim to recruit consecutive patients with stable angina undergoing elective invasive coronary angiography. Eligible patients with ANOCA (n=150) will be randomised to invasive coronary artery function-guided diagnosis and treatment (intervention group) or not (control group). Based on these test results, patients will be stratified into disease endotypes: microvascular angina, vasospastic angina, mixed microvascular/vasospastic angina, obstructive epicardial coronary artery disease and non-cardiac chest pain. After randomisation in CorMicA, subjects will be invited to participate in the Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) substudy. Patients will undergo multiparametric CMR and have assessments of MBF (using a novel pixel-wise fully quantitative method), left ventricular function and mass, and tissue characterisation (T1 mapping and late gadolinium enhancement imaging). Abnormalities of myocardial perfusion and associations between MBF and invasive coronary artery function tests will be assessed. The CorCMR substudy represents the largest cohort of ANOCA patients with paired multiparametric CMR and comprehensive invasive coronary vascular function tests. Ethics/dissemination: The CorMicA trial and CorCMR substudy have UK REC approval (ref.16/WS/0192). Trial registration number: NCT03193294

Displacement encoding with stimulated echoes enables the identification of infarct transmurality early postmyocardial infarction

Background Segmental extent of infarction assessed by late gadolinium enhancement (LGE) imaging early post‐ST‐segment elevation myocardial infarction (STEMI) has utility in predicting left ventricular functional recovery. Hypothesis: We hypothesized that segmental circumferential strain with displacement encoding with stimulated echoes (DENSE) would be a stronger predictor of infarct transmurality than feature‐tracking strain, and noninferior to extracellular volume fraction (ECV). Study Type: Prospective. Population: Fifty participants (mean ± SD, 59 ± 9 years, 40 [80%] male) underwent cardiac MRI on day 1 post‐STEMI. Field‐Strength/Sequences: 1.5T/cine, DENSE , T1 mapping, ECV , LGE. Assessment Two observers assessed segmental percentage LGE extent, presence of microvascular obstruction (MVO), circumferential and radial strain with DENSE and feature‐tracking, T1 relaxation times, and ECV. Statistical Tests: Normality was tested using the Shapiro–Wilk test. Skewed distributions were analyzed utilizing Mann–Whitney or Kruskal–Wallis tests and normal distributed data using independent t ‐tests. Diagnostic cutoff values were identified using the Youden index. The difference in area under the curve was compared using the z‐statistic. Results: Segmental circumferential strain with DENSE was associated with the extent of infarction ≥50% (AUC [95% CI], cutoff value = 0.9 [0.8, 0.9], −10%) similar to ECV (AUC = 0.8 [0.8, 0.9], 37%) (P = 0.117) and superior to feature‐tracking circumferential strain (AUC = 0.7[0.7, 0.8], −19%) (P  < 0.05). For the detection of segmental infarction ≥75%, circumferential strain with DENSE (AUC = 0.9 [0.8, 0.9], −10%) was noninferior to ECV (AUC = 0.8 [0.7, 0.9], 42%) (P = 0.132) and superior to feature‐tracking (AUC = 0.7 [0.7, 0.8], −13%) (P  < 0.05). For MVO detection, circumferential strain with DENSE (AUC = 0.8 [0.8, 0.9], −12%) was superior to ECV (AUC = 0.8 [0.7, 0.8] 34%) (P  < 0.05) and feature‐tracking (AUC = 0.7 [0.6, 0.7] −21%) (P  < 0.05). Data Conclusion: Circumferential strain with DENSE is a functional measure of infarct severity and may remove the need for gadolinium contrast agents in some circumstances. Level of Evidence: 2 Technical Efficacy Stage:

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age

<p>Abstract</p> <p>Background</p> <p>In <it>Plasmodium falciparum</it>-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.</p> <p>Methods</p> <p>Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay.</p> <p>Results</p> <p>The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment.</p> <p>Conclusion</p> <p>The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.</p