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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
NASA NTRS2015

Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray (SI unit for ionizing radiation dosage, i.e. one joule of radiation energy per one kilogram of matter)) to facilitate risk prediction. This risk has considerable uncertainty associated with it, and no acceptable model for projecting degenerative tissue risk is currently available. In particular, risk factors such as obesity, alcohol, and tobacco use can act as confounding factors that contribute to the large uncertainties. The PELs could be violated under certain scenarios, including following a large SPE (solar proton event) or long-term GCR (galactic cosmic ray) exposure. Specifically, for a Mars mission, the accumulated dose is sufficiently high that epidemiology data and preliminary risk estimates suggest a significant risk for cardiovascular disease. Ongoing research in this area is intended to provide the evidence base for accurate risk quantification to determine criticality for extended duration missions. Data specific to the space radiation environment must be compiled to quantify the magnitude of this risk to decrease the uncertainty in current PELs and to determine if additional protection strategies are required. New research results could lead to estimates of cumulative radiation risk from CNS and degenerative tissue diseases that, when combined with the cancer risk, may have major negative impacts on mission design, costs, schedule, and crew selection. The current report amends an earlier report (Human Research Program Requirements Document, HRP-47052, Rev. C, dated Jan 2009) in order to provide an update of evidence since 2009.

Patel, Zarana↗
DOE OSTI2018

Lipidomic insight into cardiovascular diseases

Highlights: • Update on current lipidomic research in cardiovascular diseases. • Lipidomic research's discovery of novel lipid species correlated with cardiovascular risks. • Potential of lipidomics to identify biomarker lipid molecules that predict future cardiovascular events in young patients. Cardiovascular disease is a primary cause of mortality worldwide. Therefore, it is of major interest to identify sensitive molecular markers that predict cardiovascular events and point to therapeutic strategies that will increase lifespans. Dysregulated lipid metabolism is recognized as an established risk factor in cardiovascular diseases. However, it is still largely unknown which specific lipid molecular species reflect cardiovascular risk. In addition, understanding the whole lipidome signature in vascular pathophysiology is challenging. Recent advancements of mass-spectrometry allow researchers to detect each individual lipid species from unbiased small samples. In this review, we update the current research on lipidomic approaches in cardiovascular diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Urinary tungsten and incident cardiovascular disease in the Strong Heart Study: An interaction with urinary molybdenum

Highlights: • Baseline urinary tungsten levels were not associated with cardiovascular disease incidence. • Elevated urinary tungsten was associated with cardiovascular disease in the presence of low urinary molybdenum. • The association between tungsten and cardiovascular disease was inverse at higher molybdenum levels. • Molybdenum may modify the association between tungsten and incident cardiovascular disease. Tungsten (W) interferes with molybdenum (Mo) binding sites and has been associated with prevalent cardiovascular disease (CVD). We evaluated if (1) W exposure is prospectively associated with incident CVD and (2) the association between urinary W levels and incident CVD is modified by urinary Mo levels.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Ecological analysis of associations between groundwater quality and hypertension and cardiovascular disease in rural Saskatchewan, Canada using Bayesian hierarchical models and administrative health data

Highlights: • Hardness and magnesium were associated with decreased risk of cardiovascular disease. • Arsenic concentrations were not associated with the risk of cardiovascular disease. • Summarized water health standards were not associated with cardiovascular disease. Associations between groundwater quality and the prevalence of hypertension and ischemic heart disease were investigated in rural areas of the Canadian province of Saskatchewan. The partially ecological study was analyzed using Bayesian hierarchical models to account for spatial variability in risk. Exposure measures and health outcomes were estimated based on previously collected water quality surveillance data from public water supplies and private wells and administrative health data. Water quality exposures for each study region were estimated by applying geostatistical techniques to arsenic concentrations and principal component (PC) scores. The PC scores summarized groups of parameters measuring either health standards or aesthetic objectives described by the province. Generalized linear mixed models with a log link assessed associations between water quality and observed count of health outcomes relative to the expected value. The Bayesian models contained uncorrelated and spatially correlated random effects for each geographic region. Effect estimates were controlled for sex and age by stratification of case and expected case counts, for smoking by inclusion of sex- and age-specific prevalence of chronic obstructive pulmonary disease as a surrogate covariate, and for education and income by use of census data. There was no evidence for associations between groundwater arsenic concentrations in public or private water supplies and increased risk of hypertension or cardiovascular disease. An increase in the second aesthetic objectives PC score from public supplies was associated with a protective effect against ischemic heart disease. This PC value summarized hardness and magnesium Similarly, an increase in the second aesthetic objectives PC in private supplies was associated with decreased prevalence of hypertension. The results of this study are consistent with others demonstrating a relationship between elevated hardness and magnesium concentrations in drinking water and reduced risk of hypertension and cardiovascular disease. Further investigation is warranted with individual exposure history, particularly with respect to the potential beneficial effect of hard water on the prevalence of hypertension and cardiovascular disease.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Projections for temperature-related years of life lost from cardiovascular diseases in the elderly in a Chinese city with typical subtropical climate

Highlights: • First evidence on temperature-related cardiovascular diseases’ YLL in the elderly. • An important dual problem of climate change and aging was investigated. • Adaptation of the population to global warming was taken into consideration. • Heat-related YLL will increase tremendously even considering 30% adaptation. Extreme temperature is an important risk factor for cardiovascular diseases, and the elderly are particularly vulnerable to temperature variation. Global warming and the increasingly aging population are two major global challenges for human health; thus, an urgent need exists to project the temperature-related cardiovascular disease burden regarding both of the aforementioned factors. We aimed to the project temperature-related burden of cardiovascular diseases using years of life lost (YLL) in the elderly in a Chinese city with typical subtropical climate.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS2017

Cardiovascular Disease Risk in NASA Astronauts Across the Lifespan: Historical Cohort Studies

Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in space flight activities are potentially associated with cardiovascular disease risk factors (e.g., altered dietary and exercise habits, physical and emotional stress, circadian shifts, radiation). Further, astronauts who travel into space multiple times may be at an increased risk across their lifespan. However, comparing the risk of cardiovascular disease in astronauts to other large cohorts is difficult. For example, comparisons between astronauts and large national cohorts, such as the National Health and Nutrition Examination Survey and the National Health Information Survey, are hampered by significant differences in health status between astronauts and the general population, and most of these national studies fail to provide longitudinal data on population health. To address those limitations, NASA's Longitudinal Study of Astronaut Health previously sought to compare the astronauts to a cohort of civil servants employed at the Johnson Space Center. However, differences between the astronauts and civil servants at the beginning of the study, as well as differential follow up, limited the ability to interpret the results. To resolve some of these limitations, two unique cohorts of healthy workers, U.S. Air Force aviators and Cooper Center Longitudinal Study participants, have been identified as potential comparison populations for the astronaut corps. The Air Force cohort was chosen due to similarities in health at selection, screening, and some occupational exposures that Air Force aviators endure, many of which mirror that of the astronaut corps. The Cooper Clinic cohort, a generally healthy prevention cohort, was chosen for the vast array of clinical cardiovascular measures collected in a longitudinal manner complementary to those collected on astronauts, for a large number of subjects since 1971. The purpose of this study is to understand the incidence of cardiovascular disease outcomes and risk factors in the astronaut corps and determine whether the rates of disease are different than these two cohorts. The research questions are: 1. Are there differences in the incidence of CVD outcomes (MI, revascularization, and stroke) between each cohort and the NASA Astronaut cohort? 2. Are there differences in the incidence of CVD risks (hypertension, hyperlipidemia, arrhythmias, and diabetes) between each cohort and the NASA Astronaut cohort? 3. Are there differences between each cohort and the NASA Astronaut cohort in how CVD risk factors (e.g., lipids, behaviors) change across time? Collectively, results from these studies will enhance our understanding of how cardiovascular disease outcomes and risk factors change across time in astronauts compared to other longitudinally-studied healthy cohorts and determine if there are interactions between or additive effects of the occupational health effects of spaceflight exposure and normal aging.

Charvat, Jacqueline M.↗
NASA NTRS2018

Cardiovascular Disease Outcomes Among the NASA Astronaut Corps

BACKGROUND: Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in spaceflight activities are associated with changes in the cardiovascular system such as decreased carotid artery distensibility and decreased ventricular mass which may lead to an increased risk of cardiovascular disease. Additionally, astronauts who travel into space multiple times or for longer durations may be at an increased risk across their lifespan. To that end, the purpose of this study was to determine the incidence of common cardiovascular disease (CVD) outcomes among the NASA astronaut corps during their active career and through retirement. METHODS: Cardiovascular disease outcomes were defined as reports of any of the following: myocardial infarction (MI), revascularization procedures (coronary artery bypass graft surgery [CABG] or percutaneous coronary intervention [PCI]), hypertension, stroke or transient ischemic attack [TIA], heart failure, or total CVD (as defined by the AHA - combined outcome of MI, Angina Pectoris, heart failure, stroke, and hypertension). Each outcome was identified individually from review of NASA's Electronic Medical Record (EMR), EKG reports, and death certificates using ICD-9 codes as well as string searches of physician notes of astronaut exams that occurred between 1959 and 2016. RESULTS: Of 338 NASA astronauts selected as of 2016, 9 reported an MI, 12 reported a revascularization procedure, (7 PCI and 5 CABG), 4 reported Angina (without MI), 5 reported heart failure, 9 reported stroke/TIA, and 96 reported hypertension. Total CVD was reported in 105 astronauts. No astronaut who had an MI or revascularization procedure flew a spaceflight mission following the event. All MI, revascularization, and stroke events occurred in male astronauts. When reviewing astronaut ECG reports, abnormal ECG reports were found in only 8% of records (n=430) and mainly among retired astronauts (82%), with marked sinus bradycardia being the reason for the abnormal classification.

Charvat, Jacqueline M.↗
NASA NTRSDate not supplied

Cardiovascular Disease Spaceflight Equivalent Stressor Risk Modeling Project

The risk of cardiovascular disease (CVD) may be exacerbated by spaceflight hazards including radiation, isolation, distance from the Earth, gravity fields, and closed or confined environments. This project aims to use epidemiologic, scientific research evidence of surrogate spaceflight stressors on analog populations in terrestrial cohorts to model CVD risk for spaceflight conditions. To date, Dr. Butler and the multi-disciplinary CVD Spaceflight Equivalent Stressors (SES) team have conducted a formal systematic literature review on the risk of sleep loss as it relates to cardiovascular disease outcomes and are currently working on a meta-analysis for the data gathered from nearly 100 studies and their various CVD outcomes. The research will continue to examine other surrogate stressors in depth, such as altered gravity, radiation exposure, noise, etc. with cardiovascular outcomes to determine an overall combined spaceflight risk for long term future missions such as Artemis Lunar and Mars missions.

Jennifer Butler↗
NASA NTRS2019

Simulated Weightlessness Alters Cardiomyocyte Structure and Transcriptional Regulation of Mediators Related to Immunity and Cardiovascular Disease

Spaceflight and the ensuing fluid shifts, together with an overall reduction in physical activity, lead to acute and latent effects on the cardiovascular system. This current study makes use of the rodent hindlimb unloading (HU) model to determine how factors such as sex, age, and duration of exposure impact cardiac responses to weightlessness. We hypothesize that extended exposure to simulated weightlessness and the ensuing recovery alters cardiac structure and expression of select genes, including those involved in redox signaling which together, negatively impact long-term cardiac tissue health. To begin to test this hypothesis, male and female rats underwent HU at various durations up to 90 days, with a subset reambulated after 90 days of HU. Physiological stress or contractility changes lead to alterations in ventricular cardiomyocyte size and ventricular wall thickness to adapt to greater functional demand and mitigate mechanical stress to ventricular tissue; under certain conditions, these changes also may mark progression to cardiac failure. Hence, left ventricular cardiomyocyte size (cardiomyocyte cross sectional area, CSA) was quantified to determine if HU leads to structural adaptation responses in cardiac tissue and if age and sex had any impact on this outcome. Cardiomyocyte CSA of older males (9 months) were altered by HU in a time-dependent manner, where HU led to decreases in CSA at 14 days and increases at 90 days. In contrast, younger males (3 months) did not show any changes at day 14 of HU. CSA of females (3 months) was increased in response to short-term HU (14 days) suggesting sex-dependence of structural changes. In older HU males, cardiomyocyte CSA was comparable to controls after 90 days of re-ambulation. Levels of the DNA oxidative damage marker, 8-hydroxydeoxyguanosine (8-OHdG) were greater in left ventricular tissue of females that underwent HU compared to sex-matched controls, while there were no such differences in older or younger males. To gain insight into the signals that drive cardiac adaptations to HU, global transcriptomic analysis (RNAseq) was performed on left ventricular tissue of older males that underwent 14 days of HU. Short-term simulated weightlessness led to differential expression of genes involved in immune and pro-inflammatory signaling. A subset of these genes play a role in autoimmune and cardiovascular disease and are targets of current drugs used to treat bradycardia, hypertension, atherosclerosis and rheumatoid arthritis, amongst others. Oxidative damage/redox signaling pathways were not enriched at the timepoint tested in older males. Since young females displayed greater oxidative damage to DNA, activation of oxidative stress responses at earlier or later time points cannot be ruled out. In summary, simulated weightlessness in adult rats caused changes in cardiomyocyte structure in a sex and age-dependent manner, and the transcriptional regulation of key mediators of immunity and cardiovascular disease, meriting further study to define cardiac risks for interplanetary travel of human crew. Our findings also confirm the value of the rat HU model for cardiac health and countermeasure research.

Tahimic, Candice↗
DOE OSTI2023

Targeted curation of the gut microbial gene content modulating human cardiovascular disease

Despite the promise of the gut microbiome to predict human health, few studies expose the molecular-scale processes underpinning such forecasts. We mined over 200,000 gut-derived genomes from cultivated and uncultivated microbial lineages to inventory the gut microorganisms and their gene content that control trimethylamine-induced cardiovascular disease. We assigned an atherosclerotic profile to the 6,341 microbial genomes that encoded metabolisms associated with heart disease, creating the Methylated Amine Gene Inventory of Catabolism database (MAGICdb). From microbiome gene expression data sets, we demonstrate that MAGICdb enhanced the recovery of disease-relevant genes and identified the most active microorganisms, unveiling future therapeutic targets. From the feces of healthy and diseased subjects, we show that MAGICdb predicted cardiovascular disease status as effectively as traditional lipid blood tests. This functional microbiome catalog is a public, exploitable resource, designed to enable a new era of microbiota-based therapeutics and diagnostics

metatranscriptomics↗
NASA NTRSDate not supplied

Outcomes of a NASA Human Research Program’s (HRP) Space Radiation Element-sponsored Mini-Technical Interchange Meeting/workshop on Cardiovascular Disease Risk from Space Radiation

The NASA HRP’s Space Radiation Element funds research to characterize and mitigate adverse health outcomes from space radiation including cardiovascular risks to astronauts to enable deep space exploration and sustained human presence in space. Non-cancer effects such as damage to the cardiovascular system have been observed at clinically relevant high doses of ionizing radiation. However, an association between lower doses and risk of cardiovascular disease (CVD) remains somewhat controversial, especially in relation to the existence of low dose thresholds, radiation quality, and dose-rate effects, as well as gaps in characterizing the mechanisms and major pathways of disease. To facilitate, accelerate, and incubate new ideas to characterize and mitigate this risk, the Element is planning to organize a series of miniature technical interchange meetings (Tiny-TIMs) to provide a venue for HRP-funded investigators and thought leaders to present ongoing work and engage in open discussion on presented results, limitations of current approaches, incorporating better experimental strategies, model systems, etc. The initial Tiny-TIM held during the NASA HRP Investigators’ Workshop earlier this year – Upping the ante on characterizing and mitigating cardiovascular disease risk from space radiation exposure – aimed to stimulate discussion on the current state of scientific knowledge of CVD risk from space-like radiation exposure. The Tiny-TIM consisted of two 90-minute sessions; the first session concentrated on current knowledge of CVD risk from space radiation and the second session focused on innovative ideas, newer approaches, and techniques to accelerate research. The second session was followed by an open spirited discussion amongst peers on the current issues impeding the characterization of CVD risk from space radiation. The Element facilitated the discussion using a set of pressing open questions/gaps in knowledge that need to be addressed by the scientific community. The outcomes of the Tiny-TIM will be presented along with a plan of proposed future workshops and other initiatives of the Space Radiation Element.

Janapriya Saha↗
NASA NTRS2018

Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts: Space for Exploration

Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to establish whether there is evidence for excess cardiovascular disease or cancer mortality in an early NASA astronaut cohort and determine if a correlation exists between space radiation exposure and mortality.

Elgart, S. R.↗
DOE OSTI2019

New Insights in the Control of Low-Density Lipoprotein Cholesterol to Prevent Cardiovascular Disease

Purpose of Review: Low-density lipoprotein cholesterol (LDL-C) is one major cause of cardiovascular disease (CVD). In this review, we discuss current developments in the understanding of LDL-C as lifelong risk factor, treatment targets, and emerging approaches to reduce cardiovascular risk by lowering LDL-C. Recent Findings: Recent evidence underscores the importance of LDL-C lowering in CVD prevention by mechanisms that increase the hepatic clearance of apolipoprotein B-containing lipoproteins from the plasma. Mendelian randomization studies provided evidence on both safety and efficacy of lower LDL-C in the long term. For young individuals, metrics other than 10-year CVD risk are required. Despite this evidence, LDL-C treatment target attainment is poor. Novel approaches are therefore needed. These include individualized strategies and new LDL-C-lowering pharmaceuticals. Summary: Early, long-term treatment with LDL-C-lowering therapies has the potential to markedly reduce CVD incidence and progression. Future research should aim to identify patient characteristics that enable physicians to tailor therapy to each individual patient.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
NASA NTRSDate not supplied

Outcomes of a Mini Technical Interchange Meeting Concerning the Risk of Cardiovascular Disease from Exposure to Space Radiation

The NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation to enable deep space exploration and sustained human presence in space. Damage to the cardiovascular system has been observed after exposure to clinically relevant doses of ionizing radiation. However, an association between lower radiation doses and cardiovascular disease (CVD) remains controversial, and questions pertaining to dose thresholds, radiation quality and dose-rate effects, and gaps in characterizing the mechanisms and major pathways of CVD remain. To solicit new ideas for characterizing and mitigating this risk, the SRE is organizing a series of miniature technical interchange meeting (Tiny-TIM) that provide a venue for HRP-funded investigators and thought leaders to present ongoing work and engage in open discussion on relevant topics. The initial Tiny-TIM: Upping the Ante on Characterizing and Mitigating Cardiovascular Disease Risk from Space Radiation Exposure, held at the NASA HRP Investigators’ Workshop (IWS) earlier this year, consisted of two 90-minute sessions; the first focused on current knowledge of CVD risk from space radiation exposure, and the second focused on innovative ideas, and newer approaches and techniques to accelerate research. The second session was followed by an open, spirited discussion amongst peers on the current issues impeding the characterization of CVD risk. SRE leadership facilitated the discussion using a set of pressing questions and gaps in knowledge that need to be addressed by the scientific community. This poster presents the outcomes of the Tiny-TIM, along with proposed future workshops and the SRE’s other initiatives.

Janapriya Saha↗
DOE OSTI2018

Whole blood mercury and the risk of cardiovascular disease among the Greenlandic population

Highlights: • The Greenlandic Inuit have very high levels of whole blood mercury. • Whole blood mercury was not associated with incident CVD in Greenland. • CVD was associated with traditional risk factors such as HbA{sub 1c} and physical activity. Studies have found mercury to be associated with cardiovascular disease (CVD), however, primarily in populations with low exposure. The highest levels, and variations in the levels, of whole blood mercury (WBM) worldwide have been found in Greenland. We prospectively assessed the association between WBM and the risk of developing CVD in the Greenlandic population.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Simulated Microgravity Alters Gene Regulation Linked to Immunity and Cardiovascular Disease

Microgravity exposure induces a cephalad fluid shift and an overall reduction in physical activity levels which can lead to cardiovascular deconditioning in the absence of countermeasures. Future spaceflight missions will expose crew to extended periods of microgravity among other stressors, the effects of which on cardiovascular health are not fully known. In this study, we determined cardiac responses to extended microgravity exposure using the rat hindlimb unloading (HU) model. We hypothesized that exposure to prolonged simulated microgravity and subsequent recovery would lead to increased oxidative damage and altered expression of genes involved in the oxidative response. To test this hypothesis, we examined hearts of male (three and nine months of age) and female (3 months of age) Long–Evans rats that underwent HU for various durations up to 90 days and reambulated up to 90 days post-HU. Results indicate sex-dependent changes in oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) and antioxidant gene expression in left ventricular tissue. Three-month-old females displayed elevated 8-OHdG levels after 14 days of HU while age-matched males did not. In nine-month-old males, there were no differences in 8-OHdG levels between HU and normally loaded control males at any of the timepoints tested following HU. RNAseq analysis of left ventricular tissue from nine-month-old males after 14 days of HU revealed upregulation of pathways involved in pro-inflammatory signaling, immune cell activation and differential expression of genes associated with cardiovascular disease progression. Taken together, these findings provide a rationale for targeting antioxidant and immune pathways and that sex differences should be taken into account in the development of countermeasures to maintain cardiovascular health in space.

Genetics & Heredity↗
NASA NTRSDate not supplied

Utility of Terrestrial Cardiovascular Disease Data in Astronaut Radiation Risk Assessment – A Case Study Showing Increased Risk with Clonal Hematopoiesis of Indeterminate Potential

Cardiovascular disease (CVD) is associated with high doses of radiation and is are cognized health risk for astronauts on multiple or long duration exploration missions to the Moon or Mars. Currently, radiation risk assessment is based on background population disease rates and does not consider individual risk factors that may modify analysis, especially at lower radiation doses.

Zarana S Patel↗