The Michelson Interferometer for Global High-resolution Thermospheric Imaging (MIGHTI) instrument was built for launch and operation on the NASA Ionospheric Connection Explorer (ICON) mission. The ...instrument was designed to measure thermospheric horizontal wind velocity profiles and thermospheric temperature in altitude regions between 90 km and 300 km, during day and night. For the wind measurements it uses two perpendicular fields of view pointed at the Earth’s limb, observing the Doppler shift of the atomic oxygen red and green lines at 630.0 nm and 557.7 nm wavelength. The wavelength shift is measured using field-widened, temperature compensated Doppler Asymmetric Spatial Heterodyne (DASH) spectrometers, employing low order échelle gratings operating at two different orders for the different atmospheric lines. The temperature measurement is accomplished by a multichannel photometric measurement of the spectral shape of the molecular oxygen A-band around 762 nm wavelength. For each field of view, the signals of the two oxygen lines and the A-band are detected on different regions of a single, cooled, frame transfer charge coupled device (CCD) detector. On-board calibration sources are used to periodically quantify thermal drifts, simultaneously with observing the atmosphere. The MIGHTI requirements, the resulting instrument design and the calibration are described.
Marine coastal ecosystems, commonly referred to as blue ecosystems, provide valuable services to society but are under increasing threat worldwide due to a variety of drivers, including ...eutrophication, development, land‐use change, land reclamation, and climate change. Ecological restoration is sometimes necessary to facilitate recovery in coastal ecosystems. Blue restoration (i.e., in marine coastal systems) is a developing field, and projects to date have been small scale and expensive, leading to the perception that restoration may not be economically viable. We conducted a global cost–benefit analysis to determine the net benefits of restoring coral reef, mangrove, saltmarsh, and seagrass ecosystems, where the benefit is defined as the monetary value of ecosystem services. We estimated costs from published restoration case studies and used an adjusted‐value‐transfer method to assign benefit values to these case studies. Benefit values were estimated as the monetary value provided by ecosystem services of the restored habitats. Benefits outweighed costs (i.e., there were positive net benefits) for restoration of all blue ecosystems. Mean benefit:cost ratios for ecosystem restoration were eight to 10 times higher than prior studies of coral reef and seagrass restoration, most likely due to the more recent lower cost estimates we used. Among ecosystems, saltmarsh had the greatest net benefits followed by mangrove; coral reef and seagrass ecosystems had lower net benefits. In general, restoration in nations with middle incomes had higher (eight times higher in coral reefs and 40 times higher in mangroves) net benefits than those with high incomes. Within an ecosystem type, net benefit varied with restoration technique (coral reef and saltmarsh), ecosystem service produced (mangrove and saltmarsh), and project duration (seagrass). These results challenge the perceptions of the low economic viability of blue restoration and should encourage further targeted investment in this field.
Análisis de Rentabilidad Espacial de la Restauración Azul y de los Factores Determinantes del Beneficio Neto Mundial
Resumen
Los ecosistemas costeros marinos, llamados comúnmente ecosistemas azules, proporcionan servicios valiosos para la sociedad, pero se encuentran bajo una amenaza creciente a nivel mundial causada por una variedad de determinantes, incluyendo la eutrofización, el desarrollo, el cambio en el uso de suelo, la reclamación de tierra y el cambio climático. Algunas veces se necesita de la restauración ecológica para facilitar la recuperación en los ecosistemas costeros. La restauración azul (es decir, en los sistemas costeros marinos) es un campo en desarrollo, con proyectos que a la fecha han sido a pequeña escala y costosos, lo que resulta en la percepción de que la restauración puede no ser viable económicamente. Realizamos un análisis de rentabilidad mundial para determinar los beneficios netos de la restauración de ecosistemas de arrecife de coral, manglar, marisma y pastos marinos en donde el beneficio está definido como el valor monetario de los servicios ambientales. Estimamos los costos a partir de estudios de caso de restauración publicados y usamos un método de transferencia de valor ajustado para asignar los valores de beneficio a estos estudios de caso. Los valores de los beneficios fueron estimados como el valor monetario proporcionado por los servicios ambientales de los hábitats restaurados. Los beneficios superaron los costos (es decir, fueron beneficios netos positivos) de la restauración de todos los ecosistemas azules. El beneficio promedio consistió en que la proporción de costos para la restauración del ecosistema fue 8‐10 veces mayor que en los estudios anteriores de la restauración de los arrecifes de coral y los pastos marinos, probablemente debido a que usamos estimaciones de costo más bajas. Entre los ecosistemas, las marismas tuvieron los mayores beneficios netos seguidos por los manglares; los arrecifes de coral y los pastos marinos tuvieron los beneficios netos más bajos. En general, la restauración en los países con niveles medios de ingreso tuvo más beneficios netos (ocho veces más en los arrecifes de coral y 40 veces más en los manglares) que aquellos países con niveles altos de ingreso. En cuanto al tipo de ecosistema, el beneficio neto varió de acuerdo con la técnica de restauración (arrecife de coral y marisma), servicio ambiental producido (manglar y marisma) y duración del proyecto (pastos marinos). Estos resultados desafían las percepciones de la baja viabilidad económica que tiene la restauración azul y deberían fomentar una mayor inversión focalizada en este campo.
Article impact statement: Blue restoration produces net benefits for all ecosystems assessed. Net benefits are driven by technique, duration, and ecosystem services.
Genome-wide DNA methylation (DNAm) profiling has allowed for the development of molecular predictors for a multitude of traits and diseases. Such predictors may be more accurate than the ...self-reported phenotypes and could have clinical applications.
Here, penalized regression models are used to develop DNAm predictors for ten modifiable health and lifestyle factors in a cohort of 5087 individuals. Using an independent test cohort comprising 895 individuals, the proportion of phenotypic variance explained in each trait is examined for DNAm-based and genetic predictors. Receiver operator characteristic curves are generated to investigate the predictive performance of DNAm-based predictors, using dichotomized phenotypes. The relationship between DNAm scores and all-cause mortality (n = 212 events) is assessed via Cox proportional hazards models. DNAm predictors for smoking, alcohol, education, and waist-to-hip ratio are shown to predict mortality in multivariate models. The predictors show moderate discrimination of obesity, alcohol consumption, and HDL cholesterol. There is excellent discrimination of current smoking status, poorer discrimination of college-educated individuals and those with high total cholesterol, LDL with remnant cholesterol, and total:HDL cholesterol ratios.
DNAm predictors correlate with lifestyle factors that are associated with health and mortality. They may supplement DNAm-based predictors of age to identify the lifestyle profiles of individuals and predict disease risk.
Traditionally, patient risk scoring is done by evaluating vital signs and clinical severity scores with clinical intuition. Urinary biomarkers can add objectivity to these models to make risk ...prediction more accurate. We used metabolomics to identify prognostic urinary biomarkers of mortality or need for renal replacement therapy (RRT). Additionally, we assessed acute kidney injury (AKI) diagnosis, injury severity score (ISS), and AKI stage.
Urine samples (n = 82) from a previous study of combat casualties were evaluated using proton nuclear magnetic resonance (
H-NMR) spectroscopy. Chenomx software was used to identify and quantify urinary metabolites. Metabolite concentrations were normalized by urine output, autoscaled, and log-transformed. Partial least squares discriminant analysis (PLS-DA) and statistical analysis were performed. Receiver operating characteristic (ROC) curves were used to assess prognostic utility of biomarkers for mortality and RRT.
Eighty-four (84) metabolites were identified and quantified in each urine sample. Of these, 11 were identified as drugs or drug metabolites and excluded. The PLS-DA models for ISS and AKI diagnosis did not have acceptable model statistics. Therefore, only mortality/RRT and AKI stage were analyzed further. Of 73 analyzed metabolites, 9 were significantly associated with mortality/RRT (p < 0.05) and 11 were significantly associated with AKI stage (p < 0.05). 1-Methylnicotinamide was the only metabolite to be significantly associated (p < 0.05) with all outcomes and was significantly higher (p < 0.05) in patients with adverse outcomes. Elevated lactate and 1-methylnicotinamide levels were associated with higher AKI stage and mortality and RRT, whereas elevated glycine levels were associated with patients who survived and did not require RRT, or had less severe AKI. ROC curves for each of these metabolites and the combined panel had good predictive value (lactate AUC = 0.901, 1-methylnicotinamide AUC = 0.864, glycine AUC = 0.735, panel AUC = 0.858).
We identified urinary metabolites associated with AKI stage and the primary outcome of mortality or need for RRT. Lactate, 1-methylnicotinamide, and glycine may be used as a panel of predictive biomarkers for mortality and RRT. 1-Methylnicotinamide is a novel biomarker associated with adverse outcomes. Additional studies are necessary to determine how these metabolites can be utilized in clinically-relevant risk prediction models.
Radiotherapy is a major part in the treatment of most common cancers, but many patients experience local recurrence with metastatic disease. In evaluating response biomarkers, we found that low doses ...of fractionated radiotherapy led to PD-L1 upregulation on tumor cells in a variety of syngeneic mouse models of cancer. Notably, fractionated radiotherapy delivered in combination with αPD-1 or αPD-L1 mAbs generated efficacious CD8(+) T-cell responses that improved local tumor control, long-term survival, and protection against tumor rechallenge. These favorable outcomes were associated with induction of a tumor antigen-specific memory immune response. Mechanistic investigations showed that IFNγ produced by CD8(+) T cells was responsible for mediating PD-L1 upregulation on tumor cells after delivery of fractionated radiotherapy. Scheduling of anti-PD-L1 mAb was important for therapeutic outcome, with concomitant but not sequential administration with fractionated radiotherapy required to improve survival. Taken together, our results reveal the mechanistic basis for an adaptive response by tumor cells that mediates resistance to fractionated radiotherapy and its treatment failure. With attention to scheduling, combination immunoradiotherapy with radiotherapy and PD-1/PD-L1 signaling blockade may offer an immediate strategy for clinical evaluation to improve treatment outcomes.
Background Acute kidney injury (AKI) has been associated with mortality after traumatic injury. However, there is a paucity of data for military service members with injuries received in combat. We ...sought to identify risk factors for AKI after combat trauma and evaluate whether AKI is a predictor of mortality. Study Design Retrospective observational study. Settings & Participants US service members who were critically wounded in Iraq or Afghanistan from February 1, 2002, to February 1, 2011, and survived until evacuation to Landstuhl Regional Medical Center, Germany. Predictors Demographic variables, vital signs, injury severity score, presence of burn injury, and mechanism of injury as defined at the time of initial injury, as well as the presence of AKI ascertained within the first 7 days using KDIGO (Kidney Disease: Improving Global Outcomes) serum creatinine criteria. Outcomes Logistic regression models were used to identify risk factors for both AKI and death. Results Of 6,011 records, 3,807 were included for analysis after excluding patients with missing data. AKI occurred in 474 (12.5%) patients and 112 (2.9%) died. More patients with versus without AKI died (n = 62 13.1% vs n = 50 1.5%; P < 0.001). After adjustment, AKI was a predictor of mortality (OR, 5.14; 95% CI, 3.33-7.93; P < 0.001). Predictors of AKI were age, African American race, injury severity score, amputations, burns, and presenting vital signs. Limitations AKI diagnoses limited to creatinine-based definitions. Conclusions AKI predicted mortality in combat veterans injured in the wars in Iraq and Afghanistan.
Glioblastoma multiforme (GBM) is an aggressive variant of central nervous system gliomas that carries a dismal prognosis. Although GBM is the most frequently occurring and malignant type of glioma ...accounting for more than 60% of all brain tumors in adults, its overall incidence is rare, occurring at a rate of 3.21 per 100,000 persons. Little is known about the etiology of GBM, but one proposed theory is that GBM pathogenesis may be linked to a chronic inflammatory course initiated by traumatic injury to the brain. Limited case reports have suggested an association between GBMs and traumatic brain injury (TBI), but larger case-control and epidemiologic studies have been inconclusive. We present three service members (two active duty and one retired) who developed GBM near the original site of prior head trauma. Each service member's military occupation was in the special operations community and shared a common theme of TBI following head trauma/injury. The current research on the association between TBI and GBM is limited and conflicting, predominantly due to the low incidence of the disease in the general population. Evidence has indicated that TBI should be considered a chronic disease with long-term health impacts, including long-term disability, dementia, epilepsy, mental health conditions, and cardiovascular diseases. With the addition of our patients, as well as a recently published study proposing a molecular association between trauma and GBM, further research is needed to better understand the potential relationship.
Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer ...the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70-79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3-51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal.
Energy metabolism supports neuronal function. While it is well established that changes in energy metabolism underpin brain plasticity and function, less is known about how individual neurons ...modulate their metabolic states to meet varying energy demands. This is because most approaches used to examine metabolism in living organisms lack the resolution to visualize energy metabolism within individual circuits, cells, or subcellular regions. Here, we adapted a biosensor for glycolysis, HYlight, for use in
to image dynamic changes in glycolysis within individual neurons and in vivo. We determined that neurons cell-autonomously perform glycolysis and modulate glycolytic states upon energy stress. By examining glycolysis in specific neurons, we documented a neuronal energy landscape comprising three general observations: 1) glycolytic states in neurons are diverse across individual cell types; 2) for a given condition, glycolytic states within individual neurons are reproducible across animals; and 3) for varying conditions of energy stress, glycolytic states are plastic and adapt to energy demands. Through genetic analyses, we uncovered roles for regulatory enzymes and mitochondrial localization in the cellular and subcellular dynamic regulation of glycolysis. Our study demonstrates the use of a single-cell glycolytic biosensor to examine how energy metabolism is distributed across cells and coupled to dynamic states of neuronal function and uncovers unique relationships between neuronal identities and metabolic landscapes in vivo.
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