Background Few studies have evaluated both the overall effect of ICU telemedicine programs and the effect of individual components of the intervention on clinical outcomes. Methods The effects of ...nonrandomized ICU telemedicine interventions on crude and adjusted mortality and length of stay (LOS) were measured. Additionally, individual intervention components related to process and setting of care were evaluated for their association with mortality and LOS. Results Overall, 118,990 adult patients (11,558 control subjects, 107,432 intervention group patients) from 56 ICUs in 32 hospitals from 19 US health-care systems were included. After statistical adjustment, hospital (hazard ratio HR = 0.84; 95% CI, 0.78-0.89; P < .001) and ICU (HR = 0.74; 95% CI, 0.68-0.79; P < .001) mortality in the ICU telemedicine intervention group was significantly better than that of control subjects. Moreover, adjusted hospital LOS was reduced, on average, by 0.5 (95% CI, 0.4-0.5), 1.0 (95% CI, 0.7-1.3), and 3.6 (95% CI, 2.3-4.8) days, and adjusted ICU LOS was reduced by 1.1 (95% CI, 0.8-1.4), 2.5 (95% CI, 1.6-3.4), and 4.5 (95% CI, 1.5-7.2) days among those who stayed in the ICU for ≥ 7, ≥ 14, and ≥ 30 days, respectively. Individual components of the interventions that were associated with lower mortality, reduced LOS, or both included (1) intensivist case review within 1 h of admission, (2) timely use of performance data, (3) adherence to ICU best practices, and (4) quicker alert response times. Conclusions ICU telemedicine interventions, specifically interventions that increase early intensivist case involvement, improve adherence to ICU best practices, reduce response times to alarms, and encourage the use of performance data, were associated with lower mortality and LOS.
Photosynthesis is the process by which plants harvest sunlight to produce sugars from carbon dioxide and water. It is the primary source of energy for all life on Earth; hence it is important to ...understand how this process responds to climate change and human impact. However, model-based estimates of gross primary production (GPP, output from photosynthesis) are highly uncertain, in particular over heavily managed agricultural areas. Recent advances in spectroscopy enable the space-based monitoring of sun-induced chlorophyll fluorescence (SIF) from terrestrial plants. Here we demonstrate that spaceborne SIF retrievals provide a direct measure of the GPP of cropland and grassland ecosystems. Such a strong link with crop photosynthesis is not evident for traditional remotely sensed vegetation indices, nor for more complex carbon cycle models. We use SIF observations to provide a global perspective on agricultural productivity. Our SIF-based crop GPP estimates are 50-75% higher than results from state-of-the-art carbon cycle models over, for example, the US Corn Belt and the Indo-Gangetic Plain, implying that current models severely underestimate the role of management. Our results indicate that SIF data can help us improve our global models for more accurate projections of agricultural productivity and climate impact on crop yields. Extension of our approach to other ecosystems, along with increased observational capabilities for SIF in the near future, holds the prospect of reducing uncertainties in the modeling of the current and future carbon cycle.
Nitrous oxide (N₂O) has a global warming potential that is 300 times that of carbon dioxide on a 100-y timescale, and is of major importance for stratospheric ozone depletion. The climate sensitivity ...of N₂O emissions is poorly known, which makes it difficult to project how changing fertilizer use and climate will impact radiative forcing and the ozone layer. Analysis of 6 y of hourly N₂O mixing ratios from a very tall tower within the US Corn Belt—one of the most intensive agricultural regions of the world—combined with inverse modeling, shows large interannual variability in N₂O emissions (316 Gg N₂O-N·y−1 to 585 Gg N₂O-N·y−1). This implies that the regional emission factor is highly sensitive to climate. In the warmest year and spring (2012) of the observational period, the emission factor was 7.5%, nearly double that of previous reports. Indirect emissions associated with runoff and leaching dominated the interannual variability of total emissions. Under current trends in climate and anthropogenic N use, we project a strong positive feedback to warmer and wetter conditions and unabated growth of regional N₂O emissions that will exceed 600 Gg N₂O-N·y−1, on average, by 2050. This increasing emission trend in the US Corn Belt may represent a harbinger of intensifying N₂O emissions from other agricultural regions. Such feedbacks will pose a major challenge to the Paris Agreement, which requires large N₂O emission mitigation efforts to achieve its goals.
Aerodynamic canopy height (ha) is the effective height of vegetation canopy for its influence on atmospheric fluxes and is a key parameter of surface‐atmosphere coupling. However, methods to estimate ...ha from data are limited. This synthesis evaluates the applicability and robustness of the calculation of ha from eddy covariance momentum‐flux data. At 69 forest sites, annual ha robustly predicted site‐to‐site and year‐to‐year differences in canopy heights (R2 = 0.88, 111 site‐years). At 23 cropland/grassland sites, weekly ha successfully captured the dynamics of vegetation canopies over growing seasons (R2 > 0.70 in 74 site‐years). Our results demonstrate the potential of flux‐derived ha determination for tracking the seasonal, interannual, and/or decadal dynamics of vegetation canopies including growth, harvest, land use change, and disturbance. The large‐scale and time‐varying ha derived from flux networks worldwide provides a new benchmark for regional and global Earth system models and satellite remote sensing of canopy structure.
Plain Language Summary
Vegetation canopy height is a key descriptor of the Earth surface and is in use by many modeling and conservation applications. However, large‐scale and time‐varying data of canopy heights are often unavailable. This synthesis evaluates the applicability and robustness of the calculation of canopy heights from the momentum flux data measured at eddy covariance flux tower sites (i.e., meteorological observation towers with high frequency measurements of wind speed and surface fluxes). We show that the aerodynamic estimation of annual canopy heights robustly predicts the site‐to‐site and year‐to‐year differences in canopy heights across a wide variety of forests. The weekly aerodynamic canopy heights successfully capture the dynamics of vegetation canopies over growing seasons at cropland and grassland sites. Our results demonstrate the potential of aerodynamic canopy heights for tracking the seasonal, interannual, and/or decadal dynamics of vegetation canopies including growth, harvest, land use change, and disturbance. Given the amount of data collected and the diversity of vegetation covered by the global networks of eddy covariance flux tower sites, the flux‐derived canopy height has great potential for providing a new benchmark for regional and global Earth system models and satellite remote sensing of canopy structure.
Key Points
Aerodynamic canopy height can be calculated robustly and routinely from the eddy covariance momentum flux data
Our estimates match well with in situ measurements of canopy heights across a wide variety of vegetation and ecosystem types
Aerodynamic canopy height can be used to track the dynamics of vegetation canopies, including plant growth, harvest, and disturbance
Mutations of genes within the phosphatidylinositol-3-kinase (PI3K)-AKT-MTOR pathway are well known causes of brain overgrowth (megalencephaly) as well as segmental cortical dysplasia (such as ...hemimegalencephaly, focal cortical dysplasia and polymicrogyria). Mutations of the AKT3 gene have been reported in a few individuals with brain malformations, to date. Therefore, our understanding regarding the clinical and molecular spectrum associated with mutations of this critical gene is limited, with no clear genotype-phenotype correlations. We sought to further delineate this spectrum, study levels of mosaicism and identify genotype-phenotype correlations of AKT3-related disorders. We performed targeted sequencing of AKT3 on individuals with these phenotypes by molecular inversion probes and/or Sanger sequencing to determine the type and level of mosaicism of mutations. We analysed all clinical and brain imaging data of mutation-positive individuals including neuropathological analysis in one instance. We performed ex vivo kinase assays on AKT3 engineered with the patient mutations and examined the phospholipid binding profile of pleckstrin homology domain localizing mutations. We identified 14 new individuals with AKT3 mutations with several phenotypes dependent on the type of mutation and level of mosaicism. Our comprehensive clinical characterization, and review of all previously published patients, broadly segregates individuals with AKT3 mutations into two groups: patients with highly asymmetric cortical dysplasia caused by the common p.E17K mutation, and patients with constitutional AKT3 mutations exhibiting more variable phenotypes including bilateral cortical malformations, polymicrogyria, periventricular nodular heterotopia and diffuse megalencephaly without cortical dysplasia. All mutations increased kinase activity, and pleckstrin homology domain mutants exhibited enhanced phospholipid binding. Overall, our study shows that activating mutations of the critical AKT3 gene are associated with a wide spectrum of brain involvement ranging from focal or segmental brain malformations (such as hemimegalencephaly and polymicrogyria) predominantly due to mosaic AKT3 mutations, to diffuse bilateral cortical malformations, megalencephaly and heterotopia due to constitutional AKT3 mutations. We also provide the first detailed neuropathological examination of a child with extreme megalencephaly due to a constitutional AKT3 mutation. This child has one of the largest documented paediatric brain sizes, to our knowledge. Finally, our data show that constitutional AKT3 mutations are associated with megalencephaly, with or without autism, similar to PTEN-related disorders. Recognition of this broad clinical and molecular spectrum of AKT3 mutations is important for providing early diagnosis and appropriate management of affected individuals, and will facilitate targeted design of future human clinical trials using PI3K-AKT pathway inhibitors.
Atmospheric Chemistry of Iodine Saiz-Lopez, Alfonso; Plane, John M. C; Baker, Alex R ...
Chemical reviews,
03/2012, Letnik:
112, Številka:
3
Journal Article
Recenzirano
Odprti dostop
A comprehensive examination of the atmospheric chemistry of iodine is presented. Iodine accrues in aersols and is the topic of studies in photochemistry as well.
Cardiomyopathy is characterized by the pathological accumulation of resident cardiac fibroblasts that deposit ECM (extracellular matrix) and generate a fibrotic scar. However, the mechanisms that ...control the timing and extent of cardiac fibroblast proliferation and ECM production are not known, hampering the development of antifibrotic strategies to prevent heart failure.
We used the Tcf21 (transcription factor 21)
mouse line for fibroblast-specific lineage tracing and
(tumor protein p53) gene deletion. We characterized cardiac physiology and used single-cell RNA-sequencing and in vitro studies to investigate the p53-dependent mechanisms regulating cardiac fibroblast cell cycle and fibrosis in left ventricular pressure overload induced by transaortic constriction.
Cardiac fibroblast proliferation occurs primarily between days 7 and 14 following transaortic constriction in mice, correlating with alterations in p53-dependent gene expression. p53 deletion in fibroblasts led to a striking accumulation of Tcf21-lineage cardiac fibroblasts within the normal proliferative window and precipitated a robust fibrotic response to left ventricular pressure overload. However, excessive interstitial and perivascular fibrosis does not develop until after cardiac fibroblasts exit the cell cycle. Single-cell RNA sequencing revealed
null fibroblasts unexpectedly express lower levels of genes encoding important ECM proteins while they exhibit an inappropriately proliferative phenotype. in vitro studies establish a role for p53 in suppressing the proliferative fibroblast phenotype, which facilitates the expression and secretion of ECM proteins. Importantly,
(cyclin-dependent kinase inhibitor 2a) expression and the p16
-retinoblastoma cell cycle control pathway is induced in
null cardiac fibroblasts, which may eventually contribute to cell cycle exit and fulminant scar formation.
This study reveals a mechanism regulating cardiac fibroblast accumulation and ECM secretion, orchestrated in part by p53-dependent cell cycle control that governs the timing and extent of fibrosis in left ventricular pressure overload.
N₂O is an important greenhouse gas and the primary stratospheric ozone depleting substance. Its deleterious effects on the environment have prompted appeals to regulate emissions from agriculture, ...which represents the primary anthropogenic source in the global N₂O budget. Successful implementation of mitigation strategies requires robust bottom-up inventories that are based on emission factors (EFs), simulation models, or a combination of the two. Top-down emission estimates, based on tall-tower and aircraft observations, indicate that bottom-up inventories severely underestimate regional and continental scale N₂O emissions, implying that EFs may be biased low. Here, we measured N₂O emissions from streams within the US Corn Belt using a chamber-based approach and analyzed the data as a function of Strahler stream order (S). N₂O fluxes from headwater streams often exceeded 29 nmol N₂O-N m⁻²·s⁻¹ and decreased exponentially as a function of S. This relation was used to scale up riverine emissions and to assess the differences between bottom-up and top-down emission inventories at the local to regional scale. We found that the Intergovernmental Panel on Climate Change (IPCC) indirect EF for rivers (EF5r) is underestimated up to ninefold in southern Minnesota, which translates to a total tier 1 agricultural underestimation of N₂O emissions by 40%. We show that accounting for zero-order streams as potential N₂O hotspots can more than double the agricultural budget. Applying the same analysis to the US Corn Belt demonstrates that the IPCC EF5runderestimation explains the large differences observed between top-down and bottom-up emission estimates.
Aspergillus niger and other filamentous fungi are widely used in industry, but efficient genetic engineering of these hosts remains nascent. For example, while molecular genetic tools have been ...developed, including CRISPR/Cas9, facile genome engineering of A. niger remains challenging. To address these challenges, we have developed a simple Cas9-based gene targeting method that provides selectable, iterative, and ultimately marker-free generation of genomic deletions and insertions. This method leverages locus-specific "pop-out" recombination to suppress off-target integrations. We demonstrated the effectiveness of this method by targeting the phenotypic marker albA and validated it by targeting the glaA and mstC loci. After two selection steps, we observed 100% gene editing efficiency across all three loci. This method greatly reduces the effort required to engineer the A. niger genome and overcomes low Cas9 transformations efficiency by eliminating the need for extensive screening. This method represents a significant addition to the A. niger genome engineering toolbox and could be adapted for use in other organisms. It is expected that this method will impact several areas of industrial biotechnology, such as the development of new strains for the secretion of heterologous enzymes and the discovery and optimization of metabolic pathways.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction ...models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks' with ultrasound parameters at 20±1 weeks' gestation.
Data from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE) cohort study were divided into Training (n = 3735) and Validation datasets (n = 1871). The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile), Normotensive-SGA (small for gestational age with a normotensive mother) and Hypertensive-SGA (small for gestational age with an hypertensive mother). The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler) variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve.
633 (11.2%) infants were All-SGA, 465(8.2%) Normotensive-SGA and 168 (3%) Hypertensive-SGA. Area under the curve (95% Confidence Intervals) for All-SGA using 15±1 weeks' clinical variables, 15±1 weeks' clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks' were: 0.63 (0.59-0.67), 0.64 (0.60-0.68) and 0.69 (0.66-0.73) respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57-0.66), 0.61 (0.56-0.66) and 0.68 (0.64-0.73) with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals) for Hypertensive-SGA were: 0.76 (0.70-0.82), 0.80 (0.75-0.86) and 0.84 (0.78-0.89) with minimal change in the Training datasets.
Models for prediction of small for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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