Purpose
To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure.
...Methods
The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12 h.
Results
Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2 % (95 % CI, 38.8–57.6 %). New-onset tachyarrhythmia (49.1 %), prolonged elevated heart rate (23.7 %), and myocardial cell damage (17.5 %) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95 % CI, 1.08–2.77;
p
= 0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95 % CI, 1–1.01;
p
= 0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (
p
< 0.001) and mechanical ventilation (
p
< 0.001) for longer and had longer intensive care unit stays (
p
< 0.001) and greater mortality (25.9 vs. 1.7 %;
p
< 0.001) than patients who did not.
Conclusions
Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events.
Municipal solid waste incineration (MSWI) fly ash is considered as a hazardous waste that requires specific treatment before disposal. The principal treatments encompass thermal treatment, ...stabilization/solidification, and resource recovery. To maximize environmental, social, and economic benefits, the development of low-carbon and sustainable treatment technologies for MSWI fly ash has attracted extensive interests in recent years. This paper critically reviewed the state-of-the-art treatment technologies and novel resource utilization approaches for the MSWI fly ash. Innovative technologies and future perspectives of MSWI fly ash management were highlighted. Moreover, the latest understanding of immobilization mechanisms and the use of advanced characterization technologies were elaborated to foster future design of treatment technologies and the actualization of sustainable management for MSWI fly ash.
Display omitted
•Review the state-of-the-art treatment technologies and recycling approaches for MSWI fly ash.•Compare the merits and demerits of various technologies for MSWI fly ash treatment.•Elaborate the latest immobilization mechanisms based on advanced characterization techniques.•Provide future perspectives for sustainable management of MSWI fly ash.
Abstract
We present estimates for the number of shadow-resolved supermassive black hole (SMBH) systems that can be detected using radio interferometers, as a function of angular resolution, flux ...density sensitivity, and observing frequency. Accounting for the distribution of SMBHs across mass, redshift, and accretion rate, we use a new semianalytic spectral energy distribution model to derive the number of SMBHs with detectable and optically thin horizon-scale emission. We demonstrate that (sub)millimeter interferometric observations with ∼0.1
μ
as resolution and ∼1
μ
Jy sensitivity could access >10
6
SMBH shadows. We then further decompose the shadow source counts into the number of black holes for which we could expect to observe the first- and second-order lensed photon rings. Accessing the bulk population of first-order photon rings requires ≲2
μ
as resolution and ≲0.5 mJy sensitivity, whereas doing the same for second-order photon rings requires ≲0.1
μ
as resolution and ≲5
μ
Jy sensitivity. Our model predicts that with modest improvements to sensitivity, as many as ∼5 additional horizon-resolved sources should become accessible to the current Event Horizon Telescope (EHT), whereas a next-generation EHT observing at 345 GHz should have access to ∼3 times as many sources. More generally, our results can help guide enhancements of current arrays and specifications for future interferometric experiments that aim to spatially resolve a large population of SMBH shadows or higher-order photon rings.
Despite their great promise for providing a pathway for very efficient and fast manipulation of magnetization, spin‐orbit torque (SOT) operations are currently energy inefficient due to a low ...damping‐like SOT efficiency per unit current bias, and/or the very high resistivity of the spin Hall materials. This work reports an advantageous spin Hall material, Pd1−xPtx, which combines a low resistivity with a giant spin Hall effect as evidenced with three independent SOT ferromagnetic detectors. The optimal Pd0.25Pt0.75 alloy has a giant internal spin Hall ratio of >0.60 (damping‐like SOT efficiency of ≈0.26 for all three ferromagnets) and a low resistivity of ≈57.5 µΩ cm at a 4 nm thickness. Moreover, it is found that the Dzyaloshinskii–Moriya interaction (DMI), the key ingredient for the manipulation of chiral spin arrangements (e.g., magnetic skyrmions and chiral domain walls), is considerably strong at the Pd1−xPtx/Fe0.6Co0.2B0.2 interface when compared to that at Ta/Fe0.6Co0.2B0.2 or W/Fe0.6Co0.2B0.2 interfaces and can be tuned by a factor of 5 through control of the interfacial spin‐orbital coupling via the heavy metal composition. This work establishes a very effective spin current generator that combines a notably high energy efficiency with a very strong and tunable DMI for advanced chiral spintronics and spin torque applications.
Spin‐orbit torque (SOT) operations are currently energy inefficient due to a low damping‐like SOT efficiency and/or the very high resistivity of the spin Hall materials. This work establishes a very effective spin current generator Pd1−xPtx that combines a notably high energy efficiency with a very strong and tunable Dzyaloshinskii–Moriya interaction for advanced chiral spintronics and spin torque applications.
The Event Horizon Telescope image of the supermassive black hole in the galaxy M87 is dominated by a bright, unresolved ring. General relativity predicts that embedded within this image lies a thin ..."photon ring," which is composed of an infinite sequence of self-similar subrings that are indexed by the number of photon orbits around the black hole. The subrings approach the edge of the black hole "shadow," becoming exponentially narrower but weaker with increasing orbit number, with seemingly negligible contributions from high-order subrings. Here, we show that these subrings produce strong and universal signatures on long interferometric baselines. These signatures offer the possibility of precise measurements of black hole mass and spin, as well as tests of general relativity, using only a sparse interferometric array.
Electroplating sludge is a hazardous waste due to its high potential to leach toxic elements into the natural environment. To alleviate this issue, we tailored magnesium phosphate cement (MPC) as a ...low-carbon material for stabilization/solidification (S/S) of Zn-rich electroplating sludge. The interaction between MPC and ZnO was investigated to clarify the precipitate chemistry, microstructure transition, and chemical environment of Zn species in the MPC-treated Zn sludge system. Comprehensive characterization (by X-ray diffraction (XRD), 31P nuclear magnetic resonance (NMR), and extended X-ray absorption fine structure spectroscopy (EXAFS)) and thermodynamic modeling results revealed that the incorporated ZnO preferentially reacted with phosphate to form Zn3(PO4)2·2H2O/Zn3(PO4)2·4H2O, changing the orthophosphate environment in the MPC system. Stronger chemical bonding between Zn and phosphate in comparison to the bonding between Mg and phosphate also resulted in the formation of amorphous Zn3(PO4)2·2H2O/Zn3(PO4)2·4H2O. Zn3(PO4)2·4H2O precipitate appears to predominate at high {K+}{H+}{HPO4 2–} values, and the formation of Zn3(PO4)2·2H2O/Zn3(PO4)2·4H2O competed for the Mg sites in the MPC system, leading to the inhibition of formation of Mg–phosphate precipitates. Overall, this work uncovers the precipitate chemistry and microstructure transition of Zn species in the MPC system, providing new insights into the sustainable S/S of Zn-contaminated wastes by adopting MPC.
The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required ...for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons.
We define a class of machine-learned flow-based sampling algorithms for lattice gauge theories that are gauge invariant by construction. We demonstrate the application of this framework to U(1) gauge ...theory in two spacetime dimensions, and find that, at small bare coupling, the approach is orders of magnitude more efficient at sampling topological quantities than more traditional sampling procedures such as hybrid Monte Carlo and heat bath.
Data from 8 breast cancer genome-sequencing projects identified 25 patients with HER2 somatic mutations in cancers lacking HER2 gene amplification. To determine the phenotype of these mutations, we ...functionally characterized 13 HER2 mutations using in vitro kinase assays, protein structure analysis, cell culture, and xenograft experiments. Seven of these mutations are activating mutations, including G309A, D769H, D769Y, V777L, P780ins, V842I, and R896C. HER2 in-frame deletion 755-759, which is homologous to EGF receptor (EGFR) exon 19 in-frame deletions, had a neomorphic phenotype with increased phosphorylation of EGFR or HER3. L755S produced lapatinib resistance, but was not an activating mutation in our experimental systems. All of these mutations were sensitive to the irreversible kinase inhibitor, neratinib. These findings show that HER2 somatic mutation is an alternative mechanism to activate HER2 in breast cancer and they validate HER2 somatic mutations as drug targets for breast cancer treatment.
We show that the majority of HER2 somatic mutations in breast cancer patients are activating mutations that likely drive tumorigenesis. Several patients had mutations that are resistant to the reversible HER2 inhibitor lapatinib, but are sensitive to the irreversible HER2 inhibitor, neratinib. Our results suggest that patients with HER2 mutation–positive breast cancers could benefit from existing HER2-targeted drugs.
Tumor relapse from treatment‐resistant cells (minimal residual disease, MRD) underlies most breast cancer‐related deaths. Yet, the molecular characteristics defining their malignancy have largely ...remained elusive. Here, we integrated multi‐omics data from a tractable organoid system with a metabolic modeling approach to uncover the metabolic and regulatory idiosyncrasies of the MRD. We find that the resistant cells, despite their non‐proliferative phenotype and the absence of oncogenic signaling, feature increased glycolysis and activity of certain urea cycle enzyme reminiscent of the tumor. This metabolic distinctiveness was also evident in a mouse model and in transcriptomic data from patients following neo‐adjuvant therapy. We further identified a marked similarity in DNA methylation profiles between tumor and residual cells. Taken together, our data reveal a metabolic and epigenetic memory of the treatment‐resistant cells. We further demonstrate that the memorized elevated glycolysis in MRD is crucial for their survival and can be targeted using a small‐molecule inhibitor without impacting normal cells. The metabolic aberrances of MRD thus offer new therapeutic opportunities for post‐treatment care to prevent breast tumor recurrence.
SYNOPSIS
Despite their normal morphology and non‐proliferative phenotype, treatment‐resistant breast cancer cells retain epigenetic imprinting and metabolic characteristics of their prior tumour state.
Multi‐omics analysis and flux modelling reveals elevated glycolysis and abnormal urea cycle pathway activity in residual cells (Minimal Residual Disease, MRD).
Transcriptome data from human samples also indicate elevated glycolysis of MRD.
In contrast to normal epithelial cells and cancer, MRD is dependent on glycolysis for survival and can be selectively targeted using a small‐molecule inhibitor.
Epigenetic similarity between MRD‐ and tumour‐cells suggests a mechanistic basis for metabolic memory.
Despite their normal morphology and non‐proliferative phenotype, treatment‐resistant breast cancer cells retain epigenetic imprinting and metabolic characteristics of their prior tumour state.
PDF
