Patients with chronic coronary disease were randomly assigned to receive 0.5 mg of colchicine once daily or matching placebo. The incidence of the composite end point of cardiovascular death, ...spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was significantly lower with colchicine than with placebo.
Because patients with stable coronary artery disease are at continued risk of major atherosclerotic events despite effective secondary prevention strategies, there is a need to continue to develop ...additional safe, effective and well-tolerated therapies for secondary prevention of cardiovascular disease.
The LoDoCo (Low Dose Colchicine) pilot trial showed that the anti-inflammatory drug colchicine 0.5 mg once daily appears safe and effective for secondary prevention of cardiovascular disease. Colchicine's low cost and long-term safety suggest that if its efficacy can be confirmed in a rigorous trial, repurposing it for secondary prevention of cardiovascular disease would have the potential to impact the global burden of cardiovascular disease.
LoDoCo2 is an investigator-initiated, international, multicentre, double-blind, event driven trial in which 5522 patients with stable coronary artery disease tolerant to colchicine during a 30-day run-in phase have been randomized to colchicine 0.5 mg daily or matching placebo on a background of optimal medical therapy. The study will have 90% power to detect a 30% reduction in the composite primary endpoint: cardiovascular death, myocardial infarction, ischemic stroke and ischemia-driven coronary revascularization. Adverse events potentially related to the use of colchicine will also be collected, including late gastrointestinal intolerance, neuropathy, myopathy, myositis, and neutropenia.
The LoDoCo2 Trial will provide information on the efficacy and safety of low-dose colchicine for secondary prevention in patients with stable coronary artery disease.
Clay minerals and pedogenic metal (oxyhydr)oxides are the most reactive soil mineral constituents controlling the long-term persistence of organic carbon (OC) in terrestrial ecosystems. However, ...their co-occurrence in most soils complicates direct assessment of their individual contribution to OC persistence. Making use of unique mineralogical combinations in soils located in the East Usambara Mountains of Tanzania, we disentangled the contribution of clay-sized aluminous minerals (kaolinite, gibbsite) and pedogenic Fe (oxyhydr)oxides (predominant goethite and hematite) on OC storage and stabilization under natural forests and croplands. Topsoil samples, varying in contents but not types of aluminous clays and pedogenic Fe (oxyhydr)oxides, were identified by selective extractions, X-ray diffraction, and Mössbauer spectroscopy. Associated abundance of particulate and mineral-associated organic matter (OM) was quantified by density fractionation and their changes during land-use conversion were determined as a measure of OC persistence. Additionally, we assessed the resistance of OC to chemical oxidation as well as microbial decomposition in a 50-day laboratory incubation. We found that the ratio of pedogenic Fe to aluminous clay is more consequential for OC storage and stabilization than their individual contents, despite the fact that Fe (oxyhydr)oxides generally exert a stronger impact on OC than aluminous clays. Conjunction of large amounts of Fe (oxyhydr)oxides with low aluminous clay contents caused the strongest accumulation of mineral-associated OC, a low soil respiration, high OC stability against chemical oxidation, and high OC persistence during land-use change. Our study suggests that certain mineralogical combinations in the humid tropics alleviate OM losses during land conversion because of the strong and selective mineral control on OC stabilization, particular if the weight ratio of pedogenic Fe to aluminous clay exceeds the threshold range of 0.44‒0.56.
A single-particle soot photometer (SP2) was flown on a NASA WB-57F high-altitude research aircraft in November 2004 from Houston, Texas. The SP2 uses laser-induced incandescence to detect individual ...black carbon (BC) particles in an air sample in the mass range of approx.3-300 fg (approx.0.15-0.7 microns volume equivalent diameter). Scattered light is used to size the remaining non-BC aerosols in the range of approx.0.17-0.7 microns diameter. We present profiles of both aerosol types from the boundary layer to the lower stratosphere from two midlatitude flights. Results for total aerosol amounts in the size range detected by the SP2 are in good agreement with typical particle spectrometer measurements in the same region. All ambient incandescing particles were identified as BC because their incandescence properties matched those of laboratory-generated BC aerosol. Approximately 40% of these BC particles showed evidence of internal mixing (e.g., coating). Throughout profiles between 5 and 18.7 km, BC particles were less than a few percent of total aerosol number, and black carbon aerosol (BCA) mass mixing ratio showed a constant gradient with altitude above 5 km. SP2 data was compared to results from the ECHAM4/MADE and LmDzT-INCA global aerosol models. The comparison will help resolve the important systematic differences in model aerosol processes that determine BCA loadings. Further intercomparisons of models and measurements as presented here will improve the accuracy of the radiative forcing contribution from BCA.
Ultraviolet light-induced electron−hole pair excitations in anatase TiO2 powders were studied by a combination of electron paramagnetic resonance and infrared spectroscopy measurements. During ...continuous UV irradiation in the mW.cm-2 range, photogenerated electrons are either trapped at localized sites, giving paramagnetic Ti3+ centers, or remain in the conduction band as EPR silent species which may be observed by their IR absorption. Using low temperatures (90 K) to reduce the rate of the electron−hole recombination processes, trapped electrons and conduction band electrons exhibit lifetimes of hours. The EPR-detected holes produced by photoexcitation are O- species, produced from lattice O2- ions. It is found that under high vacuum conditions, the major fraction of photoexcited electrons remains in the conduction band. At 298 K, all stable hole and electron states are lost from TiO2. Defect sites produced by oxygen removal during annealing of anatase TiO2 are found to produce a Ti3+ EPR spectrum identical to that of trapped electrons, which originate from photoexcitation of oxidized TiO2. Efficient electron scavenging by adsorbed O2 at 140 K is found to produce two long-lived O2 - surface species associated with different cation surface sites. Reduced TiO2, produced by annealing in vacuum, has been shown to be less efficient in hole trapping than oxidized TiO2.
We report the discovery of a nearby, embedded cluster of young stellar objects, associated filamentary infrared dark cloud, and 4.5 mu m shock emission knots from outflows detected in Spltzer IRAC ...mid-infrared imaging of the Serpens-Aquila Rift obtained as part of the Spitzer Gould Belt Legacy Survey. We also present radial velocity measurements of the region from molecular line observations obtained with the Submillimeter Array (SMA) that suggest the cluster is comoving with the Serpens Main embedded cluster 3 degree to the north. We therefore assign it the same distance, 260 pc. The core of the new cluster, which we call Serpens South, is composed of an unusually large fraction of protostars (77%) at high mean surface density (>430 pc- sub(2)) and short median nearest neighbor spacing (3700 AU). We perform basic cluster structure characterization using nearest neighbor surface density mapping of the YSOs and compare our findings to other known clusters with equivalent analyses available in the literature.
Abstract
Aims
Recent randomized trials demonstrated a benefit of low-dose colchicine added to guideline-based treatment in patients with recent myocardial infarction or chronic coronary disease. We ...performed a systematic review and meta-analysis to obtain best estimates of the effects of colchicine on major adverse cardiovascular events (MACE).
Methods and results
We searched the literature for randomized clinical trials of long-term colchicine in patients with atherosclerosis published up to 1 September 2020. The primary efficacy endpoint was MACE, the composite of myocardial infarction, stroke, or cardiovascular death. We combined the results of five trials that included 11 816 patients. The primary endpoint occurred in 578 patients. Colchicine reduced the risk for the primary endpoint by 25% relative risk (RR) 0.75, 95% confidence interval (CI) 0.61–0.92; P = 0.005, myocardial infarction by 22% (RR 0.78, 95% CI 0.64–0.94; P = 0.010), stroke by 46% (RR 0.54, 95% CI 0.34–0.86; P = 0.009), and coronary revascularization by 23% (RR 0.77, 95% CI 0.66–0.90; P < 0.001). We observed no difference in all-cause death (RR 1.08, 95% CI 0.71–1.62; P = 0.73), with a lower incidence of cardiovascular death (RR 0.82, 95% CI 0.55–1.23; P = 0.34) counterbalanced by a higher incidence of non-cardiovascular death (RR 1.38, 95% CI 0.99–1.92; P = 0.060).
Conclusion
Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE as well as that of myocardial infarction, stroke, and the need for coronary revascularization in a broad spectrum of patients with coronary disease. There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.
Graphical Abstract
Colchicine in coronary disease
Pancreatic Cancer (PDA) is an aggressive malignancy characterized by early spread and a high mortality. Current studies suggest that a subpopulation of cells exist within tumors, cancer stem cell ...(CSC), which are capable of self-renewal and give rise to unique progeny which form the major neoplastic cellular component of tumors. While CSCs constitute a small cellular subpopulation within the tumor, their resistance to chemotherapy and radiation make them an important therapeutic target for eradication. Along with distinctive phenotypic properties, CSCs possess a unique metabolic plasticity allowing them to rapidly respond and adapt to environmental changes. These cells and their progeny also display a significantly altered epigenetic state with distinctive patterns of DNA methylation. Several mechanisms of cross-talk between epigenetic and metabolic pathways in PDA exist which ultimately contribute to the observed cellular plasticity and enhanced tumorigenesis. In this review we discuss various examples of this metabolic-epigenetic interplay and how it may constitute a new avenue for therapy specifically targeting CSCs in PDA.
New active materials are needed to improve the performance and reduce the cost of non-aqueous redox flow batteries (RFBs) for grid-scale energy storage applications. Efforts to develop better ...performing materials, which have largely been empirical, would benefit from a better understanding of relationships between structural, electronic and RFB-relevant functional properties. This paper focuses on metal-acetylacetonates, a class of metal coordination complexes that has shown promise for use in RFBs, and describes correlations between their experimentally measured standard potentials, solubilities, and stabilities (cycle lifes), and selected chemical, structural and electronic properties determined from Density Functional Theory (DFT) calculations. The training set consisted of 16 complexes including 5 different metals and 11 different substituents on the acetylacetonate ligand. Standard potentials for those compounds were calculated and are in good agreement with experimentally measured results. A predictive equation based on the solvation energies and dipole moments, two easily computed properties, reasonably modeled the experimentally determined solubilities. Importantly, we were able to identify a descriptor for the stability of acetylacetonates. The experimentally determined stability, quantified as the cycle life to a given degree of degradation, correlated with the percentage of the highest occupied (HOMO) or lowest unoccupied molecular orbital (LUMO) on the metal of the complex. This percentage is influenced by the degree of ligand innocence (irreducibility), and complexes with the most innocent ligands yielded the most stable redox reactions. To this end, VO(acetylacetonate)2 and Fe(acetylacetonate)3, with nearly 80% of the HOMO and LUMO on the metal, possessed the most stable oxidation and reduction half-reactions, respectively. The structure-function relationships and correlations presented in this paper could be used to predict new, highly soluble and stable complexes for RFB applications.
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