Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Genesis type of ore deposits indicated by trace elements of chalcopyrite

Trace elements of metallic minerals are important to constrain the formation processes and genetic types of ore deposits. Trace elements have been mainly focused on pyrite, magnetite, and sphalerite but have rarely been applied to chalcopyrite. To reveal the relationships between chalcopyrite trace elements and ore deposit types, ore petrography and LA-ICP-MS trace element of chalcopyrite in collected copper concentrate samples from porphyry copper deposits (PCD), magmatic copper-nickel sulfide deposits (MSD), sedimentary rock-hosted stratiform copperdeposits (SSC), iron oxide copper-gold deposits (IOCG), sedimentary exhalative deposits (SEDEX) and volcanogenic massive sulfide deposits (VMS) have been carried out. In chalcopyrite, Mn, Co, Ni, Se, Ag, Sn, Pb, and Bi contents are more than 1 000×10-6, and Ga, Ge, Mo, Cd, In, Sb, Te, Au and Tl contents are up to 100×10-6, which together indicate chalcopyrite is an important carrier for many trace elements. Antimony-Tl, In-Sn, Pb-Bi, and Mn-Ni in the chalcopyrite are positively correlated.Meanwhile, in chalcopyrite, Sb, Tl, In, and Sn mainly occur in the form of solid solution, Pb and Bi in the form of galena inclusions, and Mn, Co, As, Te, Ag, and Ni are both developed. Trace elements of chalcopyrite from PCD and VMS are variable. The concentrations of Ni and In in chalcopyrite from MSD are high and low, and Ge and Sn from SSC are higher and lower than other types, respectively. Moreover, the concentration of Se in chalcopyrite is higher from MSD and VMS, but is lower from SEDEX and SSC. Different concentrations of Ni, In, and Sn in the chalcopyrite are mainly related to different magmatism, and Se is principally controlled by temperature. The high concentrations of Ge in chalcopyrite from SSC may be related to ore-forming temperature and host rocks.Therefore, based on the above trace elements characteristics, Ni-Co and Ni-In diagrams can distinguish MSD from other deposit types, the diagram of Ni-Se can differentiate SEDEX, SSC from VMS, and the diagram of Ge-Sn is used to isolate SSC from SEDEX. In addition, the diagram of Co/Ni-Ag/Bi can differentiate between MSD and PCD, while Zn-Sn/In can discriminate IOCG from others to some extent.These first systematically proposed diagrams will provide a new reference for distinguishing the genetic types of deposits

Cenozoic Depositional Evolution and Stratal Patterns in the Western Pearl River Mouth Basin, South China Sea: Implications for Hydrocarbon Exploration

Investigating the deposition evolution and stratal stacking patterns in continental rift basins is critical not only to better understand the mechanism of basin fills but also to reveal the enrichment regularity of hydrocarbon reservoirs. The Pearl River Mouth Basin (PRMB) is a petroliferous continental rift basin located in the northern continental shelf of the South China Sea. In this study, the depositional evolution process and stacking pattern of the Zhu III Depression, western PRMB were studied through the integration of 3D seismic data, core data, and well logs. Five types of depositional systems formed from the Eocene to the Miocene, including the fan delta, meandering river delta, tidal flat, lacustrine system, and neritic shelf system. The representative depositional systems changed from the proximal fan delta and lacustrine system in the Eocene–early Oligocene, to the tidal flat and fan delta in the late Oligocene, and then the neritic shelf system in the Miocene. The statal stacking pattern varied in time and space with a total of six types of slope break belts developed. The diversity of sequence architecture results from the comprehensive effect of tectonic activities, sediment supply, sea/lake level changes, and geomorphic conditions. In addition, our results suggest that the types of traps are closely associated with stratal stacking patterns. Structural traps were developed in the regions of tectonic slope breaks, whereas lithological traps occurred within sedimentary slope breaks. This study highlights the diversity and complexity of sequence architecture in the continental rift basin, and the proposed hydrocarbon distribution patterns are applicable to reservoir prediction in the PRMB and the other continental rift basins

Analysis of mineralogical characteristics of imported iron ore from different countries: Constraints from maceral compositions and elemental analysis

China is the largest importer of iron ore resources. Analyzing the mineralogical characteristics of imported iron ore samples imported from different countries can provide a reference for identifying the source of iron ore and solid waste attributes. In this paper, iron ore samples imported from 11 countries were used to determine their elemental compositions and mineral assemblages by polarized light microscopy investigation, X-ray fluorescence spectroscopy (XRF) and pyrite/magnetite LA-ICP-MS element analysis. These results are applied to explore the formation environment of iron minerals. XRF analysis results show that the main elements of iron ore samples are Fe and O, followed by Si, Ca, Al, Mn, Tb, Ti, Mg, P, and S. These elements are significant differences in iron ore among different countries. Polarizing microscopy investigation shows that there are great differences not only in mineral types but also in other aspects (e.g., accessory mineral types, accessory mineral content, and structure). These differences can be used as proxies for the identification of iron ore origin. Finally, in situ major and trace elements of magnetite were used to distinguish the genetic types of iron deposits. The magnetite deposits from Burma and Laos are skarn type, while those from Australia are mainly BIF type. In this study, multiple techniques were used to characterize the differences in element content, mineral facies composition and mineral-forming environment of iron ore samples and to comprehensively analyze the mineralogical characteristics of iron ore samples from different countries. These differences are of great significance for the identification, quality control and origin of imported iron ore resources

Sedimentary architecture and evolution of a Quaternary sand-rich submarine fan in the South China Sea

Investigating the sedimentary architecture and evolution of sand-rich submarine fans is vital for comprehending deep-water sedimentary processes and enhancing the success rate of hydrocarbon resource exploration. Recent drilling activities in the Qiongdongnan Basin, northern South China Sea, have unveiled significant gas hydrate and shallow gas potential. However, exploration in this area faces substantial challenges due to the limited understanding of sandy reservoirs. Leveraging extensive newly acquired extensive 3D seismic data (~9000 km2) and well data, our study reveals five distinct deep-water depositional systems in the Quaternary Ledong Formation, including a submarine fan system, mass transport deposits, deepwater channel-levee systems, slope fans, and hemipelagic sediments. Notably, the targeted sand-rich submarine fan lies within the abyssal plain, situated at a water depth of 1300-1700 m. This fan exhibits a unique tongue-shape configuration and a SW-NE flow direction within the plane and spans an expansive area of ~2800 km2 with maximum length and width reaching 140 km and 35 km, respectively. Vertically, the fan comprises five stages of distributary channel-lobe complexes, progressing from Unit 1 to Unit 5. Their distribution ranges steadily increase from Unit 1 to Unit 3, followed by a rapid decrease from Unit 4 to Unit 5. Our results suggest that the occurrence and evolution of the submarine fan are primarily controlled by sea level fluctuation, confined geomorphology, and sediment supply. Specifically, sea level fluctuation and sediment supply influenced the occurrence of the submarine fan. Concurrently, the confined geomorphology in the abyssal plain provided accumulation space for sediments and shaped the fan into its distinct tongue-like form. In contrast to the deepwater channels within the deepwater channel-levee systems, the distributary turbidite channels within the submarine fan are marked by lower erosion depth with “U” shapes, greater channel width, and higher ratios of width to depth. The comparative analysis identifies turbidite channels as the focal points for offshore gas hydrate and shallow gas exploration in the Qiongdongnan Basin. Furthermore, the temporal evolution of submarine fan offers valuable insights into Quaternary deep-water sedimentary processes and hydrocarbon exploration within shallow strata of marginal ocean basins

Modeling ammonia emissions and abatement potential from the rice-wheat rotation fields using the calibrated DNDC model: A case study in Shanghai, China

10 Pág.Abating ammonia (NH3) volatilization from intensive cropping system is of great importance for preventing the pollution of atmospheric environment and sustainable agriculture. Urea, a common nitrogen fertilizer, can convert to an unstable carbamate and further releases NH3 from the fields. However, few investigations of NH3 volatilization loss following fertilizer application to agricultural soils have been done using process-based models. In this study, a two-year field study was conducted to calibrate and evaluate the DeNitrification-DeComposition (DNDC) model for simulating NH3 volatilizations and crop production for the rice-wheat rotation system under four fertilizer regimes: control group without N fertilizer (CK), chemical fertilizer (CF), mixed application of inorganic and organic fertilizer (MF), and organic fertilizer (OF) treatments. The calibrated and modified DNDC performed effectively in simulating cumulative NH3 volatilization (coefficient of determination (R2) = 0.96 for rice and 0.92 for wheat field, relative deviation (RD) = −6.3% - 2.1% for rice and −22.5 to −4.6% for wheat) and grain yields for both crops (R2 = 0.94 for rice and 0.91 for wheat, RD of rice: 4.94%–9.59%; wheat: −1.84%–11.51%). The sensitivity analysis demonstrated that NH3 volatilization from rice-wheat rotation field was most sensitive to N application rate. Compared to CF and OF, MF treatments significantly mitigated NH3 volatilization and improved crop yield. Therefore, scenario simulation was conducted to confirm the optimal N application rate under MF. The results revealed that 250 kg N ha−1 and 112.5 kg N ha−1 in MF were recommended for rice- and wheat-growing, respectively. Compared to the current N fertilizer rate, the recommended rate saved 50 kg N ha−1 and mitigated NH3 volatilization loss by 28.31% from rice field and saved 37.5 kg N ha−1 and mitigated NH3 volatilization loss by 19.29% from wheat field. Overall, the calibrated DNDC model proved to be an effective tool to simulate NH3 volatilization from the rice-wheat rotation system and provides a promising fertilizer management strategy to decrease N input and mitigate NH3 volatilization.This work was funded by Shanghai Science and Technology Innovation Action Plan Project (22002400300) and Qingpu Science and Technology Development Program, Shanghai, China, and Foundation of Key Laboratory of Technology and Model for Cyclic utilization from Agricultural Resources, Ministry of Agriculture and Rural, P. R. China (KLTMCUAR 2018-1).Peer reviewe

A new technology of basin fluid geochronology: In-situ U-Pb dating of calcite

Basin fluid is the most active geological agent in sedimentary basins, having a close relationship with the generation, migration and accumulation of hydrocarbon resources. Accurate determination of fluid flow history has been a challenging and frontier research topic. In general, the previous studies of basin fluids mainly rely on the analysis of fluid inclusions, which is difficult to successfully reconstruct the events of basin fluids. More seriously, this method is unable to determine the timing of fluid flow events. Authigenic calcite is the direct product of basin fluids. Thus, accurate dating of authigenic calcite provides a new approach to determine the history of fluid flow events. In the field of calcite geochronology, the most widely used dating method was the isotope dilution U-Pb dating approach. However, this approach is time-consuming, and has a low success rate. In recent years, laser ablation technology has greatly facilitated U-Pb dating of accessory minerals (including calcite) because of its high spatial resolution and rapid data acquisition. It has been confirmed that the newly-developed in-situ U-Pb dating method is able to accurately determine the age of calcite with U content less than 10×10 . This method has successfully reconstructed the history of fluid flow events in the sedimentary basins, suggesting that it has a good application prospect in the field of basin fluid geochronology. In the future, it can be expected that the application of in-situ U-Pb dating of calcite together with C-O isotope and rare earth element analysis will be a significant development direction in the field of basin fluid studies. It is worth noting that the determination of stage of authigenic calcite through systematic microscopic identification and diagenetic observation is the premise of application success

Response of pore network fractal dimensions and gas adsorption capacities of shales exposed to supercritical CO2: Implications for CH4 recovery and carbon sequestration

The injection of CO2 into shale reservoirs potentially increases rates and masses of CH4 recovery and simultaneously contributes to the sequestration of CO2. At typical reservoir conditions (T≥31.08 °C, P≥7.38 MPa) the CO2 will be supercritical. We compile, analyze, and supplement experimental data of shales from several basins across China, and use X-ray diffraction, scanning electron microscopy and low-pressure gas adsorption to characterize variations in shale pore structure before and after supercritical CO2 (ScCO2) treatment, and supplement these with CH4/CO2 adsorption experiments to characterize changes in shale adsorption capacity. The results show that clay and carbonate contents significantly decrease, and the relative content of quartz is increased after ScCO2 treatment. Pore structure changes significantly after ScCO2 treatment, with the majority of the shales showing a decrease in total specific surface area and total pore volume and an increase in average pore size — indicating the transformation of some micropores and smaller mesopores into mesopores and macropores. After ScCO2 treatment, the experimentally derived absolute adsorption volumes of both CH4 and CO2 decrease, and the volumes of both CH4 and CO2 fitting a Langmuir isotherm decrease with an increase in treatment pressure and increase with an increase in temperature. The adsorption selectivity factors αCO2/CH4all remain greater than 1 with αCO2/CH4primarily controlled by the pore structure. The fractal dimension is positively correlated with Langmuir volume and negatively correlated with Langmuir pressure while the fractal dimensions are negatively correlated with αCO2/CH4. The selectivity factor αCO2/CH4decreases rapidly above a fractal dimension threshold (D1>2.65, D2>2.80). This paper further reveals critical interactions between ScCO2 and shale and defines controls on and of pore structure and adsorption capacity to speculate on physical and chemical storage mechanisms of CO2 in shale reservoirs. This provides several theoretical bases for shale gas recovery and the sequestration of CO2

CH4 accumulation characteristics and relationship with deep CO2 fluid in Lishui sag, East China Sea Basin

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