Effect of dapagliflozin on 24-hour glycemic variables in Japanese patients with type 2 diabetes mellitus receiving basal insulin supported oral therapy (DBOT) : a multicenter, randomized, open-label, parallel-group study

Introduction: This study aimed to evaluate the impacts of dapagliflozin on 24-hour glucose variability and diabetes-related biochemical variables in Japanese patients with type 2 diabetes who had received basal insulin supported oral therapy (BOT). Research design and methods: Changes in mean daily blood glucose level before and after 48–72 hours of add-on or no add-on of dapagliflozin (primary end point) and diabetes-related biochemical variables and major safety variables during the 12 weeks (secondary end point) were evaluated in the multicenter, randomized, two-arm, open-label, parallel-group comparison study. Results: Among 36 participants, 18 were included in the no add-on group and 18 were included in the dapagliflozin add-on group. Age, gender, and body mass index were comparable between the groups. There were no changes in continuous glucose monitoring metrics in the no add-on group. In the dapagliflozin add-on group, mean glucose (183–156mg/dL, p=0.001), maximum glucose (300–253, p<0.01), and SD glucose (57–45, p<0.05) decreased. Time in range increased (p<0.05), while time above the range decreased in the dapagliflozin add-on group but not in the no add-on group. After 12-week treatment with dapagliflozin add-on, 8-hydroxy-2’-deoxyguanosine (8OHdG), as well as hemoglobin A1c (HbA1c), decreased. Conclusions: This study showed that the mean daily blood glucose and other daily glucose profiles were amended after 48–72 hours of dapagliflozin add-on in Japanese patients with type 2 diabetes who received BOT. The diabetes-related biochemical variables such as HbA1c and urinary 8OHdG were also obtained during the 12 weeks of dapagliflozin add-on without major adverse events. A preferable 24-hour glucose profile in ‘time in ranges’ and an improvement in reactive oxygen species by dapagliflozin warrant us to evaluate these benefits in larger clinical studies

Demand-side decarbonization and electrification: EMF 35 JMIP study

Japan’s long-term strategy submitted to the United Nations Framework Convention on Climate Change emphasizes the importance of improving the electrification rates to reducing GHG emissions. Using the five models participating in Energy Modeling Forum 35 Japan Model Intercomparison project (JMIP), we focused on the demand-side decarbonization and analyzed the final energy composition required to achieve 80% reductions in GHGs by 2050 in Japan. The model results show that the electricity share in final energy use (electrification rate) needs to reach 37–66% in 2050 (26% in 2010) to achieve the emissions reduction of 80%. The electrification rate increases mainly due to switching from fossil fuel end-use technologies (i.e. oil water heater, oil stove and combustion-engine vehicles) to electricity end-use technologies (i.e. heat pump water heater and electric vehicles). The electricity consumption in 2050 other than AIM/Hub ranged between 840 and 1260 TWh (AIM/Hub: 1950TWh), which is comparable to the level seen in the last 10 years (950–1035 TWh). The pace at which electrification rate must be increased is a challenge. The model results suggest to increase the electrification pace to 0.46–1.58%/yr from 2030 to 2050. Neither the past electrification pace (0.30%/year from 1990 to 2010) nor the outlook of the Ministry of Economy, Trade and Industry (0.15%/year from 2010 to 2030) is enough to reach the suggested electrification rates in 2050. Therefore, more concrete measures to accelerate dissemination of electricity end-use technologies across all sectors need to be established

The Effect of Three-Dimensional Preoperative Simulation on Liver Surgery

BackgroundIn the past decade, three-dimensional (3D) simulation has been commonly used for liver surgery. However, few studies have analyzed the usefulness of this 3D simulation. The aim of this study was to evaluate the effect of 3D simulation on the outcome of liver surgery.MethodsWe retrospectively analyzed 240 consecutive patients who underwent liver resection. The patients were divided into two groups: those who received 3D preoperative simulation (“3D group”, n = 120) and those who did not undergo 3D preoperative simulation (“without 3D group”, n = 120). The perioperative outcomes, including operation time, blood loss, maximum aspartate transaminase level, length of postoperative stay, postoperative complications and postoperative mortality, were compared between the two groups. The predicted resected liver volume was compared with the actual resected volume.ResultsThe median operation time for the 3D group was 36 min shorter than that for the without 3D group (P = 0.048). There were no significant differences in other outcomes between the two groups. A subgroup analysis revealed that the operation time of repeated hepatectomy and segmentectomy for the 3D group was shorter than that for the without 3D group (P = 0.03). There was a strong correlation between the predicted liver volume and the actual resected liver weight (r = 0.80, P < 0.001).ConclusionThese findings demonstrate that 3D preoperative simulation may reduce the operation time, particularly for repeated hepatectomy and segmentectomy

Looking under the hood: A comparison of techno-economic assumptions across national and global integrated assessment models

Integrated assessment models are extensively used in the analysis of climate change mitigation and are informing national decision makers as well as contribute to international scientific assessments. This paper conducts a comprehensive review of techno-economic assumptions in the electricity sector among fifteen different global and national integrated assessment models. Particular focus is given to six major economies in the world: Brazil, China, the EU, India, Japan and the US. The comparison reveals that techno-economic characteristics are quite different across integrated assessment models, both for the base year and future years. It is, however, important to recognize that techno-economic assessments from the literature exhibit an equally large range of parameters as the integrated assessment models reviewed. Beyond numerical differences, the representation of technologies also differs among models, which needs to be taken into account when comparing numerical parameters. While desirable, it seems difficult to fully harmonize techno-economic parameters across a broader range of models due to structural differences in the representation of technology. Therefore, making techno-economic parameters available in the future, together with of the technology representation as well as the exact definitions of the parameters should become the standard approach as it allows an open discussion of appropriate assumptions. © 2019 The Author

Taking stock of national climate policies to evaluate implementation of the Paris Agreement

Many countries have implemented national climate policies to accomplish pledged Nationally Determined Contributions and to contribute to the temperature objectives of the Paris Agreement on climate change. In 2023, the global stocktake will assess the combined effort of countries. Here, based on a public policy database and a multi-model scenario analysis, we show that implementation of current policies leaves a median emission gap of 22.4 to 28.2 GtCO2eq by 2030 with the optimal pathways to implement the well below 2 °C and 1.5 °C Paris goals. If Nationally Determined Contributions would be fully implemented, this gap would be reduced by a third. Interestingly, the countries evaluated were found to not achieve their pledged contributions with implemented policies (implementation gap), or to have an ambition gap with optimal pathways towards well below 2 °C. This shows that all countries would need to accelerate the implementation of policies for renewable technologies, while efficiency improvements are especially important in emerging countries and fossil-fuel-dependent countries

Cost and attainability of meeting stringent climate targets without overshoot

Global emissions scenarios play a critical role in the assessment of strategies to mitigate climate change. The current scenarios, however, are criticized because they feature strategies with pronounced overshoot of the global temperature goal, requiring a long-term repair phase to draw temperatures down again through net-negative emissions. Some impacts might not be reversible. Hence, we explore a new set of net-zero CO2 emissions scenarios with limited overshoot. We show that upfront investments are needed in the near term for limiting temperature overshoot but that these would bring long-term economic gains. Our study further identifies alternative configurations of net-zero CO2 emissions systems and the roles of different sectors and regions for balancing sources and sinks. Even without net-negative emissions, CO2 removal is important for accelerating near-term reductions and for providing an anthropogenic sink that can offset the residual emissions in sectors that are hard to abate

Proteome and Membrane Fatty Acid Analyses on Oligotropha carboxidovorans OM5 Grown under Chemolithoautotrophic and Heterotrophic Conditions

Oligotropha carboxidovorans OM5 T. (DSM 1227, ATCC 49405) is a chemolithoautotrophic bacterium able to utilize CO and H2 to derive energy for fixation of CO2. Thus, it is capable of growth using syngas, which is a mixture of varying amounts of CO and H2 generated by organic waste gasification. O. carboxidovorans is capable also of heterotrophic growth in standard bacteriologic media. Here we characterize how the O. carboxidovorans proteome adapts to different lifestyles of chemolithoautotrophy and heterotrophy. Fatty acid methyl ester (FAME) analysis of O. carboxidovorans grown with acetate or with syngas showed that the bacterium changes membrane fatty acid composition. Quantitative shotgun proteomic analysis of O. carboxidovorans grown in the presence of acetate and syngas showed production of proteins encoded on the megaplasmid for assimilating CO and H2 as well as proteins encoded on the chromosome that might have contributed to fatty acid and acetate metabolism. We found that adaptation to chemolithoautotrophic growth involved adaptations in cell envelope, oxidative homeostasis, and metabolic pathways such as glyoxylate shunt and amino acid/cofactor biosynthetic enzymes

Land-based implications of early climate actions without global net-negative emissions

Delaying climate mitigation action and allowing a temporary overshoot of temperature targets require large-scale carbon dioxide removal (CDR) in the second half of this century that may induce adverse side effects on land, food and ecosystems. Meanwhile, meeting climate goals without global net-negative emissions inevitably needs early and rapid emission reduction measures, which also brings challenges in the near term. Here we identify the implications for land-use and food systems of scenarios that do not depend on land-based CDR technologies. We find that early climate action has multiple benefits and trade-offs, and avoids the need for drastic (mitigation-induced) shifts in land use in the long term. Further long-term benefits are lower food prices, reduced risk of hunger and lower demand for irrigation water. Simultaneously, however, near-term mitigation pressures in the agriculture, forest and land-use sector and the required land area for energy crops increase, resulting in additional risk of food insecurity

Taking stock of national climate policies to evaluate implementation of the Paris Agreement

Many countries have implemented national climate policies to accomplish pledged Nationally Determined Contributions and to contribute to the temperature objectives of the Paris Agreement on climate change. In 2023, the global stocktake will assess the combined effort of countries. Here, based on a public policy database and a multi-model scenario analysis, we show that implementation of current policies leaves a median emission gap of 22.4 to 28.2 GtCO2eq by 2030 with the optimal pathways to implement the well below 2 °C and 1.5 °C Paris goals. If Nationally Determined Contributions would be fully implemented, this gap would be reduced by a third. Interestingly, the countries evaluated were found to not achieve their pledged contributions with implemented policies (implementation gap), or to have an ambition gap with optimal pathways towards well below 2 °C. This shows that all countries would need to accelerate the implementation of policies for renewable technologies, while efficiency improvements are especially important in emerging countries and fossil-fuel-dependent countries