Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Potential lighting and thermal demand reduction in office buildings using blind control considering surrounding buildings

Automated blind control has been found to be more effective in controlling solar penetration than manual blind operation. Existing automated blind control methods mainly focus on improving indoor conditions, but considering the outside obstructions may offer a potential method to admit diffused solar radiation, reducing lighting, cooling, and heating demands. Accordingly, in this study, blind control considering surrounding buildings (BCCSB) was applied to determine potential demand reductions considering 20 736 cases of different surrounding building heights, orientations, locations, and climate change projections using EnergyPlus. The results demonstrate that BCCSB can reduce lighting demand by up to 30% when the building obstruction angle is greater 30°; however, this reduction decreased as the angle factor between the fenestration surface and sky decreased due to the accompanying reduction in admitted diffused solar radiation. The reduction in lighting demand also reduced the cooling demand as fewer active lighting fixtures were required. The use of BCCSB did not significantly reduce heating demand. The BCCSB can thus facilitate the reduction of lighting and cooling demand in highly glazed buildings, especially in warm climates. This evaluation of the positive effects of BCCSB can help to develop related design guidelines, standards, and practices for automated blind control strategies

Wind Resistance Performance Evaluation of Cable-Type Curtain Wall System on Reinforced Concrete High-Rise Buildings

Abstract In this research, a cable-type wall system that could replace the conventional aluminum curtain wall system for reinforced concrete high-rise buildings is proposed. The cable-type wall system is a newly developed system, which could be used as an existing exterior skin system, and can effectively support the wind load acting on the exterior of the high-rise buildings by the pre-induced initial tension force to the cable supporting the glass. The main advantages of the cable-type wall system are that the expense of construction could be reduced due to the simplicity of the construction. The experiment of structural analysis and air/water tightness was performed to evaluate its feasibility of industrialization. The structural performance of the cable-type wall system was evaluated through the structural analysis and the full-scale experiment to predict the initial pre-tension force and the design load displacement of the vertical one-way cable-type wall system that can be used for a typical floor of the high-rise building. The initial pre-tension force and structural behavior of the cable were analyzed by using the structural design program MIDAS-Gen. The maximum deformation value in the structural test was found to satisfy the AAMA condition, which is equal to the size of the facade skin system. The air/water tightness test was conducted to verify the performance. Test results show that the cable-type wall system satisfies the air/water tightness performance standards ASTM E283, E331 and AAMA 501.1-05 which are the most basic standards that the facade system must provide. As a result of this study, it is expected that the proposed cable-type wall system could be used for facade system, not only the structural performance but also air/water tightness performance are secured

Analysis of Infection Transmission Routes through Exhaled Breath and Cough Particle Dispersion in a General Hospital

Identifying infection transmission routes in hospitals may prevent the spread of respiratory viruses and mass infections. Most previous related research focused on the air movement of passive tracers, which typically represent breathing. In this study, particle evaporation and dispersions with various particle sizes were applied to evaluate particle movement because of breathing and coughing using computational fluid dynamics (CFD) simulations. Pyeongtaek St. Mary Hospital, where a Middle East respiratory syndrome (MERS) index patient infected several patients on the same floor, was used for a case study. We compared the dispersion characteristics of various particle sizes and validated results by comparing infection rates in different ward. Results indicated that droplets spread across the corridor and dispersed to wards that were more than 17 m apart from the index patient by natural ventilation. Droplets from exhaled breath under steady-state simulation showed a wider range of dispersion than cough droplets under transient simulation, but cough droplet dispersion was more consistent with the actual infection rate in each ward. Cough droplets sized under 75 µm evaporated to 26% of the initial size and started to disperse into the corridor within one minute; in nine minutes, droplets dispersed throughout every ward. This study may increase awareness on the dispersion characteristics of infectious particles

A pilot study for intraocular pressure measurements based on vibroacoustic parameters

Abstract The present study aimed to identify vibroacoustic properties associated with intraocular pressure (IOP) changes and to suggest a new way to measure the IOP based on these properties. Ten ex vivo porcine eyeballs were used in this study. Each eyeball was fixated in a central hole of a Styrofoam block, and vibration applied to the Styrofoam block was transmitted to the eyeball. An accelerometer directly attached to the eyeball measured the vibration response. Excitations and measurements were performed for 1 s, and the excitation magnitude was varied for the same signal in repeat measurements. A 30-gauge needle was inserted into the anterior chamber of the eyeball to inject a balanced salt solution, and the height of the bottle was adjusted to adjust the IOP. A tonometer was used under identical conditions to measure the IOP five times, and the mean value was determined for further analyses. The measurements showed that the parameters resonance frequency and change in the magnitude of the vibration response (CMVR) increased with rising IOP values. The CMVR was highly correlated with the IOP (p-value < 0.0001). A linear mixed effects model (LMM) was used as a statistical analysis method. We confirmed that vibroacoustic properties of the eyeball are correlated with IOP changes. It is expected that the CMVR will serve as a new parameter for IOP measurements. Thus, in the future, continuous IOP measurements would be easily performed using the CMVR

Activation of a flavin monooxygenase gene YUCCA7 enhances drought resistance in Arabidopsis

Auxin regulates diverse molecular and physiological events at the cellular and organismal levels during plant growth and development in response to environmental stimuli. It acts either through distinct signaling pathways or in concert with other growth hormones. Its biological functions are adjusted by modulating biosynthesis, conjugate formation, and polar transport and distribution. Several tryptophan-dependent and -independent auxin biosynthetic pathways have been proposed. Recent studies have shown that a few flavin monooxygenase enzymes contribute to the tryptophan-dependent auxin biosynthesis. Here, we show that activation of a flavin monooxygenase gene YUCCA7 (YUC7), which belongs to the tryptophan-dependent auxin biosynthetic pathway, enhances drought resistance. An Arabidopsis activation-tagged mutant yuc7-1D exhibited phenotypic changes similar to those observed in auxin-overproducing mutants, such as tall, slender stems and curled, narrow leaves. Accordingly, endogenous levels of total auxin were elevated in the mutant. The YUC7 gene was induced by drought, primarily in the roots, in an abscisic acid (ABA)-dependent manner. The yuc7-1D mutant was resistant to drought, and drought-responsive genes, such as RESPONSIVE TO DESSICATION 29A (RD29A) and COLD-REGULATED 15A (COR15A), were up-regulated in the mutant. Interestingly, whereas stomatal aperture and production of osmoprotectants were not discernibly altered, lateral root growth was significantly promoted in the yuc7-1D mutant when grown under drought conditions. These observations support that elevation of auxin levels in the roots enhances drought resistance possibly by promoting root growth

Drp1-Zip1 interaction regulates mitochondrial quality surveillance system

Cho et al. report that Drp1 that is the executioner for mitochondrial fission can reduce the mitochondrial membrane potential (MMP) during the mitochondrial division, and this new action helps identify bad sectors in the interconnected mitochondria. © 2018 Elsevier Inc.Mitophagy, a mitochondrial quality control process for eliminating dysfunctional mitochondria, can be induced by a response of dynamin-related protein 1 (Drp1) to a reduction in mitochondrial membrane potential (MMP) and mitochondrial division. However, the coordination between MMP and mitochondrial division for selecting the damaged portion of the mitochondrial network is less understood. Here, we found that MMP is reduced focally at a fission site by the Drp1 recruitment, which is initiated by the interaction of Drp1 with mitochondrial zinc transporter Zip1 and Zn 2+ entry through the Zip1-MCU complex. After division, healthy mitochondria restore MMP levels and participate in the fusion-fission cycle again, but mitochondria that fail to restore MMP undergo mitophagy. Thus, interfering with the interaction between Drp1 and Zip1 blocks the reduction of MMP and the subsequent mitophagic selection of damaged mitochondria. These results suggest that Drp1-dependent fission provides selective pressure for eliminating “bad sectors” in the mitochondrial network, serving as a mitochondrial quality surveillance system. © 2018 Elsevier Inc.1