Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Investigation of ion-induced etch damages on trench surface of Ge2Sb2Te5 in high density Ar/SF6 plasma

© 2022 Korean Physical SocietyIon-induced etch damage on trench surfaces of Ge2Sb2Te5 (GST) by reactive ion etching (RIE) is investigated with Ar/SF6 capacitively coupled plasma (CCP). Etch damage on the sidewall increases with higher plasma density and decreases with the bias power. The roughness of the bottom decreases with the bias power due to the ion sputtering. It is demonstrated that the optimum process condition to minimize the ion-induced damage can be obtained from the feature analysis of the virtual metrology, which was developed with plasma information parameters named PI-VM, and it predicted the GST etch rate and surface roughness. It reveals that the energetic ions play a crucial role in removing the halogenated surfaces by high-energy ion sputtering. In addition, the sidewall damage by the lower F radicals is significant because the collisional diffused F radicals are enhanced in the high-density plasma. It explains the control of bias power required to achieve the profiling etch in the high-density plasma.N

Initiated Chemical Vapor Deposition (iCVD) of Highly Cross-Linked Polymer Films for Advanced Lithium-Ion Battery Separators

We report an initiated chemical vapor deposition (iCVD) process to coat polyethylene (PE) separators in Li-ion batteries with a highly cross-linked, mechanically strong polymer, namely, polyhexavinyldisiloxane (pHVDS). The highly cross-linked but ultrathin pHVDS films can only be obtained by a vapor-phase process, because the pHVDS is insoluble in most solvents and thus infeasible with conventional solution-based methods. Moreover, even after the pHVDS coating, the initial porous structure of the separator is well preserved owing to the conformal vapor-phase deposition. The coating thickness is delicately controlled by deposition time to the level that the pore size decreases to below 7% compared to the original dimension. The pHVDS-coated PE shows substantially improved thermal stability and electrolyte wettability. After incubation at 140 degrees C for 30 min, the pHVDS-coated PE causes only a 12% areal shrinkage (versus 90% of the pristine separator). The superior wettability results in increased electrolyte uptake and ionic conductivity, leading to significantly improved rate performance. The current approach is applicable to a wide range of porous polymeric separators that suffer from thermal shrinkage and poor electrolyte wetting.

Rapid and high-throughput analysis of N-glycans from ovarian cancer serum using a 96-well plate platform

We present a rapid and high-throughput human serum N-glycan preparation technology using 96-well plate-based procedures, The released N-glycans front polyvinylidene fluoride (PVDF) membrane filter plate are subsequently loaded to porous graphitic carbon (PGC) containing a 96-well plate to remove salts and other contaminants without sacrificing accuracy or reproducibility. This robust glycan Preparation technology is applied to ovarian cancer diagnosis using 5 mu l of patient Serum. (C) 2009 Elsevier Inc. All rights reserved.LEE KJ, 2009, BIOCHEM BIOPH RES CO, V309, P223Gil GC, 2008, ANAL BIOCHEM, V379, P45, DOI 10.1016/j.ab.2008.04.039Ruhaak LR, 2008, ANAL CHEM, V80, P6119, DOI 10.1021/ac800630xKim YG, 2008, PROTEOMICS, V8, P2596, DOI 10.1002/pmic.200700972Royle L, 2008, ANAL BIOCHEM, V376, P1, DOI 10.1016/j.ab.2007.12.012Brooks SA, 2008, ANTI-CANCER AGENT ME, V8, P2Saldova R, 2007, GLYCOBIOLOGY, V17, P1344, DOI 10.1093/glycob/cwm100Badgwell D, 2007, DIS MARKERS, V23, P397Duffy MJ, 2005, INT J GYNECOL CANCER, V15, P679Garson K, 2005, MOL CELL ENDOCRINOL, V239, P15, DOI 10.1016/j.mce.2005.03.019Jacobs IJ, 2004, MOL CELL PROTEOMICS, V3, P355, DOI 10.1074/mcp.R400006-MCP200VARKI A, 1993, GLYCOBIOLOGY, V3, P97CHANDRASEKARAN EV, 1992, J BIOL CHEM, V267, P23806

Modified Laparoscopic Transabdominal Cervicoisthmic Cerclage for the Surgical Management of Recurrent Pregnancy Loss due to Cervical Factors

This study aimed evaluate the feasibility of modified laparoscopic transabdominal cervicoisthmic cerclage (LTCC) and its impact on recurrent pregnancy loss (RPL) and is a retrospective observational cohort study of patients who underwent modified LTCC from 2003 to 2018 (n = 299). The surgery was performed at a mean gestational age of 12.5 weeks (range 10.5–17.5 weeks). Of the 299 patients, 190 were reported as having undergone abortion (one abortion: 91 (47.9%), two: 59 (31.1%), three or more: 40 (21.1%)) before the present pregnancy and prior to the surgery. The mean operation time was 47.4 min (range 15–100 min). We followed up with 205 of 299 patients and recorded their obstetric outcomes. There were 176 successful deliveries via cesarean section, and the fetal survival rate was 85.9% (176/205). The results of this study suggest that modified LTCC is a safe and feasible surgical option during pregnancy for patients with a history of RPL due to cervical factors

Plasma information-based virtual metrology (PI-VM) and mass production process control

© 2022, The Korean Physical Society.In this paper, we review the development of plasma engineering technology that improves dramatically the production efficiency of OLED (organic light-emitting diode) displays and semiconductor manufacturing by utilizing a process monitoring methodology based on the physical domain knowledge. The domain knowledge consists of plasma-heating and sheath physics, plasma chemistry and plasma-material surface reaction kinetics, and plasma diagnostics. Based on this, a plasma information-based virtual metrology (PI-VM) algorithm was developed drastically enhanced process prediction performance by parameterizing plasma information (PI) which can trace the states of processing plasmas. PI-VM has superior process prediction accuracy compared to the classical statistics-based virtual metrologies. The developed PI-VM algorithms adopted for practical processing issues such as the control and management of the OLED-display mass production demonstrated savings of approximately 25% of the yield loss over the past 5 years. This improvement was achieved with the development of FDC (fault detection and classification) and APC (advanced process control) logic, which can be developed through the analysis of the physical characteristics of the feature parameters used in PI-VM with the evaluation of their contributions and their correlations to the processing results. PI-VM provides leverage that can be applied in the development of process equipment and factory automation technologies.N