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

Graphene and Related Materials for Resistive Random Access Memories

Graphene and related materials (GRMs) are promising candidates for the fabrication of resistive random access memories (RRAM). Here, we analyze, classify and evaluate this emerging field, and summarize the performance of the RRAM prototypes using GRMs. Graphene oxide, amorphous carbon films, transition metal dichalcogenides, hexagonal boron nitride and black phosphorous can be used as resistive switching media, in which the switching can be governed either by the migration of intrinsic species or penetration of metallic ions from adjacent layers. Graphene can be used as electrode to provide flexibility and transparency, as well as an interface layer between the electrode and dielectric to block atomic diffusion, reduce power consumption, suppress surface effects, limit the number of conductive filaments in the dielectric, and improve device integration. GRMs-based RRAMs fit some non-volatile memory technological requirements like low operating voltages 10 years, endurance >109 cycles and power consumption ~10 pJ/transition still remain a challenge. More technology-oriented studies including reliability and variability analyses may lead to the development of GRMs-based RRAMs with realistic possibilities of commercialization.We acknowledge support from the Young 1000 Global Talent Recruitment Program of the Ministry of Education of China, the National Natural Science Foundation of China (grants no. 61502326, 41550110223), the Jiangsu Government (grant no. BK20150343), the Ministry of Finance of China (grant no. SX21400213), the Young 973 National Program of the Chinese Ministry of Science and Technology (grant no. 2015CB932700), the Collaborative Innovation Center of Suzhou Nano Science & Technology, the Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, the Priority Academic Program Development of Jiangsu Higher Education Institutions, the National Natural Science Foundation of China under Grant Nos. 61521064, 61322408, 61422407, the Beijing Training Project for the Leading Talents in S&T under Grant No. ljrc201508, the Opening Project of Key Laboratory of Microelectronic Devices & Integrated Technology, Institute of Microelectronics, Chinese Academy of Sciences, the EU Graphene Flagship, FP7 Grant CARERAMM, ERC Grants Hetero2D and Highgraink, EPSRC Grants EP/K01711X/1, EP/K017144/1, EP/N010345/1, EP/M507799/1, EP/L016087/1, EP/M013243/1

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Toward a new understanding of environmental and financial performance through corporate social responsibility, green innovation, and sustainable development

Abstract The study’s primary objective is to advance the environmental management research field by examining the relationship between corporate social responsibility (CSR), environmental and financial performance while considering the mediating effect of sustainable development and green innovation. In addition, the study also analyzes the moderating effect of green innovation actions and green innovation strategies. Employees in the manufacturing sector in Pakistan completed a self-administered survey. Data gathered from 497 employees was analyzed using the structural analysis. The study results show that corporate social responsibility to the environment (CSREM), corporate social responsibility to employees (CSREM), to the community (CSRCO), and to the consumers (CSRCO) positively influences environmental performance (EVP) and financial performance (FP). Environmental sustainable development (ESD) and green innovation (GI) mediate the relationship between CSR, environmental, and firm financial performance. Green innovation strategies (GINS) and green innovation actions (GINAs) moderate the relationship between a firm’s environmental and financial aspects. The study deepens the understanding of CSR through an integrated model of mediator and moderator variables. It attempts to boost the firms’ performance (i.e., environmental, and financial) by applying the concept of green innovation and sustainable development. This study brings significant results for manufacturing firms, managers, entrepreneurs, policymakers, practitioners, employees, and other stakeholders. The study’s outcomes make the stakeholders adopt CSR consideration to achieve ecological and financial harmony in developing economies