MDCC: Multi-Data Center Consistency

Replicating data across multiple data centers not only allows moving the data closer to the user and, thus, reduces latency for applications, but also increases the availability in the event of a data center failure. Therefore, it is not surprising that companies like Google, Yahoo, and Netflix already replicate user data across geographically different regions. However, replication across data centers is expensive. Inter-data center network delays are in the hundreds of milliseconds and vary significantly. Synchronous wide-area replication is therefore considered to be unfeasible with strong consistency and current solutions either settle for asynchronous replication which implies the risk of losing data in the event of failures, restrict consistency to small partitions, or give up consistency entirely. With MDCC (Multi-Data Center Consistency), we describe the first optimistic commit protocol, that does not require a master or partitioning, and is strongly consistent at a cost similar to eventually consistent protocols. MDCC can commit transactions in a single round-trip across data centers in the normal operational case. We further propose a new programming model which empowers the application developer to handle longer and unpredictable latencies caused by inter-data center communication. Our evaluation using the TPC-W benchmark with MDCC deployed across 5 geographically diverse data centers shows that MDCC is able to achieve throughput and latency similar to eventually consistent quorum protocols and that MDCC is able to sustain a data center outage without a significant impact on response times while guaranteeing strong consistency

The Atomic Manifesto: a Story in Four Quarks

This report summarizes the viewpoints and insights gathered in the Dagstuhl Seminar on Atomicity in System Design and Execution, which was attended by 32 people from four different scientific communities: database and transaction processing systems, fault tolerance and dependable systems, formal methods for system design and correctness reasoning, and hardware architecture and programming languages. Each community presents its position in interpreting the notion of atomicity and the existing state of the art, and each community identifies scientific challenges that should be addressed in future work. In addition, the report discusses common themes across communities and strategic research problems that require multiple communities to team up for a viable solution. The general theme of how to specify, implement, compose, and reason about extended and relaxed notions of atomicity is viewed as a key piece in coping with the pressing issue of building and maintaining highly dependable systems that comprise many components with complex interaction patterns

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