A trigger-based middleware cache for ORMs

ACM/IFIP/USENIX 12th International Middleware Conference, Lisbon, Portugal, December 12-16, 2011. ProceedingsCaching is an important technique in scaling storage for high-traffic web applications. Usually, building caching mechanisms involves significant effort from the application developer to maintain and invalidate data in the cache. In this work we present CacheGenie, a caching middleware which makes it easy for web application developers to use caching mechanisms in their applications. CacheGenie provides high-level caching abstractions for common query patterns in web applications based on Object-RelationalMapping (ORM) frameworks. Using these abstractions, the developer does not have to worry about managing the cache (e.g., insertion and deletion) or maintaining consistency (e.g., invalidation or updates) when writing application code. We design and implement CacheGenie in the popular Django web application framework, with PostgreSQL as the database backend and memcached as the caching layer. To automatically invalidate or update cached data, we use triggers inside the database. CacheGenie requires no modifications to PostgreSQL or memcached. To evaluate our prototype, we port several Pinax web applications to use our caching abstractions. Our results show that it takes little effort for application developers to use CacheGenie, and that CacheGenie improves throughput by 2-2.5× for read-mostly workloads in Pinax.Quanta Computer (Firm

Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)

Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months

Distributed database management systems : Architectural design choices for the cloud

Cloud computing has changed the way we used to exploit software and systems. The two decades’ practice of architecting solutions and services over the Internet has just revolved within the past few years. End users are now relying more on paying for what they use instead of purchasing a full-phase license. System owners are also in rapid hunt for business profits by deploying their services in the Cloud and thus maximising global outreach and minimising overall management costs. However, deploying and scaling Cloud applications regionally and globally are highly challenging. In this context, distributed data management systems in the Cloud promise rapid elasticity and horizontal scalability so that Cloud applications can sustain enormous growth in data volume, velocity, and value. Besides, distributed data replication and rapid partitioning are the two fundamental hammers to nail down these challenges. While replication ensures database read scalability and georeachability, data partitioning favours database write scalability and system-level load balance. System architects and administrators often face difficulties in managing a multi-tenant distributed database system in Cloud scale as the underlying workload characteristics change frequently. In this chapter, the inherent challenges of such phenomena are discussed in detail alongside their historical backgrounds. Finally, potential way outs to overcome such architectural barriers are presented under the light of recent research and development in this area

An international expanded-access programme of Everolimus : Addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy

BACKGROUND AND OBJECTIVES: The RECORD-1 trial established the clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) after failure of initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to address an unmet medical need by providing everolimus prior to commercial availability, and also to further assess the safety and efficacy of everolimus in patients with VEGFr-TKI-refractory mRCC. PATIENTS AND METHODS: REACT (Clinicaltrials.gov: NCT00655252) was a global, open-label, expanded-access programme in patients with mRCC who were intolerant of, or who had progressed on or after stopping treatment with, any available VEGFr-TKI therapy. Patients received everolimus 10mg once daily, with dose and schedule modifications allowed for toxicity. Patients were closely monitored for the development of serious and grades 3/4 adverse events (AEs). Response was assessed by RECIST every 3months for the first year and every 6months thereafter. RESULTS: A total of 1367 patients were enroled. Safety findings and tumour responses were consistent with those observed in RECORD-1, with no new safety issues identified. The most commonly reported serious AEs were dyspnoea (5.0%), pneumonia (4.7%) and anaemia (4.1%), and the most commonly reported grades 3/4 AEs were anaemia (13.4%), fatigue (6.7%) and dyspnoea (6.5%). Best overall response was stable disease in 51.6% and partial response in 1.7% of patients. Median everolimus treatment duration was 14weeks. CONCLUSION: Everolimus is well tolerated in patients with mRCC and demonstrates a favourable risk-benefit ratio