IceDust: Incremental and Eventual Computation of Derived Values in Persistent Object Graphs

Derived values are values calculated from base values. They can be expressed in object-oriented languages by means of getters calculating the derived value, and in relational or logic databases by means of (materialized) views. However, switching to a different calculation strategy (for example caching) in object-oriented programming requires invasive code changes, and the databases limit expressiveness by disallowing recursive aggregation. In this paper, we present IceDust, a data modeling language for expressing derived attribute values without committing to a calculation strategy. IceDust provides three strategies for calculating derived values in persistent object graphs: Calculate-on-Read, Calculate-on-Write, and Calculate-Eventually. We have developed a path-based abstract interpretation that provides static dependency analysis to generate code for these strategies. Benchmarks show that different strategies perform better in different scenarios. In addition we have conducted a case study that suggests that derived value calculations of systems used in practice can be expressed in IceDust

Eating Your Own Dog Food: WebDSL Case Studies to Improve Academic Workflows

SDF, Stratego and Spoofax provide a platform for development of domain-specific programming languages. On this platform, the WebDSL project started out as a case study in language engineering, and grew into a reliable tool for rapid prototyping and continuous development of web applications. Our team led by Eelco Visser develops and operates several web applications to support academic workflows. EvaTool governs the process of course quality control, importing questionnaire data, and providing lecturers and education directors with a platform to discuss and agree on improvements. WebLab is an online learning management system with a focus on programming education, with support for lab work and digital exams, used by over 40 courses. Conf Researchr is a domain-specific content management system for creating and hosting integrated websites for conferences with multiple co-located events, used by all ACM SIGPLAN and SIGSOFT conferences. MyStudyPlanning is an application for composition of individual study programs by students and verification of those programs by the exam board, used by multiple faculties at the Delft University of Technology. These tools served as practical case studies for applying the research, and ensure the continued development of the underlying platform

Conf Researchr: A Domain-Specific Content Management System for Managing Large Conference Websites

Conferences are great opportunities for sharing research, debating solutions, and networking. For the organizing committee there is a considerable deal of complexity and effort required to provide attendees and organizers with ways to find and manage programs, sessions, papers, tracks, talks, and authors. Eelco Visser found an opportunity to provide an integrated solution to these problems by designing the Conf Researchr conference management system in 2014 using our own domain-specific web programming language WebDSL. In this paper, we highlight the impact Eelco had on conference management, and how Conf Researchr evolved to become the platform of choice for hosting over 900 conference and workshop editions in SIGPLAN and SIGSOFT, among other areas of computer science research

Real-world Data of Nivolumab for Patients With Advanced Renal Cell Carcinoma in the Netherlands:An Analysis of Toxicity, Efficacy, and Predictive Markers

Background: Nivolumab, a programmed death 1 inhibitor, has been approved as second-line treatment for advanced renal cell carcinoma (RCC) in Europe since 2016. We investigated the toxicity and efficacy of nivolumab as well as potential predictive biomarkers in the Dutch population. Patients and Methods: This was a retrospective, multicenter study of the Dutch national registry of nivolumab for the treatment of advanced RCC. The main outcome parameters included toxicity, objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and time to treatment failure (TTF). In addition, potential predictive and prognostic biomarkers for outcomes were evaluated. Results: Data on 264 patients were available, of whom 42% were International Metastatic RCC Database Consortium (IMDC) poor risk at start of nivolumab, 16% had ≥ 3 lines of previous therapy, 7% had non–clear-cell RCC, 11% had brain metastases, and 20% were previously treated with everolimus. Grade 3/4 immune-related adverse events occurred in 15% of patients. The median OS was 18.7 months (95% confidence interval, 13.7-23.7 months). Progression occurred in 170 (64.4%) of 264 patients, with a 6-and 12-months TTP of 49.8% and 31.1%, respectively. The ORR was 18.6% (49 of 264; 95% confidence interval, 14%-23%). Elevated baseline lymphocytes were associated with improved PFS (P =.038) and elevated baseline lactate dehydrogenase with poor OS, PFS, and TTF (P =.000). On-treatment increase in eosinophils by week 8 predicted improved OS (P =.003), PFS (P =.000), and TTF (P =.014), whereas a decrease of neutrophils was associated with significantly better TTF (P =.023). Conclusions: The toxicity and efficacy of nivolumab for metastatic RCC after previous lines of therapy are comparable with the results in the pivotal phase III trial and other real-world data. On-treatment increase in eosinophil count is a potential biomarker for efficacy and warrants further investigation

Code generation by model transformation: A case study in transformation modularity

The realization of model-driven software development requires effective techniques for implementing code generators for domain-specific languages. This paper identifies techniques for improving separation of concerns in the implementation of generators. The core technique is code generation by model transformation, that is, the generation of a structured representation (model) of the target program instead of plain text. This approach enables the transformation of code after generation, which in turn enables the extension of the target language with features that allow better modularity in code generation rules. The technique can also be applied to ‘internal code generation’ for the translation of high-level extensions of a DSL to lower-level constructswithin the sameDSL using model-to-model transformations. This paper refines our earlier description of code generation by model transformation with an improved architecture for the composition of model-to-model normalization rules, solving the problem of combining type analysis and transformation. Instead of coarse-grained stages that alternate between normalization and type analysis, we have developed a new style of type analysis that can be integrated with normalizing transformations in a fine-grained manner. The normalization strategy has a simple extension interface and integrates non-local, context-sensitive transformation rules. We have applied the techniques in a realistic case study of domain-specific language engineering, i.e. the code generator for WebDSL, using Stratego, a high-level transformation language that integrates model-to-model, model-to-code, and code-to-code transformations.Software TechnologyElectrical Engineering, Mathematics and Computer Scienc

Real-world Data of Nivolumab for Patients With Advanced Renal Cell Carcinoma in the Netherlands: An Analysis of Toxicity, Efficacy, and Predictive Markers

BACKGROUND: Nivolumab, a programmed death 1 inhibitor, has been approved as second-line treatment for advanced renal cell carcinoma (RCC) in Europe since 2016. We investigated the toxicity and efficacy of nivolumab as well as potential predictive biomarkers in the Dutch population. PATIENTS AND METHODS: This was a retrospective, multicenter study of the Dutch national registry of nivolumab for the treatment of advanced RCC. The main outcome parameters included toxicity, objective response rate (ORR), overall survival (OS), progression-free survival (PFS), time to progression (TTP), and time to treatment failure (TTF). In addition, potential predictive and prognostic biomarkers for outcomes were evaluated. RESULTS: Data on 264 patients were available, of whom 42% were International Metastatic RCC Database Consortium (IMDC) poor risk at start of nivolumab, 16% had ≥ 3 lines of previous therapy, 7% had non-clear-cell RCC, 11% had brain metastases, and 20% were previously treated with everolimus. Grade 3/4 immune-related adverse events occurred in 15% of patients. The median OS was 18.7 months (95% confidence interval, 13.7-23.7 months). Progression occurred in 170 (64.4%) of 264 patients, with a 6-and 12-months TTP of 49.8% and 31.1%, respectively. The ORR was 18.6% (49 of 264; 95% confidence interval, 14%-23%). Elevated baseline lymphocytes were associated with improved PFS (P = .038) and elevated baseline lactate dehydrogenase with poor OS, PFS, and TTF (P = .000). On-treatment increase in eosinophils by week 8 predicted improved OS (P = .003), PFS (P = .000), and TTF (P = .014), whereas a decrease of neutrophils was associated with significantly better TTF (P = .023). CONCLUSIONS: The toxicity and efficacy of nivolumab for metastatic RCC after previous lines of therapy are comparable with the results in the pivotal phase III trial and other real-world data. On-treatment increase in eosinophil count is a potential biomarker for efficacy and warrants further investigation