An overview of Mirjam and WeaveC

In this chapter, we elaborate on the design of an industrial-strength aspectoriented programming language and weaver for large-scale software development. First, we present an analysis on the requirements of a general purpose aspect-oriented language that can handle crosscutting concerns in ASML software. We also outline a strategy on working with aspects in large-scale software development processes. In our design, we both re-use existing aspect-oriented language abstractions and propose new ones to address the issues that we identified in our analysis. The quality of the code ensured by the realized language and weaver has a positive impact both on maintenance effort and lead-time in the first line software development process. As evidence, we present a short evaluation of the language and weaver as applied today in the software development process of ASML

An Evaluation of Clone Detection Techniques for Identifying Crosscutting Concerns

Code implementing a crosscutting concern is often spread over many different parts of an application. Identifying such code automatically greatly improves both the maintainability and the evolvability of the application. First of all, it allows a developer to more easily find the places in the code that must be changed when the concern changes, and thus makes such changes less time consuming and less prone to errors. Second, it allows a developer to refactor the code, so that it uses modern and more advanced abstraction mechanisms, thereby restoring its modularity. In this paper, we evaluate the suitability of clone detection as a technique for the identification of crosscutting concerns. To that end, we manually identify four specific concerns in an industrial C application, and analyze to what extent clone detection is capable of finding these concerns. We consider our results as a stepping stone toward an automated "concern miner" based on clone detection

Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood

Background: Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Through a process of reverse engineering, this study aims to identify druggable molecular biomarkers associated with the clinical improvement in the OPTIMISTIC cohort. Methods: Based on full blood samples collected during OPTIMISTIC, we performed paired mRNA sequencing for 27 patients before and after the CBT intervention. Linear mixed effect models were used to identify biomarkers associated with the disease-causing CTG expansion and the mean clinical improvement across all clinical outcome measures. Results: We identified 608 genes for which their expression was significantly associated with the CTG-repeat expansion, as well as 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes associated with both returned to more normal levels in patients who benefited the most from CBT. This main finding has been replicated based on an external dataset of mRNA data of DM1 patients and controls, singling these genes out as candidate biomarkers for therapy response. Among these candidate genes were DNAJB12, HDAC5, and TRIM8, each belonging to a protein family that is being studied in the context of neurological disorders or muscular dystrophies. Across the different gene sets, gene pathway enrichment analysis revealed disease-relevant impaired signaling in, among others, insulin-, metabolism-, and immune-related pathways. Furthermore, evidence for shared dysregulations with another neuromuscular disease, Duchenne muscular dystrophy, was found, suggesting a partial overlap in blood-based gene dysregulation. Conclusions: DM1-relevant disease signatures can be identified on a molecular level in peripheral blood, opening new avenues for drug discovery and therapy efficacy assessments.</p

Social media posts and online search behaviour as early-warning system for MRSA outbreaks

Background: Despite many preventive measures, outbreaks with multi-drug resistant micro-organisms (MDROs) still occur. Moreover, current alert systems from healthcare organizations have shortcomings due to delayed or incomplete notifications, which may amplify the spread of MDROs by introducing infected patients into a new healthcare setting and institutions. Additional sources of information about upcoming and current outbreaks, may help to prevent further spread of MDROs. The study objective was to evaluate whether methicillin-resistant Staphylococcus aureus (MRSA) outbreaks could be detected via social media posts or online search behaviour; if so, this might allow earlier detection than the official notifications by healthcare organizations. Methods: We conducted an exploratory study in which we compared information about MRSA outbreaks in the Netherlands derived from two online sources, Coosto for Social Media, and Google Trends for search behaviour, to the mandatory Dutch outbreak notification system (SO-ZI/AMR). The latter provides information on MDRO outbreaks including the date of the outbreak, micro-organism involved, the region/location, and the type of health care organization. Results: During the research period of 15 months (455 days), 49 notifications of outbreaks were recorded in SO-ZI/ AMR. For Coosto, the number of unique potential outbreaks was 37 and for Google Trends 24. The use of social media and online search behaviour missed many of the hospital outbreaks that were reported to SO-ZI/AMR, but detected additional outbreaks in long-term care facilities. Conclusions: Despite several limitations, using information from social media and online search behaviour allows rapid identification of potential MRSA outbreaks, especially in healthcare settings with a low notification compliance. When combined in an automated system with real-time updates, this approach might increase early discovery and subsequent implementation of preventive measures.EPI-Net COMBACTE-MAGNET project 115737Unión Europea FP7/2007–201

Social media posts and online search behaviour as early-warning system for MRSA outbreaks

Despite many preventive measures, outbreaks with multi-drug resistant micro-organisms (MDROs) still occur. Moreover, current alert systems from healthcare organizations have shortcomings due to delayed or incomplete notifications, which may amplify the spread of MDROs by introducing infected patients into a new healthcare setting and institutions. Additional sources of information about upcoming and current outbreaks, may help to prevent further spread of MDROs.The study objective was to evaluate whether methicillin-resistant Staphylococcus aureus (MRSA) outbreaks could be detected via social media posts or online search behaviour; if so, this might allow earlier detection than the official notifications by healthcare organizations

An overview of Mirjam and WeaveC

In this chapter, we elaborate on the design of an industrial-strength aspectoriented programming language and weaver for large-scale software development. First, we present an analysis on the requirements of a general purpose aspect-oriented language that can handle crosscutting concerns in ASML software. We also outline a strategy on working with aspects in large-scale software development processes. In our design, we both re-use existing aspect-oriented language abstractions and propose new ones to address the issues that we identified in our analysis. The quality of the code ensured by the realized language and weaver has a positive impact both on maintenance effort and lead-time in the first line software development process. As evidence, we present a short evaluation of the language and weaver as applied today in the software development process of ASML

Editors:

software-intensive high-tech system

Detecting behavioral conflicts among crosscutting concerns

Aspects have been successfully promoted as a means to improve the modularization of software in the presence of crosscutting concerns. Within the Ideals project, aspects have been shown to be valuable for improving the modularization of idioms (see also Chapter 1). The so-called aspect interference problem is considered to be one of the remaining challenges of aspect-oriented software development: aspects may interfere with the behavior of the base code or other aspects. Especially interference among aspects is dif��?cult to prevent, as this may be caused solely by the composition of aspects that behave correctly in isolation. A typical situation where this may occur is when multiple advices are applied at the same, or shared, join point. In this chapter we explain the problem of behavioral conflicts among aspects at shared join points, illustrated by aspects that represent idioms: Parameter checking and Error propagation. We present an approach for the detection of behavioral conflicts that is based on a novel abstraction model for representing the behavior of advice. The approach employs a set of conflict detection rules which can be used to detect both generic conflicts as well as domain or application speci��?c conflicts. One of the benefits of the approach is that it neither requires the application programmers to deal with the conflict models, nor does it require a background in formal methods for the aspect programmers

An Accessible Diagnostic Toolbox to Detect Bacterial Causes of Ovine and Caprine Abortion

Results of laboratory investigations of ovine and caprine cases of abortion in the lambing season 2015–2016 were analyzed, using pathology records of submissions to Royal GD (Deventer, the Netherlands) from January until and including April 2016, in comparison with the results of two accessible alternative techniques for sampling aborted lambs and kids, swabbing the fetal oropharynx and puncture of the fetal lung. Chlamydia abortus was the main cause of abortion in sheep as well as in goats. Other causes of abortion were Campylobacter spp., Listeria spp., Escherichia coli, and Yersinia enterocolitica. Ovine pathological submissions resulted more often in detecting an infectious agent compared to caprine submissions. For the three main bacterial causes of abortion, Campylobacter spp., Listeria spp., and Chlamydia spp., compared to results of the pathological examination, oropharynx mucus, and fetal lung puncture samples showed an observed agreement of 0.87 and 0.89, an expected agreement of 0.579 and 0.584, and a kappa value of 0.691 and 0.737 (95% CI: 0.561–0.82 and 0.614–0.859), respectively. The agreement between the results of the pathological examination and both fetal lung puncture and oropharynx mucus samples was classified as good. In conclusion, although a full step-wise post-mortem examination remains the most proper way of investigating small ruminant abortions, the easily accessible, low-threshold tools for practitioners and farmers as described in this paper not only provide reliable results compared to results of the post-mortem examination but also stimulates farmers and veterinarians to submit fetuses and placentas if necessary. Suggestions for further improvement of both alternatives have been summarized. Both alternatives could also be tailor-made for specific regions with their specific causes of abortion