From Out-Place Transformation Evolution to In-Place Model Patching

Model transformation is a key technique to automate software engineering tasks. Like any other software, transformations are not resilient to change. As changes to transformations can invalidate previously produced models, these changes need to be reflected on existing models. Currently, revised out-place transformations are re-executed entirely to achieve this co-evolution task. However, this induces an unnecessary overhead, particularly when computation- intensive transformations are marginally revised, and if existing models have undergone updates prior the re-execution, these updates get discarded in the newly produced models. To overcome this co-evolution challenge, our idea is to infer from evolved out-place transformations patch transformations that propagate changes to existing models by re-executing solely the affected parts based on an in-place execution strategy. Thereby, existing models are only updated by a patch instead of newly produced. In this paper, we present the conceptual foundation of our approach and report on its evaluation in a real-world case study.European Commission ICT Policy Support Programme 31785

Prototyping the Semantics of a DSL using ASF+SDF: Link to Formal Verification of DSL Models

A formal definition of the semantics of a domain-specific language (DSL) is a key prerequisite for the verification of the correctness of models specified using such a DSL and of transformations applied to these models. For this reason, we implemented a prototype of the semantics of a DSL for the specification of systems consisting of concurrent, communicating objects. Using this prototype, models specified in the DSL can be transformed to labeled transition systems (LTS). This approach of transforming models to LTSs allows us to apply existing tools for visualization and verification to models with little or no further effort. The prototype is implemented using the ASF+SDF Meta-Environment, an IDE for the algebraic specification language ASF+SDF, which offers efficient execution of the transformation as well as the ability to read models and produce LTSs without any additional pre or post processing.Comment: In Proceedings AMMSE 2011, arXiv:1106.596

Daunorubicin and doxorubicin but not BCNU have deleterious effects on organotypic multicellular spheroids of gliomas.

In the present study organotypic multicellular spheroids (OMS) were used to study the effects of chemotherapeutic agents on malignant gliomas. Compared with the frequently used cell line models, OMS have several advantages with respect to the preservation of the cellular heterogeneity and the structure of the original tumour. OMS prepared from seven glioma specimens were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), daunorubicin or doxorubicin. After exposure to these drugs, the histology and cell proliferation of the OMS were analysed by immunohistochemistry and image analysis. Furthermore, the expression of P-glycoprotein (P-gp) and multidrug resistance-related protein (MRP), which both can contribute to resistance to daunorubicin and doxorubicin, were immunohistochemically investigated. We found that OMS from gliomas are sensitive for daunorubicin and doxorubicin but not for BCNU in terms of tissue destruction and decrease in cell proliferation. In addition, all gliomas were P-gp and MRP negative, which is in accordance with the sensitivity for daunorubicin and doxorubicin. Considering the potential use of several new alternative drug delivery methods, such as intratumoural implantation of drug-impregnated polymers or liposomal encapsulation of cytostatic drugs, daunorubicin and doxorubicin might be effective in the treatment of malignant gliomas

Approach to diagnosing a pediatric patient with severe insulin resistance in low- or middle-income countries

Diabetes mellitus (DM) in children is most often caused by impaired insulin secretion (type 1 DM). In some children, the underlying mechanism for DM is increased insulin resistance, which can have different underlying causes. While the majority of these children require insulin dosages less than 2.0 U/kg/day to achieve normoglycemia, higher insulin requirements indicate severe insulin resistance. Considering the therapeutic challenges in patients with severe insulin resistance, early diagnosis of the underlying cause is essential in order to consider targeted therapies and to prevent diabetic complications. Although rare, several disorders can attribute to severe insulin resistance in pediatric patients. Most of these disorders are diagnosed through advanced diagnostic tests, which are not commonly available in low- or middle-income countries. Based on a case of DM with severe insulin resistance in a Surinamese adolescent who was later confirmed to have autosomal recessive congenital generalized lipodystrophy, type 1 (Berardinelli–Seip syndrome), we provide a systematic approach to the differential diagnosis and work-up. We show that a thorough review of medical history and physical examination generally provide sufficient information to diagnose a child with insulin-resistant DM correctly, and, therefore, our approach is especially applicable to low- or middle-income countries

Pain at home during childhood cancer treatment:Severity, prevalence, analgesic use, and interference with daily life

Background Pain is a common symptom in childhood cancer. Since children spend more time at home, families are increasingly responsible for pain management. This study aimed at assessing pain at home. Procedure In this longitudinal observational study (April 2016-January 2017), pain severity and prevalence, analgesic use, and pain interference with daily life (Brief Pain Inventory Short Form) were assessed for 4 consecutive days around the time of multiple chemotherapy appointments. Descriptive statistics (frequencies and percentages) were used to report pain severity (with clinically significant pain defined as: score >= 4 on "worst pain" or "average pain in the last 24 h"), pain prevalence, and analgesic use. Mixed models were estimated to assess whether patient characteristics were associated with pain severity, and whether pain severity was associated with interference with daily life. Results Seventy-three children (50.7% male) participated (1-18 years). A majority (N = 57, 78%) experienced clinically significant pain at least once, and 30% reported clinically significant pain at least half the time. In 33.6% of scores >= 4, no medication was used. We found an association between pain severity and interference with daily life: the higher the pain, the bigger the interference (estimated regression coefficient = 1.01 [95% CI 0.98-1.13]). Conclusions The majority of children experienced clinically significant pain at home, and families frequently indicated no medication use. A stronger focus on education and coaching of families seems essential, as well as routine screening for pain in the home setting

Generic model transformations: Write once, reuse everywhere

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-21732-6_5Proceedings of 4th International Conference, ICMT 2011, Zurich, Switzerland, June 27-28, 2011Model transformation is one of the core techniques in Model Driven Engineering. Many transformation languages exist nowadays, but few offer mechanisms directed to the reuse of whole transformations or transformation fragments in different contexts. Taking inspiration from generic programming, in this paper we define model transformation templates. These templates are defined over meta-model concepts which later can be bound to specific meta-models. The binding mechanism is flexible as it permits mapping concepts and meta-models with certain kinds of structural heterogeneities. The approach is general and can be applied to any model transformation language. In this paper we report on its application to ATL.Work funded by the Spanish Ministry of Science (projects TIN2008-02081 and TIN2009-11555), and the R&D programme of the Madrid Region (project S2009 /TIC-1650

Gastrointestinal symptoms in patients with isolated oligodontia and a Wnt gene mutation

OBJECTIVE: Since Wnt signaling plays an important role in both tooth agenesis and altered intestine homeostasis, the aim was to compare gastrointestinal symptoms in patients with isolated oligodontia caused by a Wnt pathway gene mutation and controls. METHODS: A case-control study was designed to compare self-reported gastrointestinal symptoms among patients with isolated oligodontia, caused by a Wnt signaling gene mutation, and fully dentate controls. The Gastrointestinal Symptom Rating Scale (GSRS) was used to assess gastrointestinal symptoms. Prevalence and severity of gastrointestinal symptoms among patients and age- and gender-matched controls was evaluated. RESULTS: Twenty patients with isolated oligodontia and a pathogenic variant in the wnt pathway genes WNT10A, LRP6 or PAX9 participated. The prevalence of gastrointestinal symptoms was higher in the oligodontia patients compared to their controls (Χ2 (1) = 87.33, p = .008). Mean GSRS total scores (p = .011) and domain scores for 'abdominal pain' (p = .022), 'reflux' (p = .003) and constipation (p = .030) were higher for these oligodontia patients compared to their controls. CONCLUSION: Gastrointestinal symptoms are more prevalent and more severe in patients with isolated oligodontia and a deficiency in a Wnt pathway related gene, when compared to controls without tooth agenesis

The limitation of genetic testing in diagnosing patients suspected for congenital platelet defects

Thrombosis and Hemostasi

Qualitative evaluation of a form for standardized information exchange between orthopedic surgeons and occupational physicians

BACKGROUND: Both occupational physicians and orthopedic surgeons can be involved in the management of work relevant musculoskeletal disorders. These physicians hardly communicate with each other and this might lead to different advices to the patient. Therefore, we evaluated a standardized information exchange form for the exchange of relevant information between the orthopedic surgeon and the occupational physician. The main goals of this qualitative study are to evaluate whether the form improved information exchange, whether the form gave relevant information, and to generate ideas to further improve this information exchange. METHODS: The information exchange form was developed in two consensus meetings with five orthopedic surgeons and five occupational physicians. To evaluate the information exchange form, a qualitative evaluation was set up. Structured telephone interviews were undertaken with the patients, interviews with the physicians were face-to-face and semi-structured, based on a topic list. These interviews were recorded and literally transcribed. Each interview was analyzed separately in Atlas-Ti. RESULTS: The form was used for 8 patients, 7 patients agreed to participate in the qualitative evaluation. All three orthopedic surgeons involved and three of the six involved occupational physicians agreed to be interviewed. The form was transferred to 4 occupational physicians, the other 3 patients recovered before they visited the occupational physician. The information on the form was regarded to be useful. All orthopedic surgeons agreed that the occupational physician should take the initiative. Most physicians felt that the form should not be filled out for each patient visiting an orthopedic surgeon, but only for those patients who do not recover as expected. Orthopedic surgeons suggested that a copy of the medical information provided to the general practitioner could also be provided to occupational physicians. CONCLUSION: The information exchange form was regarded to be useful and could be used in practice. The occupational physician should take the initiative for using this form and most physicians felt the information should only be exchanged for patients who do not recover as expected. That means that the advantage of giving information early in the treatment is lost