Type inference in flexible model-driven engineering using classification algorithms

Flexible or bottom-up model-driven engineering (MDE) is an emerging approach to domain and systems modelling. Domain experts, who have detailed domain knowledge, typically lack the technical expertise to transfer this knowledge using traditional MDE tools. Flexible MDE approaches tackle this challenge by promoting the use of simple drawing tools to increase the involvement of domain experts in the language definition process. In such approaches, no metamodel is created upfront, but instead the process starts with the definition of example models that will be used to infer the metamodel. Pre-defined metamodels created by MDE experts may miss important concepts of the domain and thus restrict their expressiveness. However, the lack of a metamodel, that encodes the semantics of conforming models has some drawbacks, among others that of having models with elements that are unintentionally left untyped. In this paper, we propose the use of classification algorithms to help with the inference of such untyped elements. We evaluate the proposed approach in a number of random generated example models from various domains. The correct type prediction varies from 23 to 100% depending on the domain, the proportion of elements that were left untyped and the prediction algorithm used

FDG uptake is a surrogate marker for defining the optimal biological dose of the mTOR inhibitor everolimus in vivo

This study aimed to test whether [18F]fluoro-D-glucose (FDG) uptake of tumours measured by positron emission tomography (PET) can be used as surrogate marker to define the optimal biological dose (OBD) of mTOR inhibitors in vivo. Everolimus at 0.05, 0.5, 5 and 15 mg kg−1 per day was administered to gastric cancer xenograft-bearing mice for 23 days and FDG uptake of tumours was measured using PET from day 1 to day 8. To provide standard comparators for FDG uptake, tumour volume, S6 protein phosphorylation, Ki-67 staining and everolimus blood levels were evaluated. Everolimus blood levels increased in a dose-dependent manner but antitumour activity of everolimus reached a plateau at doses ⩾5 mg kg−1 per day (tumour volume treated vs control (T/C): 51% for 5 mg kg−1 per day and 57% for 15 mg kg−1 per day). Correspondingly, doses ⩾5 mg kg−1 per day led to a significant reduction in FDG uptake of tumours. Dose escalation above 5 mg kg−1 per day did not reduce FDG uptake any further (FDG uptake T/C: 49% for 5 mg kg−1 per day and 52% for 15 mg kg−1 per day). Differences in S6 protein phosphorylation and Ki-67 index reflected tumour volume and changes in FDG uptake but did not reach statistical significance. In conclusion, FDG uptake might serve as a surrogate marker for dose finding studies for mTOR inhibitors in (pre)clinical trials

Benthic and Hyporheic Macroinvertebrate Distribution Within the Heads and Tails of Riffles During Baseflow Conditions

The distribution of lotic fauna is widely acknowledged to be patchy reflecting the interaction between biotic and abiotic factors. In an in-situ field study, the distribution of benthic and hyporheic invertebrates in the heads (downwelling) and tails (upwelling) of riffles were examined during stable baseflow conditions. Riffle heads were found to contain a greater proportion of interstitial fine sediment than riffle tails. Significant differences in the composition of benthic communities were associated with the amount of fine sediment. Riffle tail habitats supported a greater abundance and diversity of invertebrates sensitive to fine sediment such as EPT taxa. Shredder feeding taxa were more abundant in riffle heads suggesting greater availability of organic matter. In contrast, no significant differences in the hyporheic community were recorded between riffle heads and tails. We hypothesise that clogging of hyporheic interstices with fine sediments may have resulted in the homogenization of the invertebrate community by limiting faunal movement into the hyporheic zone at both the riffle head and tail. The results suggest that vertical hydrological exchange significantly influences the distribution of fine sediment and macroinvertebrate communities at the riffle scale

Diagnostic Accuracy of Videofluoroscopy for Symptomatic Cervical Spine Injury Following Whiplash Trauma

Background: Intervertebral instability is a relatively common finding among patients with chronic neck pain after whiplash trauma. Videofluoroscopy (VF) of the cervical spine is a potentially sensitive diagnostic tool for evaluating instability, as it offers the ability to examine relative intervertebral movement over time, and across the entire continuum of voluntary movement of the patient. At the present time, there are no studies of the diagnostic accuracy of VF for discriminating between injured and uninjured populations. Methods: Symptomatic (injured) study subjects were recruited from consecutive patients with chronic (>6 weeks) post-whiplash pain presenting to medical and chiropractic offices equipped with VF facilities. Asymptomatic (uninjured) volunteers were recruited from family and friends of patients. An ethical review and oversight were provided by the Spinal Injury Foundation, Broomfield, CO. Three statistical models were utilized to assess the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of positive VF findings to correctly discriminate between injured and uninjured subjects. Results: A total of 196 subjects (119 injured, 77 uninjured) were included in the study. All three statistical models demonstrated high levels of sensitivity and specificity (i.e., receiver operating characteristic (ROC) values of 0.71 to 0.95), however, the model with the greatest practical clinical utility was based on the number of abnormal VF findings. For 2+ abnormal VF findings, the ROC was 0.88 (93% sensitivity, 79% specificity) and the PPV and NPV were both 88%. The highest PPV (1.0) was observed with 4+ abnormal findings. Conclusions: Videofluoroscopic examination of the cervical spine provides a high degree of diagnostic accuracy for the identification of vertebral instability in patients with chronic pain stemming from whiplash trauma