Using virtual topology operations to generate analysis topology

Virtual topology operations have been utilized to generate an analysis topology definition suitable for downstream mesh generation. Detailed descriptions are provided for virtual topology merge and split operations for all topological entities. Current virtual topology technology is extended to allow the virtual partitioning of volume cells and the topological queries required to carry out each operation are provided. Virtual representations are robustly linked to the underlying geometric definition through an analysis topology. The analysis topology and all associated virtual and topological dependencies are automatically updated after each virtual operation, providing the link to the underlying CAD geometry. Therefore, a valid description of the analysis topology, including relative orientations, is maintained. This enables downstream operations, such as the merging or partitioning of virtual entities, and interrogations, such as determining if a specific meshing strategy can be applied to the virtual volume cells, to be performed on the analysis topology description. As the virtual representation is a non-manifold description of the sub-divided domain the interfaces between cells are recorded automatically. This enables the advantages of non-manifold modelling to be exploited within the manifold modelling environment of a major commercial CAD system, without any adaptation of the underlying CAD model. A hierarchical virtual structure is maintained where virtual entities are merged or partitioned. This has a major benefit over existing solutions as the virtual dependencies are stored in an open and accessible manner, providing the analyst with the freedom to create, modify and edit the analysis topology in any preferred sequence, whilst the original CAD geometry is not disturbed. Robust definitions of the topological and virtual dependencies enable the same virtual topology definitions to be accessed, interrogated and manipulated within multiple different CAD packages and linked to the underlying geometry.

Utility of sarcoma-specific fusion gene analysis in paraffin-embedded material for routine diagnosis at a specialist centre.

AIMS: Diagnosis of soft tissue sarcomas can be difficult. It can be aided by detection of specific genetic aberrations in many cases. This study assessed the utility of a molecular genetics/cytogenetics service as part of the routine diagnostic service at the Royal Marsden Hospital. METHODS: A retrospective audit was performed over a 15-month period to evaluate the diagnostic usefulness for soft tissue sarcomas with translocations of fluorescence in situ hybridisation (FISH) and reverse-transcriptase PCR (RT-PCR) in paraffin-embedded (PE) material. Results were compared with histology, and evaluated. RESULTS: Molecular investigations were performed on PE material in 158 samples (total 194 RT-PCR and 174 FISH tests), of which 85 were referral cases. Synovial sarcoma, Ewing sarcoma and low-grade fibromyxoid sarcoma were the most commonly tested tumours. Myxoid liposarcoma showed the best histological and molecular concordance, and alveolar rhabdomyosarcoma showed the best agreement between methods. FISH had a higher sensitivity for detecting tumours (73%, compared with 59% for RT-PCR) with a better success rate than RT-PCR, although the latter was specific in identifying the partner gene for each fusion. In particular, referral blocks in which methods of tissue fixation and processing were not certain resulted in higher RT-PCR failure rates. CONCLUSIONS: FISH and RT-PCR on PE tissue are practical and effective ancillary tools in the diagnosis of soft tissue sarcomas. They are useful in confirming doubtful histological diagnoses and excluding malignant diagnoses. PCR is less sensitive than FISH, and the use of both techniques is optimal for maximising the detection rate of translocation-positive sarcomas.

Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia

Children with Down syndrome (DS) have a greatly increased risk of acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia (ALL). Both DS-AMKL and the related transient myeloproliferative disorder (TMD) have GATA1 mutations as obligatory, early events. To identify mutations contributing to leukemogenesis in DS-ALL, we undertook sequencing of candidate genes, including FLT3, RAS, PTPN11, BRAF, and JAK2. Sequencing of the JAK2 pseudokinase domain identified a specific, acquired mutation, JAK2R683, in 12 (28%) of 42 DS-ALL cases. Functional studies of the common JAK2R683G mutation in murine Ba/F3 cells showed growth factor independence and constitutive activation of the JAK/STAT signaling pathway. High-resolution SNP array analysis of 9 DS-ALL cases identified additional submicroscopic deletions in key genes, including ETV6, CDKN2A, and PAX5. These results infer a complex molecular pathogenesis for DS-ALL leukemogenesis, with trisomy 21 as an initiating or first hit and with chromosome aneuploidy, gene deletions, and activating JAK2 mutations as complementary genetic events. (Blood. 2009; 113: 646-648)

Number comparison and number ordering as predictors of arithmetic performance in adults: Exploring the link between the two skills, and investigating the question of domain-specificity.

Recent evidence has highlighted the important role that number ordering skills play in arithmetic abilities (e.g., Lyons & Beilock, 2011). In fact, Lyons et al. (2014) demonstrated that although at the start of formal mathematics education number comparison skills are the best predictors of arithmetic performance, from around the age of 10, number ordering skills become the strongest numerical predictors of arithmetic abilities. In the current study we demonstrated that number comparison and ordering skills were both significantly related to arithmetic performance in adults, and the effect size was greater in the case of ordering skills. Additionally, we found that the effect of number comparison skills on arithmetic performance was partially mediated by number ordering skills. Moreover, performance on comparison and ordering tasks involving the months of the year was also strongly correlated with arithmetic skills, and participants displayed similar (canonical or reverse) distance effects on the comparison and ordering tasks involving months as when the tasks included numbers. This suggests that the processes responsible for the link between comparison and ordering skills and arithmetic performance are not specific to the domain of numbers. Finally, a factor analysis indicated that performance on comparison and ordering tasks loaded on a factor which included performance on a number line task and self-reported spatial thinking styles. These results substantially extend previous research on the role of order processing abilities in mental arithmetic.