The mechanical properties of the dentine and cement of the tusk of the narwhal Monodon monoceros compared with those of other mineralized tissues

Values for Young's modulus of elasticity, ultimate and yield stresses, ultimate and yield strains, work under the stress-strain curve and work of fracture were obtained from tensile and bending tests on specimens of narwhal tusk dentine and cement, femoral bone from young and mature cattle, and reindeer antler. Compared with the cattle bone the narwhal tissues had low Young's moduli, low yield stresses, rather low ultimate stresses and high ultimate strains. In all these properties they were similar to reindeer antler. The calcium content and hardness of the narwhal tissues were compared with those of human and cattle dental tissues. The narwhal dentine was considerably softer and less mineralized than human and cattle dentine. Human cementum was softer and less mineralized than cattle cementum, and was like narwhal cementum. In general, the mechanical properties of the narwhal tusk tissues were as would be expected from their mineral content, except that the stiffness of the cementum was low. It is likely that narwhal dentine is not very similar to human and cattle dentine in its mechanical properties.     

KRAS mutations and CDKN2A promoter methylation show an interactive adverse effect on survival and predict recurrence of rectal cancer

Colonic and rectal cancers differ in their clinicopathologic features and treatment strategies. Molecular markers such as gene methylation, microsatellite instability and KRAS mutations, are becoming increasingly important in guiding treatment decisions in colorectal cancer. However, their association with clinicopathologic variables and utility in the management of rectal cancer is still poorly understood. We analyzed CDKN2A gene methylation, CpG island methylator phenotype (CIMP), microsatellite instability and KRAS/BRAF mutations in a cohort of 381 rectal cancers with extensive clinical follow‐up data. BRAF mutations (2%), CIMP‐high (4%) and microsatellite instability‐high (2%) were rare, whereas KRAS mutations (39%), CDKN2A methylation (20%) and CIMP‐low (25%) were more common. Only CDKN2A methylation and KRAS mutations showed an association with poor overall survival but these did not remain significant when analyzed with other clinicopathologic factors. In contrast, this prognostic effect was strengthened by the joint presence of CDKN2A methylation and KRAS mutations, which independently predicted recurrence of cancer and was associated with poor overall and cancer‐specific survival. This study has identified a subgroup of more aggressive rectal cancers that may arise through the KRAS‐p16 pathway. It has been previously shown that an interaction of p16 deficiency and oncogenic KRAS promotes carcinogenesis in the mouse and is characterized by loss of oncogene‐induced senescence. These findings may provide avenues for the discovery of new treatments in rectal cancer.     

Analysis of clinical judgment helps to improve agreement in the assessment of rheumatoid arthritis.

Experienced rheumatologists differ widely in their assessments of rheumatoid arthritis even after extensive efforts to improve agreement by discussion and consensus. The use of computer feedback to provide an analysis of clinicians' judgment policies in a highly structured investigation has been shown to improve agreement, but this may not apply in normal clinical practice. Here the successful convergence of clinical agreements by three rheumatologists using computer assisted feedback over several months in a National Health Service outpatient department is reported. In the three months without feedback their pooled agreement for assessing the severity of rheumatoid arthritis was r2 = 0.62. During the three months in which feedback was provided agreement rose to r2 = 0.92. The principal component of all three judgment policies at the end of the feedback period was 'articular index'.