Effect of Axial Load on the Flexural Properties of an Elastomeric Total Disc Replacement

Study Design. Twelve Cadisc-L devices were subjected to flexion (0°–6°) and extension (0° to -3°) motions at compressive loads between 500 N and 2000 N at a flexural rate between 0.25°/s and 3.0°/s.\ud \ud Objective. To quantify the change in flexural properties of the Cadisc-L (elastomeric device), when subjected to increasing magnitudes of axial load and at different flexural rates.\ud \ud Summary of Background Data. The design of motion preservation devices, used to replace degenerated intervertebral discs, is commonly based on a low-friction, ball-and-socket-articulating joint. Recently, elastomeric implants have been developed that attempt to provide mechanical and motion properties that resemble those of the natural disc more closely.\ud \ud Methods. Twelve Cadisc-L devices (MC-10 mm-9° and MC-10 mm-12° size) were supplied by Ranier Technology Ltd (Cambridge, United Kingdom). The devices were hydrated and tested using a Bose spinal disc-testing machine (Bose Corporation, ElectroForce Systems Group, Eden Prairie, MN) in Ringer's solution at 37°C. A static load of 500 N was applied to a device and it was then subjected to motions of 0° to 6° to 0° (flexion) and 0° to -3° to 0° (extension) at a flexural rate of 0.25°/s, 0.5°/s, 1.0°/s, 1.5°/s, 2.0°/s, and 3.0°/s. Tests were repeated at 1000 N, 1500 N, and 2000 N.\ud \ud Results. Regression analyses showed a significant ($R^2$ > 0.99, $\rho$< 0.05) linear increase in bending moment and flexural stiffness with flexion and extension angles (at 1000 N and higher loads)—a significant ($R^2$> 0.994, $\rho$< 0.05) linear decrease in flexural stiffness in flexion and extension as flexural rate increased.\ud \ud Conclusion. The bending moment of the Cadisc-L increased linearly with flexion and extension angles at 1000 N and higher loads. Flexural stiffness increased with compressive load but decreased with flexural rate.\ud \u

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes