Trabecular bone organoids: a micron-scale 'humanised' prototype designed to study the effects of microgravity and degeneration.

Bone is a highly responsive organ, which continuously adapts to the environment it is subjected to in order to withstand metabolic demands. These events are difficult to study in this particular tissue in vivo, due to its rigid, mineralised structure and inaccessibility of the cellular component located within. This manuscript presents the development of a micron-scale bone organoid prototype, a concept that can allow the study of bone processes at the cell-tissue interface. The model is constructed with a combination of primary female osteoblastic and osteoclastic cells, seeded onto femoral head micro-trabeculae, where they recapitulate relevant phenotypes and functions. Subsequently, constructs are inserted into a simulated microgravity bioreactor (NASA-Synthecon) to model a pathological state of reduced mechanical stimulation. In these constructs, we detected osteoclastic bone resorption sites, which were different in morphology in the simulated microgravity group compared to static controls. Once encapsulated in human fibrin and exposed to analogue microgravity for 5 days, masses of bone can be observed being lost from the initial structure, allowing to simulate the bone loss process further. Constructs can function as multicellular, organotypic units. Large osteocytic projections and tubular structures develop from the initial construct into the matrix at the millimetre scale. Micron-level fragments from the initial bone structure are detected travelling along these tubules and carried to sites distant from the native structure, where new matrix formation is initiated. We believe this model allows the study of fine-level physiological processes, which can shed light into pathological bone loss and imbalances in bone remodelling.

Cross-border portfolio investment networks and indicators for financial crises.

Cross-border equity and long-term debt securities portfolio investment networks are analysed from 2002 to 2012, covering the 2008 global financial crisis. They serve as network-proxies for measuring the robustness of the global financial system and the interdependence of financial markets, respectively. Two early-warning indicators for financial crises are identified: First, the algebraic connectivity of the equity securities network, as a measure for structural robustness, drops close to zero already in 2005, while there is an over-representation of high-degree off-shore financial centres among the countries most-related to this observation, suggesting an investigation of such nodes with respect to the structural stability of the global financial system. Second, using a phenomenological model, the edge density of the debt securities network is found to describe, and even forecast, the proliferation of several over-the-counter-traded financial derivatives, most prominently credit default swaps, enabling one to detect potentially dangerous levels of market interdependence and systemic risk.

An assessment of pediatric all-terrain vehicle injuries.

OBJECTIVES: All-terrain vehicle (ATV) related injuries and deaths have been increasing since 1996. The objective of this study is to define the impact on the morbidity and mortality of the pediatric population of the referral area of one of Kentucky's level-1 trauma centers. METHODS: Data were collected retrospectively from the University of Kentucky Trauma Registry on all patients younger than 18 years of age admitted to the level 1 trauma center between 1996 and 2000 with ATV related injuries. RESULTS: One hundred fifty-one pediatric patients were hospitalized from an ATV-related injury during the study period. There were five deaths. The male/female ratio was 3.2:1. The mean revised trauma score was 7.3 +/- 1.3. The mean injury severity score was 12.3 +/- 8.9. Helmet use was only 4%. The average hospitalization was 4.4 +/- 5.2 days, 32% went to the intensive care unit and 52% to the operating room. Forty percent of patients had multisystem injuries. Passengers were younger than drivers (9.3 +/- 4.9 and 13.3 +/- 2.7 years, respectively). Hospital charges exceeded dollar 2.1 million. CONCLUSION: All-terrain vehicle-related injuries led to significant morbidity and mortality for the pediatric population of southern and southeastern Kentucky. Encouraging helmet use and discouraging passengers from riding through safety education or a new state law may help to reduce ATV related mortality and morbidity. Prohibiting children younger than 16 years from operating or riding on an ATV seems justified.