A model for integrating clinical care and basic science research, and pitfalls of performing complex research projects for addressing a clinical challenge

The collaboration of clinicians with basic science researchers is crucial for addressing clinically relevant research questions. In order to initiate such mutually beneficial relationships, we propose a model where early career clinicians spend a designated time embedded in established basic science research groups, in order to pursue a postgraduate qualification. During this time, clinicians become integral members of the research team, fostering long term relationships and opening up opportunities for continuing collaboration. However, for these collaborations to be successful there are pitfalls to be avoided. Limited time and funding can lead to attempts to answer clinical challenges with highly complex research projects characterised by a large number of "clinical" factors being introduced in the hope that the research outcomes will be more clinically relevant. As a result, the complexity of such studies and variability of its outcomes may lead to difficulties in drawing scientifically justified and clinically useful conclusions. Consequently, we stress that it is the basic science researcher and the clinician's obligation to be mindful of the limitations and challenges of such multi-factorial research projects. A systematic step-by-step approach to address clinical research questions with limited, but highly targeted and well defined research projects provides the solid foundation which may lead to the development of a longer term research program for addressing more challenging clinical problems. Ultimately, we believe that it is such models, encouraging the vital collaboration between clinicians and researchers for the work on targeted, well defined research projects, which will result in answers to the important clinical challenges of today.

Can the contra-lateral limb be used as a control with respect to analyses of bone remodelling?

Bone loss may result from remodelling initiated by implant stress protection. Quantifying remodelling requires bone density distributions which can be obtained from computed tomography scans. Pre-operative scans of large animals however are rarely possible. This study aimed to determine if the contra-lateral bone is a suitable control for the purpose of quantifying bone remodelling. CT scans of 8 pairs of ovine tibia were used to determine the likeness of left and right bones. The deviation between the outer surfaces of the bone pairs was used to quantify geometric similarity. The density differences were determined by dividing the bones into discrete volumes along the shaft of the tibia. Density differences were also determined for fractured and contra-lateral bone pairs to determine the magnitude of implant related remodelling. Left and right ovine tibiae were found to have a high degree of similarity with differences of less than 1.0 mm in the outer surface deviation and density difference of less than 5% in over 90% of the shaft region. The density differences (10–40%) as a result of implant related bone remodelling were greater than left-right differences. Therefore, for the purpose of quantifying bone remodelling in sheep, the contra-lateral tibia may be considered an alternative to a pre-operative control.

The HarmonyGrid : music, space and performance in grid music systems

This research explores music in space, as experienced through performing and music-making with interactive systems. It explores how musical parameters may be presented spatially and displayed visually with a view to their exploration by a musician during performance. Spatial arrangements of musical components, especially pitches and harmonies, have been widely studied in the literature, but the current capabilities of interactive systems allow the improvisational exploration of these musical spaces as part of a performance practice. This research focuses on quantised spatial organisation of musical parameters that can be categorised as grid music systems (GMSs), and interactive music systems based on them. The research explores and surveys existing and historical uses of GMSs, and develops and demonstrates the use of a novel grid music system designed for whole body interaction. Grid music systems provide plotting of spatialised input to construct patterned music on a two-dimensional grid layout. GMSs are navigated to construct a sequence of parametric steps, for example a series of pitches, rhythmic values, a chord sequence, or terraced dynamic steps. While they are conceptually simple when only controlling one musical dimension, grid systems may be layered to enable complex and satisfying musical results. These systems have proved a viable, effective, accessible and engaging means of music-making for the general user as well as the musician. GMSs have been widely used in electronic and digital music technologies, where they have generally been applied to small portable devices and software systems such as step sequencers and drum machines. This research shows that by scaling up a grid music system, music-making and musical improvisation are enhanced, gaining several advantages: (1) Full body location becomes the spatial input to the grid. The system becomes a partially immersive one in four related ways: spatially, graphically, sonically and musically. (2) Detection of body location by tracking enables hands-free operation, thereby allowing the playing of a musical instrument in addition to “playing” the grid system. (3) Visual information regarding musical parameters may be enhanced so that the performer may fully engage with existing spatial knowledge of musical materials. The result is that existing spatial knowledge is overlaid on, and combined with, music-space. Music-space is a new concept produced by the research, and is similar to notions of other musical spaces including soundscape, acoustic space, Smalley's “circumspace” and “immersive space” (2007, 48-52), and Lotis's “ambiophony” (2003), but is rather more textural and “alive”—and therefore very conducive to interaction. Music-space is that space occupied by music, set within normal space, which may be perceived by a person located within, or moving around in that space. Music-space has a perceivable “texture” made of tensions and relaxations, and contains spatial patterns of these formed by musical elements such as notes, harmonies, and sounds, changing over time. The music may be performed by live musicians, created electronically, or be prerecorded. Large-scale GMSs have the capability not only to interactively display musical information as music representative space, but to allow music-space to co-exist with it. Moving around the grid, the performer may interact in real time with musical materials in music-space, as they form over squares or move in paths. Additionally he/she may sense the textural matrix of the music-space while being immersed in surround sound covering the grid. The HarmonyGrid is a new computer-based interactive performance system developed during this research that provides a generative music-making system intended to accompany, or play along with, an improvising musician. This large-scale GMS employs full-body motion tracking over a projected grid. Playing with the system creates an enhanced performance employing live interactive music, along with graphical and spatial activity. Although one other experimental system provides certain aspects of immersive music-making, currently only the HarmonyGrid provides an environment to explore and experience music-space in a GMS.

Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration.

There is a growing need for successful bone tissue engineering strategies and advanced biomaterials that mimic the structure and function of native tissues carry great promise. Successful bone repair approaches may include an osteoconductive scaffold, osteoinductive growth factors, cells with an osteogenic potential and capacity for graft vascularisation. To increase osteoinductivity of biomaterials, the local combination and delivery of growth factors has been developed. In the present study we investigated the osteogenic effects of calcium phosphate (CaP)-coated nanofiber mesh tube-mediated delivery of BMP-7 from a PRP matrix for the regeneration of critical sized segmental bone defects in a small animal model. Bilateral full-thickness diaphyseal segmental defects were created in twelve male Lewis rats and nanofiber mesh tubes were placed around the defect. Defects received either treatment with a CaP-coated nanofiber mesh tube (n = 6), an un-coated nanofiber mesh tube (n=6) a CaP-coated nanofiber mesh tube with PRP (n=6) or a CaP-coated nanofiber mesh tube in combination with 5 μg BMP-7 and PRP (n = 6). After 12 weeks, bone volume and biomechanical properties were evaluated using radiography, microCT, biomechanical testing and histology. The results demonstrated significantly higher biomechanical properties and bone volume for the BMP group compared to the control groups. These results were supported by the histological evaluations, where BMP group showed the highest rate of bone regeneration within the defect. In conclusion, BMP-7 delivery via PRP enhanced functional bone defect regeneration, and together these data support the use of BMP-7 in the treatment of critical sized defects.

Influence of plate bending stiffness on mechanical properties of healing fracture, mouse femora

Mechanically well-defined stabilization systems have only recently become available, providing standardized conditions for studying the role of the mechanical environment on mouse bone fracture healing. The aim of this study was to characterize the time course of strength recovery and callus development of mouse femoral osteotomies stabilized with either low or high flexibility (in bending and torsion) internal fixation plates. Animals were euthanized and femora excised at 14, 21, and 28 days post-osteotomy for microCT analysis and torsional strength testing. While a larger mineralized callus was observed in osteotomies under more flexible conditions at all time points, the earlier bridging of the mineralized callus under less flexible conditions by 1 week resulted in an earlier recovery of torsional strength in mice stabilized with low flexibility fixation. Ultimate torque values for these bones were significantly higher at 14 and 21 days post-osteotomy compared to bones with the more flexible stabilization. Our study confirms the high reproducibility of the results that are achieved with this new implant system, therefore making it ideal for studying the influence of the mechanical environment on murine fracture healing under highly standardized conditions.