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Glioblastoma (GBM) is one of the most common and aggressive forms of brain cancer. It is typically associated with poor survival rates, in part due to the characteristically infiltrative nature of GBM tumour cells. This allows GBM cells to disseminate through the brain via existing white matter tracts and perivascular spaces making complete surgical resection unachievable and contributing to high recurrence rates. For the majority of patients treatment of GBM includes radiotherapy. However, radiation resistance results in populations of surviving tumour cells with the potential for modified behaviour through radiation-induced alterations in signalling and gene expression profiles Myotonic dystrophy kinase-related CDC42- binding kinase (MRCK) is involved in regulating actin-myosin dynamics during cell migration through phosphorylation of its targets MLC2 and MYPT. Upon radiation of GBM cell lines in vivo we observed an increase in MRCK activity which was concomitant with a significant increase in GBM cell motility and invasion in in vitro and ex vivo assays. In support of these data we have observed increased MRCK activity at the invasive edges of both clinical GBM samples and an orthotopic GBM xenograft model that recapitulates key histological features of human GBM. Furthermore, therapeutic doses of irradiation were found to promote GBM invasion in vivo in this xenograft model. These observations suggest that MRCK activity may be required to promote invasion following irradiation and therefore may present a promising novel target for GBM treatment. To explore this further we performed MRCK RNAi on GBM cells and found we were able to reverse the radiation dependent promotion of GBM cell motility. We then used a novel MRCK selective inhibitor BDP-9066 to recapitulate this effect, observing dose dependent effects on both MRCK biomarkers, PMLC2 and PMYPT, and motility in vitro and ex vivo. These data suggest that MRCK activity is indeed required for GBM invasion and can be targeted effectively in multiple GBM cell lines. These observations provide evidence that glioblastoma cell migration may be enhanced following radiation therapy. As such, this might provide a substrate for therapy resistance and early recurrence in these tumours whilst offering a potential target for novel therapies in GBM management.

An electrode unit capable of detecting voluntarily elicited nerve signals for prolonged periods of time has been developed and tested. The electrode unit has been implanted around the distal ends of severed sciatic and peroneal nerves in rabbits. This electrode may prove suitable for implantation in human amputees for the purpose of recording neural control signals to activate prostheses with many degrees of freedom.

The effect of rapid as well as sustained compressive forces applied to the surface of intact and severed peroneal nerves of rabbits was studied. Considerable effort was taken to ensure a quantitative and consistent experimental paradigm. Stimuli were delivered to the sciatic nerve, and the compound action potential was recorded in the peroneal nerve, with compressive forces applied more proximally on the peroneal nerve. It was found that the conduction of action potentials on the larger nerve fibers was more sensitive to compressive force than that of the smaller nerve fibers, although all nerve fibers stopped conducting when sufficient compression was applied to the nerve. The effect on the conduction of action potentials on the nerve fibers appeared to be determined both by Laplace's law (as previously reported by others) and the viscoelastic properties of the entire nerve. Relatively low compressive forces (20 gm applied over approximately 7 sq mm) were found to decrease the neutral conduction of the larger nerve fibers for at least two hours, whereas stagnation of blood circulation was not found to affect measurably the neural conduction of all the nerve fibers for up to two hours.

Prescription of assistive devices for motor-handicapped individuals requires assessment of their motor capabilities. When patients' motor deficits are particularly severe, wide individual differences in the location and type of abnormalities complicate the assessment process. The precision of assessment has been greatly increased in recent years by the use of quantitative, computer-aided motion analysis, which facilitates statistical examination and comparison with normal individuals. This paper discusses a case study wherein a 24-year-old male nonvocal cerebral palsy patient was assessed for his ability to operate assistive communication devices. Three computer-aided measurement protocols were employed to evaluate the patient and two controls: performance using the patient's existing communication aid was evaluated in terms of rate and accuracy of communication using standardized spelling and response time tasks; volitional myoelectric activity was surveyed to identify possible myoelectric control sites for communication aid operation; a study of head position and its time derivatives was conducted to explore the feasibility of proportional control of a communication aid. Comparison of handicapped and control subject data indicated that, despite several characteristic motor control deficits, the handicapped subject was capable of proportional control of lateral head rotation and binary control of frontalis myoelectric signals. These movements could be used to operate a proportionally-controlled, direct-selection communication aid that could substantially increase the subject's communication rate. Work in progress includes the expansion of the handicapped and unimpaired subject databases and further development of the techniques discussed here to include three-dimensional motion analysis and objective measurement of muscle fatigue.