Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05)

Background and purpose: Despite numerous randomized trials investigating radiotherapy (RT) fractionation schedules for painful bone metastases, there are very few data on RT for bone metastases causing pain with a neuropathic component. The Trans-Tasman Radiation Oncology Group undertook a randomized trial comparing the efficacy of a single 8 Gy (8/1) with 20 Gy in 5 fractions (20/5) for this type of pain. Materials and methods: Eligible patients had radiological evidence of bone metastases from a known malignancy with no change in systemic therapy within 6 weeks before or anticipated within 4 weeks after RT, no other metastases along the distribution of the neuropathic pain and no clinical or radiological evidence of cord/cauda equina compression. All patients gave written informed consent. Primary endpoints were pain response within 2 months of commencement of RT and time to treatment failure (TTF). The hypothesis was that 8/1 is at least as effective as 20/5 and the planned sample size was 270 patients. Results: Between February 1996 and December 2002, 272 patients were randomized (8/1:20/5 = 137:135) from 15 centres (Australia 11, New Zealand 3, UK 1). The commonest primary cancers were lung (31%), prostate (29%) and breast (8%); index sites were spine (89%), rib (9%), other (2%); 72% of patients were males and the median age was 67 (range 2989). The median overall survival (95% CI) for all randomized patients was 4.8 mo (4.2-5.7 mo). The intention-to-treat overall response rates (95% Cl) for 8/1 vs 20/5 were 53% (45-62%) vs 61% (53-70%), P = 0.18. Corresponding figures for complete response were 26% (18-34%) vs 27% (19-35%), P = 0.89. The estimated median TTFs (95% CI) were 2.4 mo (2.0-3.3 mo) vs 3.7 mo (3.1-5.9 mo) respectively. The hazard ratio (95% Cl) for the comparison of TTF curves was 1.35 (0.99-1.85), log-rank P = 0.056. There were no statistically significant differences in the rates of re-treatment, cord compression or pathological fracture by arm. Conclusions: 8/1 was not shown to be as effective as 20/5, nor was it statistically significantly worse. Outcomes were generally poorer for 8/1, although the quantitative differences were relatively small. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Quality assurance experience with the randomized neuropathic bone pain trial (Trans-Tasman Radiation Oncology Group, 96.05)

Background and purpose: Trans-Tasman Radiation Oncology Group 96.05 is a prospective randomized controlled trial comparing a single 8 Gy with 20 Gy in five fractions of radiotherapy (RT) for neuropathic pain due to bone metastases. This paper summarizes the quality assurance (QA) activities for the first 234 patients (accrual target 270). Materials and methods: Independent audits to assess compliance with eligibility/exclusion criteria and appropriateness of treatment of the index site were conducted after each cohort of approximately 45 consecutive patients. Reported serious adverse events (SAEs) in the form of cord/cauda equina compression or pathological fracture developing at the index site were investigated and presented in batches to the Independent Data Monitoring Committee. Finally, source data verification of the RT prescription page and treatment records was undertaken for each of the first 234 patients to assess compliance with the protocol. Results: Only one patient was found conclusively not to have genuine neuropathic pain, and there were no detected 'geographical misses' with RT fields. The overall rate of detected infringements for other eligibility criteria over five audits (225 patients) was 8% with a dramatic improvement after the first audit. There has at no stage been a statistically significant difference in SAEs by randomization arm. There was a 22% rate of RT protocol variations involving ten of the 14 contributing centres, although the rate of major dose violations (more than +/- 10% from protocol dose) was only 6% with no statistically significant difference by randomization arm (P = 0.44). Conclusions: QA auditing is an essential but time-consuming component of RT trials, including those assessing palliative endpoints. Our experience confirms that all aspects should commence soon after study activation. Crown Copyright (C) 2003 Published by Elsevier Science Ltd. All rights reserved.

Hall-Petch parameters for tension and compression in cast Mg

The flow stress in tensile and compressive deformation has been determined in cast Mg, for a wide range of grain sizes between 36 mum and 1.5 mm. The grain size was varied by alloying Mg with small amounts of Zr. It was found that the 0.2% offset flow stress, sigma(y) (MPa), varies with the grain size, d (m), as sigma(y) = 17.7 + 0.25 d(-1/2) in tension, while sigma(y) = -2.3 + 0.39 d(-1/2) in compression. Possible reasons for the difference between tension and compression are discussed.

A diffusion and T2 relaxation MRI study of the ovine lumbar intervertebral disc under compression in vitro

The ovine lumbar intervertebral disc is a useful model for the human lumbar disc. We present preliminary estimates of diffusion coefficients and T-2 relaxation times in a pilot MRI study of the ovine lumbar intervertebral disc during uniaxial compression in vitro, and identify factors that hamper the ability to accurately monitor the temporal evolution of the effective diffusion tensor at high spatial resolution.

Hall-Petch parameters in tension and compression in cast Mg-2Zn alloys

The flow stress in tension and compression has been measured as a function of plastic strain in Mg-2Zn castings with grain sizes ranging from 55 to 340 mum. Hall-Petch parameters have been calculated and are compared to those previously reported. In contrast to the behaviour of pure Mg grain refined with Zr and of hot-worked and recrystallised pure Mg and Mg-Zn alloys, the cast material shows little tension/compression asymmetry of the flow stress. The possible effects of texture and of twinning are noted. (C) 2004 Elsevier B.V. All rights reserved.

Satisfaction with medical rehabilitation after spinal cord injury

Study Design. Retrospective Objective. To predict satisfaction with medical rehabilitation. Summary of Background Data. While spinal cord injury (SCI) patient satisfaction with life and community services has been investigated, satisfaction with medical rehabilitation has not. Methods. Information submitted to the Uniform Data System for Medical Rehabilitation ( 1998 - 2001) by 134 hospitals/rehabilitation facilities in the United States (n = 6,205 patients with SCI) was examined. Predictors were sociodemographic variables, Case Mix Groupings (CMG) ( 401 - 505, 5001), length of stay, rehospitalization, followup therapy, and health maintenance. Satisfaction was assessed at a mean of 92.2 days (SD 11.9 days) postdischarge. Data were analyzed according to who reported the outcome ( patient, n = 3,858 or family/other, n = 1,869). Statistical modeling was conducted using logistic regression. Results. High overall satisfaction was reported (94%). Significant predictors for the patient report data were CMG and rehospitalization. Compared with CMG 5001 ( short stay,

Infrasound initiates directional fast-start escape responses in juvenile roach Rutilus rutilus

Acoustic stimuli within the sonic range are effective triggers of C-type escape behaviours in fish. We have previously shown that fish have an acute sensitivity to infrasound also, with acceleration thresholds in the range of 10(-5) m s(-2). In addition, infrasound at high intensities around 10(-2) m s(-2) elicits strong and sustained avoidance responses in several fish species. In the present study, the possible triggering of C-escapes by infrasonic single-cycle vibrations was examined in juvenile roach Rutilus rutilus. The fish were accelerated in a controlled and quantifiable manner using a swing system. The applied stimuli simulated essential components of the accelerations that a small fish would encounter in the hydrodynamic flow field produced by a predatory fish. Typical C- and S-type escape responses were induced by accelerations within the infrasonic range with a threshold of 0.023 m s(-2) for an initial acceleration at 6.7 Hz. Response trajectories were on average in the same direction as the initial acceleration. Unexpectedly, startle behaviours mainly occurred in the trailing half of the test chamber, in which the fish were subjected to linear acceleration in combination with compression, i.e. the expected stimuli produced by an approaching predator. Very few responses were observed in the leading half of the test chamber, where the fish were subjected to acceleration and rarefaction, i.e. the stimuli expected from a suction type of predator. We conclude that particle acceleration is essential for the directionality of the startle response to infrasound, and that the response is triggered by the synergistic effects of acceleration and compression.

Effect of granule morphology on breakage behaviour during compression

In the area of dry particle breakage, Discrete Element Method (DEM) simulations have been widely used to analyse the sensitivity of various physical parameters to the behaviour of agglomerates during breakage. This paper looks at the effect of agglomerate shape and structure on the mechanisms and extent of breakage of dry agglomerates under compressive load using DEM simulations. In the simulations, a spherical-shaped agglomerate produced within the DEM code is compared with an irregularly shaped agglomerate, whose structure is that of an actual granule that was characterised with X-ray microtomography (muCT). Both agglomerates have identical particle size distribution, coordination number and surface energy values, with only the agglomerate shape and structure differing between the two. The work here details the breakage behaviour with a number of traditional DEM output parameters (i.e., contact/cluster distributions) with showing vastly different behaviour between the two agglomerates. (C) 2004 Elsevier B.V. All rights reserved.

An experimental and finite element poroelastic creep response analysis of an intervertebral hydrogel disc model in axial compression

A hydrogel intervertebral disc (lVD) model consisting of an inner nucleus core and an outer anulus ring was manufactured from 30 and 35% by weight Poly(vinyl alcohol) hydrogel (PVA-H) concentrations and subjected to axial compression in between saturated porous endplates at 200 N for 11 h, 30 min. Repeat experiments (n = 4) on different samples (N = 2) show good reproducibility of fluid loss and axial deformation. An axisymmetric nonlinear poroelastic finite element model with variable permeability was developed using commercial finite element software to compare axial deformation and predicted fluid loss with experimental data. The FE predictions indicate differential fluid loss similar to that of biological IVDs, with the nucleus losing more water than the anulus, and there is overall good agreement between experimental and finite element predicted fluid loss. The stress distribution pattern indicates important similarities with the biological lVD that includes stress transference from the nucleus to the anulus upon sustained loading and renders it suitable as a model that can be used in future studies to better understand the role of fluid and stress in biological IVDs. (C) 2005 Springer Science + Business Media, Inc.

Effect of cyclic pneumatic soft tissue compression on simulated distal radius fractures

We investigated the effect of pneumatic pressure applied to the proximal musculature of the sheep foreleg on load at the site of a transverse osteotomy of the distal radius. The distal radii of 10 fresh sheep foreleg specimens were osteotomized and a pressure sensor was inserted between the two bone fragments. An inflatable cuff, connected to a second pressure sensor, was positioned around the proximal forelimb musculature and the leg then was immobilized in a plaster cast. The inflatable cuff was inflated and deflated repeatedly to various pressures. Measurements of the cuff pressure and corresponding change in pressure at the osteotomy site were recorded. The results indicated that application of pneumatic pressure to the proximal foreleg musculature produced a corresponding increase in load at the osteotomy site. For the cuff pressures tested (109.8-238.4 mm Hg), there was a linear correlation with the load at the osteotomy site with a gradient of 12 mm Hg/N. It is conceivable, based on the results of this study, that a technique could be developed to provide dynamic loading to accelerate fracture healing in the upper limb of humans.

Integrating technology in the workplace for people with spinal cord injury

Computer technology can overcome mobility and functional limitations resulting from spinal cord injury (SCI) and enable re-employment. This study aimed to identify barriers and supports to effective technology use at work from the unique perspectives of technology users themselves. A qualitative research design was used to explore the perspectives of 11 technology users with SCI. In-depth, open-ended interviews and observations were conducted at each person’s workplace. Five major themes emerged: identifying the best or right technology; acquiring the technology; customizing and learning to use the technology; supporting the technology; and empowerment. Understanding these consumer perspectives enables professionals to empower people with SCI to optimize their work potential.

Patterns of neuronal activation in the rat brain and spinal cord in response to increasing durations of restraint stress

By most accounts the psychological stressor restraint produces a distinct pattern of neuronal activation in the brain. However, some evidence is incongruous with this pattern, leading us to propose that the restraint- induced pattern in the central nervous system might depend on the duration of restraint used. We therefore determined the pattern of neuronal activation ( as indicated by the presence of Fos protein) seen in the paraventricular nucleus (PVN), bed nucleus of the stria terminalis, amygdala, locus coeruleus, nucleus tractus solitarius (NTS), ventrolateral medulla (VLM) and thoracic spinal cord of the rat in response to 0, 15, 30 or 60 min periods of restraint. We found that although a number of cell groups displayed a linear increase in activity with increasing durations of restraint ( e. g. hypothalamic corticotrophin-releasing factor (CRF) cells, medial amygdala neurons and sympathetic preganglionic neurons of the thoracic spinal cord), a number of cell groups did not. For example, in the central amygdala restraint produced both a decrease in CRF cell activity and an increase in non-CRF cell activity. In the locus coeruleus, noradrenergic neurons did not display Fos in response to 15 min of restraint, but were significantly activated by 30 or 60 min restraint. After 30 or 60 min restraint a greater degree of activation of more rostral A1 noradrenergic neurons was observed compared with the pattern of A1 noradrenergic neurons in response to 15 min restraint. The results of this study demonstrate that restraint stress duration determines the amount and the pattern of neuronal activation seen in response to this psychological stressor.

Characteristics of speech following cervical spinal cord injury

The present study examined 24 individuals with either complete or incomplete injuries to the cervical spinal cord through the use of standardized assessments of dysarthria and a perceptual rating scale. Perceptual assessment revealed predominantly prosodic and phonatory disturbances, while physical impairments were common in the respiratory and laryngeal subsystems of speech production. A reduction in intelligibility and speaking rate resulted in a diminished communicative effectiveness ratio for most participants. Individuals showed a high degree of variation, with no clear relationship between lesion type and impairments present. Further investigation is required to verify the physiological nature of the respiratory and laryngeal impairments found in the present investigation and to determine the relative contributions of these to the overall presentation of speech and voice post cervical spinal cord injury (CSI).