Addressing unpredictability may be the key to improving performance with current clinically prescribed myoelectric prostheses.

The efferent control chain for an upper-limb myoelectric prosthesis can be separated into 3 key areas: signal generation, signal acquisition, and device response. Data were collected from twenty trans-radial myoelectric prosthesis users using their own clinically prescribed devices, to establish the relative impact of these potential control factors on user performance (user functionality and everyday prosthesis usage). By identifying the key factor(s), we can guide future developments to ensure clinical impact. Skill in generating muscle signals was assessed via reaction times and signal tracking. To assess the predictability of signal acquisition, we inspected reaction time spread and undesired hand activations. As a measure of device response, we recorded the electromechanical delay between electrode stimulation and the onset of hand movement. Results suggest abstract measures of skill in controlling muscle signals are poorly correlated with performance. Undesired activations of the hand or incorrect responses were correlated with almost all kinematics and gaze measures suggesting unpredictability is a key factor. Significant correlations were also found between several measures of performance and the electromechanical delay; however, unexpectedly, longer electromechanical delays correlated with better performance. Future research should focus on exploring causes of unpredictability, their relative impacts on performance and interventions to address this.

Upper limb activity in myoelectric prosthesis users is biased towards the intact limb and appears unrelated to goal-directed task performance.

Studies of the effectiveness of prosthetic hands involve assessing user performance on functional tasks, typically collected in the lab, sometimes combined with self-report of real-world use. In this paper we compare real-world upper limb activity between a group of 20 myoelectric prosthesis users and 20 anatomically intact adults. Activity was measured from wrist-worn accelerometers over a 7-day period. The temporal patterns in upper limb activity are presented and the balance of activity between the two limbs quantified. We also evaluated the prosthesis users' performance on a goal-directed task, characterised using measures including task success rate, completion time, gaze behaviour patterns, and kinematics (e.g. variability and patterns in hand aperture). Prosthesis users were heavily reliant on their intact limb during everyday life, in contrast to anatomically intact adults who demonstrated similar reliance on both upper limbs. There was no significant correlation between the amount of time a prosthesis was worn and reliance on the intact limb, and there was no significant correlation between either of these measures and any of the assessed kinematic and gaze-related measures of performance. We found participants who had been prescribed a prosthesis for longer to demonstrate more symmetry in their overall upper limb activity, although this was not reflected in the symmetry of unilateral limb use. With the exception of previously published case studies, this is the first report of real world upper limb activity in myoelectric prosthesis users and confirms the widely held belief that users are heavily reliant on their intact limb.

A generalisable methodology for stability assessment of walking aid users.

To assist balance and mobility, older adults are often prescribed walking aids. Nevertheless, surprisingly their use has been associated with increased falls-risk. To address this finding we first need to characterise a person's stability while using a walking aid. Therefore, we present a generalisable method for the assessment of stability of walking frame (WF) users. Our method, for the first time, considers user and device as a combined system. We define the combined centre of pressure (CoPsystem) of user and WF to be the point through which the resultant ground reaction force for all feet of both the WF and user acts if theresultant moment acts only around an axisperpendicular tothe ground plane. We also define the combined base of support (BoSsystem) to be the convex polygon formed by the boundaries of the anatomical and WF feet in contact with the ground and interconnecting lines between them. To measure these parameters we have developed an instrumented WF with a load cell in each foot which we use together with pressure-sensing insoles and a camera system, the latter providing the relative position of the WF and anatomical feet. Software uses the resulting data to calculate the stability margin of the combined system, defined as the distance between CoPsystem and the nearest edge of BoSsystem. Our software also calculates the weight supported through the frame and when each foot (of user and/or frame) is on the floor. Finally, we present experimental work demonstrating the value of our approach.

Effects of shoe sole geometry on toe clearance and walking stability in older adults.

Thirty-five percent of people above age 65 fall each year, and half of their falls are associated with tripping: tripping, an apparently 'mundane' everyday problem, therefore, significantly impacts on older people's health and associated medical costs. To avoid tripping and subsequent falling, sufficient toe clearance during the swing phase is crucial. We previously found that a rocker-shaped shoe sole enhances toe clearance in young adults, thereby decreasing their trip-risk. This study investigates whether such sole design also enhances older adults' toe clearance, without inadvertently affecting their walking stability. Toe clearance and its variability are reported together with measures of walking stability for twelve older adults, walking in shoes with rocker angles of 10°, 15°, and 20°. Surface inclinations (flat, incline, decline) were chosen to reflect a potential real-world environment. Toe clearance increased substantially from the 10° to the 15° rocker angle (p=0.003) without compromising measures of walking stability (p>0.05). A further increase in rocker angle to 20° resulted in less substantial enhancement of toe clearance and came at the cost of a decrease in gait speed on the decline. The novelty of this investigation lies in the exploration of the trade-off between reduction of trip-risk through footwear design and adverse effects on walking stability on real-life relevant surfaces. Our two studies suggest that the current focus on slip-resistance in footwear design may need to be generalised to include other factors that affect trip-risk.

Automatic detection of lift-off and touch-down of a pick-up walker using 3D kinematics.

Walking aids have been associated with falls and it is believed that incorrect use limits their usefulness. Measures are therefore needed that characterize their stable use and the classification of key events in walking aid movement is the first step in their development. This study presents an automated algorithm for detection of lift-off (LO) and touch-down (TD) events of a pick-up walker. For algorithm design and initial testing, a single user performed trials for which the four individual walker feet lifted off the ground and touched down again in various sequences, and for different amounts of frame loading (Dataset_1). For further validation, ten healthy young subjects walked with the pick-up walker on flat ground (Dataset_2a) and on a narrow beam (Dataset_2b), to challenge balance. One 88-year-old walking frame user was also assessed. Kinematic data were collected with a 3D optoelectronic camera system. The algorithm detected over 93% of events (Dataset_1), and 95% and 92% in Dataset_2a and b, respectively. Of the various LO/TD sequences, those associated with natural progression resulted in up to 100% correctly identified events. For the 88-year-old walking frame user, 96% of LO events and 93% of TD events were detected, demonstrating the potential of the approach.

Effects of ramp negotiation, paving type and shoe sole geometry on toe clearance in young adults.

Trips are a major cause of falls and result from involuntary contact of the foot with the ground during the swing phase of gait. Adequate toe clearance during swing is therefore crucial for safe locomotion. To date, little is known about the effects of environmental factors and footwear on toe clearance. This study reports on modulation of toe clearance and toe clearance variability in response to changes in ground inclination, paving type, and shoe sole geometry. Toe clearance and toe clearance variability for ten healthy young adults were calculated two-fold: a) for the commonly-used position on the foremost part of the sole of the shoe and b) for the lowest of a total of 7 sole positions, located between the metatarsals and the toe tip across the entire width of the sole. Utilizing a full-factorial design we found that toe clearance was affected by ground inclination, paving type, and sole geometry regardless of the computational method used (with p-values<0.01) but the use of the foremost part of the sole for toe clearance calculation results is an overestimation of this value. Our findings highlight the importance of considering footwear and environmental factors when assessing the risk of tripping. Future work needs to investigate to which extent the same factors affect toe clearance in more vulnerable parts of the population.

Biomechanics for inclusive urban design: Effects of tactile paving on older adults' gait when crossing the street.

In light of our ageing population it is important that the urban environment is easily accessible and hence supports older adults' independence. Tactile 'blister' paving was originally designed to provide guidance for visually impaired people at pedestrian crossings. However, as research links irregular surfaces to falls in older adults, such paving may have an adverse effect on older people. We investigated the effects of tactile paving on older adults' gait in a scenario closely resembling crossing the street. Gait analysis of 32 healthy older adults showed that tactile, as compared to smooth, paving increases the variability in timing of foot placement by 20%, thereby indicating a disturbance of the rhythmic gait pattern. Moreover, toe clearance during the swing phase increased by 7% on tactile paving, and the ability to stop upon cue from the traffic light was compromised. These results need to be viewed under the consideration of limitations associated with laboratory studies and real world analysis is needed to fully understand their implications for urban design.

[Intrahepatic sarcoma of the follicular dendritic cells]. / Intrahepatisches Sarkom der follikulär-dendritischen Zellen.

We report an intrahepatic sarcoma of the follicular dendritic cells in a 76-year-old woman with a medical history of a hyaline-vascular type of Castleman's disease. We discuss the clinico-pathological findings, the pathogenesis and the differential diagnosis of this rare tumour entity.

[Patient Questionnaire for Assessment of Rehabilitation Motivation (PAREMO-20) - psychometric evaluation and validation in a sample of cancer patients with different tumour sites]. / Patientenfragebogen zur Erfassung der Reha-Motivation (PAREMO-20) - Testtheoretische Uberprüfung und Validierung an einer Stichprobe von Krebspatienten unterschiedlicher Diagnosegruppen.

OBJECTIVES: A significant body of research suggests that patient motivation is related to better rehabilitation outcome with regard to psychosocial and physical well-being. Thus, patient motivation gains increasing attention with regard to the course of treatment and individual treatment planning in the practice and research in medical rehabilitation. This study aims to validate the PAREMO-20, a measure of rehabilitation motivation in a sample of cancer patients with different tumour sites. METHODS: 1193 cancer patients participated in a prospective study evaluating the medical and psychosocial effects of inpatient cancer rehabilitation. A set of various questionnaires was completed at the beginning and at the end of the rehabilitation measure as well as at one year follow-up (participation rate at follow-up: 78%). The PAREMO-20 was psychometrically examined on this sample. Validity was examined using a cancer-specific questionnaire for individual therapy goals, as well as the HADS-D and the SF-8. RESULTS: The original six factors were replicated. The factor solution emerging through PCA was tested with a confirmatory factor analysis. Maximum likelihood estimation of this model produced good fit statistics. Internal consistencies were high to satisfactory with Cronbach's Alpha=0.88 to Alpha=0.59. Psychological distress and physical impairments were positively associated with anxiety and depression, as well as with therapy goal dimensions. Moderate to high (negative) correlations were observed with health related quality of life, in particular with the mental-health dimension (r=-0.74, p=0.01). DISCUSSION: The PAREMO-20 is a reliable, valid and economic instrument, which can be recommended for use in clinical care.

A clinical set-up tool (CST) for rapid stimulator programming.

This paper presents an intuitive approach to the programming of Functional Electrical Stimulation (FES) hardware. A stimulation sequence is defined as a Finite State Machine (FSM) that is created and modified via an easy-to-use interface. Using a USB-equipped stimulator, data from an internal accelerometer are streamed to a PC whilst the subject undergoes the motion of interest. Simultaneously, the clinician labels the collected data via a number of key presses in order to train a sequence of simple classifiers. The 'optimal' (in a quantitative sense) parameters are then uploaded directly back to the stimulator for immediate stand-alone operation.

Comparison of linear accelerations from three measurement systems during "reach & grasp".

Given the increased use of accelerometers in movement analysis, validation of such inertial sensors against conventional 3D camera systems and performance comparisons of different sensors have become important topics in biomechanics. This paper evaluates and compares linear acceleration trajectories obtained from two different 3D accelerometers and derived from Vicon position data for an upper limb "reach & grasp" task. Overall, good correspondence between the three measurement systems was obtained. Sources of error are discussed.

Bone morphogenetic protein 9 is a potent synergistic factor for murine hemopoietic progenitor cell generation and colony formation in serum-free cultures.

The effect of the recently cloned cytokine bone morphogenetic protein 9 (BMP-9) on colony formation and generation in vitro clonable hematopoietic progenitors (CFU-C) in serum-free liquid cultures (LC) of both normal and post-5-fluorouracil murine bone marrow cells was studied in the presence of various other cytokines. In LC, BMP-9 concentrations of 100 ng or more per ml led to complete inhibition of Steel Factor (SF) + interleukin-11 (IL-11) or IL-12 supported CFU-C generation, which was partly abrogated when IL-3 was additionally included. We found this inhibitory effect of BMP-9 to be mediated by an increased TGF-beta1 elaboration and TGF-beta1 mRNA expression in bone marrow cells with increasing BMP-9 concentrations. In the presence of neutralizing antibodies (Ab) against TGF-beta1, BMP-9 concentrations of 3 ng or higher synergized with IL-3, SF+IL-3, SF+IL-11/12, or IL-3+SF+IL-11/12 to increase CFU-C generation. Similarly, high BMP-9 concentrations dramatically inhibited primary colony formation induced by SF+IL-11/12, whereas in the presence of TGF-beta1 neutralizing Ab only 3 ng or more BMP-9 per ml stimulated both the time of colony appearance, the colony size and colony numbers in the presence of IL-3, M-CSF, GM-CSF, SF, SF+Flt3-L, SF+IL-3, SF+IL-11/12 or IL-3+SF+IL-11/12. BMP-9 neither stimulated CFU-C generation nor colony formation as a single factor, nor did it synergize with thrombopoietin (Tpo), erythropoietin (Epo), Flt3-L, IL-11, IL-12 or G-CSF. The effect of BMP-9 on its target cells was direct as demonstrated using single-sorted stem cells. These observations demonstrate that BMP-9 plays a dual role in regulating proliferation of primitive hemopoietic progenitor cells. Thus, in addition to its ability to enhance TGF-beta1 elaboration in bone marrow cells, it acts as a potent synergistic activity that is different from SF, Flt3-L, IL-11 or IL-12. BMP-9 mRNA was exclusively detected in the liver of adult mice, whilst no expression was found in stromal cell lines propagated from day-16 fetal liver or neonatal or adult bone marrow. 125I-BMP-9 bound specifically to a high percentage of blast cells in lineage-depleted post-fluorouracil bone marrow cells and to megakaryocytes in normal and post-fluorouracil bone marrow, indicating that BMP-9R are expressed on these cells. The dissociation between the site of BMP-9 production and its target cells in the bone marrow makes BMP-9 a hemopoietic hormone.

Customer service: moving from slogan to point of differentiation.

To make its commitment to customer-centered care real, Dean Medical Center interviewed patients and created a "Vital Signs" scorecard. Performance is now measured according to those key areas specified by patients. Face-to-face communication from upper management to all employees and employee training has facilitated the program.

Neutrophil endopeptidase inhibitor improves pulmonary function during reperfusion after eighteen-hour preservation.

BACKGROUND: Reperfusion injury remains a significant problem after lung transplantation and is thought to be in part mediated by neutrophils. Ulinastatin inhibits release of elastase and cathepsin G from neutrophil granules. We hypothesized that inhibition of these neutrophi endopeptidases (proteases) would attenuate pulmonary reperfusion injury. METHODS: With an isolated, whole blood-perfused, ventilated rabbit lung model, we studied the effects of ulinastatin. All lungs were flushed with cold Euro-Collins solution, harvested en bloc, stored inflated at 4 degrees C for 18 hours, and reperfused with whole blood. The 18-hour control lungs (n = 8) were stored and reperfused. Low-dose (n = 8) and high-dose (n = 7) groups were treated with total doses of ulinastatin of 25,000 and 50,000 units, respectively, during flush and reperfusion. An additional control group of lungs (n = 8) was harvested, flushed, and immediately reperfused. RESULTS: The pulmonary artery pressure was significantly lower in the high-dose group than in the 18-hour control group (36.7 +/- 1.8 vs 44.8 +/- 2.9 mm Hg, p = 0.034). The percentage decrease in dynamic airway compliance was significantly less in the high-dose group than in the 18-hour control group (-13.8% +/- 4.4% vs -25.1% +/- 3.7%, p = 0.032). Both low-dose and high-dose ulinastatin treatments did not result in a significant improvement in oxygenation with respect to the 18-hour control group (72.2 +/- 25.8 vs 32.5 +/- 4.9 mm Hg, p = 0.21). CONCLUSIONS: Ulinastatin diminishes reperfusion injury after 18 hours of hypothermic pulmonary ischemia, with resultant improvements in pulmonary artery pressure and airway compliance. Improvement in pulmonary function after preservation and reperfusion with a neutrophil endopeptidase inhibitor confirms the role of endopeptidases in reperfusion injury and suggests an intervention to reduce their detrimental effects on early graft function.

Thromboxane receptor blockade improves oxygenation in an experimental model of acute lung injury.

BACKGROUND: Adult respiratory distress syndrome remains a major cause of morbidity and mortality. We investigated the role of thromboxane receptor antagonism in an experimental model of acute lung injury that mimics adult respiratory distress syndrome. METHODS: Three groups of rabbit heart-lung preparations were studied for 30 minutes in an ex vivo blood perfusion/ventilation system. Saline control (SC) lungs received saline solution during the first 20 minutes of study. Injury control (IC) lungs received an oleic acid-ethanol solution during the first 20 minutes. Thromboxane receptor blockade (TRB) lungs received the same injury as IC lungs, but a thromboxane receptor antagonist (SQ30741) was added to the blood perfusate just prior to study. Blood gases were obtained at 10-minute intervals, and tidal volume, pulmonary artery pressure, and lung weight were continuously recorded. Oxygenation was assessed by measuring the percent change in oxygen tension over the 30-minute study period. Tissue samples were collected from all lungs for histologic evaluation. RESULTS: Significant differences were found between SC and IC lungs as well as TRB and IC lungs when comparing pulmonary artery pressure (SC = 33.1 +/- 2.2 mm Hg, TRB = 35.4 +/- 2.1 mm Hg, IC = 60.4 +/- 11.1 mm Hg; p < 0.02) and percent change in oxygenation (SC = -20.6% +/- 10.3%, TRB = -24.2% +/- 9.5%, IC = -57.1% +/- 6.2%; p < 0.03). None of the other variables demonstrated significant differences. CONCLUSIONS: Thromboxane receptor blockade prevents the pulmonary hypertension and the decline in oxygenation seen in an experimental model of acute lung injury that mimics adult respiratory distress syndrome.

Insulin receptors with defective tyrosine kinase inhibit normal receptor function at the level of substrate phosphorylation.

Rat 1 fibroblasts have been transfected with the cDNA encoding a kinase-defective mutant human insulin receptor (A/K1018). Expression of this cDNA results in a receptor that is not only biologically inactive but also inhibits normal insulin action through the normal endogenous rat receptors in this fibroblast line (McClain, D. A., Maegawa, H., Lee, J., Dull, T. J., Ullrich, A., and Olefsky, J. M. (1987) J. Biol. Chem. 262, 14663-14671). We have investigated the mechanism of this inhibition and show that: 1) rat receptors are expressed at normal to increased levels in two cell lines which also express A/K1018 receptors at low (A/K1018-A, 5700 total receptors) or high (A/K1018-B, 2.2 x 10(5) total receptors) levels. 2) The rat receptors in the A/K1018 lines can be normally autophosphorylated under the control of insulin in vitro. 3) A/K1018 receptors do not inhibit the kinase activity of normal receptors when mixed together in vitro. 4) In intact A/K1018-B cells, the ability of insulin to stimulate autophosphorylation of the rat receptor is unimpaired; furthermore, the autophosphorylated rat receptor becomes normally activated as a tyrosine kinase. 5) The expression of receptors for insulin-like growth factor I and stimulation of hexose uptake mediated by this receptor are unaffected in cells expressing inhibitory A/K1018 receptors. 6) Expression of the A/K1018 receptor inhibits insulin-stimulated phosphorylation of two endogenous protein substrates (pp220 and pp170) by the native rat receptors. We conclude that the inhibition of insulin action seen in the A/K1018 cells is not mediated at the levels of native receptor expression or activation, nor is the effector (hexose uptake) mechanism affected by the A/K1018 receptors. The expression of this kinase-defective receptor does, however, inhibit the phosphorylation of substrate molecules by the normally activated endogenous rat receptors.

Protein induced by bacteriophage T4 which is absent in Escherichia coli infected with nuclear disruption-deficient phage mutants.

A protein induced by wild-type T4 phage which is absent in Escherichia coli infected with nuclear disruption-deficient phage (with mutations in gene ndd) was identified by polacrylamide gel electrophoresis. This protein was synthesized at maximum rate at 3 to 6 min after infection. It had a molecular weight of 15,000 determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was associated with sedimentable fractions of the cell from which it can be dissociated with 1 M guanidine-hydrochloride. The dissociated protein can be partly recovered in a form soluble in dilute buffer after partial purification and dialysis. The occurrence of this protein in a particulate cell fraction is of interest because of the postulated role of the bacterial cell membrane in nuclear disruption.