Correlation between in vivo stresses and oxidation of UHMWPE in total hip arthroplasty.

The possibility of in vivo, stress-induced oxidation in orthopaedic UHMWPE has been investigated. EtO sterilised, uncrosslinked UHMWPE liners, explanted or shelf-aged, have been collected. Linear wear and wear rate were assessed and FTIR spectroscopy was employed to detect oxidation and to build up oxidation products spatial maps across the liners section. Oxidation profiles have been compared to stress distribution profiles, resulting from a FE analysis conducted on the same liners geometries and couplings. It was found that oxidised and stressed areas followed the same asymmetrical, localized distribution profile. It was therefore possible to establish a correlation between stressed areas and observed oxidation.

Inter-trial neuronal activity in inferior temporal cortex: a putative vehicle to generate long-term visual associations.

When monkeys perform a delayed match-to-sample task, some neurons in the anterior inferotemporal cortex show sustained activity following the presentation of specific visual stimuli, typically only those that are shown repeatedly. When sample stimuli are shown in a fixed temporal order, the few images that evoke delay activity in a given neuron are often neighboring stimuli in the sequence, suggesting that this delay activity may be the neural correlate of associative long-term memory. Here we report that stimulus-selective sustained activity is also evident following the presentation of the test stimulus in the same task. We use a neural network model to demonstrate that persistent stimulus-selective activity across the intertrial interval can lead to similar mnemonic representations (distributions of delay activity across the neural population) for neighboring visual stimuli. Thus, inferotemporal cortex may contain neural machinery for generating long-term stimulus-stimulus associations.

Cardioventilatory responses during real or imagined walking at low speed.

There is increasing evidence that motor imagery involves at least in part central processes used in motor control. In order to deepen our understanding on the neural mechanisms underlying vegetative responses to real and imagined exercise, we determined cardioventilatory variables during actual or imagined treadmill walking on flat terrain at speeds of 2, 3.5 or 5 km/h, in a group of 14 healthy volunteers. During actual walking, as expected, a comparable intensity-dependent increase was found in ventilation, oxygen consumption, tidal volume and respiratory rate. Imagined walking led to a significant, albeit small (less than 10%), increase in ventilation and oxygen consumption, and to larger increases (up to 40%) in respiratory rate, which was paralleled by a non significant trend towards a decline of tidal volume. These results confirm and extend previous observations showing that motor imagery is accompanied by centrally induced changes in vegetative responses, and provide evidence for a differential control on respiratory rate and tidal volume.

Abstract Context Representations in Primate Amygdala and Prefrontal Cortex.

Neurons in prefrontal cortex (PFC) encode rules, goals, and other abstract information thought to underlie cognitive, emotional, and behavioral flexibility. Here we show that the amygdala, a brain area traditionally thought to mediate emotions, also encodes abstract information that could underlie this flexibility. Monkeys performed a task in which stimulus-reinforcement contingencies varied between two sets of associations, each defining a context. Reinforcement prediction required identifying a stimulus and knowing the current context. Behavioral evidence indicated that monkeys utilized this information to perform inference and adjust their behavior. Neural representations in both amygdala and PFC reflected the linked sets of associations implicitly defining each context, a process requiring a level of abstraction characteristic of cognitive operations. Surprisingly, when errors were made, the context signal weakened substantially in the amygdala. These data emphasize the importance of maintaining abstract cognitive information in the amygdala to support flexible behavior.

Spike-driven synaptic plasticity for learning correlated patterns of mean firing rates.

Long term synaptic changes induced by neural spike activity are believed to underlie learning and memory. Spike-driven long-term synaptic plasticity has been investigated in simplified situations in which the patterns of mean rates to be encoded were statistically independent. An additional regulatory mechanism is required to extend the learning capability to more complex and natural stimuli. This mechanism can be provided by those effects of the action potentials that are believed to be responsible for spike-timing dependent plasticity. These effects, when combined with the dependence of synaptic plasticity on the post-synaptic depolarization, produce the non-monotonic learning rule needed for storing correlated patterns of mean rates.

Influence of standard and novel LTB4 analogs on human neutrophil chemotaxis measured by the multiwell cap assay.

Standard and novel LTB4 analogs were tested for neutrophil chemoattractant activity using the multiwell cap assay (Evans et al. (1986) Biosc. Rep. 6, 1041). The assay uses disposable equipment and measures chemotaxis by the number of cells able to migrate across the full thickness of cellulose nitrate filters. Under standard conditions (90 min incubation at 37 degrees C in buffer containing 2% bovine albumin), LTB4 and 6-cis-LTB1 had EC50 values of 3.5 and 15,000 nM, respectively. 20-hydroxy-LTB4 was equipotent with LTB4 and exhibited a similar biphasic chemotactic response, however, only one third of the number of cells migrated through the filter. 20-carboxy-LTB4 was inactive up to 1,000 nM. 5-desoxy-((6,7)-cis-cyclopropyl)-LTB2, (6,7)-benzo-LTB2 and 5-desoxy-(8,10)-LTB2 had EC50 values of 11,300, 50,000 and 84,000 nM, respectively. Checkerboard analysis indicated a chemokinetic component of 42% for LTB4 at a concentration causing peak chemotaxis. Reduction of albumin in the buffer to 0.5% increased the apparent potencies of LTB4 and 6-cis-LTB1 five-fold. Since LTB4 is a mediator of inflammation, various anti-inflammatory agents were tested at peak concentrations observed in vivo for in vitro inhibition of LTB4-stimulated chemotaxis in the presence of 0.5% albumin. Under the conditions of the assay, chloroquine diphosphate, dexamethasone, indomethacin, penicillamine, piroxicam and diclofenac sodium were inactive; gold sodium thiomalate was inhibitory (IC50 = 20 microM).

Thick filter neutrophil chemotaxis performed in the absence of albumin.

Migration through a filter is a technique widely used for the study of cell chemotaxis. Since the original description of the technique by Boyden in 1962 (J. Exp. Med. 115, 453) using neutrophils and thick filters prepared from cellulose nitrate, albumin has been required in the incubation medium to support chemotaxis. However, the binding to albumin of compounds affecting chemotaxis can reduce their free concentration. We developed two procedures for studying neutrophil chemotaxis under reduced or albumin-free conditions. In one, cellulose nitrate filters were pretreated with albumin by a novel procedure and chemotaxis was carried out in albumin-free medium. As tested with the chemoattractant LTB4 and human neutrophils, the procedure resulted in full chemotaxis, measured by the number of cells crossing the filter, with an EC50 of 0.43 nM for LTB4. The LTB4-receptor antagonist LY 223982 inhibited the chemotactic action of LTB4 with a Ki of 62 nM in the albumin-pretreated filter system, thus showing 58 times greater potency than in medium containing 0.5% albumin. The second procedure makes use, for the first time, of a relatively new filter (Hydrophilic Durapore). This filter has the same dimensions and pore rating of the cellulose nitrate filter but did not require pretreatment with albumin to support chemotaxis in the albumin-free medium. LTB4 stimulated neutrophil chemotaxis across this filter with an EC50 of 0.29 nM. LY 223982 had a Ki of 11 nM, thus exhibiting a potency even greater than in the albumin-pretreated cellulose nitrate filter system. fMLP and C5a also stimulated chemotaxis in the absence of albumin. These results suggest that albumin is not obligatory for neutrophil chemotaxis through thick filters. The role of albumin in the chemotaxis assay using cellulose nitrate filters may be to counteract the adherence of cells or chemotactic agents to the filters.

Carboxy-substituted cinnamides: a novel series of potent, orally active LTB4 receptor antagonists.

A series of carboxy-substituted cinnamides were investigated as antagonists of the human cell surface leukotriene B4 (LTB4) receptor. Binding was determined through measurement of [3H]LTB4 displacement from human neutrophils. Receptor antagonism was confirmed through a functional assay, which measures inhibition of Ca2+ release in human neutrophils. Potent antagonists were discovered through optimization of a random screening hit, a p-(alpha-methylbenzyloxy)cinnamide, having low-micromolar activity. Substantial improvement of in vitro potency was realized by the attachment of a carboxylic acid moiety to the cinnamide phenyl ring through a flexible tether, leading to identification of compounds with low-nanomolar potency. Modification of the benzyloxy substituent, either through ortho-substitution on the benzyloxy phenyl group or through replacement of the ether oxygen with a methylene or sulfur atom, produced achiral antagonists of equal or greater potency. The most potent compounds in vitro were assayed for oral activity using the arachidonic acid-induced mouse ear edema model of inflammation. Several compounds in this series were found to significantly inhibit edema formation and myeloperoxidase activity in this model up to 17 h after oral administration. Representatives of this series have been shown to be potent and long-acting orally active inhibitors of the LTB4 receptor.

Reversal of postburn immunosuppression by the administration of vitamin A.

The effect of high doses of vitamin A was evaluated on the suppression of cellular immunity after a 30% body surface area experimental scald burn in a mouse model. Male CBA/J mice were treated postburn with daily intraperitoneal injections of either 3000 IU of vitamin A or an equal volume of 0.9N saline. Similar groups of unburned mice were also studied as controls. At the seventh postburn day, one-way mixed lymphocyte reactions were tested for each group with whole spleen cells of CBA/J mice used as responders and mitomycin C-treated whole spleen cells of C57 BL/6 mice used as stimulators. When results were expressed as mean percentage of the values of control animals, no significant difference was observed between the saline-injected unburned control group (taken as 100%) and the vitamin A-treated unburned control groups (89%). The burned animals treated with saline showed suppression to 21% of the control values. However, the burned animals treated postburn with vitamin A improved the response rate dramatically to 52% of control values. This improvement over the untreated burned animals was significant in all experiments performed (p less than 0.02). This study suggests that vitamin A may be an effective agent in the reversal of cellular immunosuppression after burns.

Data on first recurrence after treatment for malignant melanoma in a large patient population.

Recurrent malignant melanoma is a clinical entity that behaves distinctly differently from the primary disease. The purpose of this study was to determine whether there are significant trends in the prognostic factors or in the timing and sites of recurrence. We reviewed 250 patients with recurrent malignant melanoma from the Sydney Melanoma Unit in Australia who were followed in their Tumor Registry between 1960 and 1981 (median follow-up was 7 years). Fifty-two percent of all first recurrences were to regional nodes, 17 percent were local recurrences, 8 percent were in-transit metastases, and 23 percent of all first recurrences were to a distant organ. We found that 67 percent of all recurrences were diagnosed within 24 months and 81 percent were diagnosed by 36 months after the primary melanoma. Regional nodal recurrences were diagnosed earlier (with 63 percent at 18 months and 74 percent at 24 months). Local recurrences and in-transit metastases were comparable (with 55 percent of each at 18 months and about 66 percent of each at 24 months), and systemic recurrences were diagnosed later (52 percent at 24 months and 71 percent at 36 months). Of significant interest was the fact that survival after the diagnosis of recurrence was independent of thickness of the primary tumor or duration of disease-free interval (local, in-transit, or regional nodal). Only the diagnosis of distant organ metastasis correlated with shorter survival; local recurrence, in-transit metastasis, and regional nodal metastasis were all associated with comparable survivals.(ABSTRACT TRUNCATED AT 250 WORDS)

A VLSI recurrent network of integrate-and-fire neurons connected by plastic synapses with long-term memory.

Electronic neuromorphic devices with on-chip, on-line learning should be able to modify quickly the synaptic couplings to acquire information about new patterns to be stored (synaptic plasticity) and, at the same time, preserve this information on very long time scales (synaptic stability). Here, we illustrate the electronic implementation of a simple solution to this stability-plasticity problem, recently proposed and studied in various contexts. It is based on the observation that reducing the analog depth of the synapses to the extreme (bistable synapses) does not necessarily disrupt the performance of the device as an associative memory, provided that 1) the number of neurons is large enough; 2) the transitions between stable synaptic states are stochastic; and 3) learning is slow. The drastic reduction of the analog depth of the synaptic variable also makes this solution appealing from the point of view of electronic implementation and offers a simple methodological alternative to the technological solution based on floating gates. We describe the full custom analog very large-scale integration (VLSI) realization of a small network of integrate-and-fire neurons connected by bistable deterministic plastic synapses which can implement the idea of stochastic learning. In the absence of stimuli, the memory is preserved indefinitely. During the stimulation the synapse undergoes quick temporary changes through the activities of the pre- and postsynaptic neurons; those changes stochastically result in a long-term modification of the synaptic efficacy. The intentionally disordered pattern of connectivity allows the system to generate a randomness suited to drive the stochastic selection mechanism. We check by a suitable stimulation protocol that the stochastic synaptic plasticity produces the expected pattern of potentiation and depression in the electronic network.

The carpal boss. A 20-year review of operative management.

Between 1969 and 1989, 116 patients were evaluated and treated surgically for symptomatic carpal boss. Their mean age was 32 years and male and female patients were equally affected. 28 patients gave a history of previous injury. Surgical treatment consisted of excision of the localized bony abnormality and the associated degenerative arthritic process to the level of normal articular surfaces and normal adjacent cancellous bone. The mean follow-up period for the patients in this study was 42 months. Complete symptomatic relief was observed in 94% of the patients undergoing surgical treatment. Recurrence or persistence of symptoms developed in seven surgical patients. Six had a second operation with more extensive removal of sclerotic bone and degenerate cartilage, and all patients had relief of symptoms.

Hybrid diffusive/PVD treatments to improve the tribological resistance of Ti-6Al-4V.

Titanium alloys are nowadays used for a wide range of biomedical applications thanks to their combination of high mechanical resistance, high corrosion resistance and biocompatibility. Nevertheless, the applicability of titanium alloys is sometimes limited due to their low microhardness and tribological resistance. Thus the titanium alloys cannot be successfully applied to prosthetic joint couplings. A wide range of surface treatments, in particular PVD coatings such as CrN and TiN, have been used in order to improve the tribological behaviour of titanium alloys. However, the low microhardness of the titanium substrate often results in coating failure due to cracks and delamination. For this reason, hybrid technologies based on diffusive treatments and subsequent PVD coatings may improve the overall coating resistance. In this work, conventional PVD coatings of CrN or TiCN, deposited on Titanium Grade 5, were characterized and then combined with a standard thermal diffusive nitriding treatment in order to improve the tribological resistance of the titanium alloys and avoid coating delamination. The different treatments were studied by means of scanning electron microscopy both on the sample surface and in cross-section. In-depth composition profiles were obtained using glow discharge optical emission spectrometry (GDOES) and localized energy dispersive X-ray diffraction on linear scan-lines. The microhardness and adhesion properties of the different treatments were evaluated using Vickers microhardness tests at different load conditions. The indentations were observed by means of SEM in order to evaluate delaminated areas and the crack's shape and density. The tribological behaviour of the different treatments was tested in dry conditions and in solution, in alternate pin-on-flat configuration, with a frequency of 0.5 Hz. After testing, the surface was investigated by means of stylus profilometry and SEM both on the surface and in cross-section. The standalone PVD coatings show a limited tribological resistance due to the low hardness of the substrate, which results in fractures and delamination. The combination of a diffusive process and a subsequent PVD coating shows a stronger effect in improving the tribological resistance of the substrate.

Characterization of grade 2 commercially pure Trabecular Titanium structures.

In this work, two different cellular solid structures, obtained by EBM using grade 2 Titanium powders, were investigated. Relative density was evaluated comparing different methods, the mean diameter of the singular open porosity was calculated by SEM image post-processing; the chemical composition was evaluated using Energy Dispersive X-Ray Spectroscopy (EDXS); the microstructure and grain dimension were investigated using chemical etching and, the mechanical properties were investigated using UMTS 810 Materials Test System. The mean porosity values resulted to be similar to spongy bone (around 77% for sample A and 89% for sample B). The mean diameter of the single porosity resulted to be 640 µm for A and 1250 µm for B. The Vickers microhardness results were homogeneous among the structure and the chemical etching showed a complex microstructure characterized by irregular shaped grains. Sample A, as expected, is more resistant than sample B, while sample B shows a lower elastic modulus.

Characterization of cellular solids in Ti6Al4V for orthopaedic implant applications: Trabecular titanium.

EBM (Electron Beam Melting) technology can be used successfully to obtain cellular solids in metallic biomaterials that can greatly increase osseointegration in arthroprothesis and at the same time maintain good mechanical properties. The investigated structures, called Trabecular Titanium, usually cannot be obtained by traditional machining. Two samples: (A) with a smaller single cell area and, (B) with a bigger single cell area, were produced and studied in this project. They have been completely characterized and compared with the results in similar literature pertinent to Ti6Al4V EBM structures. Relative density was evaluated using different methods, the mean diameter of the open porosities was calculated by Scanning Electron Microscope images; the composition was evaluated using Energy-Dispersive X-Ray Spectroscopy; the microstructure (alpha-beta) was investigated using chemical etching and, the mechanical proprieties were investigated using UMTS. The mean porosity values resulted comparable with spongy bone (63% for A and 72% for B). The mean diameter of the single porosity (650 mum for A and 1400 mum for B) resulted compatible with the osseointegration data from the literature, in particular for sample A. The Vickers micro-hardness tests and the chemical etching demonstrated that the structure is fine, uniform and well distributed. The mechanical test proved that sample (A) was more resistant than sample (B), but sample (B) showed an elastic modulus almost equal to the value of spongy bone. The results of this study suggest that the two Ti6Al4V cellular solids can be used in biomedical applications to promote osseointegration demonstrating that they maybe successfully used in prosthetic implants. Additional implant results will be published in the near future.

Real-Time Classification of Complex Patterns Using Spike-Based Learning in Neuromorphic VLSI.

Real-time classification of patterns of spike trains is a difficult computational problem that both natural and artificial networks of spiking neurons are confronted with. The solution to this problem not only could contribute to understanding the fundamental mechanisms of computation used in the biological brain, but could also lead to efficient hardware implementations of a wide range of applications ranging from autonomous sensory-motor systems to brain-machine interfaces. Here we demonstrate real-time classification of complex patterns of mean firing rates, using a VLSI network of spiking neurons and dynamic synapses which implement a robust spike-driven plasticity mechanism. The learning rule implemented is a supervised one: a teacher signal provides the output neuron with an extra input spike-train during training, in parallel to the spike-trains that represent the input pattern. The teacher signal simply indicates if the neuron should respond to the input pattern with a high rate or with a low one. The learning mechanism modifies the synaptic weights only as long as the current generated by all the stimulated plastic synapses does not match the output desired by the teacher, as in the perceptron learning rule. We describe the implementation of this learning mechanism and present experimental data that demonstrate how the VLSI neural network can learn to classify patterns of neural activities, also in the case in which they are highly correlated.

Multiple views of the response of an ensemble of spectro-temporal features support concurrent classification of utterance, prosody, sex and speaker identity.

Models of auditory processing, particularly of speech, face many difficulties. These difficulties include variability among speakers, variability in speech rate and robustness to moderate distortions such as time compression. In contrast to the 'invariance of percept' (across different speakers, of different sexes, using different intonation, and so on) is the observation that we are sensitive to the identity, sex and intonation of the speaker. In previous work we have reported that a model based on ensembles of spectro-temporal feature detectors, derived from onset sensitive pre-processing of a limited class of stimuli, preserves significant information about the stimulus class. We have also shown that this is robust with respect to the exact choice of feature set, moderate time compression in the stimulus and speaker variation. Here we extend these results to show a) that by using a classifier based on a network of spiking neurons with spike-driven plasticity, the output of the ensemble constitutes an effective rate coding representation of complex sounds; and b) that the same set of spectro-temporal features concurrently preserve information about a range of qualitatively different classes into which the stimulus might fall. We show that it is possible for multiple views of the same pattern of responses to generate different percepts. This is consistent with suggestions that multiple parallel processes exist within the auditory 'what' pathway with attentional modulation enhancing the task-relevant classification type. We also show that the responses of the ensemble are sparse in the sense that a small number of features respond for each stimulus type. This has implications for the ensembles' ability to generalise, and to respond differentially to a wide variety of stimulus classes.

Sprint running: a new energetic approach.

The speed of the initial 30 m of an all-out run from a stationary start on a flat track was determined for 12 medium level male sprinters by means of a radar device. The peak speed of 9.46+/-0.19 m s(-1) (mean +/- s.d.) was attained after about 5 s, the highest forward acceleration (a(f)), attained immediately after the start, amounting to 6.42+/-0.61 m s(-2). During acceleration, the runner's body (assumed to coincide with the segment joining the centre of mass and the point of contact foot terrain) must lean forward, as compared to constant speed running, by an angle alpha = arctang/a(f) (g = acceleration of gravity). The complement (90-alpha) is the angle, with respect to the horizontal, by which the terrain should be tilted upwards to bring the runner's body to a position identical to that of constant speed running. Therefore, accelerated running is similar to running at constant speed up an ;equivalent slope' ES = tan(90-alpha). Maximum ES was 0.643+/-0.059. Knowledge of ES allowed us to estimate the energy cost of sprint running (C(sr), J kg(-1) m(-1)) from literature data on the energy cost measured during uphill running at constant speed. Peak Csr was 43.8+/-10.4 J kg(-1) m(-1); its average over the acceleration phase (30 m) was 10.7+/-0.59 J kg(-1) m(-1), as compared with 3.8 for running at constant speed on flat terrain. The corresponding metabolic powers (in W kg(-1)) amounted to 91.9+/-20.5 (peak) and 61.0+/-4.7 (mean).