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At least 595 records · Page 33Linked to original sources

Post-loosening mechanical behavior of femoral resurfacing prostheses.

The survival rate of femoral surface replacements has been low relative to conventional total hip replacements. The purpose of this investigation was to determine whether the early clinical loosening can be explained by mechanical causes. Using linear and nonlinear finite element methods, the pre- and post-failure load-transfer characteristics of the femoral surface replacement were analysed, and stress patterns and relative motions at the implant/bone interface were evaluated for a particular hip-loading cycle. Using histology of revision material as a guideline, implant loosening, bone resorption and fibrous interface formation were introduced in the model and their mechanical consequences analysed. The results suggest that the high failure rates are not correlated directly with the chances for primary mechanical failure of the implant-bone interface, but rather indirectly with the sensitivity of the implant design to implant loosening and the propagation of bone resorption and fibrous tissue formation. This mechanism appears to be governed by the proliferation of relative motions between implant and bone. We conclude that the 'secondary stability' of implants in general and their capacity to obtain a stable post-loosening configuration is an important design criterion for long-term survival.

Bone Cements↗

Regional multiaxial mechanical properties of the porcine anterior lens capsule.

The lens capsule of the eye plays fundamental biomechanical roles in both normal physiological processes and clinical interventions. There has been modest attention given to the mechanical properties of this important membrane, however, and prior studies have focused on 1-D analyses of the data. We present results that suggest that the porcine anterior lens capsule has a complex, regionally dependent, nonlinear, anisotropic behavior. Specifically, using a subdomain inverse finite element method to analyze data collected via a new biplane video-based test system, we found that the lens capsule is nearly isotropic (in-plane) near the pole but progressively stiffer in the circumferential compared to the meridional direction as one approaches the equator. Because the porcine capsule is a good model of the young human capsule, there is strong motivation to determine if similar regional variations exist in the human lens capsule for knowledge of such complexities may allow us to improve the design of surgical procedures and implants.

Animals↗

Exposure-response analysis of risk of respiratory disease associated with occupational exposure to chrysotile asbestos.

OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.

Adult↗

Fluoroimaging-based immunoassay of DNA photoproducts in ultraviolet-B-irradiated tadpoles.

Sensitive and accurate measurement of photoproducts induced in DNA by natural or artificial ultraviolet-B (UVB; and UVC) light is essential to evaluate the toxic and mutagenic effects of this radiation. Monoclonal antibodies specific for the two major classes of photoproducts-cyclobutane pyrimidine dimers (CPDs) and pyrimidine-[6-4]-pyrimidinone photoproducts ([6-4]PPs)-have made possible highly specific and sensitive assays. Described here is the use of these primary antibodies with fluorescent secondary antibodies to generate 96-spot arrays. Stable fluorescence signals are rapidly and sensitively scored by fluoroimaging and computer analysis of peak-and-valley traces. CPD levels in a series of calibration standards are determined by acid hydrolysis/thin-layer chromatography analyses of radiolabeled bacterial DNA, UV-irradiated to known high fluences, and linear extrapolation to known lower fluences. The nonlinear fluorescence vs CPD curve reflects the effect of photoproduct concentration on single vs double binding by divalent antibody proteins. This technique is applied to photoproducts in whole inbred Xenopus laevis tadpoles, chronically irradiated at a series of UVB fluences that reach a lethality threshold when in vivo steady-state photoproduct levels are still quite low. As few as 0.01-0.02 CPDs per DNA kbp can be reliably detected, at signal/noise ratios of roughly 3:1.

Animals↗

[Biomechanical studies and finite element analysis of a bone-implant interface].

In the present study, the fixation system of a femoral medullary nail connection was investigated. In surgical treatment of fractured femurs, the fracture is bridged by a medullary nail that is fixed by interlocking screws in the bone. Bone failure around these screws is the most common complication associated with the treatment of fractures of osteoporotic bone. The present study analyses the stresses present in the region of the implant/bone system. Three-dimensional finite element models were generated, a nonlinear structure analysis performed, and the stresses at material interfaces investigated. The highest concentration of stresses is to be found in the middle of the interlocking screws and the holes drilled in the bone. This is in agreement with the results of experimental investigations.

Biomechanical Phenomena↗

[Changes in transient evoked otoacoustic emissions contralateral suppression in infants].

BACKGROUND: It has been suggested that the function of the medial olivocochlear system (MOCS) can be evaluated by the suppression effect of the transient evoked otoacoustic emission (TEOAE). The competitive noise has an inhibitory effect on the functioning of the outer hair-cell, reducing the level of otoacoustic emissions. Despite the fact that there is no postnatal growth of the cochlea, middle ear growth and auditory processing development continue after birth. AIM: To analyze age-related changes of MOCS using the TEOAE suppression in healthy infants. METHOD: 25 full-term infants with no risk factors for hearing loss were evaluated in two moments: at birth and at the age of six months. At both ages TEOAE were recorded in the "Quickscreen" mode, nonlinear stimulation at 78dB peSPL, for both ears, with and without contralateral noise presented at 60dB SPL. RESULTS: The data analyses, using ANOVA, revealed significant contralateral suppression of otoacoustic emissions in both groups, but the TEOAE levels and the amount of TEOAE contralateral suppression were smaller at six-month of age when compared to the neonatal period (p < 0.01). The TEOAE suppression effect for neonatals was 2.81dB (+/- 0.19dB) and at the age of six months was 1.41dB (+/- 0.29dB). CONCLUSION: The amount of TEOAE suppression decreased from birth to six months of age. The association between contralateral acoustic stimulation and a commercially available rapid TEOAE measurement system enables a non-invasive monitoring of the auditory efferent mechanism and seems to be clinically feasible to evaluate cochlear status and auditory efferent function development in infants at risk.

Acoustic Stimulation↗

Genetic improvement of mastitis resistance: validation of somatic cell score and clinical mastitis as selection criteria.

Mean daughter deviations for clinical mastitis among second-crop daughters were regressed on predicted transmitting abilities for clinical mastitis and lactation mean somatic cell score in first-crop daughters to validate the predictive ability of these traits as selection criteria for reduced incidence of clinical mastitis. A total of 321 sires had 684,897 second-crop daughters, while predicted transmitting abilities were calculated for 2159 sires, based on 495,681 records of first-crop daughters. Predictive ability, as a measure of efficiency of selection, was 23 to 43% higher for clinical mastitis than for lactation mean somatic cell score. Compared to single-trait selection, predictive ability improved 8 to 13% from utilizing information on both traits. The relative weight that should be assigned to standardized predicted transmitting abilities from univariate genetic analyses were 60 to 67% for clinical mastitis and 33 to 40% for lactation mean somatic cell score. No significant nonlinear genetic relationship between the two traits was found.

Analysis of Variance↗

Effects of age on dopamine transporters in healthy humans.

UNLABELLED: 99mTc-TRODAT-1 is a new radiopharmaceutical that selectively binds the dopamine transporters. This study characterized the effects of aging on its regional cerebral distribution in healthy human volunteers. METHODS: The sample consisted of 27 men and 28 women with a mean age of 41.1 +/- 17.1 y (age range 18.7-73.8 y). Dynamic SPECT scans of the brain were obtained with a standardized acquisition and processing protocol on a triple-head camera. Mean counts per pixel were measured in multiple regions of interest within each basal ganglia. Regression analyses were used to relate the specific uptake values at 3-4 h after administration to age. Both linear and nonlinear models of aging were tested. RESULTS: The relative concentration of radioactivity in most subregions of the basal ganglia decreased significantly with age (all P values < 0.0001). Nonlinear models of aging fit the data significantly better than a straight line. The rate of decline was significantly faster in young adults than in older volunteers (P < 0.001). The break-point age at which the rate of change slowed down and became more stable was 36 y old for the whole striatum and ranged from 32 to 44 y old depending on subregion. CONCLUSION: The effects of aging on central nervous system dopamine transporters do not appear to be linear. Most effects seem to occur during young adulthood before people reach their 40s. The distribution then appears to remain relatively stable until late in life. The findings suggest that the adult life cycle is better characterized as a series of phases than as a continuum.

Adult↗

Efficient temporal processing with biologically realistic dynamic synapses.

Synapses play a central role in neural computation: the strengths of synaptic connections determine the function of a neural circuit. In conventional models of computation, synaptic strength is assumed to be a static quantity that changes only on the slow timescale of learning. In biological systems, however, synaptic strength undergoes dynamic modulation on rapid timescales through mechanisms such as short term facilitation and depression. Here we describe a general model of computation that exploits dynamic synapses, and use a backpropagation-like algorithm to adjust the synaptic parameters. We show that such gradient descent suffices to approximate a given quadratic filter by a rather small neural system with dynamic synapses. We also compare our network model to artificial neural networks designed for time series processing. Our numerical results are complemented by theoretical analyses which show that even with just a single hidden layer such networks can approximate a surprisingly large class of nonlinear filters: all filters that can be characterized by Volterra series. This result is robust with regard to various changes in the model for synaptic dynamics.

Algorithms↗

Enzyme kinetic modelling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: application to amitriptyline N-demethylation.

1. To determine kinetic parameters (Vmax, K(m)) for cytochrome P450 (CYP) mediated metabolic pathways, nonlinear least squares regression is commonly used to fit a model equation (e.g., Michaelis Menten [MM]) to sets of data points (reaction velocity vs substrate concentration). This method can also be utilized to determine the parameters for more complex mechanisms involving allosteric or multi-enzyme systems. Akaike's Information Criterion (AIC), or an estimation of improvement of fit as successive parameters are introduced in the model (F-test), can be used to determine whether application of more complex models is helpful. To evaluate these approaches, we have examined the complex enzyme kinetics of amitriptyline (AMI) N-demethylation in vitro by human liver microsomes. 2. For a 15-point nortriptyline (NT) formation rate vs substrate (AMI) concentration curve, a two enzyme model, consisting of one enzyme with MM kinetics (Vmax = 1.2 nmol min-1 mg-1, K(m) = 24 microM) together with a sigmoidal component (described by an equation equivalent to the Hill equation for cooperative substrate binding; Vmax = 2.1 nmol min-1 mg-1, K' = 70 microM; Hill exponent n = 2.34), was favoured according to AIC and the F-test. 3. Data generated by incubating AMI under the same conditions but in the presence of 10 microM ketoconazole (KET), a CYP3A3/4 inhibitor, were consistent with a single enzyme model with substrate inhibition (Vmax = 0.74 nmol min-1 mg-1, K(m) = 186 microM, K1 = 0.0028 microM-1). 4. Sulphaphenazole (SPA), a CYP2C9 inhibitor, decreased the rate of NT formation in a concentration dependent manner, whereas a polyclonal rat liver CYP2C11 antibody, inhibitory for S-mephenytoin 4'-hydroxylation in humans, had no important effect on this reaction. 5. Incubation of AMI with 50 microM SPA resulted in a curve consistent with a two enzyme model, one with MM kinetics (Vmax = 0.72 nmol min-1 mg-1, K(m) = 54 microM) the other with 'Hill-kinetics' (Vmax = 2.1 nmol min-1 mg-1, K' = 195 microM; n = 2.38). 6. A fourth data-set was generated by incubating AMI with 10 microM KET and 50 microM SPA. The proposed model of best fit describes two activities, one obeying MM-kinetics (Vmax = 0.048 nmol min-1 mg-1, K(m) = 7 microM) and the other obeying MM kinetics but with substrate inhibition (Vmax = 0.8 nmol min-1 mg-1, K(m) = 443 microM, K1 = 0.0041 microM-1). 7. The combination of kinetic modelling tools and biological data has permitted the discrimination of at least three CYP enzymes involved in AMI N-demethylation. Two are identified as CYP3A3/4 and CYP2C9, although further work in several more livers is required to confirm the participation of the latter.

Amitriptyline↗

Structural health monitoring based on sensitivity vector fields and attractor morphing.

The dynamic responses of a thermo-shielding panel forced by unsteady aerodynamic loads and a classical Duffing oscillator are investigated to detect structural damage. A nonlinear aeroelastic model is obtained for the panel by using third-order piston theory to model the unsteady supersonic flow, which interacts with the panel. To identify damage, we analyse the morphology (deformation and movement) of the attractor of the dynamics of the aeroelastic system and the Duffing oscillator. Damages of various locations, extents and levels are shown to be revealed by the attractor-based analysis. For the panel, the type of damage considered is a local reduction in the bending stiffness. For the Duffing oscillator, variations in the linear and nonlinear stiffnesses and damping are considered as damage. Present studies of such problems are based on linear theories. In contrast, the presented approach using nonlinear dynamics has the potential of enhancing accuracy and sensitivity of detection.

Algorithms↗

How much are patients willing to pay to avoid intraoperative awareness?

STUDY OBJECTIVE: To determine how much patients are willing to pay to avoid intraoperative awareness? DESIGN: Observational study SETTING: University-affiliated metropolitan hospital. PATIENTS: 60 patients who completed a questionnaire (39 F, 21 M). The mean age was 43 years and the median household income range of 45,000-60,000 US dollars. INTERVENTIONS: Patients completed an interactive computer-generated questionnaire on the value of preventing intraoperative awareness and their willingness to pay for a "depth of anesthesia" monitor. Their willingness to pay for the prevention of postoperative pain, nausea and vomiting, postoperative grogginess, and sleepiness was also determined as a means of comparison. MEASUREMENTS AND MAIN RESULTS: Patients were willing to pay (WTP) 34 US dollars, 10 US dollars to 42 US dollars (median, interquartile range) for a monitor that would assist an anesthesia care provider assess the depth of anesthesia in an effort to avoid awareness. This increased to 43 US dollars, 20 US dollars to 77 US dollars (p < 0.0,001) (median, interquartile range), if the insurance company was making the payment and the WTP value only decreased minimally to 33 US dollars if the incidence of awareness was reduced 10-fold. CONCLUSION: The incidence of intraoperative awareness and WTP value for monitoring awareness have a nonlinear relationship (a risk averse utility function), which suggests that patients assign an intrinsic base value for a rare or very rare possibility of an event. Other healthcare economic analyses (such as cost effectiveness) do not take this factor into account and assume a linear value relationship (i.e., if something occurs ten times less frequently, it has ten times less value). IMPLICATION: The median value for patients' WTP for a monitor that might prevent awareness under anesthesia was 34 US dollars given an incidence of 5/1,000 cases. The incidence of awareness and WTP value have a nonlinear relationship suggesting that patients assign an intrinsic base value for the possibility of awareness.

Adult↗

What to do at low doses: a bounding approach for economic analysis.

To quantify the health benefits of environmental policies, economists generally require estimates of the reduced probability of illness or death. For policies that reduce exposure to carcinogenic substances, these estimates traditionally have been obtained through the linear extrapolation of experimental dose-response data to low-exposure scenarios as described in the U.S. Environmental Protection Agency's Guidelines for Carcinogen Risk Assessment (1986). In response to evolving scientific knowledge, EPA proposed revisions to the guidelines in 1996. Under the proposed revisions, dose-response relationships would not be estimated for carcinogens thought to exhibit nonlinear modes of action. Such a change in cancer-risk assessment methods and outputs will likely have serious consequences for how benefit-cost analyses of policies aimed at reducing cancer risks are conducted. Any tendency for reduced quantification of effects in environmental risk assessments, such as those contemplated in the revisions to EPA's cancer-risk assessment guidelines, impedes the ability of economic analysts to respond to increasing calls for benefit-cost analysis. This article examines the implications for benefit-cost analysis of carcinogenic exposures of the proposed changes to the 1986 Guidelines and proposes an approach for bounding dose-response relationships when no biologically based models are available. In spite of the more limited quantitative information provided in a carcinogen risk assessment under the proposed revisions to the guidelines, we argue that reasonable bounds on dose-response relationships can be estimated for low-level exposures to nonlinear carcinogens. This approach yields estimates of reduced illness for use in a benefit-cost analysis while incorporating evidence of nonlinearities in the dose-response relationship. As an illustration, the bounding approach is applied to the case of chloroform exposure.

Carcinogens↗

Novel extended tetrathiafulvalenes based on acetylenic spacers: synthesis and electronic properties.

A selection of mono- and diacetylenic dithiafulvalenes was synthesized and employed for the construction of extended tetrathiafulvalenes (TTFs) with hexa-2,4-diyne-1,6-diylidene or deca-2,4,6,8-tetrayne-1,10-diylidene spacers between the two 1,3-dithiole rings. By stepwise acetylenic scaffolding using (E)-1,2-diethynylethene (DEE) building blocks, an extended TTF containing a total of 18 C(sp) and C(sp(2)) atoms in the spacer was prepared. The versatility of the acetylenic dithiafulvene modules was also established by the efficient synthesis of a thiophene-spaced TTF, employing a palladium-catalyzed cross-coupling reaction. The developed synthetic protocols allow functionalization of the extended TTFs in three general ways: with 1) peripheral substituents on the fulvalene cores, 2) alkynyl moieties laterally appended to the spacer, and 3) cobalt clusters involving acetylenic moieties. Strong chromophoric properties of the extended TTFs were revealed by linear and nonlinear optical spectroscopies. Extensive electrochemical studies and calculations on these compounds are also reported, as well as X-ray crystallographic analyses.

Journal Article↗

A discrete, size-structured model of phytoplankton growth in the chemostat: introduction of inhomogeneous cell division size.

We introduce inhomogeneous, substrate dependent cell division in a time discrete, nonlinear matrix model of size-structured population growth in the chemostat, first introduced by Gage et al. [8] and later analysed by Smith [13]. We show that mass conservation is verified, and conclude that our system admits one non zero globally stable equilibrium, which we express explicitly. Then we run numerical simulations of the system, and compare the predictions of the model to data related to phytoplankton growth, whose obtention we discuss. We end with the identification of several parameters of the system.

Animals↗

Selective labelling of high affinity 5-hydroxytryptamine1 receptors in whole rat brain.

In synaptic membranes prepared from whole rat brain, cinanserin produced a relatively shallow inhibition curve of [3H] 5-HT binding with Hill slope of 0.68, as compared with that observed in the [3H]spiperone binding (Hill slope = 0.99). Furthermore, nonlinear regression analysis demonstrated that the former inhibition curve is best fitted by a two-site model. Regional and Scatchard analyses both clearly revealed that, in rat brain, at least two populations of binding sites were labelled by [3H]5-HT; however, high affinity binding sites (K(D) = 1.90 nM, Bmax = 0.188 pmoles/mg protein) could apparently be differentiated from the others by the action of 5 nM cinanserin.

Animals↗

Biomechanical responses of the intervertebral joints to static and vibrational loading: a finite element study.

OBJECTIVE: This study was performed to investigate the time-dependent responses of the intervertebral joint to static and vibrational loads. DESIGN: A poroelastic finite element model was established to analyse the fluid flow, stress distribution and deformation of the intervertebral disc. BACKGROUND: Long-term exposure to whole body vibration is highly associated with disc degeneration and low back pain. It is hypothesized that moderate vibrational loading may increase the efficiency of fluid and nutritional transport of the intervertebral disc while prolonged static and excessive vibrational loading may have deleterious effect. METHODS: A three-dimensional finite element model was established using the actual geometry of the L4-L5 lumber motion segment. Nonlinear poroelastic properties were assigned to the intervertebral disc and cancellous bone. Static and vibrational loads were applied and the responses of fluid flow and stress distributions were analysed. RESULTS: The finite element model showed that the loads carried by the annulus and the facets increased with time under static loading. The fluid flow and deformation of the intervertebral disc were dependent on the loading frequency. CONCLUSION: Vibration loading may be able to enhance disc fluid exchange via the fluid pumping mechanism. RELEVANCE: The predicted responses implied that vibrational motion may be important in facilitating fluid and metabolic transport of the intervertebral disc.

Biomechanical Phenomena↗

Finite element modelling of a residual lower-limb in a prosthetic socket: a survey of the development in the first decade.

A review is presented of the existing finite element models developed from 1987 to 1996 for the biomechanics of lower-limb prostheses. Finite element analysis can be a useful tool in investigating the mechanical interaction between the residual limb and its prosthetic socket, and in computer-aided design and computer-aided manufacturing of prosthetic sockets. Various assumptions and simplifications are made in these models to simplify the actual problem with complex geometry, material properties, boundary and interfacial conditions, as well as loading situations. The analyses can provide the information on the stress distribution at the stump/socket interface and within the residual limb tissues. More recently, nonlinear models have been developed taking into consideration the process of socket rectifications, the slip/friction conditions and material large deformation. The models so far developed have provided some basic understanding of the biomechanics. Comparison of the predictions of these models with experimental measurements indicated that the predicted stresses were within the ranges measured, although one-to-one correspondence was difficult to achieve. Further research is still required in order to improve these models to obtain higher precision in the results taking into account nonlinear and dynamic effects.

Artificial Limbs↗