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Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images.

There is increasing evidence that, in addition to bone mass, bone microarchitecture and its mechanical load distribution are important factors for the determination of bone strength. Recently, it has been shown that new high-resolution imaging techniques in combination with new modeling algorithms based on the finite element (FE) method can account for these additional factors. Such models thus could provide more relevant information for the estimation of bone failure load. The purpose of the present study was to determine whether results of whole-bone micro-FE (microFE) analyses with models based on three-dimensional peripheral quantitative computer tomography (3D-pQCT) images (isotropic voxel resolution of 165 microm) could predict the failure load of the human radius more accurately than results with dual-energy X-ray absorptiometry (DXA) or bone morphology measurements. For this purpose, microFE models were created using 54 embalmed cadaver arms. It was assumed that bone failure would be initiated if a certain percentage of the bone tissue (varied from 1% to 7%) would be strained beyond the tissue yield strain. The external force that produced this tissue strain was calculated from the FE analyses. These predictions were correlated with results of real compression testing on the same cadaver arms. The results of these compression tests were also correlated with results of DXA and structural measurements of these arms. The compression tests produced Colles-type fractures in the distal 4 cm of the radius. The predicted failure loads calculated from the FE analysis agreed well with those measured in the experiments (R(2) = 0.75 p < 0.001). Lower correlations were found with bone mass (R(2) = 0.48, p < 0.001) and bone structural parameters (R(2) = 0.57 p < 0.001). We conclude that application of the techniques investigated here can lead to a better prediction of the bone failure load for bone in vivo than is possible from DXA measurements, structural parameters, or a combination thereof.

Aged↗

Diagnosis of pulmonary embolism in outpatients by sequential noninvasive tools.

Considerable progress has been made in pulmonary embolism (PE) diagnosis during the last 10 years. New, noninvasive tools such as D-dimer measurement and lower limb venous compression ultrasonography have been introduced as diagnostic strategies. Clinical evaluation of the likelihood of PE has been rehabilitated and has proven to be accurate and useful. The interpretation of lung scan results has become more standardized and clear to clinicians. Finally, two diagnostic strategies have been validated in large scale outcome studies. Both rely on a sequential combination of the aforementioned instruments and have safely treated more than 90% of patients without use of pulmonary angiography. The 3-month venous thromboembolic risk in patients in whom PE was ruled out and, hence, who did not undergo anticoagulation was less than 1% in both studies. In the absence of a formal comparison of their respective cost-effectiveness, choosing between these strategies rests on local preferences or logistics. Finally, spiral computed tomography (CT) seems promising and might modify the diagnostic work-up of PE in the near future. However, it is insufficiently validated, and its place in a rational diagnostic algorithm is not defined.

Ambulatory Care Facilities↗

A three-dimensional study of bending and torsion moments for different fracture sites in the mandible: an in vitro study.

The aim of the study was to determine and compare bending and torsion moments across mandibular fractures, for different positions of the bite point and different sites of the fracture. Three identical resin mandibles, each with a single fracture, were used. The fracture sites were in the angle, body and symphyseal regions. A polyethylene bone plate was used for fixation. Simulated bite forces were applied at 13 bite points. For each bite point, the displacements of the fragments were registered and converted into bending and torsion moments across the fracture. Positive bending moments were defined as those moments that caused compression at the lower border and tension at the alveolar side of the mandible; negative bending moments did the opposite. Angle fractures had relatively high positive bending moments. Body fractures had positive as well as negative bending moments and the highest torsion moments. Symphyseal fractures had negative bending moments only and relatively high torsion moments. It was found that angle, body and symphyseal fractures each have a characteristic load pattern. These load patterns should play a decisive role in the treatment of mandibular fractures with regard to number and positioning of plates.

Adult↗

Fast JPEG 2000 decoder and its use in medical imaging.

Over the last decade, a picture archiving and communications system (PACS) has been accepted by an increasing number of clinical organizations. Today, PACS is considered as an essential image management and productivity enhancement tool. Image compression could further increase the attractiveness of PACS by reducing the time and cost in image transmission and storage as long as 1) image quality is not degraded and 2) compression and decompression can be done fast and inexpensively. Compared to JPEG, JPEG 2000 is a new image compression standard that has been designed to provide improved image quality at the expense of increased computation. Typically, the decompression time has a direct impact on the overall response time taken to display images after they are requested by the radiologist or referring clinician. In this paper, we present a fast JPEG 2000 decoder running on a low-cost programmable processor. It can decode a losslessly compressed 2048 x 2048 CR image in 1.51 s. Using this kind of a decoder, performing JPEG 2000 decompression at the PACS display workstation right before images are displayed becomes viable. A response time of 2 s can be met with an effective transmission throughput between the central short-term archive and the workstation of 4.48 Mb/s in case of CT studies and 20.2 Mb/s for CR studies. We have found that JPEG 2000 decompression at the workstation is advantageous in that the desired response time can be obtained with slower communication channels compared to transmission of uncompressed images.

Algorithms↗

[To what extent are oscillometric data of a simple resistor-volume model physically recordable?].

To obtain data on the volume-dependence of the oscillatory parameters of the Siregnost FD 5, we investigated the course of iso-volume and iso-resistance lines in a simple mechanical resistor-volume model in the different coordinate systems, initially in the absence of additional superimposed stationary flow. While the P-psi diagram reveals no uniform course, and no preferential relationship of changes in resistance to P or Ros, or of changes in volume to psi, such a relationship develops on transformation to the Rre-phi and the Rre-X diagram. Rre proves to contain not only the purely resistor component, but also a reactance-proportional or inversely volume-proportional component, which is apparently due to internal friction resulting from volume compression. On the other hand, reactance is almost totally derivable from volume compression. With reference to the theoretical Franken model and others (1981), we discussed the influence of various physical factors on the impedance of a tube segment, and the different volume-dependence of impedance of closed- and open-ended cylindrical tubes. Further work on the theoretical consideration of the forced oscillation technique will examine the influence of additional superimposed stationary flow, which has a considerable effect on the resistor-volume model. Furthermore, the critical value of Reynold's number may be expected to be exceed in the FD 5 reference tube already at low respiratory flow.

Airway Resistance↗

[Negative D-dimers and exclusion of venous thromboembolism--own experience].

The assessment of D-dimer concentration has become essential step during diagnostic algorithm of venous thromboembolism (VTE). This test characterizes high sensitivity but limited specificity. Negative D-dimer with high probability excludes VTE. The aim of this study was to assess the percentage of patients treated in Department of Internal Medicine, Endocrinology and Haemostatic Disorders, Medical University of Gdańisk, who in spite of clinical signs of VTE showed normal D-dimer level. Between 2000 and 2004 in our department 57 cases with recent deep vein thrombosis (DVT) were diagnosed, in 2 cases with co-existence of pulmonary embolism (PE). The D-dimer concentration was assessed in patients' plasma with the use of immunoturbidometry. Between 57 cases with VTE, 7 patients (12%) showed normal D-dimer level (<500 microg/ml). This group consisted of 4 men and 3 women, aged from 40 to 82 years (the mean age of 58 years). In all 7 cases DVT was diagnosed, in 2 patients with concomitent PE. The final diagnosis was confirmed by compression ultrasonography and pulmonary scintigraphy. Our analysis underlines the observation that occurrence of VTE and negative d-dimer concentration is possible and may probably be related to methodological limitations. However, the lack of increase of D-dimer could also be caused by fibrinolysis alteration.

Adult↗

Segmentation and measurement based on 3D Voronoi diagram: application to confocal microscopy.

Computational geometry provides many solutions to imaging problems, especially for three-dimensional (3D) image compression, segmentation, and measurement. We present here a new method to partition volume data by Voronoi polyhedra structured in a graph environment. A dynamic construction of the 3D Voronoi diagram is proposed, using image information interactively. The process has been applied to segment and quantitate 3D biological data acquired with a confocal laser scanning microscope (CLSM). The discrete volume acquired represents a large mass of data and can be reduced with this particular method, before measurement (processing time) or archiving (memory space). Furthermore, the structure data is a powerful tool to rapidly compute parameters that are characteristic of the volume data.

Algorithms↗

Factors influencing drug release from stearic acid based compacts.

Fatty acids are potentially suitable carriers for use in the design of drug delivery systems, being biocompatible, biodegradable inexpensive and of low toxicity. The release of the model compound benzoic acid from fatty acid compacts of stearic acid was evaluated using the USP Apparatus 2 dissolution assembly in phosphate buffer pH 7.4. Matrix controlled drug release was expected. Release profiles were approximated by square root of time kinetics. Release rate was independent of stirring speed in the rpm range 50-150, however, at 200 rpm a significant increase in release rate was observed particularly at later times, the amount released versus square root of time plots becoming non-linear. Release was independent of compression pressure in the range 1-7 tons. The particle size of the benzoic acid and stearic acid used had a significant influence on release. The use of particles in the range 250-500 microm gave release rate constants (k, g/cm(2) per min(0.5)) approximately 1.5 greater than those of smaller particle size (63-125 microm). The formation factor (F) tended to increase exponentially with drug loading, the increase being steeper for compacts prepared from the larger particle sizes. At 80% drug loading for large sized systems the matrix appeared to offer little resistance to drug release and F approached one.

Algorithms↗

Data compression of fetal Doppler ultrasound audio signals using zero-crossings analysis.

This paper outlines a method of reducing the data rate for transmitting fetal Doppler ultrasound audio signals. A specific application is cited where compression of the fetal Doppler signal is required to transmit information to cardiotocographs (CTGs) using radio telemetry. The method involves splitting the signal into amplitude and frequency components. The amplitude is represented by samples of the signal envelope whilst the frequency information is represented by the number of zero-crossings within fixed intervals (windows). With a careful choice of window size, it is shown that this method can be used to reproduce the signal with no audible difference when compared with the original waveform. A reduction in data rate of 15:1 is achieved.

Algorithms↗

Optimization of a tablet containing chlorthalidone.

In pharmaceutical technological research, optimization studies generally deal with the search for the formulation that is as effective and as functional as possible. The effect of a formulation parameter (the amount of lactose in the composition of the tablets) and of a technological parameter (compression pressure) on four physical characteristics (tablet thickness, friability, hardness, and drug dissolution rate) of tablets containing the antihypertensive drug chlorthalidone were studied. The results obtained indicate that, in the development of a tablet formulation, it is possible to identify the most suitable formulation by applying a simple optimization method. The effect of the microclimatic stress (temperature and humidity) was also evaluated, and it was found that the optimized tablets were no longer within limits that had been established for them. This may indicate that it is opportune to keep the storage conditions of the excipients under control before their use.

Algorithms↗

Improved tools for DNA comparison and clustering.

DNA sequence clustering is an effective aid of the comprehension, summarization and compression of DNA sequence databases. Previous work created programs suitable for the comparison and clustering of cDNA sequences but new enhanced programs have been written to cluster genomic DNA fragments, large EST projects, and entire DNA databases. Three new programs (ICAtools) are discussed: ICAass, N2tool, and ICAmatches. ICAass has been used to compress the EMBL database by hiding or removing sequences with various degrees of redundancy. It also has the fastest database querying mode. N2tool provides fast and sensitive clustering of genomic fragment databases on the basis of small areas of local similarity. N2tool has proven utility in the discovery of contaminating vector or other artefactual sequence when the potential contaminant is not otherwise known. ICAmatches is a new cluster analysis program that uses a novel alignment style to present multiple alignment summaries. All the tools are convenient to use because they share a common memory-frugal index format and accept most DNA sequence formats directly.

Algorithms↗

Three-dimensional reconstruction of microcalcification clusters from two mammographic views.

Classification of benign/malignant microcalcification clusters is a major diagnostic challenge for radiologists. Clinical studies have revealed that the shape of the cluster, and the spatial distribution of individual microcalcifications within it, are important indicators of its malignancy. However, mammographic images of clustered microcalcifications confound their three-dimensional (3-D) distribution with image projection and breast compression. This paper presents a novel model-based method for reconstructing microcalcification clusters in 3-D from two mammographic views (cranio-caudal and medio-lateral oblique--"shoulder to the opposite hip" or lateral-medio). We develop a 3-D breast representation and a parameterised breast compression model which constraints geometrically the possible 3-D positions of a calcification in a two-dimensional image. Corresponding calcifications in the two views are matched using an estimate of the calcification volume. Both the geometric constraint and the matching criterion are utilized in the final reconstruction step to build the 3-D reconstructed clusters. Validation experiments are described using 30 clusters to verify the individual steps of the model, and results consistent with known ground truth are obtained. Some of the approximations in the model and future work are discussed in the concluding section.

Algorithms↗

Co-extrusion of biocompatible polymers for scaffolds with co-continuous morphology.

A methodology for the preparation of porous scaffolds for tissue engineering using co-extrusion is presented. Poly(epsilon-caprolactone) is blended with poly(ethylene oxide) in a twinscrew extruder to form a two-phase material with micron-sized domains. Selective dissolution of the poly(ethylene oxide) with water results in a porous material. A range of blend volume fractions results in co-continuous networks of polymer and void spaces. Annealing studies demonstrate that the characteristic pore size may be increased to larger than 100 microm. The mechanical properties of the scaffolds are characterized by a compressive modulus on the order of 1 MPa at low strains but displaying a marked strain-dependence. The results of osteoblast seeding suggest it is possible to use co-extrusion to prepare polymer scaffolds without the introduction of toxic contaminants. Polymer co-extrusion is amenable to both laboratory- and industrial-scale production of scaffolds for tissue engineering and only requires rheological characterization of the blend components. This method leads to scaffolds that have continuous void space and controlled characteristic length scales without the use of potentially toxic organic solvents.

Algorithms↗

An investigation of the mechanism of release of the amphoteric drug amoxycillin from poly(D,L-lactide-co-glycolide) matrices.

Amoxycillin-poly (D,L-lactide-co-glycolide) (PLGA) compacts were prepared by direct compression of both powder mixtures or films in a pre-heated press. Release profiles generally showed two phases separated by an induction period. Thus, both diffusion and polymer degradation mechanisms were involved in drug release, the relative importance of each depending on processing type and drug loading. Drug release parameters for each phase were determined. The fraction of total drug released, in the initial release phase, increased with drug loading and was much larger for compressed physical mixtures than for compressed composites prepared from co-evaporate films. Comparison of the polymer mass loss profiles of drug-loaded and drug-free discs indicated that the presence of the amphoteric drug amoxycillin had little impact on the polymer degradation rate, in contrast to the marked acceleration previously reported for basic drugs. Significant drug degradation occurred and was associated with release at later times. Release data was fitted to an equation accounting for degradation of the drug on release and suggested accelerated amoxycillin degradation during the polymer degradation controlled release phase, consistent with changes in pH in the microenvironment of the eroding compact.

Algorithms↗

Viscoelasticity of a protein monolayer from anisotropic surface pressure measurements.

We present a method to completely characterize the viscoelasticity of Langmuir monolayers. In contrast to existing techniques, both the compression and shear moduli are determined at the same time, in a single experiment and with a standard apparatus. This approach relies on the measurement of anisotropy in the surface pressure: the tension is measured in orientations perpendicular and parallel to the compression direction. We apply this technique to the study of beta-lactoglobulin spread monolayers, a system that has been shown to develop a shear modulus at high concentration. Beta-lactoglobulin monolayers are interesting both because of their importance in food science and because they exhibit universally slow dynamical behavior that is not fully understood. Our results confirm that the compressional modulus dominates the total viscoelastic response and also provide a complex shear modulus, emerging above a critical concentration. We are able to describe how each of the dynamical response moduli is related to the surface concentration and to the equilibrium osmotic pressure.

Algorithms↗

Morphological & morphometric studies on liver in rats subjected to repetitive heat stress.

Morphological and morphometric studies were conducted under light microscope on paraffin sections (H&E) of liver from controls and experimental rats subjected to repeated heat stress for 4 h/day, at 38 degrees +/- 0.5 degree C (relative humidity 65-82%) for 2-8 consecutive days. The morphometric variables were derived by intersection-point counting method, using simple square lattice test system A100. Twinning of liver cell plates and anisocytosis characterised morphological changes in rats exposed to heat twice. Following five heat exposures, rat liver showed ballooning degeneration of hepatocytes, associated with sinusoidal compression and loss of normal liver cell plate pattern. The degenerative changes in liver parenchyma were more pronounced in rats that underwent eight heat exposures. Despite hepatocytic degeneration, the numerical density of hepatocytes (Nvh) and the volume density of hepatocytes (Vvh) increased with the increase in number of heat exposures, indicating associated heat induced acceleration in hepatocytic proliferation. A successive fall, with increase in the number of heat exposures, in the sinusoidal length density (Jvs) and in the numerical density of Kupffer cells on area (Nak) revealed progressive damage to hepatic-vascular endothelium, which suggest an adverse effect on the immune status of the animals.

Algorithms↗

Estimation of ultrasonic attenuation in a bone using coded excitation.

This paper describes a novel approach to estimate broadband ultrasound attenuation (BUA) in a bone structure in human in vivo using coded excitation. BUA is an accepted indicator for assessment of osteoporosis. In the tested approach a coded acoustic signal is emitted and then the received echoes are compressed into brief, high amplitude pulses making use of matched filters and correlation receivers. In this way the acoustic peak pressure amplitude probing the tissue can be markedly decreased whereas the average transmitted intensity increases proportionally to the length of the code. This paper examines the properties of three different transmission schemes, based on Barker code, chirp and Golay code. The system designed is capable of generating 16 bits complementary Golay code (CGC), linear frequency modulated (LFM) chirp and 13-bit Barker code (BC) at 0.5 and 1 MHz center frequencies. Both in vivo data acquired from healthy heel bones and in vitro data obtained from human calcaneus were examined and the comparison between the results using coded excitation and two cycles sine burst is presented. It is shown that CGC system allows the effective range of frequencies employed in the measurement of broadband acoustic energy attenuation in the trabecular bone to be doubled in comparison to the standard 0.5 MHz pulse transmission. The algorithm used to calculate the pairs of Golay sequences of the different length, which provide the temporal side-lobe cancellation is also presented. Current efforts are focused on adapting the system developed for operation in pulse-echo mode; this would allow examination and diagnosis of bones with limited access such as hip bone.

Acoustics↗

How enzyme dynamics helps catalyze a reaction in atomic detail: a transition path sampling study.

We have applied the Transition Path Sampling algorithm to the reaction catalyzed by the enzyme Lactate Dehydrogenase. This study demonstrates the ease of scaling Transition Path Sampling for applications on many degree of freedom systems, whose energy surface is a complex terrain of valleys and saddle points. As a Monte Carlo importance sampling method, transition path sampling is capable of surmounting barriers in path phase space and focuses simulation on the rare event of enzyme catalyzed atom transfers. Generation of the transition path ensemble, for this reaction, resolves a paradox in the literature in which some studies exposed the catalytic mechanism of hydride and proton transfer by lactate dehydrogenase to be concerted and others stepwise. Transition path sampling has confirmed both mechanisms as possible paths from reactants to products. With the objective to identify a generalized, reduced reaction coordinate, time series of both donor-acceptor distances and residue distances from the active site have been examined. During the transition from pyruvate to lactate, residues located behind the transferring hydride collectively compress toward the active site causing residues located behind the hydride acceptor to relax away. It is demonstrated that an incomplete compression/relaxation transition across the donor-acceptor axis compromises the reaction.

Catalysis↗