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Is silicified wet-granulated microcrystalline cellulose better than original wet-granulated microcrystalline cellulose?

The purpose of this study was to investigate the effect of granulating water level on the physical-mechanical properties of microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (SMCC). Granulations containing either MCC or SMCC were manufactured at different water levels using a high-shear mixer and were then tray-dried. The water level ranged from 0 to 100%. The granules were evaluated for size, granular and true density, porosity, flow, compactibility, compressibility, and strain-rate sensitivity index (SRS). Increasing the water level affected the size, increased the granular density and flow properties of the granules, and decreased the porosity and compactibility. The compactibilities for both materials were similar and acceptable at each granulating water level up to 40%. They both showed poor compactibility at higher water levels. Yield values and SRSs revealed that MCC and SMCC have similar compressibility, and that both exhibit a plastic component to the deformation process. The granulating water level had no statistically significant effect on the compressibility or the SRS for MCC or SMCC. SMCC did not offer practical advantages over MCC, other than better flow in the powder form, which could be attributed to slightly larger particle size and the presence of silicon dioxide in its structure.

Algorithms↗

Variability of a three-dimensional finite element model constructed using magnetic resonance images of a knee for joint contact stress analysis.

Magnetic resonance (MR) imaging has been widely used to evaluate the thickness and volume of articular cartilage both in vivo and in vitro. While morphological information on the cartilage can be obtained using MR images, image processing for extracting geometric boundaries of the cartilage may introduce variations in the thickness of the cartilage. To evaluate the variability of using MR images to construct finite element (FE) knee cartilage models, five investigators independently digitized the same set of MR images of a human knee. The topology of cartilage thickness was determined using a minimal distance algorithm. Less than 8 percent variation in cartilage thickness was observed from the digitized data. The effect of changes in cartilage thickness on contact stress analysis was then investigated using five FE models of the knee. One FE model (average FE model) was constructed using the mean values of the digitized contours of the cartilage, and the other four were constructed by varying the thickness of the average FE model by +/- 5 percent and +/- 10 percent, respectively. The results demonstrated that under axial tibial compressive loading (up to 1,400 N), variations of cartilage thickness caused by digitization of MR images may result in a difference of approximately 10 percent in peak contact stresses (surface pressure, von Mises stress, and hydrostatic pressure) in the cartilage. A reduction of cartilage thickness caused increases of contact stresses, while an increase of cartilage thickness reduced contact stresses. Furthermore, the effect of variation of material properties of the cartilage on contact stress analysis was investigated. The peak contact stress increased almost linearly with the Young's modulus of the cartilage. The peak von Mises stress was dramatically reduced when the Poisson,s ratio was increased from 0.05 to 0.49 under an axial compressive load of 1,400 N, while peak hydrostatic pressure was dramatically increased. Peak surface pressure was also increased with the Poisson's ratio, but with a lower magnitude compared to von Mises stress and hydrostatic pressure. In conclusion, the imaging process may cause 10 percent variations in peak contact stress, and the predicted stress distribution is sensitive to the accuracy of the material properties of the cartilage model, especially to the variation of Poisson's ratio.

Aged↗

Pseudoaneurysms and the role of minimally invasive techniques in their management.

Pseudoaneurysms are common vascular abnormalities that represent a disruption in arterial wall continuity. Some complications associated with pseudoaneurysms develop unpredictably and carry high morbidity and mortality rates. The advent of new radiologic techniques with a greater sensitivity for asymptomatic disease has allowed more frequent diagnosis of pseudoaneurysms. Conventional angiography remains the standard of reference for diagnosis but is an invasive procedure, and noninvasive diagnostic modalities (eg, ultrasonography [US], computed tomographic angiography, magnetic resonance angiography) should be included in the initial work-up if possible. A complete work-up will help in determining the cause, location, morphologic features, rupture risk, and clinical setting of the pseudoaneurysm; identifying any patient comorbidities; and evaluating surrounding structures and relevant vascular anatomy, information that is essential for treatment planning. Therapeutic options have evolved in recent years from the traditional surgical option toward a less invasive approach and include radiologic procedures such as US-guided compression, US-guided percutaneous thrombin injection, and endovascular management (embolization, stent-graft placement). The use of noninvasive treatment has led to a marked decrease in the morbidity and mortality rates for pseudoaneurysms.

Adult↗

The constitutive properties of the brain parenchyma Part 1. Strain energy approach.

In this paper we study several constitutive equations for the brain based on the strain energy density function. We use the polynomial function and hyper-elastic Ogden model for the strain energy and include the energy dissipation by a Prony series expansion. The models are compared with known unconfined compression experimental results of the human brain tissue to obtain the best fitted model and brain mechanical parameters. Finite element simulations are also performed using the given constitutive equations, and numerical solutions match the analytical results very closely. The results are compared with other analytical and numerical calculations.

Algorithms↗

Influence of dynamic compression on directional hearing in the horizontal plane.

OBJECTIVE: The purpose of this study was to assess the influence of dynamic compression on directional hearing in the frontal horizontal plane. DESIGN: Compression schemes with various compression ratios and attack times were created by using a digital signal processor. The influence of compression on isolated interaural level differences (ILDs) and interaural time differences (ITDs) was examined in discrimination experiments. The combination of ILDs and ITDs was investigated with measurements of localization based on head-related transfer functions. Five normal listeners and seven hearing-impaired subjects participated in the study. RESULTS: Dynamic compression revealed substantial effects on discrimination of ILDs but not on ITDs. With higher compression ratios and shorter attack times, just-noticeable differences for ILDs increased. Lateralization via head-related transfer functions was predominantly affected by compression in the higher frequency range because for lower frequencies, interaural time cues dominate over interaural level cues. The effect of compression was similar for normal and hearing-impaired listeners, but the latter performed worse on almost all tasks, especially with ITD discrimination at 4000 Hz. CONCLUSIONS: The influence of compression ratio and attack time could be shown for ILDs, but the effect was rather small, at least for the low compression ratios commonly used in hearing aids. The influence further decreased when attack time was prolonged. The dramatic impairment of the discrimination of ITDs with the hearing-impaired subjects in the high-frequency range suggests that they primarily rely on ILD cues.

Acoustic Stimulation↗

Potential role of nuclear magnetic resonance for the evaluation of trabecular bone quality.

This paper discusses two novel applications of nuclear magnetic resonance (NMR) as an investigational tool for the assessment of cancellous bone microarchitecture. It further outlines extensions of the method for in vivo clinical evaluation of bone strength in patients with skeletal disorders such as osteoporosis. The first method relies on the hypothesis that the presence of two phases of different magnetic permeability, i.e., bone and bone marrow, causes a spatial nonuniformity of the magnetic field across the measurement volume. The resulting spread in resonance frequency shortens the decay time constant (T2*) of the time domain proton signal in bone marrow or its substitute (water). Increased trabecular spacing, such as it occurs in osteoporosis, reduces the spatial field inhomogeneity and thus prolongs T2*, which has been shown both in vitro and in vivo. Subjects with osteoporosis, characterized by either low bone mineral density and/or spine compression fractures, have T2* values that are significantly prolonged. The second method focuses on a direct measurement of micromorphometric parameters of cancellous bone, using the principles of proton NMR microscopy in conjunction with computer processing of the resulting digital images. Image contrast between the trabeculae and the intertrabecular space is based on the marrow protons providing a signal, as opposed to bone, which appears with background intensity. Once tissues have been classified (into bone and marrow), for example, by means of a histogram-based segmentation algorithm, bone area fraction, mean trabecular plate density (MTPD), and mean trabecular plate thickness (MTPT) can be computed without the need for further operator intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The surface properties of apolipoproteins A-I and A-II at the lipid/water interface.

The monolayer system was employed to investigate the relative affinities of apolipoproteins A-I and A-II for the lipid/water interface. The adsorption of reductively 14C-methylated apolipoproteins to phospholipid monolayers spread at the air/water interface was determined by monitoring the surface pressure of the mixed monolayer and the surface concentration of the apoprotein. ApoA-II has a higher affinity than apoA-I for lipid monolayers; for a given initial surface pressure, apoA-II adsorbs more than apoA-I to monolayers of egg phosphatidylcholine (PC), distearoyl-PC and human high-density lipoprotein (HDL3) surface lipids. Comparison of the molecular packing of apolipoproteins A-I and A-II suggests that apoA-II adopts a more condensed conformation at the lipid/water interface compared to apoA-I. The ability of apoA-II to displace apoA-I from egg PC and HDL3 surface lipid monolayers was studied by following the adsorption and desorption of the reductively 14C-methylated apolipoproteins. At saturating subphase concentrations of the apoproteins (3.10(-5) g/100 ml), two molecules of apoA-II absorbed for each molecule of apoA-I displaced. This displacement was accompanied by an increase in surface pressure. An identical stoichiometry for the displacement of apoA-I from HDL particles by apoA-II has been reported by others. At low subphase concentrations of apoproteins (5.10(-6) g/100 ml), the apoA-I/lipid monolayer was not fully compressed and could accommodate the adsorbing apoA-II molecules without displacement of apoA-I molecules. ApoA-I molecules were unable to displace apoA-II from the lipid/water interface. The average residue hydrophobicity of apoA-II is higher than that of apoA-I; this may contribute to the higher affinity of apoA-II for lipids compared to apoA-I. The probable helical regions in apolipoproteins A-I and A-II were located using a secondary structure prediction algorithm. The analysis suggests that the amphiphilic properties of the alpha-helical regions of apoA-I and apoA-II are probably not significantly different. Further understanding of the differences in surface activity of these apolipoproteins will require more knowledge of their secondary and tertiary structures.

Amino Acid Sequence↗

Advances in the diagnosis of venous thromboembolism.

This review summarizes recent information about the diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) using noninvasive imaging tests, clinical assessment, and D-dimer assays, and describes how these tests can be employed in diagnostic testing algorithms for the investigation of patients with suspected DVT and PE. The clinical diagnosis of deep venous thrombosis is unreliable, but clinical prediction rules based on signs and symptoms do facilitate the categorization of patients into high, low, or medium risk categories. High sensitivity D-dimer assays further help in excluding cases but do not help in ruling in venous thromboembolism. D-dimer assays and clinical prediction rules also help in the diagnosis of pulmonary embolism. These assessments, along with objective imaging studies such as compression ultrasonography for DVT or computerized tomographic pulmonary angiograms for PE can be used in a systematic way to reliably rule in or exclude venous thromboembolism.

Fibrin Fibrinogen Degradation Products↗

A front-end automation tool supporting design, verification and reuse of SOC.

This paper describes an in-house developed language tool called VPerl used in developing a 250 MHz 32-bit high-performance low power embedded CPU core. The authors showed that use of this tool can compress the Verilog code by more than a factor of 5, increase the efficiency of the front-end design, reduce the bug rate significantly. This tool can be used to enhance the reusability of an intellectual property model, and facilitate porting design for different platforms.

Algorithms↗

Human dural thickness measured by ultrasonographic method: reflection of intracranial pressure.

We measured changes in dural thickness to estimate intracranial pressure. The dural thickness on magnetic resonance imaging with contrast enhancement was compared in a hydrocephalic patient before and after shunt operation. Dural thickness also was measured directly using a micrometer at craniotomy for aneurysmal clipping in 11 patients. A small ultrasound probe (5 MHz) was held against the temporal scalp of 10 volunteers to extract convoluted interference echoes from the dura mater using a computer--based system for fast Fourier transform-Cepstrum analysis and maximum entropy analysis. The degree of intracranial pressure in the supine position was varied in the volunteers with transient neck compression. The enhanced dural thickness of the patient with hydrocephalus, barely visualized before shunt operation, increased after surgery. Dural thickness measurements obtained ultrasonographically in the supine position were similar to direct measurements of thickness. Changes in dural thickness on ultrasonography reflect changes in intracranial pressure.

Adolescent↗

A new theoretical model to characterize the densification behavior of tableting materials.

The purpose of the study was to develop a new three-dimensional model using force, time and displacement to characterize the densification behavior of tableting materials. Normalized time (x), displacement converted to ln(1/1 - D(rel)) according to Heckel (y) and force presented as pressure (z) were used to plot a graph. A twisted plane was fitted to this three-dimensional plot. This plane was characterized by three parameters d, the slope over time called 'time plasticity', e, the slope over pressure called 'pressure plasticity' and omega, the angle of rotation called 'fast elastic decompression'. These parameters were used to characterize the densification behavior of the well-known materials microcrystalline cellulose, dicalcium phosphate dihydrate, theophylline monohydrate, cellulose acetate and hydroxypropyl methylcellulose at different rho(rel, max). It could be shown that brittle, elastic and plastic compression properties could be very well distinguished and differentiated. Further on, it could be shown whether these properties were due to pressure or time. Thus this model has the prevailing advantage to characterize tableting materials in one step according to time and pressure and it is a useful tool to develop tablet formulations or new excipients.

Algorithms↗

Structure and hydrogen bonding in neat N-methylacetamide: classical molecular dynamics and Raman spectroscopy studies of a liquid of peptidic fragments.

The results of classical molecular dynamics (MD) simulations and Raman spectroscopy studies of neat liquid N-methylacetamide (NMA), the simplest model system relevant to the peptides, are reported as a function of temperature and pressure. The MD simulations predict that near ambient conditions, the molecules form a hydrogen bond network consisting primarily of linear chains. Both the links between molecules within the hydrogen-bonded chains and the associations between chains are stabilized by weak methyl-donated "improper" hydrogen bonds. The three-dimensional structural motifs observed in the liquid show some similarity to protein beta-sheets. The temperature and pressure dependence of the hydrogen bond network, as probed by the mode frequency of the experimentally determined amide-I Raman band, blue shifts on heating and red shifts under compression, respectively, suggesting weakened and enhanced hydrogen bonding in response to temperature and pressure increases. Disruption of the hydrogen-bonding network is clearly observed in the simulation data as temperature is increased, whereas the improper hydrogen bonding is enhanced under compression to reduce the energetic cost of increasing the packing fraction. Because of the neglect of polarizability in the molecular model, the computed dielectric constant is underestimated compared to the experimental value, indicating that the simulation may underestimate dipolar coupling in the liquid.

Acetamides↗

Three dimensional modeling of the cerebrospinal fluid dynamics and brain interactions in the aqueduct of sylvius.

A computational fluid dynamics (CFD) method is presented to investigate the flow of cerebro-spinal fluid (CSF) in the cerebral aqueduct. In addition to former approaches exhibiting a rigid geometry, we propose a model which includes a deformable membrane as the wall of this flow channel. An anatomical shape of the aqueduct was computed from magnetic resonance images (MRI) and the resulting meshing was immersed in a marker-and-cell (MAC) staggered grid for to take into account fluid-structure interactions. The time derivatives were digitized using the Crank-Nicolson scheme. The equation of continuity was modified by introducing an artificial compressibility and digitized by a finite difference scheme. Calculations were validated with the simulation of laminar flow in a rigid tube. Then, comparisons were made between simulations of a rigid aqueduct and a deformable one. We found that the deformability of the walls has a strong influence on the pressure drop for a given flow.

Algorithms↗

Lane tracking software for four-color fluorescence-based electrophoretic gel images.

Software to track sample lanes automatically in four-color, fluorescence-based, electrophoretic gel images has been developed for application in large-scale DNA sequencing projects. Lanes and lane boundaries are tracked by analyzing a first difference approximation to the gradient of a vertically integrated and processed "brightness" profile. Initially lanes are located in a region of the gel image selected for good horizontal lane spacing and signal strength. The software uses models of expected lane and interlane spacing and lateral lane behavior to maintain accurate tracking on imperfect gels. In areas where intensity-based tracking is difficult, interpixel column correlation is also used to locate and define lane features. Summary statistics and compressed-in-time images are generated for user evaluation of tracking performance. The software developed has been tested successfully on gel images with degradations including significant horizontal lane motion (curving) and image artifacts, and is now in full-scale use in our sequencing projects.

Algorithms↗

[Analysis of accidental deaths in mountain tourism and sport according to statistics from the Republic of Kabardino-Balkariia].

Lethal cases in mountain tourism and sports in the Republic of Kabardino-Balkaria were studied for 1978-1995. A total of 152 accidental deaths were analysed. Most of the victims were males under 30 years of age. The greatest number of the accidents took place on Monday, in July and August. Many amateur visitors from abroad were among the victims. The main cause of death in the mountains of Kabardino-Balkaria for the 18 years studied was multitrauma of the body (69.7%). Hypothermia and obturation asphyxia with snow and compression asphyxia due to snowbreak account for 11.8 and 13.2% deaths, respectively; lightning killed 4%. Combination of high mountain hypoxia with exacerbated chronic somatic disease or hypothermia caused death in 1% victims. The authors propose how to improve forensic-medical expert examination of accidental death and safety in the mountains.

Accidents↗

Testing the geometric clutch hypothesis.

The Geometric Clutch hypothesis is based on the premise that transverse forces (t-forces) acting on the outer doublets of the eukaryotic axoneme coordinate the action of the dynein motors to produce flagellar and ciliary beating. T-forces result from tension and compression on the outer doublets when a bend is present on the flagellum or cilium. The t-force acts to pry the doublets apart in an active bend, and push the doublets together when the flagellum is passively bent and thus could engage and disengage the dynein motors. Computed simulations of this working mechanism have reproduced the beating pattern of simple cilia and flagella, and of mammalian sperm. Cilia-like beating, with a clearly defined effective and recovery stroke, can be generated using one uniformly applied switching algorithm. When the mechanical properties and dimensions appropriate to a specific flagellum are incorporated into the model the same algorithm can simulate a sea urchin or bull sperm-like beat. The computed model reproduces many of the observed behaviors of real flagella and cilia. The model can duplicate the results of outer arm extraction experiments in cilia and predicted two types of arrest behavior that were verified experimentally in bull sperm. It also successfully predicted the experimentally determined nexin elasticity. Calculations based on live and reactivated sea urchin and bull sperm yielded a value of 0.5 nN/microm for the t-force at the switch-point. This is a force sufficient to overcome the shearing force generated by all the dyneins on one micron of outer doublet. A t-force of this magnitude should produce substantial distortion of the axoneme at the switch-point, especially in spoke or spoke-head deficient motile flagella. This concrete and verifiable prediction is within the grasp of recent advances in imaging technology, specifically cryoelectron microscopy and atomic force microscopy.

Animals↗

Exclusion of venous thromboembolism: evaluation of D-Dimer PLUS for the quantitative determination of D-dimer.

The objective of this study was to evaluate if D-Dimer PLUS (Dade Behring, USA), a rapid fully automated assay, could be used as an initial screening test in the diagnosis of venous thromboembolism (VTE). Samples from 274 consecutive symptomatic patients with suspected pulmonary embolism (n=229; 79% outpatients, 21% inpatients), deep venous thrombosis (n=37; 84% outpatients, 16% inpatients) or suspected for both complications (n=8) were tested with this D-dimer assay with a Sysmex CA-1500 Coagulation Analyzer. Clinical probability for pulmonary embolism (PE) or deep venous thrombosis (DVT) was staged according to a pretest risk score proposed by Wells. Final diagnosis of PE and/or DVT was established by spiral-computed tomography of the pulmonary arteries or compression ultrasonography, respectively. PE was diagnosed in 13.5% of the patients, whereas DVT was confirmed in 17.7% of the patients. The optimal cut-off value for exclusion of venous thromboembolism was 130 mug/l, and sensitivity, specificity and negative predictive value (NPV) were 95.0% (95% CI: 92.4-97.6), 30.4% (95% CI: 25.0-35.8) and 97.2% (95% CI: 95.2-99.2), respectively. In fact, two patient with PE were missed using D-Dimer PLUS; both cases were outpatients. In conclusion, this assay appears to be safe when implemented in an algorithm based on clinical assessment, D-dimer concentration, and radiological diagnostic techniques to stratify the risk for PE or DVT. However, higher sensitivities and negative predictive values were claimed in the scarce published reports for the D-Dimer PLUS assay than found in this study.

Cohort Studies↗

Effect of selective aortic arch perfusion on median frequency and peak amplitude of ventricular fibrillation in a canine model.

STUDY OBJECTIVE: To determine whether the computer-derived measures of median frequency or peak amplitude of ventricular fibrillation (VF), obtained by fast Fourier transform of the VF waveform, change during selective aortic arch perfusion in a canine model of cardiac arrest. METHODS: Eight mongrel dogs (including 4 control animals) were sedated, intubated, catheterized, and instrumented to record the electrocardiogram (digitally at 100 Hz, filtered with a finite impulse response filter at 2 Hz), right atrial pressure, and aortic pressure during resuscitation in a model of VF-induced cardiac arrest. After 10 minutes of VF-induced arrest, cardiopulmonary resuscitation (CPR) with a mechanical chest compression device was initiated. Beginning 2 minutes later, the 4 study animals received, every 2 minutes, 45 seconds of selective aortic arch perfusion (SAAP) with autologous blood infusions under high pressure. Defibrillation was attempted after 3 minutes of CPR and every minute thereafter. Both study and control groups received standard-dose epinephrine (.01 mg/kg) every 3 minutes by means of an intraaortic catheter. The median frequency, peak amplitude, and coronary perfusion pressure (CPP) during the 5-second period just before defibrillation were obtained with the use of computer algorithms. RESULTS: All SAAP animals and 1 control animal were resuscitated. Baseline measures of median frequency (8.4 +/- 1.5 versus 6.6 +/- 1.0 Hz) and peak amplitude (.18 +/- .05 versus .36 +/- .13 mV) were not different between the SAAP and control groups, respectively, at the start of CRP. SAAP infusion resulted in significant increases in the SAAP group compared with the control group: median frequency, 9.6 +/- .4 versus 7.3 +/- 1.4 Hz; peak amplitude, .74 +/- .21 versus .39 +/- .15 mV; and CPP, 40.5 +/- 7.1 versus 18.0 +/- 15.0 mm Hg, respectively. Median frequency correlated with CPP (r2 = .67). Peak amplitude did not correlate with CPP (r2 = .06). CONCLUSION: Median frequency and peak amplitude increase with SAAP during cardiac arrest in a canine model. This method of resuscitation was reliable in allowing restoration of a stable perfusing rhythm after defibrillation. Changes in measures of peak amplitude and median frequency may reflect interventions that enhance the likelihood of successful defibrillation and may thereby offer a noninvasive means of monitoring interventions during cardiac arrest.

Animals↗