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An in-vitro investigation of prosthetic heart valve cavitation in blood.

Vapor cavities produced by low pressure fluid flow conditions have been observed in the vicinity of mechanical heart valves for many years. As cavities collapse during pressure recovery, they can produce stresses large enough to cause pitting of the valve occluders and lysing or activation of blood cells. To date, no method has been presented for the quantification of mechanical heart valve cavitation in blood because it has only been detected optically in transparent blood analog fluids. This paper describes a novel method for quantifying cavitation intensities in opaque fluids such as blood. It is based on the detection of high frequency pressure oscillations (35-350 kHz) at a location 4.5 cm proximal to a Björk-Shiley monostrut mitral valve in a mock circulatory loop driven by a Penn State Electric Ventricular Assist Device. The pressure oscillations which result from cavity collapse are used to quantify cavitation intensities in blood. One time domain and three frequency domain parameters have been developed to quantify cavitation intensity during a single valve closure event and over an ensemble of closure events. The time domain parameter is the Root Mean Squared (RMS) value of the pressure signal after it has been high-pass filtered at 35 kHz. The other three parameters are derived from the power spectrum of the pressure signal. One is the maximum value of the power spectrum between 100 and 200 kHz, another is the area under the power spectrum between 35 and 400 kHz, and the last is the volume under a 3-dimensional time vs. frequency vs. power spectrum plot. The parameters are averaged over a random sample of pressure traces to determine an average cavitation intensity for each operating condition studied. In addition, cavitation pressure fluctuations and hemolysis rates were determined simultaneously at several different mock flow loop operating conditions using porcine blood, and the relationships between various measures of cavitation intensity and the associated index of hemolysis have been established. Hemolysis was shown to increase with cavitation intensity.

Animals↗

Tubeless anesthetic technique for optimal carbon dioxide laser surgery of the larynx.

PURPOSE: To evaluate the operative conditions and safety of a tubeless technique of anesthesia for carbon dioxide laser surgery of the larynx. MATERIALS AND METHODS: This prospective study evaluated 78 consecutive procedures in 72 adult patients undergoing carbon dioxide laser microlaryngeal surgery. Anesthesia was maintained by an intravenous infusion of Propofol (ICI Pharmaceuticals, Cheshire, UK) while the patient breathed spontaneously without endotracheal intubation. RESULTS: The operative conditions were optimal in 76 of the 78 procedures providing a clear uninterrupted view of the larynx with no combustible material in the surgical field. CONCLUSIONS: This series shows the technique described to be safe without risk of combustion and provides an unobstructed view to the larynx.

Adolescent↗

Trickle-bed root culture bioreactor design and scale-up: growth, fluid-dynamics, and oxygen mass transfer.

Trickle-bed root culture reactors are shown to achieve tissue concentrations as high as 36 g DW/L (752 g FW/L) at a scale of 14 L. Root growth rate in a 1.6-L reactor configuration with improved operational conditions is shown to be indistinguishable from the laboratory-scale benchmark, the shaker flask (mu=0.33 day(-1)). These results demonstrate that trickle-bed reactor systems can sustain tissue concentrations, growth rates and volumetric biomass productivities substantially higher than other reported bioreactor configurations. Mass transfer and fluid dynamics are characterized in trickle-bed root reactors to identify appropriate operating conditions and scale-up criteria. Root tissue respiration goes through a minimum with increasing liquid flow, which is qualitatively consistent with traditional trickle-bed performance. However, liquid hold-up is much higher than traditional trickle-beds and alternative correlations based on liquid hold-up per unit tissue mass are required to account for large changes in biomass volume fraction. Bioreactor characterization is sufficient to carry out preliminary design calculations that indicate scale-up feasibility to at least 10,000 liters.

Biomass↗

Immobilization of enzymes into nanocavities for the improvement of biosensor stability.

Nanoporous materials with different pore sizes are evaluated as immobilization and stabilization matrices of proteins for the development of highly stable biosensors. It has been proven experimentally that confinement of proteins in cages with a diameter that is 2-6 times larger than their size increases considerably the stability of the biomolecules, as has been shown earlier by theoretical calculations. Porous silica beads with pore sizes of 10nm were utilized for the immobilization of the enzymes HRP and GOx with diameters in the order of 5 and 7 nm, respectively. The sensitivity of the corresponding biosensor systems was monitored for 70 h under continuous operation conditions (+600 mV) and it was found that the stabilization factor of GOx is 1.7 times higher compared to HRP. Also the stabilization efficiency of enzymes against leaching and inactivation in porous polymer beads with pore diameters of 10 and 30 nm was examined. The leaching rate of the enzyme AChE from the 30 nm polymer beads was found to be 1.1 times higher than that from the 10nm beads. At the same time the remaining activity of GOx biosensors after 5 days of continuous operation conditions (+600 mV) was found to be 2.1 times higher when the enzyme had been immobilized in the 10nm beads compared to the 30 nm beads. It is thus evident that the matching between the pore size of nanoporous materials and the molecular size of enzymes is essential for the development of biosensors with extended shelf and operational lifetimes.

Biosensing Techniques↗

Preparation and evaluation of high drug content particles.

To determine how to prepare high drug content particles using a Wurster fluidized bed to determine realizing the miniaturization of solid dosage forms, aspirin was selected as the model drug and granulated without any additive. In this study, the emphasis was on evaluating the key operation factors of airflow rate and atomizing flow volume. The properties of the resulting particles, such as the average diameter, particle strength, appearance, and compressibility using different airflow rates and atomizing flow volumes, were investigated. Furthermore, detailed optimization of the operation conditions was conducted by artificial neural network (ANN) analysis. The relationship between the controlling factors (powder supplied, concentration of spray liquid, the amount of consumed spray liquid, and spray rate) and the response variables (product yield, median diameter, angle of repose, and degradation of aspirin) was investigated after evaluating the airflow rate and atomizing flow volume effects. The resulting granules under optimum operation conditions showed excellent physicochemical properties such as particle size uniformity, flowability, and compressibility.

Anti-Inflammatory Agents, Non-Steroidal↗

DGGE analysis of 16S rDNA of ammonia-oxidizing bacteria in chemical-biological flocculation and chemical coagulation systems.

Microbial community DNA was extracted from activated sludge samples taken from a chemical bioflocculation process and a chemical coagulation process in Shanghai, China. 16S rDNA of ammonia-oxidizing bacteria (AOB)was amplified by nested polymerase chain reaction and fingerprinted by denaturing gradient gel electrophoresis for microbial structure analysis. The Shannon diversity index of each sample was determined. The results indicated that the microbial structure of AOB in chemical bioflocculation process was comparable at two operational conditions. The ammonia-oxidizing bacterial communities were similar in three channels of the chemical bioflocculation process and in three serial tanks in the chemical coagulation process at the same condition. The diversity of microbial structures in the chemical bioflocculation process was higher than in the chemical coagulation process, in which the microbial structure was similar to that in the influent. Although the microbial study provides insights to the nitrification removal, higher microbial diversity of AOB does not necessarily mean higher ammonia oxidization. Molecular analysis should be combined with chemical assays to optimize operational conditions.

Ammonia↗

Analysis of lateral flow biodetectors: competitive format.

Lateral flow (LF) biodetectors facilitate low-cost, rapid identification of various analytes. The LF cell consists of a porous membrane containing immobilized ligands at various locations. Through the action of capillary forces, a mixture of sample and reporter particles is transported to the ligand sites, where the target analytes and the reporters bind to the immobilized ligand. The concentration of the reporters is measured with a scanner. A mathematical model for two different competitive assays is constructed and used to study the performance of LF devices under various operating conditions. The model predicts the signal magnitude as a function of target analyte, reporter, and ligand concentrations, reaction rate constants, and flow rate. The predictions are compared and qualitatively agree with experimental data. The model provides insights into various experimental observations. Furthermore, the model can be used to optimize the performance of LF devices and to inexpensively and rapidly test the system under various operating conditions.

Binding Sites↗

Neuronal firing patterns from epileptogenic foci of monkey and human.

The chronic, recurrent seizures induced in the monkey by cortical scarring occur spontaneously for years and share much of the phenomenology of spontaneous seizures of focal cortical onset in the human. Chronic extracellular recording in the focus of the chronic epileptic monkey reveals: A spectrum of abnormalities of unit firing ranging from grossly abnormal firing patterns to normal activity. Group I (highly epileptic) neurons fire exclusively in bursts, which are invariant during different behavioral states and during operant conditioning. Although firing within the bursts is not easily modified, the interburst interval can be modified indicating that these apparently denervated cells still have some synaptic input. All group I cells are pyramidal neurons. Group II (weakly epileptic) neurons exhibit variable burst firing, which may be intermixed with normal unit firing. The firing patterns of these cells can be modified by synaptic inputs. During operant conditioning, burst firing can decrease; during drowsiness or when inattentive, burst firing can approach that characteristic of group I cells. There is a direct relationship between the number of group I epileptic (pacemaker) neurons in the focus and the epileptogenicity of that focus as measured by frequency of spontaneous seizures in that monkey. The distribution of neurons encountered in the focus varies. On average, approximately 10% are group I (pacemaker) neurons; group II constitute 40%; and 50% of cells encountered exhibit normal firing patterns. In addition to firing in unstructured bursts, an unusual burst structure termed the long-first-interval (LFI) burst has been described that appears to be unique to the chronic focus. It is so named because the first interspike interval is longer than the remaining interspike intervals in the burst. The long first interval is extraordinarily invariant. There is little relationship between unit firing in bursts and the interictal EEG. During early parts of a spontaneous seizure, the two events become time-locked. During seizures, unit firing is synchronous with surrounding neurons and the spike portion of the EEG (as in penicillin foci). Firing of group I neurons does not change significantly preceding a spontaneous seizure. Thus, group I neurons appear to act as pacemakers to the focus and group II cells provide the critical mass that, when synchronized to the burst firing of the pacemakers, is capable of initiating the ictal event.

Animals↗

Lipase production by solid-state fermentation: cultivation conditions and operation of tray and packed-bed bioreactors.

The production of lipase by Penicillium simplicissimum in solid-state fermentation was studied using babassu cake as the basal medium. Tray-type and packed-bed bioreactors were employed. In the former, the influence of temperature; content of the medium, and medium supplementation with olive oil, sugarcane molasses, corn steep liquor, and yeast hydrolysate was studied. For all combinations of supplements, a temperature of 30 degrees C, a moisture content of 70%, and a concentration of carbon source of 6.25% (m/m, dry basis) provided optimum conditions for lipase production. When used as single supplements olive oil and molasses also were able to provide high lipase activities (20 U/g). Using packed-bed bioreactors and molasses-supplemented medium, optimum conditions for enzyme production were air superficial velocities above 55 cm/min and temperatures below 28 degrees C. The lower temperature optimum found for these reactors is probably related to radial heat gradient formation inside the packed bed. Maximum lipase activities obtained in these bioreactors (26.4 U/g) were 30% higher than in tray-type reactors.

Bioreactors↗

Emission performance and combustion efficiency of a conical fluidized-bed combustor firing various biomass fuels.

This paper summarizes the results of an experimental study on combustion of three distinct biomass fuels (sawdust, rice husk and pre-dried sugar cane bagasse) in a single fluidized-bed combustor (FBC) with a conical bed using silica sand as the inert bed material. Temperature, CO, NO and O2 concentrations along the combustor height as well as in flue (stack) gas were measured in the experimental tests. The effects of fuel properties and operating conditions (load and excess air) on these variables were investigated. Both CO and NO axial profiles were found to have a maximum whose location divides conventionally the combustor volume into formation (lower) and reduction (upper) regions for these pollutants. Based on CO emission and unburned carbon content in fly ash, the combustion efficiency of the conical FBC was quantified for the selected biomass fuels fired under different operating conditions.

Air Pollutants↗

Effective protein release from PEG/PLA nano-particles produced by compressed gas anti-solvent precipitation techniques.

Homogeneous PLA/insulin solutions containing different amounts of 350, 750 or 1900 Da PEG (0-75 wt.% PEG) were processed by semi-continuous compressed CO2 anti-solvent precipitation to fabricate protein-loaded polymeric nano-particles. Proper operative conditions (temperature, pressure, CO2 flow rate and washing time) yielded more than 70% product recovery. Scanning electron microscopy, transmission electron microscopy and light scattering demonstrated that spherical, smooth surfaced particles with size below 1 microm could be obtained. X-ray diffraction analysis showed that the gas anti-solvent process modifies the polylactide crystalline state. PEG concentration and molecular weight were found to affect both optimal operative conditions and morphological and biopharmaceutical properties of the final product. Insulin loading yield dropped from 95% to 65% by increasing the 1900 Da PEG content from 0 to 75 wt.% or the PEG molecular weight from 350 to 1900 Da. The release rate increased significantly as the PEG content in the formulation increases. After 3-month incubation the drug released raised from 10% to 100% by increasing the 1900 Da PEG content from 23 to 7 wt.%. Formulations containing the same 350, 750 or 1900 Da PEG amount (67 wt.% PEG) displayed similar release profiles. Insulin release was found to take place by diffusion mechanism, despite the observation of matrix degradation.

Carbon Dioxide↗

Simple Model of Aerosol Particle Formation by the Evaporation-Condensation Method.

From an engineering point of view the present authors have proposed the simple model of a homogeneous nucleation relationship in the liquid phase that can predict the number concentration of nucleated particles in various operating conditions. Experiments of liquid-phase nucleation in which the precursor monomers were generated by several methods have successfully confirmed the predictions of the model. In the present paper, our previous model of homogeneous nucleation is extended to the case in which the precursor monomers are generated in a gas-phase system. First, a relationship between number concentration and mean volume diameter of nucleated aerosol particles and operating conditions is obtained considering the free molecular regime around the critical nuclei, which is the main difference with the liquid phase. Second, the validity of the relation lies in experimental use of dioctyl sebacate particles generated by evaporation-condensation. As a result, the predictions are in excellent agreement with the experimental results after considering substantial losses of monomers and particles to the walls of the experimental system because in the gasphase the diffusion velocity and the critical supersaturation ratio of monomer are higher than those in the liquid phase. Copyright 2000 Academic Press.

Journal Article↗

Stability of glutaraldehyde disinfectants during storage and use in hospitals.

The problem of alkaline and acid glutaraldehyde disinfectants degradation (loss in active ingredients) during both extended shelf storage and continuous daily use under hospital practice was investigated. Glutaraldehyde disinfectants lose their potency due to three main types of reactions: aldol condensation, hydration-polymerization, and oxidation. The relative magnitude of each depends upon many variables, such as pH, dissolved gases content, and temperature. Room temperature aging studies of commercial potentiated acid glutaraldehyde (2% and 10% Sonacide) showed that the maximum loss in active ingredients is on the order of 7 per cent after 24 months. The newest type of stabilized alkaline glutaraldehyde (2% Cidex-7) loses 14 to 18 per cent of its active ingredient one month after buffer is added. Standing at room temperature, both alkaline and potentiated acid glutaraldehyde solutions generally drift towards lower pH. Several experiments and a literature search were conducted to assess the glutaraldehyde loss in alkaline and potentiated acid glutaraldehyde disinfectants under normal operating conditions in hospitals. Three independent studies showed that under continuous daily use in hospital buckets potentiated acid glutaraldehyde lasted twice as long as the alkaline glutaraldehyde formula. It was also noted that after weeks of continuous use the pH of both acid and alkaline formulas drifted towards neutrality. A six hospital study of potentiated acid glutaraldehyde in the Cidematic disinfecting machine showed that under a wide range of operating conditions it would take approximately four weeks of continuous daily use to reduce by half the concentration of active di-aldehyde.

Aldehydes↗

Isolation of a recombinant formate dehydrogenase by pseudo-affinity expanded bed adsorption.

Formate dehydrogenase (FDH) is an enzyme of industrial interest, which is recombinantly expressed as an intracellular protein in Escherichia coli. In order to establish an efficient and reliable purification protocol, an expanded bed adsorption (EBA) process was developed, starting from the crude bacterial homogenate. EBA process design was performed with the goal of finding operating conditions which, on one hand, allow efficient adsorption of the target protein and which, on the other hand, support the formation of a perfectly classified fluidised bed (expanded bed) in the crude feed solution. A pseudo-affinity ligand (Procion Red HE3B) was used to bind the FDH with high selectivity and reasonable capacity (maximum equilibrium capacity of 30 U/ml). Additionally, a simplified modelling approach, involving small packed beds for generation of process parameters, was employed for defining the operating conditions during sample application. In combination with extended elution studies, a process was set up, which could be scaled up to 7.5 l of adsorbent volume yielding a total amount of 100,000 U of 94% pure FDH per run. On this scale, 19 l of a benzonase-treated E. coli homogenate of 15% wet-weight (pH 7.5, 9 mS/cm conductivity) were loaded to the pseudo-affinity adsorbent (0.25 m sed. bed height, 5 x 10(-4) m/s fluid velocity). After a series of two wash steps, a particle-free eluate pool was obtained with 85% yield of FDH. This excellently demonstrates the suitability of expanded bed adsorption for efficient isolation of proteins by combining solid-liquid separation with adsorptive purification in a single unit operation.

Adsorption↗

Applying psychological theory to evidence-based clinical practice: identifying factors predictive of taking intra-oral radiographs.

This study applies psychological theory to the implementation of evidence-based clinical practice. The first objective was to see if variables from psychological frameworks (developed to understand, predict and influence behaviour) could predict an evidence-based clinical behaviour. The second objective was to develop a scientific rationale to design or choose an implementation intervention. Variables from the Theory of Planned Behaviour, Social Cognitive Theory, Self-Regulation Model, Operant Conditioning, Implementation Intentions and the Precaution Adoption Process were measured, with data collection by postal survey. The primary outcome was the number of intra-oral radiographs taken per course of treatment collected from a central fee claims database. Participants were 214 Scottish General Dental Practitioners. At the theory level, the Theory of Planned Behaviour explained 13% variance in the number of radiographs taken, Social Cognitive Theory explained 7%, Operant Conditioning explained 8%, Implementation Intentions explained 11%. Self-Regulation and Stage Theory did not predict significant variance in radiographs taken. Perceived behavioural control, action planning and risk perception explained 16% of the variance in number of radiographs taken. Knowledge did not predict the number of radiographs taken. The results suggest an intervention targeting predictive psychological variables could increase the implementation of this evidence-based practice, while influencing knowledge is unlikely to do so. Measures which predicted number of radiographs taken also predicted intention to take radiographs, and intention accounted for significant variance in behaviour (adjusted R(2)=5%: F(1,166)=10.28, p<.01), suggesting intention may be a possible proxy for behavioural data when testing an intervention prior to a service-level trial. Since psychological frameworks incorporate methodologies to measure and change component variables, taking a theory-based approach enabled the creation of a methodology that can be replicated for identifying factors predictive of clinical behaviour and for the design and choice of interventions to modify practice as new evidence emerges.

Adult↗

Exposure to noise on board locomotives.

Personal and area noise dosimetry measurements were taken in the cabs of leading and trailing locomotives on 48 trips, under winter and summer conditions, on 9 different routes. The mean equivalent sound level (L(EQ), 3 dB exchange rate, 50 dBA threshold) of the engineers and conductors was 84 dBA during winter and 88 dBA during summer. The corresponding time-weighted average levels (L(TWA), 5 dB exchange rate, 80 dBA threshold) were 80 and 84 dBA respectively. The L(EQ) of 56% of the engineers sampled was > or =85 dBA and of 13% was > or =90 dBA. Plots of L(EQ) time history show that under normal operating conditions L(EQ) reaches its steady-state value in about 3 hours. The mean noise levels in the trailing cabs were lower than the personal exposure levels of the engineers and conductors. The mean L(EQ) on the engineer and conductor sides was 80 dBA during winter, and 85 dBA during summer. Locomotive configuration has a significant effect on the noise levels in the trailing cab. The forward-backward configuration resulted in higher noise levels than the forward-forward configuration. Octave and one-third octave band spectra taken during a variety of locomotive operating conditions are presented. The octave band centered at 31.5 Hz contains nearly 46% of the acoustical energy, and those centered at and below 250 Hz contain nearly 99% of the acoustical energy. Wheel-rail interaction appears to be the predominant source of the low frequency noise. Recommendations for controlling exposure are made.

Ear Protective Devices↗

Enhanced separation of filamentous fungi by ultrasonic field: possible usage in repeated batch processes.

Usage of ultrasonic field-based filters in retention of filamentous fungal cells was assessed using Rhizopus arrhizus NRRL 1526 as a model organism. Effects of operating conditions, such as power input, harvest pump flow rate, run time and stop time, on the system's separation efficiency (SE) were evaluated by modulating the variables according to a Central Composite Design (CCD). The standard pump with which the ultrasonic filter was equipped was shown to be unsuitable and was, therefore, substituted for with a prime rate reverse pump that made possible separation and recycle of the mycelial biomass. The operating conditions were optimised (run time, 300 s; stop time, 3 s; power input, 6 W; harvest pump flow rate, 4 l per day) and a repeated batch process (three batches for a total of 192 h) was performed during which the SE was maintained always higher than 88%.

Bioreactors↗

Introduction to advantages and problems of shaken cultures.

Shaking bioreactors are the most frequently used reaction vessels in biotechnology and have been so for many decades. In spite of their large practical importance, very little is known about the characteristic properties of shaken cultures from an engineering point of view. The few publications available contain to some extent contradicting statements and conflicting advice concerning the correct operating conditions of shaking bioreactors. Depending on the investigated microbial system, the engineering parameters may more or less significantly influence the experimental results in a quantitative as well as in a qualitative manner. Unfortunately, these kind of interactions are often overlooked or ignored by scientists. Precise knowledge about the controlling hydrodynamic phenomena in shaking bioreactors and quantitative information about the physical parameters influencing the cultures are needed to assure reproducible and meaningful operating conditions. In this introduction, the state of the art of culturing microorganisms in shaking bioreactors is reviewed and some issues of their practical application in screening and process development projects are addressed.

Journal Article↗