Passive personal air sampling of dust in a working environment-A pilot study.

The aim of this study was to make a preliminary evaluation of the University of North Carolina passive aerosol sampler (UNC sampler) for personal air sampling of particles. Nine personal air samplings of respirable fraction were conducted in an open-pit mine, with pairwise UNC samplers and a respirable cyclone mounted on the chest of workers. UNC samples were analyzed with scanning electron microscopy (SEM) and to some extent energy dispersive X-ray spectroscopy (EDS). Respirable cyclone filter samples were weighed. Correlations and particle elemental compositions were described. Microscopic imaging of the collection surface showed that the particles were heterogeneously deposited across the surface of the UNC sampler. Collected particles were shaped as gravel particles and the resulting particle size distribution in air showed a peak at ca. 3 µm aerodynamic diameter, similarly to what has previously been reported from the same mine. The elemental composition indicated mineral origin. All correlations between the airborne mass concentrations from UNC samplers and respirable cyclones (Pearson = 0.54 and Spearman = 0.43) and between pairs of parallel UNC samplers (Pearson = 0.55 and Spearman = 0.67) were weak. The UNC sampler mass concentrations were approximately 30 times higher than those measured with the respirable cyclone. In conclusion, the UNC sampler, when used for personal sampling in a mine, provides a reasonable particle size distribution and the deposited particles appeared to be of mineral origin and not from textile or skin but the approximately 30-fold overestimation of mass concentrations when comparing with respirable cyclone sampling indicates that further improvements are necessary. Positioning of the sampler may be critical and moving the UNC sampler from the chest to e.g. the top of a helmet might be an improvement. Grounding of the sampler in order to avoid static electricity might also be useful. The UNC sampler should continue to be researched for personal sampling, as passive sampling might become a useful alternative to more laborious sampling techniques.

Prostate Cancer Detection with a Tactile Resonance Sensor-Measurement Considerations and Clinical Setup.

Tumors in the human prostate are usually stiffer compared to surrounding non-malignant glandular tissue, and tactile resonance sensors measuring stiffness can be used to detect prostate cancer. To explore this further, we used a tactile resonance sensor system combined with a rotatable sample holder where whole surgically removed prostates could be attached to detect tumors on, and beneath, the surface ex vivo. Model studies on tissue phantoms made of silicone and porcine tissue were performed. Finally, two resected human prostate glands were studied. Embedded stiff silicone inclusions placed 4 mm under the surface could be detected in both the silicone and biological tissue models, with a sensor indentation of 0.6 mm. Areas with different amounts of prostate cancer (PCa) could be distinguished from normal tissue (p < 0.05), when the tumor was located in the anterior part, whereas small tumors located in the dorsal aspect were undetected. The study indicates that PCa may be detected in a whole resected prostate with an uneven surface and through its capsule. This is promising for the development of a clinically useful instrument to detect prostate cancer during surgery.

Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates.

The possibility to affect bone formation by using crushed versus solid hydrogels as carriers for bone morphogenetic protein 2 (BMP-2) was studied. Hydrogels, based on chemical crosslinking between hyaluronic acid and poly(vinyl alcohol) derivatives, were loaded with BMP-2 and hydroxyapatite. Crushed and solid forms of the gels were analyzed both in vitro via a release study using ¹²5I radioactive labeling of BMP-2, and in vivo in a subcutaneous ectopic bone model in rats. Dramatically different morphologies were observed for the ectopic bone formed in vivo in the two types of gels, even though virtually identical release profiles were observed in vitro. Solid hydrogels induced formation of a dense bone shell around non-degraded hydrogel, while crushed hydrogels demonstrated a uniform bone formation throughout the entire sample. These results suggest that by crushing the hydrogel, the construct's three-dimensional network becomes disrupted. This could expose unreacted functional groups, making the fragment's surfaces reactive and enable limited chemical fusion between the crushed hydrogel fragments, leading to similar in vitro release profiles. However, in vivo these interactions could be broken by enzymatic activity, creating a macroporous structure that allows easier cell infiltration, thus, facilitating bone formation.

Explanatory models for a tactile resonance sensor system-elastic and density-related variations of prostate tissue in vitro.

Tactile sensors based on piezoelectric resonance have been adopted for medical applications. The sensor consists of an oscillating piezoelectric sensor-circuit system, and a change in resonance frequency is observed when the sensor tip contacts a measured object such as tissue. The frequency change at a constant applied force or mass load is used as a stiffness-sensitive parameter in many applications. Differential relations between force and frequency have also been used for monitoring intraocular pressure and stiffness variations in prostate tissue in vitro. The aim of this study was to relate the frequency change (Deltaf), measured force (F) and the material properties, density and elasticity to an explanatory model for the resonance sensor measurement principle and thereby to give explanatory models for the stiffness parameters used previously. Simulations of theoretical equations were performed to investigate the relation between frequency change and contact impedance. Measurements with a resonance sensor system on prostate tissue in vitro were used for experimental validation of the theory. Tissue content was quantified with a microscopic-based morphometrical method. Simulation results showed that the frequency change was dependent upon density (rho) and contact area (S) according to Deltaf proportional, variant rhoS(3/2). The experiments followed the simulated theory at small impression depths. The measured contact force followed a theoretical model with the dependence of the elastic modulus (E) and contact area, F proportional, variant ES(3/2). Measured density variations related to histological variations were statistically weak or non-significant. Elastic variations were statistically significant with contributions from stroma and cancer relative to normal glandular tissue. The theoretical models of frequency change and force were related through the contact area, and a material-dependent explanatory model was found as Deltaf proportional, variant rhoE(-1)F. It explains the measurement principle and the previously established stiffness parameters from the material properties point of view.

Improving the UNC Passive Aerosol Sampler Model Based on Comparison with Commonly Used Aerosol Sampling Methods.

Objectives: In an occupational environment, passive sampling could be an alternative to active sampling with pumps for sampling of dust. One passive sampler is the University of North Carolina passive aerosol sampler (UNC sampler). It is often analysed by microscopic imaging. Promising results have been shown for particles above 2.5 µm, but indicate large underestimations for PM2.5. The aim of this study was to evaluate, and possibly improve, the UNC sampler for stationary sampling in a working environment. Methods: Sampling was carried out at 8-h intervals during 24 h in four locations in an open pit mine with UNC samplers, respirable cyclones, PM10 and PM2.5 impactors, and an aerodynamic particle sizer (APS). The wind was minimal. For quantification, two modifications of the UNC sampler analysis model, UNC sampler with hybrid model and UNC sampler with area factor, were compared with the original one, UNC sampler with mesh factor derived from wind tunnel experiments. The effect of increased resolution for the microscopic imaging was examined. Results: Use of the area factor and a higher resolution eliminated the underestimation for PM10 and PM2.5. The model with area factor had the overall lowest deviation versus the impactor and the cyclone. The intraclass correlation (ICC) showed that the UNC sampler had a higher precision and better ability to distinguish between different exposure levels compared to the cyclone (ICC: 0.51 versus 0.24), but lower precision compared to the impactor (PM10: 0.79 versus 0.99; PM2.5: 0.30 versus 0.45). The particle size distributions as calculated from the different UNC sampler analysis models were visually compared with the distributions determined by APS. The distributions were obviously different when the UNC sampler with mesh factor was used but came to a reasonable agreement when the area factor was used. Conclusions: High resolution combined with a factor based on area only, results in no underestimation of small particles compared to impactors and cyclones and a better agreement with the APS's particle size distributions. The UNC sampler had lower precision than the impactors, but higher than the respirable cyclone. The UNC sampler with area factor could be used for PM2.5, PM10 and respirable fraction measurements in this working environment without wind.

Spatial variations in prostate tissue histology as measured by a tactile resonance sensor.

In recent years, tactile sensors based on piezoelectric resonance sensor technology have been used for medical diagnosis where the sensor's stiffness-measuring properties can reflect tissue pathology. The change in the frequency of the resonating system and the change in force when contact is made with tissue are used as a stiffness parameter. Earlier stiffness measurements of prostate tissue in vitro demonstrate variations related to tissue composition. In this study, measured stiffness from two human prostate specimens was compared to histological composition of prostate tissue below and around the measurement points. Tissue stiffness was measured with the resonance sensor system. Tissue composition was measured at four different depths in the tissue specimen using a microscopic-image-based morphometrical method. With this method, the proportion of tissue types was determined at the points of intersections in a circular grid on the images representing each measurement point. Numerical values were used for weighting the tissue proportions at different depths in the tissue specimen. For an impression depth of 1.0 mm, the sensing depth in this study was estimated to be 3.5-5.5 mm. Stiffness variations due to horizontal tissue variations were investigated by studying the dependence of the size of the circular grid area relative to the contact area of the sensor tip. The sensing area (grid radius) was estimated to be larger than the contact area (contact radius) between the sensor tip and the tissue. Thus, the sensor tip registers spatial variations in prostate tissue histology, both directly below and lateral to the tip itself. These findings indicate that tumours around the sensor tip could be detected, which in turn supports the idea of a future resonance-sensor-based clinical device for detecting tumours and for guiding biopsies.

A Pilot Study: The UNC Passive Aerosol Sampler in a Working Environment.

OBJECTIVES: Dust is generally sampled on a filter using air pumps, but passive sampling could be a cost-effective alternative. One promising passive sampler is the University of North Carolina passive aerosol sampler (UNC sampler). The aim of this study is to characterize and compare the UNC sampler's performance with PM10 and PM2.5 impactors in a working environment. METHODS: Area sampling was carried out at different mining locations using UNC samplers in parallel with PM2.5 and PM10 impactors. Two different collection surfaces, polycarbonate (PC) and carbon tabs (CT), were employed for the UNC sampling. Sampling was carried out for 4-25 hours. RESULTS: The UNC samplers underestimated the concentrations compared to PM10 and PM2.5 impactor data. At the location with the highest aerosol concentration, the time-averaged mean of PC showed 24% and CT 35% of the impactor result for PM2.5. For PM10, it was 39% with PC and 58% with CT. Sample blank values differed between PC and CT. For PM2.5, PC blank values were ~7 times higher than those of CT, but only 1.8 times higher for PM10. The blank variations were larger for PC than for CT. CONCLUSIONS: Particle mass concentrations appear to be underestimated by the UNC sampler compared to impactors, more so for PM2.5 than for PM10. CT may be preferred as a collection surface because the blank values were lower and less variable than for PC. Future validations in the working environment should include respirable dust sampling.

Resonance sensor measurements of stiffness variations in prostate tissue in vitro--a weighted tissue proportion model.

Prostate cancer is the most common type of cancer in men in Europe and the US. The methods to detect prostate cancer are still precarious and new techniques are needed. A piezoelectric transducer element in a feedback system is set to vibrate with its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various patho-physiological conditions. In this study the sensor's ability to measure the stiffness of prostate tissue, from two excised prostatectomy specimens in vitro, was analysed. The specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5-1.7 mm, the maximum R(2) > or = 0.60 (p < 0.05, n = 75). An increase in the proportion of prostate stones (corpora amylacea), stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Cancer and stroma had the greatest effect on the measured stiffness. The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. Tissue sections deeper in the tissue were assigned a lower mathematical weighting than sections closer to the sensor probe. It is concluded that cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differ from cancer.

Prostate cancer detection with an improved resonance sensor system: parameter evaluation in a silicone model and on human prostate tissue in vitro.

The purpose of this study was to improve a resonance sensor system for prostate cancer detection and evaluate its performance on silicone with different hardness. Furthermore, to investigate if the instrument could distinguish between cancerous and normal prostate tissue in one in vitro prostate specimen. The system could measure the frequency shift, impression depth and the rise time of the force signal. The frequency shift, impression depth and the rise time described the relative hardness of silicone (n = 50, P < 0.05). The results from measurements on the prostate specimen indicated that there is a significant difference in the parameter data between cancerous and normal prostate tissue (n = 15, P < 0.05). The parameters' impression depth and force rise time adds important information for cancer detection. Further studies on prostate tissue with different tumour types must be performed in order to understand the full value of the new sensor system.

Prostate tissue stiffness as measured with a resonance sensor system: a study on silicone and human prostate tissue in vitro.

Prostate cancer is the most common form of cancer in men in Europe and in the USA. Some prostate tumours are stiffer than the surrounding normal tissue, and it could therefore be of interest to measure prostate tissue stiffness. Resonance sensor technology based on piezoelectric resonance detects variations in tissue stiffness due to a change in the resonance frequency. An impression-controlled resonance sensor system was used to detect stiffness in silicone rubber and in human prostate tissue in vitro using two parameters, both combinations of frequency change and force. Variations in silicone rubber stiffness due to the mixing ratio of the two components could be detected (p<0.05) using both parameters. Measurements on prostate tissue showed that there existed a statistically significant (MANOVA test, p<0.001) reproducible difference between tumour tissue (n=13) and normal healthy tissue (n=98) when studying a multivariate parameter set. Both the tumour tissue and normal tissue groups had variations within them, which were assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces and different levels of dehydration for the prostates. Our results indicated that the resonance sensor could be used to detect stiffness variations in silicone and in human prostate tissue in vitro. This is promising for the development of a future diagnostic tool for prostate cancer.

Modeling the high-frequency complex modulus of silicone rubber using standing Lamb waves and an inverse finite element method.

To gain an understanding of the high-frequency elastic properties of silicone rubber, a finite element model of a cylindrical piezoelectric element, in contact with a silicone rubber disk, was constructed. The frequency-dependent elastic modulus of the silicone rubber was modeled by a fourparameter fractional derivative viscoelastic model in the 100 to 250 kHz frequency range. The calculations were carried out in the range of the first radial resonance frequency of the sensor. At the resonance, the hyperelastic effect of the silicone rubber was modeled by a hyperelastic compensating function. The calculated response was matched to the measured response by using the transitional peaks in the impedance spectrum that originates from the switching of standing Lamb wave modes in the silicone rubber. To validate the results, the impedance responses of three 5-mm-thick silicone rubber disks, with different radial lengths, were measured. The calculated and measured transitional frequencies have been compared in detail. The comparison showed very good agreement, with average relative differences of 0.7%, 0.6%, and 0.7% for the silicone rubber samples with radial lengths of 38.0, 21.4, and 11.0 mm, respectively. The average complex elastic moduli of the samples were (0.97 + 0.009i) GPa at 100 kHz and (0.97 + 0.005i) GPa at 250 kHz.

A FEM-based method using harmonic overtones to determine the effective elastic, dielectric, and piezoelectric parameters of freely vibrating thick piezoelectric disks.

To gain an understanding of the electroelastic properties of tactile piezoelectric sensors used in the characterization of soft tissue, the frequency-dependent electric impedance response of thick piezoelectric disks has been calculated using finite element modeling. To fit the calculated to the measured response, a new method was developed using harmonic overtones for tuning of the calculated effective elastic, piezoelectric, and dielectric parameters. To validate the results, the impedance responses of 10 piezoelectric disks with diameter-to-thickness ratios of 20, 6, and 2 have been measured from 10 kHz to 5 MHz. A two-dimensional, general purpose finite element partial differential equation solver with adaptive meshing capability run in the frequency-stepped mode, was used. The equations and boundary conditions used by the solver are presented. Calculated and measured impedance responses are presented, and resonance frequencies have been compared in detail. The comparison shows excellent agreement, with average relative differences in frequency of 0.27%, 0.19%, and 0.54% for the samples with diameter-to-thickness ratios of 20, 6, and 2, respectively. The method of tuning the effective elastic, piezoelectric, and dielectric parameters is an important step toward a finite element model that describes the properties of tactile sensors in detail.

Indentation loading response of a resonance sensor--discriminating prostate cancer and normal tissue.

Prostate cancer is the most common type of cancer among men worldwide. Mechanical properties of prostate tissue are promising for distinguishing prostate cancer from healthy prostate tissue. The aim was to investigate the indentation loading response of a resonance sensor for discriminating prostate cancer tissue from normal tissue. Indentation measurements were done on prostate tissue specimens ex vivo from 10 patients from radical prostatectomy. The measurement areas were analysed using standard histological methods. The stiffness parameter was linearly dependent on the loading force (average R(2 )= 0.90) and an increased loading force caused a greater stiffness contrast of prostate cancer vs normal tissue. The accuracy of the stiffness contrast was assessed by the ROC curve with the area under the curve being 0.941 for a loading force of 12.8 mN. The results are promising for the development of a resonance sensor instrument for detecting prostate cancer.

Contact angle and indentation velocity dependency for a resonance sensor--evaluation on soft tissue silicone models.

Human tissue stiffness can vary due to different tissue conditions such as cancer tumours. Earlier studies show that stiffness may be detected with a resonance sensor that measures frequency shift and contact force at application. Through the frequency shift and the contact force, a tissue stiffness parameter can be derived. This study evaluated how the probe application angle and indentation velocity affected the results and determined the maximum parameter errors. The evaluation was made on flat silicone discs with specified hardness. The frequency shift, the force and the stiffness parameter all varied with contact angle and indentation velocity. A contact angle of ≤10° was acceptable for reliable measurements. A low indentation velocity was recommended. The maximum errors for the system were <1.1% of the measured values. It was concluded that contact angle and indentation velocity have to be considered in the clinical setting. The angular dependency is especially important in clinical use for studying stiffness of human soft tissue, e.g. in prostate cancer diagnosis.

Oxidative stress and cytokine expression in respiratory epithelial cells exposed to well-characterized aerosols from Kabul, Afghanistan.

In this study aerosol samples collected in an Asian mega-city (Kabul, Afghanistan) were compared to PM samples collected in a European location with traffic (Umeå, Sweden) and a reference urban dust material (SRM 1649b). The toxicity of each sample towards normal human bronchial epithelial (NHBE) cells and a human bronchial epithelial cell line (BEAS-2B) was tested along with their ability to induce reactive oxygen species (ROS) formation and inflammatory responses. The extracts' morphology and elemental composition was studied by SEM-EDXRF, and filter samples were analyzed for metals and organic compounds. The PM from Kabul contained a larger fraction of fine particles, 19 times more polyaromatic hydrocarbons (PAH) and 37 times more oxygenated PAH (oxy-PAH) compared to samples from Umeå. The PM-samples from Kabul and the reference material (SRM 1649b) induced significantly stronger oxidative stress responses than the samples from Umeå. Furthermore, samples collected in Kabul induced significantly higher secretion of the cytokines IL-6, IL-8 and GM-CSF while SRM1649b induced a cytokine pattern more similar to samples collected in Umeå. Several properties of the particles could potentially explain these differences, including differences in their size distribution and contents of PAH and oxy-PAH, possibly in combination with their relative transition metal contents.

Surface properties of hydrous manganite (gamma-MnOOH). A potentiometric, electroacoustic, and X-ray photoelectron spectroscopy study.

The acid-base characteristics of the manganite (gamma-MnOOH) surface have been studied at pH above 6, where dissolution is negligible. Synthetic microcrystalline particles of manganite were used in the experiments. From potentiometric titrations, electrophoretic mobility measurements, and X-ray photoelectron spectroscopy (XPS), a one pK(a) model was constructed that describes the observed behavior. The data show no ionic strength effect at pH < 8.2, which is the pH at the isoelectric point (pH(iep)), but ionic strength effects were visible above this pH. To explain these observations, Na(+) ions were suggested to form a surface complex. The following equilibria were established: =MnOH(2)(+1/2) right harpoon over left harpoon =MnOH(-)(1/2) + H(+), log beta(0) (intr.) = -8.20; =MnOH(2)(+1/2) + Na(+) right harpoon over left harpoon =MnOHNa(+1/2) + H(+), log beta(0) (intr.) = -9.64. The excess of Na(+) at the surface was supported by XPS measurements of manganite suspensions containing 10 mM NaCl. The dielectric constant of synthetic manganite powder was also determined in this study.

Synthesis and Biological activity of kappa opioid receptor agonists. Part 2: preparation of 3-aryl-2-pyridone analogues generated by solution- and solid-phase parallel synthesis methods.

New analogues of the previously described 3-aryl pyridone KOR agonists have been synthesised by parallel synthetic methods, both in solution- and with solid-phase chemistry, making use of the well known and versatile Mitsunobu, Suzuki and Buchwald reactions. Opioid receptor binding data for the compounds produced is reported.

3-Aryl pyridone derivatives. Potent and selective kappa opioid receptor agonists.

A new series of 3-aryl pyridone based kappa opioid receptor agonists was designed and synthesised, based on an understanding of the classical kappa opioid receptor pharmacophore. The most potent of the new compounds were comparable to U-69,593 in receptor affinity, selectivity and functional agonist effect at the cloned human kappa opioid receptor.