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Raman spectroscopic measurement of tablet-to-tablet coating variability.

We report new results suggesting the feasibility of Raman spectrometry as a tool by which to examine the variability of tablet coatings. Our experiments feature a probe that can operate with a revolving laser focus to average content and coating non-uniformity. Raman spectral changes are correlated with tablet exposure times in a pan coater by means of partial least squares (PLS) multivariate analysis. Statistical models are found to be improved by pre-processing schemes that emphasize spectral changes while minimizing the effects of background light scattering and fluorescence. These pre-processing techniques include multiplicative scatter correction (MSC) and standard normal variate (SNV) transformation, used in concert with Savitzky-Golay second derivative smoothing (SGSD). The two approaches give comparable results yielding R2 values for PLS calibration and cross-calibrated prediction variance regression of 0.999 and 0.997, respectively. Correlation results and model residual values demonstrate that Raman spectroscopy serves sensitively to reflect the coating thickness of the tablets studied.

Algorithms↗

Insight into pollutant bioavailability and toxicity using Raman confocal microscopy.

Raman confocal microscopy was used to discriminate between cultures of Burkholderia xenovorans LB400 exposed to four different common environmental pollutants: phenanthrene, dodecane, 3-chlorobiphenyl and pentachlorophenol. Evidence is presented for the application of Raman spectroscopy as a bioassay for pollutant bioavailability and toxicity.

Alkanes↗

How default is the default mode of brain function? Further evidence from intrinsic BOLD signal fluctuations.

The default mode of brain function hypothesis and the presence of spontaneous intrinsic low-frequency signal fluctuations during rest have recently attracted attention in the neuroscience community. In this study we asked two questions: First, is it possible to attenuate intrinsic activity in the self-referential, default mode of brain function by directing the brains resources to a goal-oriented and attention-demanding task? Second, what effect does a sustained attention-demanding overt task performance have on the two intrinsically active networks in the brain, those being the task-negative, default-mode and the anticorrelated, task-positive network? We used functional magnetic resonance imaging to monitor spontaneous intrinsic activity during rest and sustained performance of a sequential two-back working memory task. We compared intrinsic activity during rest and the two-back task to the signal increases and decreases observed in an epoch-related version of the working memory task. Our results show that spontaneous intrinsic activity in the default-mode network is not extinguished but rather attenuated during performance of the working memory task. Moreover, we show that the intrinsic activity in the task-positive network is reorganized in response to the working memory task. The results presented here complements earlier work that have shown that task-induced signal deactivations in the default-mode regions is modulated by cognitive load to also show that intrinsic, spontaneous signal fluctuations in the default-mode regions persist and reorganize in response to changes in external work load.

Adult↗

Conversion from mild cognitive impairment to Alzheimer's disease is predicted by sources and coherence of brain electroencephalography rhythms.

Objective. Can quantitative electroencephalography (EEG) predict the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD)? Methods. Sixty-nine subjects fulfilling criteria for MCI were enrolled; cortical connectivity (spectral coherence) and (low resolution brain electromagnetic tomography) sources of EEG rhythms (delta=2-4 Hz; theta=4-8 Hz; alpha 1=8-10.5 Hz; alpha 2=10.5-13 Hz: beta 1=13-20 Hz; beta 2=20-30 Hz; and gamma=30-40) were evaluated at baseline (time of MCI diagnosis) and follow up (about 14 months later). At follow-up, 45 subjects were still MCI (MCI Stable) and 24 subjects were converted to AD (MCI Converted). Results. At baseline, fronto-parietal midline coherence as well as delta (temporal), theta (parietal, occipital and temporal), and alpha 1 (central, parietal, occipital, temporal, limbic) sources were stronger in MCI Converted than stable subjects (P<0.05). Cox regression modeling showed low midline coherence and weak temporal source associated with 10% annual rate AD conversion, while this rate increased up to 40% and 60% when strong temporal delta source and high midline gamma coherence were observed respectively. Interpretation. Low-cost and diffuse computerized EEG techniques are able to statistically predict MCI to AD conversion.

Aged↗

Study of the protein distribution in the pig lens cross section by Raman spectroscopy.

The distribution of proteins in the cross section of a normal pig lens was studied by near-infrared Raman spectroscopy. The Raman spectra were measured in the visual and equatorial axes of this cross section and the protein peak intensities were determined. It was found that along each axis the protein intensities fluctuate. They have a considerable increment along the visual axis with the exception of the C-N bond peak intensities at 1087.2 cm(-1), which decrease, and along the equatorial axis the increment is slight. This increment in protein distribution along the visual axis is related with the refractive gradient of the lens. The classification of pig lens spectra in these axes was performed using principal component analysis (PCA) and linear discriminant analysis (LDA). Cross-validation shows an excellent group separation.

Animals↗

Principal and independent components analysis of overlapping spectra in the context of multichannel time-resolved absorption spectroscopy.

The separation of overlapping absorption spectra in the context of multichannel time-resolved absorption spectroscopy and chemical kinetics is a particular case in the general problem of splitting the observed data into several linear components. Here, principal and independent components analysis are applied to kinetic data of iodine--ozone chemistry, which contains overlapping spectra of different absorbers. The objective of this work is to demonstrate a method which in spite of this overlap is able to extract separated time traces of such absorbers. These time traces are clearly a pre-requisite for any further accurate quantitative analysis. The statistical properties of data recordings obtained from flash photolysis of I(2) and O(3) have been studied to check if the requirements of the model are fulfilled. Results of separation in appropriate spectral windows displaying overlapped vibrational features are presented. Validation is made using prior information and conventional techniques.

Chemistry Techniques, Analytical↗

Qualitative study of ethanol content in tequilas by Raman spectroscopy and principal component analysis.

Using Raman spectroscopy, with an excitation radiation source of 514.5 nm, and principal component analysis (PCA) was elaborated a method to study qualitatively the ethanol content in tequila samples. This method is based in the OH region profile (water) of the Raman spectra. Also, this method, using the fluorescence background of the Raman spectra, can be used to distinguish silver tequila from aged tequilas. The first three PCs of the Raman spectra, that provide the 99% of the total variance of the data set, were used for the samples classification. The PCA1 and PCA2 are related with the water (or ethanol) content of the sample, whereas the PCA3 is related with the fluorescence background of the Raman spectra.

Alcoholic Beverages↗

Application of principal component analysis and Raman spectroscopy in the analysis of polycrystalline BaTiO3 at high pressure.

The principal component analysis (PCA) was applied to Raman spectra of polycrystalline BaTiO(3) under pressure from atmospheric pressure to approximately 6.72 GPa. For the system utilized, PCA was able to distinguish spectral features and to determine the phase transition pressure: tetragonal to cubic at approximately 2.0 GPa. The present study demonstrates the potentialities of the application of PCA to the investigation on phase transitions at high pressure by Raman spectroscopy.

Barium Compounds↗

Precise measurement of third-order spherical aberration using low-order zone-axis Ronchigrams.

A method for the measurement of third-order spherical aberration coefficients (C(s)) is suggested, using low-order zone-axis Ronchigrams of a crystalline material. The validity of the method is confirmed using simulated and experimental Ronchigrams taken with various probe-forming lens configurations. The precision of the measured C(s) value is drastically improved compared with that obtained from the power spectrum-analysis method. In addition, a method for roughly estimating defocus values is presented.

Journal Article↗

Differential ultrasonic imaging for the characterization of lesions induced by high intensity focused ultrasound.

High intensity focused ultrasound (HIFU) is an effective technique for noninvasive local creating coagulative necrotic lesions in deep target volumes without damage to the overlaying or surrounding tissues. It is very important to detect and evaluate lesions generated by HIFU during treatment procedures. This study describes the development of several differential ultrasonic imaging techniques to characterize lesions based on estimation of relative changes in tissue properties derived from backscattered RF data. A single, spherical HIFU transducer was used to produce lesions in soft tissues. The RF signals were recorded as outputs from a modified diagnostic ultrasound system. After some preprocessing, the integrated backscatter values, which can be used as an indicator of the microstructure and backscattering property of tissues, were calculated before and after HIFU treatment. The differential integrated backscatter values were subsequently used to form images revealing the lesion areas. The differential attenuation imaging with the same RF data was also performed, which has been proposed by a few researchers. The results of the differential integrated backscatter imaging were compared with that of the differential attenuation imaging and the former method offers some advantages over the latter method. The two methods above are both based on spectrum analysis and would spend much computational time. Therefore, some simple digital differential imaging methods, including absolute difference (AD), sum absolute differences (SAD), and sum squared differences (SSD) algorithms, were also proposed to detect HIFU-induced lesions. However, these methods cannot provide the information of the degree of tissue damage. Experiments in vitro bovine muscle and liver validated the method of differential integrated backscatter imaging for the characterization of HIFU-induced lesions. And the AD, SAD, and SSD algorithms can be implemented in real-time during HIFU therapy to visualize the lesions.

Image Enhancement↗

Ultrasonic vibration dectection with wavelets: preliminary results.

Several arterial disorders are known to cause systolic audio vibrations in tissue: they include stenoses, vasospasm, aneurysms, bleeds and arteriovenous fistulas. High-amplitude vibrations can be discovered with conventional Doppler ultrasound (US) instruments; however, differentiating brief, low-amplitude vibrations from other nonstationary echo sources is difficult. Further, characterizing the frequency and amplitude of vibrations is not feasible with conventional Doppler US. The automated detection and estimation of both the frequency and amplitude of vibrations with durations less than 100 ms and amplitudes of a micrometer or less have remained a signal-processing challenge. These vibrations may be associated with both nonstationary colored noise and strong low-frequency clutter. The normalized continuous Morlet wavelet power-spectrum analysis of quadrature Doppler echoes, followed by a binary hypothesis test for noise, results in simulated detection rates above 99.9%, with 0.1% false alarms for signal-on signal-to-noise ratios (SNRs) as low as one. Two clinical examples are included.

Algorithms↗

Physical enviroment of 2-D animal cell aggregates formed in a short pathlength ultrasound standing wave trap.

2-D mammalian cell aggregates can be formed and levitated in a 1.5 MHz single half wavelength ultrasound standing wave trap. The physical environment of cells in such a trap has been examined. Attention was paid to parameters such as temperature, acoustic streaming, cavitation and intercellular forces. The extent to which these factors might be intrusive to a neural cell aggregate levitated in the trap was evaluated. Neural cells were exposed to ultrasound at a pressure amplitude of 0.54 MPa for 30 s; a small aggregate had been formed at the center of the trap. The pressure amplitude was then decreased to 0.27 MPa for 2 min, at which level the aggregation process continued at a slower rate. The pressure amplitude was then decreased to 0.06 MPa for 1 h. Temperature measurements that were conducted in situ with a 200 microm thermocouple over a 30 min period showed that the maximum temperature rise was less than 0.5 K. Acoustic streaming was measured by the particle image velocimetry method (PIV). It was shown that the hydrodynamic stress imposed on cells by acoustic streaming is less than that imposed by gentle preparative centrifugation procedures. Acoustic spectrum analysis showed that cavitation activity does not occur in the cell suspensions sonicated at the above pressures. White noise was detected only at a pressure amplitude of 1.96 MPa. Finally, it was shown that the attractive acoustic force between ultrasonically agglomerated cells is small compared with the normal attractive van der Waals force that operates at close cell surface separations. It is concluded that the standing wave trap operates only to concentrate cells locally, as in tissue, and does not modify the in vitro expression of surface receptor interactions.

Animals↗

Characterization of in vitro healthy and pathological human liver tissue periodicity using backscattered ultrasound signals.

This work studied the periodicity of in vitro healthy and pathologic liver tissue, using backscattered ultrasound (US) signals. It utilized the mean scatterer spacing (MSS) as a parameter of tissue characterization, estimated by three methods: the spectral autocorrelation (SAC), the singular spectrum analysis (SSA) and the quadratic transformation method (SIMON). The liver samples were classified in terms of tissue status using the METAVIR scoring system. Twenty tissue samples were classified in four groups: F0, F1, F3 and F4 (five samples for each). The Kolmogorov-Smirnov test (applied on group pairs) resulted as nonsignificant (p > 0.05) for two pairs only: F1/F3 (for SSA) and F3/F4 (for SAC). A discriminant analysis was applied using as parameters the MSS mean (MSS) and standard deviation (sigmaMSS), the estimates histogram mode (mMSS), and the speed of US (mc(foie)) in the medium, to evaluate the degree of discrimination among healthy and pathologic tissues. The better accuracy (Ac) with SAC (80%) was with parameter group (MSS, sigmaMSS, mc(foie)), achieving a sensitivity (Ss) of 92.3% and a specificity (Sp) of 57.1%. For SSA, the group with all four parameters showed an Ac of 75%, an Ss of 78.6% and an Sp of 66.70%. SIMON obtained the best Ac of all (85%) with group (MSS, mMSS, mc(foie)), an Ss of 100%, but with an Sp of 50%.

Acoustics↗

Mutagenesis and reconstitution of middle-to-long-wave-sensitive visual pigments of New World monkeys for testing the tuning effect of residues at sites 229 and 233.

The colour vision polymorphism of New World monkeys results from allelic variations of the middle-to-long-wave-sensitive (M/LWS) visual pigments. On the basis of sequence comparison, spectral differences among the alleles have been ascribed to amino acid residues at sites 180, 229, 233, 277, and 285. While the significant spectral effects have been demonstrated for sites 180, 277, and 285 by site-directed mutagenesis for a large number of vertebrate M/LWS pigments (the "three-site rule"), effects at sites 229 and 233 remain untested. Here we measured absorption spectra of the reconstituted M/LWS pigments from the tri-allelic squirrel monkey (Saimiri sciureus) and the mono-allelic owl monkey (Aotus trivirgatus). The peak absorption spectra (lambdamax) of Saimiri pigments were 532, 545, and 558 nm and that of Aotus pigment 539 nm, being consistent with the prediction from the three-site rule. Our site-directed mutagenesis for sites 229 and 233 showed that their mutational effects for lambdamax values were negligible. These results preclude the necessity of examining exon 4, encoding the residues at sites 229 and 233, of M/LWS pigment genes for colour-vision typing of New World monkeys.

Amino Acid Sequence↗

Diffuse reflectance patterns in cervical spectroscopy.

OBJECTIVES: Our laboratory seeks to develop minimally invasive cost-effective methods to improve screening and detection of curable precursors to cervical cancer. Previously, we have presented pilot studies that assess the diagnostic power of auto-fluorescence and diffuse reflectance spectroscopy. In the present study, we evaluate diffuse reflectance spectra from a comprehensive 850 patient clinical trial to determine its ability to discriminate normal tissue from several grades of abnormal cervical tissue. METHODS: Diffuse reflectance spectra at four source detector separations measured from 549 cervical sites were available for analysis. Three classifiers were implemented: one used spectral data directly as input, a second used simple spectral features such as peak position and intensity, and one used principal component analysis for feature selection. Algorithms were developed and evaluated using leave-one-out cross-validation to classify normal and precancerous cervical tissue. The percentage of samples correctly classified was used to evaluate and compare the performance of the algorithms, as compared to histology. RESULTS: Diffuse reflectance spectra of cervical precancer showed consistent differences from that of normal tissue at all source detector separations; reflectance intensity of precancer was lower than that of normal tissue on average. Normal cervical tissue spectra show more intensity variation between patients than other tissue grades. Reflectance spectra acquired from the closest source detector separations consistently demonstrated the most relevant information for tissue classification. Two persistent spectral patterns demonstrated that the contribution of hemoglobin absorption and the wavelength-dependent spectral slope contained relevant information for classification. CONCLUSIONS: Spectral patterns in diffuse reflectance spectra can be used for the discrimination of normal cervical tissue from low grade and high grade squamous intraepithelial lesions.

Algorithms↗

[Preoperative evaluation in thyroplasty: the laryngeal lateral compression].

Thyroplasty type I has provided significant improvement to the treatment of patients with glottal incompetence. It is essential that patients be preoperatively evaluated using objective criteria. Laryngeal manual compression test are manipulations of the thyroid and cricoid cartilages that result in modifications of the position of the vocal folds. The most valuable laryngeal manual compression test for patients with glottal insufficiency is the lateral compression test. When this test results in a preoperative improvement in voice suggest that surgery will be successful. In this paper we present the objective evaluation of the effects of lateral compression test upon glottic incompetence by means of narrow band power spectrum analysis.

Adult↗

Neurohumoral cardiovascular responses to alcohol and their modulation by peroral fluid.

Reports on the physiologic effects of acute alcohol are far from uniform and probably reflect differences in study designs, which seldom or never consider the effects of coadministered volumes. We therefore measured blood pressure, heart rate, and heart rate variability (HRV) by power spectrum analysis, baroreceptor sensitivity, arterial blood flow, pulsed-wave velocity (PWV), and plasma levels of vasoactive hormones according to 2 protocols: group A = alcohol, 1 g/kg body weight, mixed with 500 ml of juice; and group B = similar to A plus 750 ml of mineral water. Each group comprised 9 healthy men, studied before and during the subsequent 1 and 1/2 hours after finishing the alcohol. In A, but not in B, alcohol increased heart rate (p = 0.01) and lowered systolic pressure (p <0.05). Plasma renin activity decreased only in B (p <0.01). Atrial natriuretic factor decreased in A, but increased in B (both p <0.02). Pancreatic polypeptide decreased (both p <0.001), and catecholamines did not change. In both groups, alcohol reduced PWV and increased blood flow. Baroreceptor sensitivity and the high-frequency band of HRV decreased in both groups. The physiologic response to acute administration of alcohol appears to depend on the volume of coadministered volumes. Alcohol further appears to interfere with vagal, rather than with sympathetic activity.

Adult↗

Cardiac positron emission tomography imaging with [11C]hydroxyephedrine, a specific tracer for sympathetic nerve endings, and its functional correlates in congestive heart failure.

The integrative mechanisms of autonomic dysfunction in congestive heart failure (CHF) remain poorly understood. We sought to study cardiac retention of [11C]hydroxyephedrine (HED), a specific tracer for sympathetic presynaptic innervation, and its functional correlates in CHF. Thirty patients with mild to moderate heart failure underwent resting cardiac HED positron emission tomography imaging, spectrum analysis testing of systolic pressure and heart rate variability in the resting supine and 70 degrees head-up tilt positions, and testing of baroreflex sensitivity. Compared with control subjects, global myocardial HED retention index was reduced by 30% (p <0.01) in patients with CHF. The HED retention index did not correlate significantly with heart rate variability. However, it correlated with baroreflex sensitivity at rest (r = 0.43, p = 0.05) and with systolic pressure low-frequency (0.03 to 0.15 Hz) variability at head-up tilt (r = 0.76, p <0.01), as well as with low-frequency systolic pressure variability response from baseline to tilt (r = 0.75, p <0.01). We conclude that cardiac HED retention is reduced in patients with CHF. This correlates with blunted vascular sympathetic effector responses during posture-induced reflex activation and baroreflex control of heart rate, suggesting an interdependence between cardiac presynaptic innervation abnormalities and neural mechanisms important to blood pressure maintenance in CHF.

Blood Pressure↗