bluuebunny/crossref_metadata_2025 huggingface dataset:
A note on preliminary tests of equality of variances
Authors: Zimmerman Donald W.
Published: June 2004

Preliminary tests of equality of variances used before a test of location are no longer widely recommended by statisticians, although they persist in some textbooks and software packages. The present study extends the findings of previous studies and provides further reasons for discontinuing the use of preliminary tests. The study found Type I error rates of a two‐stage procedure, consisting of a preliminary Levene test on samples of different sizes with unequal variances, followed by either a Student pooled‐variances t test or a Welch separate‐variances t test. Simulations disclosed that the twostage procedure fails to protect the significance level and usually makes the situation worse. Earlier studies have shown that preliminary tests often adversely affect the size of the test, and also that the Welch test is superior to the t test when variances are unequal. The present simulations reveal that changes in Type I error rates are greater when sample sizes are smaller, when the difference in variances is slight rather than extreme, and when the significance level is more stringent. Furthermore, the validity of the Welch test deteriorates if it is used only on those occasions where a preliminary test indicates it is needed. Optimum protection is assured by using a separate‐variances test unconditionally whenever sample sizes are unequal.
Three Mahalanobis distances and their role in assessing unidimensionality
Authors: Yuan Ke‐Hai , Fung Wing Kam , Reise Steven P.
Published: June 2004

Unidimensionality is the hallmark psychometric feature of a well‐constructed measurement scale. However, in determining the degree to which a set of items form a unidimensional scale, aberrant item response patterns may distort our investigations. For example, aberrant response patterns may adversely impact interitem covariances which, in turn, can distort estimates of a scale's dimensionality and reliability. In this study, we investigate and compare the utility of three Mahalanobis distance (M‐distance) measures in identifying and downweighting aberrant item response patterns. Our findings indicated that a residual‐based M‐distance measure had the best properties. Specifically, response patterns having greater residual‐based M‐distances were responsible for observed violations of unidimensionality. When these response patterns were properly downweighted according to this M‐distance, the data fitted a one‐factor model better and scale reliability increased. The procedures are illustrated using three real data sets.
On the chi‐square approximation to the exact distribution of goodness‐of‐fit statistics in multinomial models with composite hypotheses
Authors: García‐Pérez Miguel A. , Núñez‐Antón Vicente A.
Published: June 2004

Multinomial models are increasingly being used in psychology, and this use always requires estimating model parameters and testing goodness of fit with a composite null hypothesis. Goodness of fit is customarily tested with recourse to the asymptotic approximation to the distribution of the statistics. An assessment of the quality of this approximation requires a comparison with the exact distribution, but how to compute this exact distribution when parameters are estimated from the data appears never to have been defined precisely. The main goal of this paper is to compare two different approaches to defining this exact distribution. One of the approaches uses the marginal distribution and is, therefore, independent of the data; the other approach uses the conditional distribution of the statistics given the estimated parameters and, therefore, is data—dependent. We carried out a thorough study involving various parameter estimation methods and goodness‐of‐fit statistics, all of them members of the general class of power‐divergence measures. Included in the study were multinomial models with three to five cells and up to three parameters. Our results indicate that the asymptotic distribution is rarely a good approximation to the exact marginal distribution of the statistics, whereas it is a good approximation to the exact conditional distribution only when the vector of expected frequencies is interior to the sample space of the multinomial distribution.
Bayesian analysis of two‐level nonlinear structural equation models with continuous and polytomous data
Authors: Song Xin‐Yuan , Lee Sik‐Yum
Published: June 2004

Two‐level structural equation models with mixed continuous and polytomous data and nonlinear structural equations at both the between‐groups and within‐groups levels are important but difficult to deal with. A Bayesian approach is developed for analysing this kind of model. A Markov chain Monte Carlo procedure based on the Gibbs sampler and the Metropolis‐Hasting algorithm is proposed for producing joint Bayesian estimates of the thresholds, structural parameters and latent variables at both levels. Standard errors and highest posterior density intervals are also computed. A procedure for computing Bayes factor, based on the key idea of path sampling, is established for model comparison.
Delta: A new measure of agreement between two raters
Authors: Andrés A. Martín , Marzo P. Femia
Published: June 2004

The most common measure of agreement for categorical data is the coefficient kappa. However, kappa performs poorly when the marginal distributions are very asymmetric, it is not easy to interpret, and its definition is based on hypothesis of independence of the responses (which is more restrictive than the hypothesis that kappa has a value of zero). This paper defines a new measure of agreement, delta, ‘the proportion of agreements that are not due to chance’, which comes from model of multiple‐choice tests and does not have the previous limitations. The paper shows that kappa and delta generally take very similar values, except when the marginal distributions are strongly unbalanced. The case of the 2 × 2 tables (which admits very simple solutions) is considered in detail.
A note on alternative parameterizations of a model for evaluating agreement between two tests
Authors: Alanen Erkki , Leskinen Esko
Published: June 2004

The agreement between two competing tests which purport to measure the same trait is a common concern in test development. In this paper three alternative parameterizations of the measurement model useful in this context are presented. Both one‐factor and two‐factor approaches are applied. Lord's classic example, where the main problem is to investigate whether time limits represent an extra speed component in a vocabulary test, is used to illustrate the ideas.
Estimation of maximal reliability: A note on a covariance structure modelling approach
Authors: Raykov Tenko
Published: June 2004

A one‐step covariance structure analysis procedure for estimation of maximal reliability of linear composites with congeneric measures is outlined. The approach is readily employed within a single modelling session using popular covariance structure analysis software, and permits simultaneous estimation of the optimal measure weights with standard errors. The method is illustrated by a numerical example.
The meta‐analysis of partial effect sizes
Authors: Keef Stephen P. , Roberts Leigh A.
Published: June 2004

This paper discusses the synthesis of partial effect sizes derived from multivariate settings. The general statistical properties of the d‐effect size are derived, extending Hedges's statement of zero‐order properties. These general properties have direct relevance in the synthesis of a set of independent effect sizes arising from empirical studies predicated on a common theoretical model. We discuss possible solutions to the problem of comparing effect sizes arising from models employing differing sets of covariates. We apply the general statistical properties in the synthesis of gender performance differences in first‐level economics courses at three New Zealand universities. The model of academic performance is based on Spearman's conception of general academic ability and specific ability in economics.
Raman Spectroscopic Detection for Perchlorate at Low Concentrations
Authors: Gu Baohua , Tio Jacqueline , Wang Wei , Ku Yee-Kyoung , Dai Sheng
Published: June 2004

Perchlorate (ClO4−) has recently emerged as a widespread environmental contaminant found in groundwater and surface water, and there is a great need for rapid detection and monitoring of this contaminant. In this study, we explore the use of surface-enhanced (SERS) and normal Raman spectroscopy for detecting ClO4− at low concentrations. We found that ClO4− is SERS active and, for the first time, were able to detect ClO4− at concentrations as low as 10−6–10−7 M (or 10–100 μg/L) through the application of silver SERS substrates or selective sorbents such as bifunctional anion-exchange resins. The use of selective sorbents greatly enhanced the reproducibility and sensitivity of ClO4− detection by normal Raman spectroscopy. Further exploration and research may allow application of these techniques for in situ, real-time detection and monitoring of ClO4− in environmental samples at even lower concentrations.
Fast-Gated Intensified Charge-Coupled Device Camera to Record Time-Resolved Fluorescence Spectra of Tryptophan
Authors: Stortelder Aike , Buijs Joost B. , Bulthuis Jaap , Gooijer Cees , Van Der Zwan Gert
Published: June 2004

The possibilities of a 200 ps gated intensified charge-coupled device (CCD) camera to record time-resolved fluorescence were explored using the fluorescing amino acid tryptophan and its derivative N-acetyl-tryptophan amide (NATA) as model compounds. The results were compared to complementary data from time-correlated single-photon counting (TCSPC) experiments. If a spectral resolution of 1–2 nm is desired, the fast-gated intensified CCD (ICCD) camera is the method of choice. For a 10−5 M tryptophan solution, time-resolved emission spectra and intensity decays (measured over 12 ns at 25 ps resolution) could be obtained in typically 10 minutes, giving the well-known lifetimes of 0.5 and 3 ns. In addition, a longer lifetime of 7 ns was found at the red edge of the spectrum. The very short gate time of the ICCD camera allowed us to observe a shift in the emission maximum of tryptophan even within the first nanosecond of decay of the fluorescence emission. As expected from the tryptophan rotamer model, such a shift is not observed in NATA. Using amplitudes obtained by global analysis, decay-associated spectra of these lifetimes were constructed.
Energy Absorption and Propagation in Laser-Created Sparks
Authors: Bindhu C. V. , Harilal S. S. , Tillack M. S. , Najmabadi F. , Gaeris A. C.
Published: June 2004

The energy absorption and laser propagation characteristics of air and argon sparks at one atmosphere have been investigated. To create the sparks, 532 nm pulses from a frequency doubled Q-switched Nd:YAG laser are used. We employed 2 ns gated fast photography for studying the time evolution of the kernel at early times. Optical emission spectroscopy is used to infer temperature and density of the sparks. Significant energy absorption by the plasma is observed just above the breakdown threshold. The energy absorption and propagation in the spark indicated that argon plasma is more absorptive than air plasma. The absorption of the spark increases with laser energy, and at higher energies absorption saturation is observed. A spiky behavior is observed in the transmitted temporal profiles of lasers at higher energies and this is explained as due to the formation of a self-regulating regime.
Dual Source Fourier Transform Polarization Modulation Spectroscopy: An Improved Method for the Measurement of Circular and Linear Dichroism
Authors: Nafie Laurence A. , Buijs Henry , Rilling Allan , Cao Xiaolin , Dukor Rina K.
Published: June 2004

It is shown that the use of two sources in a four-port interferometer equipped with cube-corner mirrors leads to increased signal-to-noise ratios in Fourier transform (FT-IR) circular and linear dichroism spectra. The output beam to the sample is a superposition of two interferograms, one from each source, having opposite Fourier phases. These two interferograms cancel one another to the degree that the two sources are matched in intensity. If the radiation from each of the two sources is first polarized orthogonally with respect to the other and passed through a polarization modulator before reaching the sample, the resulting polarization-modulation interferograms are out of Fourier phase and out of polarization-modulation phase. As a result, the polarization-modulation interferograms, due to circular or linear dichroism in the sample, from the two sources combine positively rather than negatively. An improvement in signal-to-noise ratio of up to two (or a factor of four in scan-time reduction for the same signal-to-noise ratio) compared to single source operation can be realized, while at the same time, the potential for saturation of the detector signal is significantly reduced due to the reduction in magnitude of the combined ordinary infrared transmission interferogram. Absorption and circular dichroism spectra from a dual-source FT-IR spectrometer are presented and analyzed.
Quantitative Determination of Silanol in Quartz Applying Diffuse Reflectance Infrared Fourier Transform and Chemometrics
Authors: Haider Markus M. , Hartinger Ingrid , Göschl Karin , Demmelmair Andreas
Published: June 2004

The silanol concentration of quartz was determined by mixing 50 mg ground silica sample with 500 mg KBr followed by diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy and chemometric data analysis. Reference samples were prepared by blending ground quartz of different silanol content. Good correlation was achieved between 10 and 240 ppm Si–OH by mass. The chemometric model's quality is characterized by a correlation coefficient of 0.965 (cross-validation) using five latent variables (factors) and a root mean square error of calibration (RMSEC) of 7 ppm. Chemometric data is compared to results from univariate data analysis. The biggest impact on the reproducibility is due to sample preparation (grinding and blending), which is dependant on the operator involved.
Eliminating the Interference Pattern in Near-Infrared Spectra Used for Identification of Thin Plastic Foils
Authors: Jeszenszky Éva , Kocsányi László , Richter Péter
Published: June 2004

A Fourier type filtering method is proposed for the pretreatment of near-infrared (NIR) spectra of thin (<100 μm) transparent plastic foils before their identification by means of multivariate calibration methods. The interference of multiply reflected beams from the boundary surfaces of the foil causes a disturbing signal component in the spectrum and the identification becomes impossible. The purpose of the filtering is to eliminate the interference pattern from the spectrum. In the Fourier transformed NIR spectrum against the wavenumber there appears a discrete spectral component caused by the interference. This component can be recognized and cut off. After inverse Fourier transformation of such pretreated spectra, absorption peaks are free from interference modulation, so application of multivariate calibration methods is much more effective. With principal component analysis (PCA) on cluster plots, visual distinction between different plastics becomes possible. Correct class membership is provided by use of the Mahalanobis distance.
Automated Fourier Transform Infrared Analysis of Urinary Stones: Technical Aspects and Example of Procedures Applied to Carbapatite/Weddellite Mixtures
Authors: Cohen-Solal Fabrice , Dabrowsky Béatrice , Boulou Jean Claude , Lacour Bernard , Daudon Michel
Published: June 2004

New software (ScanLith) was developed to provide an automated procedure for identifying and quantifying crystalline species in urinary calculi. The first step was to strictly define operative conditions of sample preparation because they have a significant influence on the stability of various crystalline phases. Second, we determined the quantification coefficients of a polynomial curve required to develop the automated procedure. This was illustrated by the study of carbapatite and weddellite, as both constituents represent one of the most frequent associations found in stones analyzed in our laboratory. The following quadratic equation was obtained with a correlation coefficient r2 = 0.9997: Y = −0.5144 x2 + 1.5239 x – 0.0141, where Y is the absorbance ratio carbapatite/weddellite and x is the percentage of carbapatite in the mixture. The absorbance of carbapatite and weddellite was measured at 1035 cm−1 and 1325 cm−1, respectively. The third step was to validate the ScanLith procedure in routine analysis by comparing computed results with those of an expert. Concordance ( r2 = 0.9824) was better than that previously reported using various computerized systems with a mean deviation of 4%. Algorithms developed in ScanLith to identify main and minor components found in urinary stones, even in complex mixtures containing up to seven constituents, allowed us to lower the detection threshold down to 1 to 10% depending on the main component.
Direct Determination of Carbon Dioxide in Aqueous Solution Using Mid-Infrared Quantum Cascade Lasers
Authors: Schaden S. , Haberkorn M. , Frank J. , Baena J. R. , Lendl B.
Published: June 2004

A method for the direct determination of carbon dioxide in aqueous solutions using a room-temperature mid-infrared (MIR) quantum cascade laser at 2330 cm−1 is reported. The absorption values of different carbon dioxide concentrations were measured in a 119 μm CaF2 flow-through cell. An optical system made of parabolic mirrors was used to probe the flow cell and to focus the laser beam on the mercury cadmium telluride (MCT) detector. Aqueous carbon dioxide standards were prepared by feeding different mixtures of gaseous N2 and CO2 through wash bottles at controlled temperature. The concentration of the dissolved CO2 was calculated according to Henry's law, taking into account the temperature and the partial pressure of CO2. The carbon dioxide standards were connected via a selection valve to a peristaltic pump for subsequent, automated measurement in the flow-through cell. A calibration curve was obtained in the range of 0.338 to 1.350 g/L CO2 with a standard deviation of the method sxo equal to 19.4 mg/L CO2. The limit of detection was calculated as three times the baseline noise over time and was determined to be 39 mg/L.
Characterization of Aqueous and Solid Inclusion Complexes of Diuron and Isoproturon with β-Cyclodextrin
Authors: Dupuy N. , Marquis S. , Vanhove G. , Bria M. , Kister J. , Vrielynck L.
Published: June 2004

The interaction of diuron and isoproturon herbicides with β-cyclodextrin is conducive to the formation of inclusion compounds in aqueous solution as well as in the solid state. The physico-chemical study of these complexes was carried out by various analytical techniques such as ultraviolet (UV), Fourier transform infrared (FT-IR), Raman, X-ray diffraction, and 1H-NMR (nuclear magnetic resonance) spectroscopies. The existence of inclusion complexes in water solution between the β-cyclodextrin and each of the herbicides was revealed by electronic absorption and 1H-NMR spectroscopies. A 1:1 stoichiometry was determined for both complexes in aqueous medium from UV absorption spectra by using the Benesi–Hildebrand method; the relative stability constants at room temperature were calculated at 2700 ± 300 L mol−1 and 750 ± 50 L mol−1 for isoproturon and diuron, respectively. In the solid state, inclusion processes with β-cyclodextrin were characterized by means of infrared and Raman techniques and confirmed by X-ray diffraction spectra.
Measurements of OH Radicals in a Low-Power Atmospheric Inductively Coupled Plasma by Cavity Ringdown Spectroscopy
Authors: Wang Chuji , Mazzotti Fabio J. , Koirala Sudip P. , Winstead Christopher B. , Miller George P.
Published: June 2004

Cavity ringdown spectroscopy is applied to line-of-sight measurements of OH radicals in an atmospheric-pressure argon inductively coupled plasma, operating at low power (200 W) and low gas flows (∼18 liters/min). Density populations of the single S21(1) rotational line in the OH A2 Σ+– X2Π (0–0) band are extracted from the measured line-of-sight absorbance. Plasma gas kinetic temperatures, derived from the recorded line shapes of the S21(1) line, ranged from 1858 to 2000 K with an average uncertainty of 10%. Assuming local thermodynamic equilibrium, an assumption supported by the comparison of the experimental and simulated spectra, the spatially averaged total OH number density at different observation heights was determined to be in the range of 1.7 × 1020–8.5 × 1020 (m−3) with the highest OH density in the plasma tail. This work demonstrates that ringdown spectra of the OH radical may be used both as a thermometer for high-temperature environments and as a diagnostic tool to probe the thermodynamic properties of plasmas.
Angular Dependence in Infrared Linear Dichroism: A Reevaluation of the Theory
Authors: Gregoriou Vasilis G. , Tzavalas Spiros , Bollas Stavros T.
Published: June 2004

Parameters such as the viewing angle and the extinction ratio (the ratio of the transmitted light over the total light intensity that reaches the sample) are very important in the design of novel optical devices such as new types of polarizers, liquid crystal displays, etc. The initial aim of this work was the comparison of experimentally obtained results to the currently accepted theoretical model that is based on Zbinden's theory of intensity ellipsoid. Due to observed discrepancies between the above theory and experimental data, a new mathematical model was generated in order to adequately explain the experimental results. This new theory allows the calculation of light absorbance at every combination of azimuthal and tilt angles in complete agreement with the experimentally determined values. In addition, in this paper we settle, once and for all, the confusion that exists in the spectroscopic literature with regard to the dependence of absorption and transmission values vis-à-vis the angle of incidence of the incoming light. We conclusively show that it is absorptance (α) and not absorption or absorbance ( A) which shows a cos2 dependence on the angle formed by the electric vector and the dipole.
Separation and On-Line Distinction of Enantiomers: A Non-Aqueous Capillary Electrophoresis Fourier Transform Infrared Spectroscopy Study
Authors: Hinsmann Peter , Arce Lourdes , Svasek Peter , Lämmerhofer Michael , Lendl Bernhard
Published: June 2004

We report on the separation and on-line distinction of (R,S)-3,5-dinitrobenzoyl leucine (DNB-Leu) enantiomers with non-aqueous capillary electrophoresis (CE) and Fourier transform infrared (FT-IR) spectroscopic detection using O-( tert-butyl carbamoyl) quinine (tBuCQN) as the chiral selector (CS). Due to stereoselective intermolecular interactions—particularly ionic interactions, hydrogen bonding, and π–π-interactions—the enantiomers undergo enantio-selective complex and ion-pair formation, respectively, with the CS enabling CE separation and direct identification with FT-IR detection. Especially the (S)-enantiomer of the analyte shows significant changes in the mid-infrared region upon complexation, allowing for a clear spectral distinction between both enantiomers. In this way FT-IR spectroscopy represents a novel and attractive detection method for CE enantiomeric separations providing qualitative stereochemical information on the interactions between the chiral selector and the enantiomers, which is hardly accessible by other CE detection methods.
Chemometric Correction of Drift Effects in Optical Spectra
Authors: Vogt Frank , Steiner Hannes , Booksh Karl , Mizaikoff Boris
Published: June 2004

All quantitative data evaluation techniques applied to spectroscopy are based on the assumption that the baseline is stable in time. If this prerequisite is violated, major concentration errors can result since drifts are evaluated along with true spectroscopic features. For handling baseline drifts two improved principal component regression (PCR) methods are presented and compared to conventional Savitzky–Golay preprocessing followed by conventional PCR. The proposed drift-correction methods take advantage of baseline drifts being rather broad compared to the absorption features. The only assumption made is that drift effects can be modeled sufficiently by polynomials of user-selectable order. One correction method modifies principal components such that drifts of polynomial shape are orthogonal to the calibration model and thus cannot influence the concentration result. The second method extends the calibration model by synthetic so-called pseudo-principal components. While the principal components model the true spectral features, the pseudo-principal components describe drifts simultaneously and independently. Hence, drifts are explicitly included into the calibration and cannot cause erroneous concentration results. It is demonstrated that both correction methods are equivalently as powerful as the conventional PCR in the absence of drifts and superior if drifts are present. The overall performance—in the absence and presence of baseline drifts—of the novel methods makes them more versatile and reliable than the conventional Savitzky–Golay data preprocessing. In almost all investigated cases, the average concentration errors were significantly smaller than those obtained by Savitzky– Golay preprocessing. Furthermore, polyPCR and pPCR do not need laborious optimizations as Savitzky–Golay does for preventing suppression of relevant signal components. polyPCR demands less computation expense than Savitzky–Golay, and pPCR extracts the drift spectrum as additional qualitative information not provided by Savitzky–Golay.
Performance and Application of a New Planar Array Infrared Spectrograph Operating in the Mid-Infrared (2000–975 cm−1) Fingerprint Region
Authors: Pellerin Christian , Snively Christopher M. , Chase D. Bruce , Rabolt John F.
Published: June 2004

A no-moving-part planar array infrared spectrograph (PA-IR) equipped with a 256 × 256 mercury cadmium telluride (MCT) focal plane array has been designed and constructed. The performance of the instrument, whose frequency range extends from 2000–975 cm−1, has been assessed in terms of resolution, bandwidth, and signal-to-noise ratio. The PA-IR spectrograph is able to record spectra with an 8.7 ms time resolution and has peak-to-peak noise levels as low as 2.4 × 10−4 A.U. As a demonstration of the potential of PA-IR, the dynamics of reorientation of a liquid crystalline sample exposed to a single electric field pulse has been studied. It was shown that PA-IR can be used for the simultaneous acquisition of two orthogonally polarized spectra. The advantages and limitations of PA-IR, step-scan Fourier transform infrared (FT-IR), and ultra-rapid-scanning FT-IR for real-time studies of reversible and irreversible phenomena are thoroughly discussed.
Multielemental Laser-Enhanced Ionization Spectrometry for the Determination of Lead at the Trace Level in Pelletized Coal Using Laser Ablation and Internal Standard Signal Normalization
Authors: Gravel Jean-François Y. , Viger Mathieu L. , Nobert Philippe , Boudreau Denis
Published: June 2004

Laser ablation laser-enhanced ionization (LA-LEI) was used for the simultaneous measurement of lead and indium in pelletized graphite and coal samples. UV Laser ablation of the solid samples was performed in an ablation cell and the ablated material was carried by a flow of gas to a miniature LEI flame where lead was detected. The influence of parameters such as binder content of the solid pellets and dispersion of the analytes spiked in the sample material, as well as the number of ablation pulses per crater on signal repeatability and on the size and shape of ejected particles was examined. Measurement repeatability values of 2 to 5% of relative standard deviation were obtained using indium as an internal standard to correct for variations in the ablation rate. A limit of detection of 120 nanograms per gram was calculated for the determination of Pb in high-purity graphite. The Pb concentration in the NIST 1632c Bituminous Coal certified reference material was determined to within 1% of its certified value, using graphite as the matrix-matching material and In as the internal standard in pelletized solid samples.
1H MAS NMR (Magic-Angle Spinning Nuclear Magnetic Resonance) Techniques for the Quantitative Determination of Hydrogen Types in Solid Catalysts and Supports
Authors: Kennedy Gordon J. , Afeworki Mobae , Calabro David C. , Chase Clarence E. , Smiley Randolph J.
Published: June 2004

Distinct hydrogen species are present in important inorganic solids such as zeolites, silicoaluminophosphates (SAPOs), mesoporous materials, amorphous silicas, and aluminas. These H species include hydrogens associated with acidic sites such as Al(OH)Si, non-framework aluminum sites, silanols, and surface functionalities. Direct and quantitative methodology to identify, measure, and monitor these hydrogen species are key to monitoring catalyst activity, optimizing synthesis conditions, tracking post-synthesis structural modifications, and in the preparation of novel catalytic materials. Many workers have developed several techniques to address these issues, including 1H MAS NMR (magic-angle spinning nuclear magnetic resonance). 1H MAS NMR offers many potential advantages over other techniques, but care is needed in recognizing experimental limitations and developing sample handling and NMR methodology to obtain quantitatively reliable data. A simplified approach is described that permits vacuum dehydration of multiple samples simultaneously and directly in the MAS rotor without the need for epoxy, flame sealing, or extensive glovebox use. We have found that careful optimization of important NMR conditions, such as magnetic field homogeneity and magic angle setting are necessary to acquire quantitative, high-resolution spectra that accurately measure the concentrations of the different hydrogen species present. Details of this 1H MAS NMR methodology with representative applications to zeolites, SAPOs, M41S, and silicas as a function of synthesis conditions and post-synthesis treatments (i.e., steaming, thermal dehydroxylation, and functionalization) are presented.
Toward Resolving the Challenges of Sepsis Diagnosis
Authors: Carrigan Shawn D , Scott George , Tabrizian Maryam
Published: June 2004

Sepsis in the United States has an estimated annual healthcare cost of $16.7 billion and leads to 120 000 deaths. Insufficient development in both medical diagnosis and treatment of sepsis has led to continued growth in reported cases of sepsis over the past two decades with little improvement in mortality statistics. Efforts over the last decade to improve diagnosis have unsuccessfully sought to identify a “magic bullet” proteic biomarker that provides high sensitivity and specificity for infectious inflammation. More recently, genetic methods have made tracking regulation of the genes responsible for these biomarkers possible, giving current research new direction in the search to understand how host immune response combats infection. Despite the breadth of research, inadequate treatment as a result of delayed diagnosis continues to affect approximately one fourth of septic patients. In this report we review past and present diagnostic methods for sepsis and their respective limitations, and discuss the requirements for more timely diagnosis as the next step in curtailing sepsis-related mortality. We also present a proposal toward revision of the current diagnostic paradigm to include real-time immune monitoring.
Maternal Homocysteine before Conception and throughout Pregnancy Predicts Fetal Homocysteine and Birth Weight
Authors: Murphy Michelle M , Scott John M , Arija Victoria , Molloy Anne M , Fernandez-Ballart Joan D
Published: June 2004

Background: Increased homocysteine has been associated with pregnancy complications.

Methods: We investigated prospectively the effect of maternal homocysteine on normal pregnancy outcome. The study included 93 women and their offspring; 39 of the women took folic acid during the second and/or third trimesters of pregnancy. We measured homocysteine at preconception; at weeks 8, 20, and 32 of pregnancy; during labor; and in the fetal cord; we also recorded birth weight.

Results: Geometric mean (SE) maternal total homocysteine (tHcy) increased between 32 weeks of pregnancy and labor [7.98 (1.05) μmol/L in unsupplemented women and 6.26 (1.07) μmol/L in supplemented women; P <0.0001 for both]. Fetal tHcy was lower than maternal tHcy [6.39 (1.06) μmol/L in unsupplemented pregnancies (P <0.0001), and 5.18 (1.06) μmol/L in supplemented pregnancies (P <0.05)]. Maternal tHcy was correlated from preconception throughout pregnancy (8 weeks, r = 0.708; 20 weeks, r = 0.637; 32 weeks, r = 0.537; labor, r = 0.502; P <0.0001 for all time points) and with fetal tHcy [preconception, r = 0.255 (P <0.05); 8 weeks, r = 0.321 (P <0.01); 20 weeks, r = 0.469; 32 weeks, r = 0.550; labor, r = 0.624 (P <0.0001)]. Mothers in the highest tHcy tertile at 8 weeks of pregnancy were three times [odds ratio, 3.26 (95% confidence interval, 1.05–10.13); P <0.05] and at labor were four times [3.65 (1.15–11.56); P <0.05] more likely to give birth to a neonate in the lowest birth weight tertile. Neonates of mothers in the highest tHcy tertile at labor weighed, on average, 227.98 g less than those of mothers in the low and medium tertiles (P = 0.014).

Conclusions: Supplemented mothers had lower tHcy at labor than unsupplemented mothers, as did their neonates. Maternal and fetal tHcy was significantly correlated throughout the study. Neonates of mothers in the highest tertile of homocysteine weighed less.
Measurement of Urinary d- and l-2-Hydroxyglutarate Enantiomers by Stable-Isotope-Dilution Liquid Chromatography–Tandem Mass Spectrometry after Derivatization with Diacetyl-l-Tartaric Anhydride
Authors: Struys Eduard A , Jansen Erwin E W , Verhoeven Nanda M , Jakobs Cornelis
Published: May 2004

Background: The differential diagnosis of d-2-hydroxyglutaric aciduria (d-2-HGA), l-2-hydroxyglutaric aciduria (l-2-HGA), and the combined d/l-2-hydroxyglutaric aciduria (d/l-2-HGA) can be accomplished only by the measurement of the corresponding 2-hydroxyglutarate (2-HG). Available methods for the determination of d- and l-2-HG in urine are either time-consuming and expensive or have not been extensively validated. We aimed to develop a method for their rapid and sensitive measurement.

Methods: We used liquid chromatography–tandem mass spectrometry (LC-MS/MS) for the determination of d- and l-2-HG with stable-isotope-labeled internal standards. Urine samples of 20 μL were mixed with 250 μL of methanol containing the internal standards and subsequently dried under nitrogen. The analytes were derivatized by use of diacetyl-l-tartaric anhydride (DATAN) to obtain diastereomers, which were separated on an achiral C18 HPLC column and detected by MS/MS in multiple-reaction-monitoring mode.

Results: The use of DATAN as chiral derivatization reagent provided very well separated peaks of the formed diastereomers of d- and l-2-HG, with a total runtime of 5 min. The inter- and intraassay CVs for d- and l-2-HG ranged from 3.4% to 6.2%. Mean recoveries of d- and l-2-HG, evaluated on two concentrations, were 94%. Detection limit of the presented method was 20 pmol for a sample volume of 20 μL. Method comparison of the LC-MS/MS method with a gas chromatography–mass spectrometry method, in which d- and l-2-HG were derivatized with R-(−)-butanol, showed good agreement between the two methods.

Conclusions: Urinary d- and l-2-HG can be analyzed by MS/MS after derivatization with DATAN. The presented method may be suitable for the differential diagnosis of 2-HGA.
Closed-Tube Genotyping with Unlabeled Oligonucleotide Probes and a Saturating DNA Dye
Authors: Zhou Luming , Myers Alexander N , Vandersteen Joshua G , Wang Lesi , Wittwer Carl T
Published: June 2004

Background: Homogeneous PCR methods for genotyping usually require fluorescently labeled oligonucleotide probes. Amplicon melting with the DNA dye LCGreen™ I was recently introduced as a closed-tube method of genotyping that does not require probes or real-time PCR. However, some single-nucleotide polymorphisms (SNPs) could not be completely genotyped without addition of a known genotype, and high-resolution melting techniques were necessary.

Methods: A 3′-blocked, unlabeled oligonucleotide probe and the saturating dye, LCGreen I, were added to standard PCR reagents before amplification. After PCR, the samples were melted at 0.1–0.3 °C/s in high-resolution (HR-1™), high-throughput (LightTyper™), and rapid-cycle, real-time (LightCycler®) instruments, and fluorescence melting curves were recorded.

Results: Derivative melting curves of the probe–target duplexes were characteristic of the genotype under the probe. With synthetic plasmid templates, all SNP base combinations could be genotyped. For human genomic DNA, the technique was demonstrated with mutations associated with cystic fibrosis, including SNPs (G542X, I506V, and F508C) and 3-bp deletions (F508del and I507del).

Conclusions: Genotyping of SNPs and small deletions by melting analysis of an unlabeled probe in the presence of LCGreen I is simple and rapid. Only three unlabeled oligonucleotides (two primers and one probe), a saturating DNA dye, PCR, and a melting instrument are required. The method is closed-tube, does not require fluorescently labeled probes or real-time PCR, and can be completed in <10 min on any instrument capable of monitoring melting curves by fluorescence.
Clinical Pharmacology of Bivalirudin
Authors: Reed Michael D. , Bell Dawn
Published: June 2004

Much progress has been made in understanding and treating acute coronary syndromes. For patients undergoing percutaneous transluminal coronary angioplasty, anticoagulant therapy during the procedure must strike a balance between providing sufficient anticoagulation to prevent thrombus formation and ischemic complications while averting hemorrhagic complications. Bivalirudin, a thrombin‐specific anticoagulant, is the only anticoagulant that reduces both ischemic and bleeding complications associated with percutaneous coronary intervention (PCI). Bivalirudin is easy to use, provides predictable anticoagulation, inactivates both free and clot‐bound thrombin, and blocks thrombin‐mediated platelet activation and aggregation. Drug‐drug interaction studies have found no clinically relevant interactions between bivalirudin and ticlopidine, abciximab, tirofiban, or eptifibatide. Bivalirudin is well tolerated by patients who previously received low‐molecular‐weight heparin (LMWH), when LMWH is discontinued 8–14 hours before bivalirudin is started. Similarly, switching from heparin to bivalirudin at the time of PCI reduces both ischemic and bleeding events.
Bivalirudin Administration During Percutaneous Coronary Intervention: Emphasis on High‐Risk Patients
Authors: Seybert Amy L.
Published: June 2004

In a large phase III study of patients with unstable angina treated with percutaneous transluminal coronary angioplasty (PTCA), the thrombin‐specific anticoagulant bivalirudin produced relative risk reductions of 22% (p=0.039) for ischemic complications and 62% (p<0.001) for bleeding complications compared with heparin. Subsequent reports have shown that between‐treatment differences favoring fewer complications with bivalirudin also extend to high‐risk patients. Early heparinization promotes heparin resistance and decreases activated clotting time achieved during PTCA. These effects are relevant to patients with postinfarction angina, which is associated with a greater likelihood of early vessel closure and procedural failure. In 1006 patients with one or both of these risk factors, bivalirudin significantly reduced combined ischemic and bleeding complications compared with heparin (8.6% vs 18%, p<0.001). Treatment separations favoring bivalirudin increased with risk, suggesting decreased heparin effectiveness in patients at heightened risk. Findings in three additional risk groups—women, the elderly, and patients not receiving glycoprotein IIb/IIIa inhibitors—also showed fewer complications with bivalirudin therapy. Preliminary data suggest that bivalirudin can be combined safely with glycoprotein IIb/IIIa antagonists in percutaneous coronary intervention (PCI), including PTCA. An ongoing trial is aimed at determining the efficacy and safety of heparin with planned glycoprotein IIb/IIIa therapy versus bivalirudin with provisional glycoprotein IIb/IIIa therapy. The use of bivalirudin in patients with heparin‐induced thrombocytopenia also is being evaluated after favorable findings in early compassionate‐use studies. The fact that between‐treatment differences favoring bivalirudin were especially outstanding among the high‐risk patients considered in this review reinforces the impression that bivalirudin is a promising and unprecedented alternative to heparin in PCI.
A Practical Cost Analysis of Bivalirudin
Authors: Compton Anthony
Published: June 2004

Despite advances in percutaneous coronary intervention (PCI) techniques and adjunctive therapies, the risks of ischemic and bleeding complications with PCI remain significant. These complications are associated with significant morbidity and mortality, as well as substantially higher costs. Bivalirudin is the only antithrombotic agent that has been shown to reduce both ischemic and hemorrhagic complications associated with PCI. Cost models drawn from the results of three clinical trials of bivalirudin have estimated its potential impact on total medical costs. In addition, the number needed to treat to avoid a bleeding complication has been calculated based on patients shown to have a heightened risk of bleeding in the Bivalirudin Angioplasty Trial. In all models assessed, the use of bivalirudin offset most of its own cost through reductions in bleeding and ischemic complications.
The Biology of Thrombin in Acute Coronary Syndromes
Authors: Nappi Jean
Published: June 2004

Thrombin, a serine protease, is the keystone of the twin processes of hemostasis and thrombosis. Through procoagulant, anticoagulant, and antifibrinolytic mechanisms, thrombin helps maintain vascular integrity in the face of hemorrhage. These same mechanisms, however, allow for the pathologic formation of thrombi in response to endothelial damage, which accompanies the erosion or rupture of atherosclerotic plaques. Alone or incorporated into plaques, thrombi can cause vessel occlusion resulting in acute coronary syndromes (ACS). Inhibiting thrombin can improve clinical outcomes in ACS, as well as in procedures such as percutaneous coronary interventions, which are designed to open the occluded vessels that cause ACS. Such improvements in outcomes with thrombin inhibition reflect the central and multivariate role of thrombin in thrombus formation.
The Role of Thrombin Inhibition During Percutaneous Coronary Intervention
Authors: Wittkowsky Ann K.
Published: June 2004

Acute coronary syndromes encompass a spectrum of conditions, including myocardial infarction and unstable angina. These syndromes are related to the formation and disruption of atherosclerotic plaque. Rupture of plaque leads to thrombin generation, fibrin deposition, and platelet aggregation, ultimately resulting in restriction of blood flow and ischemia of cardiac tissue. Percutaneous coronary intervention (PCI), including angioplasty and coronary stent placement, has been developed to open occluded arteries. The frequency with which these procedures are performed speaks to their largely successful outcomes. However, the mechanical manipulations of PCI result in additional plaque rupture and damage to the vessel wall, exposing subendothelial components to blood and resulting in the initiation of the clotting cascade and in platelet activation. Left unchecked, these intertwined processes lead to formation of arterial thrombi at the site of endothelial damage, and potentially to abrupt vessel closure or embolization of thrombi into the distal microcirculation. Thrombin plays a central role in thrombus formation and platelet activation, and its inhibition significantly reduces thrombus‐related sequelae. Current antithrombotic strategies during PCI are based on the traditional indirect thrombin inhibitor heparin. Heparin has several limitations in efficacy and safety, due in part to its indirect mechanism of action. Bivalirudin, a direct thrombin inhibitor, offers significant improvement over heparin in the clinical outcomes and risks associated with PCI.
Risk Markers for Thrombocytopenia in Critically Ill Patients: A Prospective Analysis
Authors: Shalansky Stephen J. , Verma Arun K. , Levine Marc , Spinelli John J. , Dodek Peter M.
Published: June 2004

Study Objective. To identify independent risk markers for thrombocytopenia in critically ill patients.

Design. Prospective, observational study.

Setting. Eleven‐bed intensive care unit‐coronary care unit (ICU‐CCU) in a community hospital.

Patients. Three hundred sixty‐two consecutive patients meeting inclusion criteria during 1 year.

Intervention. Potential risk marker data were collected on admission to the ICU‐CCU and for the period before development of thrombocytopenia (defined as two or more consecutive platelet counts < 150 × 103/mm3 obtained at least 12 hours apart), or for the duration of ICU‐CCU stay if thrombocytopenia did not develop.

Measurements and Main Results. Thrombocytopenia developed in 68 patients (18.8%). Multivariate logistic regression analyses identified patients at risk on admission, but the predictive potential of the regression model improved when all risk marker exposures during the ICU‐CCU stay were considered. Independent risk markers included fresh frozen plasma administration, sepsis, musculoskeletal diagnosis, pulmonary artery catheter insertion, gastrointestinal diagnosis, packed red blood cell administration, and nonsurgical respiratory diagnosis. Higher admission platelet count and aspirin administration were associated with a lower risk of thrombocytopenia. Heparin administration was not identified as a risk marker, and no patient developed heparin‐induced thrombocytopenia with thrombosis. Patients with thrombocytopenia had longer ICU‐CCU and hospital stays, and higher ICU‐CCU and hospital mortality than those without thrombocytopenia.

Conclusions. Development of thrombocytopenia in critically ill patients is associated with specific diagnoses, packed red cell and fresh frozen plasma transfusions, pulmonary artery catheter insertion, and admission platelet count.
Effects of Orlistat on Fat‐Soluble Vitamins in Obese Adolescents
Authors: McDuffie Jennifer R. , Calis Karim A. , Booth Sarah L. , Uwaifo Gabriel I. , Yanovski Jack A.
Published: June 2004

Study Objectives.To determine whether orlistat causes fat‐soluble vitamin deficiencies in African‐American and Caucasian adolescents.

Design.Prospective, open‐label pilot study.

Setting.Warren Grant Magnuson Clinical Center of the National Institutes of Health.

Patients.Seventeen adolescents with body mass indexes above the 95th percentile for age, race, and gender who also had at least one obesity‐related comorbid condition.

Intervention.Subjects received orlistat 120 mg 3 times/day and a daily multivitamin supplement containing vitamin A 5000 IU, vitamin D 400 IU, vitamin E 300 IU, and vitamin K 25 μg.

Measurements and Main Results.During 3–6 months of orlistat treatment, acute absorption of retinol (vitamin A) was not significantly altered, but absorption of α‐tocopherol (vitamin E) was significantly reduced compared with baseline levels (p<0.001). Serum levels of vitamins A and E did not change significantly; however, there was a nonsignificant decrease in vitamin K. Mean vitamin D levels were significantly reduced compared with baseline (p<0.02) after 1 month of orlistat, despite multivitamin supplementation.

Conclusion.It may be prudent to monitor vitamin D concentrations in adolescents who take orlistat, even when a multivitamin is prescribed.