Guanidinium-induced differential kinetic denaturation of alkaline phosphatase isozymes

This paper examines the solution kinetics of bovine intestinal and liver alkaline phosphatase (ALP) isozymes. 4-Methylumbelliferyl phosphate is used as the substrate to study the differential kinetic behavior of ALP isozymes in the presence of guanidinium hydrochloride, a denaturant. The recursive Kalman filter algorithm for parameter estimation is used for analysis of the resulting kinetic data. A two-component first-order kinetic model with a zero-order component is used to successfully quantify intestinal and liver isozymes in synthetic mixtures. This work serves as a basis for the development of an electrophoresis separation method for ALP isozyme quantification with differential kinetic detection.     

Chemometric resolution and quantification of four-way data arising from comprehensive 2D-LC-DAD analysis of human urine

Two-dimensional liquid chromatography (LC × LC) is quickly becoming an important technique for the analysis of complex samples, owing largely to the relatively high peak capacities attainable by this analytical technique. With the increase in the complexity of the sample comes a corresponding increase in the complexity of the collected data. Thus the need for chemometric methods capable of resolving and quantifying such data is ever more urgent in order to obtain the maximum information available from the data. To this end, we have developed a chemometric method that combines iterative key set factor analysis and multivariate curve resolution-alternating least squares analysis with a spectral selectivity constraint that is shown to be capable of resolving chromatographically rank deficient, non-multilinear data. (spectrally rank deficient compounds can only be quantified if the peaks having the same spectra are chromatographically resolved). Over 50 chromatographic peaks were found in a relatively small section of a LC × LC-diode array data set of replicate urine samples (a four-way data set) using the developed method. The relative concentrations for 34 of the 50 peaks were determined with % RSD values ranging from 0.09% to 16%.     

Building therapeutic relationships with couples.

Contends that the ultimate goal for couples' work in therapy is not the salvation of the marriage but the fullest possible life for each individual. Couples are viewed as systems, and the contributions of general systems theory to couples treatment are illustrated in 4 clinical vignettes. It is suggested that the concept of projective identification is central to understanding and working with couples. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The charismatic leader: Asset or liability?

Charismatic leaders have the ability to gain a following of persons who are willing to place personal gain secondary to the will and wishes of the leader. Such a charismatic situation has tremendous potential for good or evil. Therapy groups seem to be natural arenas for the charismatic situation. Group members often perceive their leaders as "more than" human, and this seems to serve some important function in the life of the group. The present author assesses the place of the charismatic leader, along with its assets and liabilities, in the practice of group psychotherapy. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of the sources of variation affecting near-infrared spectroscopy using chemometric methods

A rapid assessment of product quality can often be made using a combination of near-infrared spectroscopy (NIR) and multivariate calibration. The robustness of such a method is determined by the sensitivity of the multivariate calibration model to variations in the spectral data. An approach is described that uses a combination of experimental design methodology and principal component analysis to identify the main sources of variation in the spectra and to estimate their influence on the quantitative predictions. This is accomplished by comparing variations in a set of measured, replicate spectra to spectra with simulated variations. The approach was applied to the hydroxyl number determination of polyols by NIR spectroscopy and partial least-squares calibration. The results indicated that the most significant sources of variation were due to a variable cell path length and a variable curved background. Correction for these errors resulted in a 58% reduction in the standard deviation of the hydroxyl number predictions, indicating that a substantial improvement in the method precision is possible.     

Analysis of four-way two-dimensional liquid chromatography-diode array data: application to metabolomics

Two-dimensional liquid chromatography (2D-LC) is rapidly gaining popularity for the analysis of very complex mixtures, including proteomic and metabolomic samples. It provides an effective strategy for separating such samples, because the resolving power of 2D-LC is far superior to that of traditional single-dimension separations. The present work focuses on the development of data analysis methods for the extremely large data sets, on the order of 10 million data points, generated by 2D-LC with diode-array detection (DAD). Specifically, we have applied and adapted chemometric methods to the analysis of maize seedling digests, focusing on compounds related to the biosynthetic pathways of indole-3-acetic acid, the primary growth regulator in plants. The chemometric techniques of window target testing factor analysis (WTTFA), along with parallel factor analysis - alternating least squares (PARAFAC-ALS) were used to analyze 2D-LC-DAD chromatograms of a sample composed of 26 indolic standards, 2 extracts of mutant orange pericarp maize seedlings, 2 extracts of wild-type maize seedlings, and a blank sample. The indolic compounds studied belonged to six spectrally unique groups, and WTTFA was able to specifically identify the presence or absence of any of the 26 indolic standards in the mutant and wild-type samples. A PARAFAC-ALS algorithm and an ALS algorithm with flexible constraints were successfully applied to resolve the spectrally rank deficient data and to demonstrate the quantitative potential of multivariate curve resolution methods. Using this procedure, 95 total peaks were resolved in the data set analyzed. Of those 95 peaks, 45 were found in both the mutant and wild-type maize samples, 16 peaks were unique to the mutant maize samples, 13 peaks were unique to the wild-type maize samples, and 15 peaks were unique to the standard chromatograms. Of the 26 standards included in the data set, several indole acetic acid conjugates were identified and quantified in the maize samples at levels of approximately 0.3-2 microg/g plant material.     

Temporal patterns of antihypertensive medication use among older adults, 1989 through 1992. An effect of the major clinical trials on clinical practice?

OBJECTIVE: To describe the changing patterns of antihypertensive medication use in the years immediately before and after the publication of the results of three major clinical trials of the treatment of hypertension in older adults. DESIGN: In this cohort study, adults 65 years or older were examined annually on four occasions between June 1989 and May 1992, and the use of antihypertensive medications was assessed by inventory at each visit. The four visits defined the boundaries of three study periods. For each study period, participants receiving antihypertensive therapy were either continuous users (n = 1667, 1643, and 1605, respectively) or starters (n = 157, 142, 120) of hypertensive therapy. The large clinical trials that convincingly proved the efficacy and safety of low-dose diuretic therapy in older adults were published during the latter parts of period 2 and the early parts of period 3. RESULTS: Among starters, the proportion initiating therapy on diuretics increased from 35.9% in period 2 to 47.5% in period 3, significantly so among women (P = .04). The proportions initiating other drugs displayed no significant trends. Among continuous users, the use of diuretics, beta-blockers, and vasodilators generally decreased over the 3-year period, while the use of calcium channel blockers and angiotensin-converting enzyme inhibitors increased significantly in each of the three periods (P < .05). The decline of 2.7% in the prevalence of diuretic use in period 1 abated during period 2 (1.8% decline), and it slowed significantly (P = .03) to almost a complete halt during period 3 (0.2% decline). The rate of increase in the use of calcium channel blockers slowed significantly (P = .01) between period 1 (+6.7%) and period 3 (+2.8%). CONCLUSIONS: Although other factors such as cost may have been important, the temporal trends in antihypertensive drug therapy coincided in time with and may have reflected in part the influence of the major clinical trials on the patterns of clinical practice.     

Study of complexation in methanol/water mixtures by infrared and Raman spectroscopy and multivariate curve resolution-alternating least-squares analysis

The structure of the mobile phase in liquid chromatography plays an important role in the determination of retention behavior on reversed-phase stationary materials. One of the most commonly employed mobile phases is a mixture of methanol and water. In this work, infrared and Raman spectroscopic methods were used to investigate the structure of species formed in methanol/water mixtures. Chemometric methods using multivariate curve resolution by alternating least-squares analysis were used to resolve the overlapped spectra and to determine concentration profiles as a function of composition. The results showed that the structure of these mixtures could be described by a mixture model consisting of four species, namely, methanol, water, and two complexes, methanol/water (1:1) and methanol/water (1:4). The spectral frequencies and concentration profiles found from the Raman and infrared measurements were consistent with one another and with theoretical calculations.     

Primary care within the VA: the firm model

Many of the VA medical centers are reorganizing total care across a continuum that includes outpatient, inpatient, long-term, and home based care, into interdisciplinary firms. The goals of reorganization are to improve patient access to care and continuity of care, to improve housestaff education by assigning a specific panel of patients for the residents to follow longitudinally in a variety of situations supervised by the same mentors, and to enhance research in primary care issues. Preliminary results show increased patient satisfaction and improvements in both quality of care and increased efficiency in its delivery. Many large health care organizations might be expected to reorganize care delivery around a similar interdisciplinary team concept.