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At least 1,117 records · Page 62Linked to original sources
PubMed2003

3D-MEDNEs: an alternative "in silico" technique for chemical research in toxicology. 1. prediction of chemically induced agranulocytosis.

A novel approach to molecular negentropy from the point of view of Markov models is introduced. Stochastic negentropies (MEDNEs) are used to develop a linear discriminant analysis. The discriminant analysis produced a set of two discriminant functions, which gave rise to a very good separation of 93.38% of 151 chemicals (training series) into two groups. The total predictability (86.67%, i.e., 52 compounds out of 60) was tested by means of an external validation set. Randić's orthogonalization procedures allowed interpretation of the model while avoiding collinearity descriptors. On the other hand, factor analysis was used to suggest the relation of MEDNEs with other molecular descriptors and properties into a property space. Three principal factors (related to three orthogonal MEDNEs) can be used to explain approximately 90% of the variance of different molecular parameters of halobenzenes including bulk, energetic, dipolar, molecular surface-related, and hydrophobic parameters. Finally, preliminary experimental results coincide with a theoretical prediction when agranulocytosis induction by G-1, a novel microcidal that presents Z/E isomerism, is not detected.

Agranulocytosis↗
PubMed2003

Stepwise discrimination between four modes of toxic action of phenols in the Tetrahymena pyriformis assay.

For a set of 220 phenols with literature data on their toxicity and associated mode of action (MOA) toward the ciliate Tetrahymena pyriformis, a stepwise classification scheme was developed that allows the identification of four MOAs from molecular hydrophobicity and AM1-based quantum chemical descriptors, employing linear discriminant analysis or binary logistic regression. Taking the AM1 lowest unoccupied molecular orbital energy as the only parameter, an initial separation of polar narcotics and proelectrophiles from oxidative uncouplers and soft electrophiles is correct to 97%, and for the subsequent discrimination between polar narcotics and proelectrophiles as well as between oxidative uncouplers and soft electrophiles, 99 and 98% correct classifications are achieved using three and two molecular descriptors, respectively. The results are discussed in terms of detailed contingency table statistics and with respect to relationships between molecular descriptors and mechanisms of toxicity. Statistical model evaluation includes simulated external validation employing complementary subset models.

Animals↗
PubMed1999

Factor analysis of the psychosocial items of the EORTC QLQ-C30 in metastatic breast cancer patients participating in a psychosocial intervention study.

The underlying factor structure of a subset of 12 items, which comprise the psychosocial subscales of the EORTC QLQ-C30 was explored in a group of women, all with metastatic breast cancer who were participating in a psychosocial intervention study. Two main factors were identified in this exploratory factor analysis, representing "emotional distress" and "functional ability" dimensions. A preliminary assessment of the external validity of the two factor structure was undertaken. The results support the validity of a summative "emotional distress" and "functional ability" score in this sample of patients. The "functional ability" score discriminated well for subgroups defined by clinical status indicators (e.g., performance status, pain, chemotherapy treatment, fatigue). The "emotional distress" subscale discriminated with respect to suffering, fatigue and sleep disturbance. Both subscales converged with related concepts measured by independent instruments, providing support for convergent validity. Summative index scores may be advantageous for application in particular research situations; applying quality adjustments in health policy analyses; for screening purposes; to monitor populations and make comparisons across broad groups and as stratification variables in clinical trials. Further research to confirm the 2 factor structure is required in other samples before the interpretation can be accepted with confidence.

Adult↗
PubMed1998

Validation of routine incidence reporting of one anaesthesia provider institution within a nation-wide quality of process assessment program.

In 1992, a long-term project was launched by the German Society for Anaesthesiology and Intensive Care Medicine to render quality comparisons between anaesthesia providers. As one of the first volunteer centres, we established the standardised reporting of perioperative anaesthesia related incidents, events, and complications (IEC) in any routine anaesthetic procedure performed. This present study is aimed to explore the longitudinal stability of IEC recordings in one institution, which should be a prerequisite for valid external comparisons. Methods. The analyses were completed on an adult population of 49945 consecutive anaesthetic procedures with peripheral surgery from July 1992 until December 1996. Attribute quality control charts with monthly samples of an average of 954 anaesthetics were used to assess statistical variability of specific IEC incidences. Results. Average proportions were 20% for moderate IEC, 2.7% for severe IEC, 13% for moderate cardio-vascular IEC, 1.3% for severe cardio-vascular IEC, and 2.4% for respiratory IEC. Moderate IEC proportions showed considerable variability during the study period. A series of excess proportions was probably due to educational activities on documentation discipline. In contrast, clinically severe IEC proportions were rather stable. Stability of cardio-vascular IEC proportions resembled the picture of the overall IEC assessment. Monthly respiratory IEC proportions showed smallest variability during the study period. Discussion. Use of the quality control statistics is suitable to distinguish random from systematic influence on quality indicators. IEC recordings that are not specific in pathophysiologic type or are of low grade of clinical severity, are heavily dependent on systematic documentation features. We assume that peak values, such as in times of optimised documentation discipline, better reflect reality than average values because missing reporting is much more likely than false positives.

Adult↗
PubMed2001

A psychometric analysis of the Quality of Life-Cancer Survivors (QOL-CS) in survivors of childhood cancer.

Given the increasing interest in quality of life research in cancer survivorship, psychometric properties of the Quality of Life-Cancer Survivors (QOL-CS) were explored in a group of childhood cancer survivors. The QOL-CS is a 41-item visual analog scale composed of four multi-item sub-scales (physical well-being, psychological well-being, social well-being, spiritual well-being) and two sub-components (fears, distress). This instrument was incorporated in a mailed survey completed by 177 respondents. The underlying factor structure and internal reliability of the instrument were explored. A preliminary assessment of the external validity of the factor structure was undertaken. Results of a factor analysis were theoretically consistent with elements assessed in the QOL-CS, although misclassification of several items was noted and discussed. Internal-consistency reliability was very good (Cronbach's alpha = 0.80-0.89) for five of the six factors. Moderate (0.30 < r < 0.45) to high (r > 0.60) concurrent validity was observed for four factors. Discriminant validity was noted across groups defined by health and social status variables. Psychometric analysis indicated that the instrument measured distinct and relevant domains of quality of life for childhood cancer survivors, but in its current form does not appear to be an optimal measure of quality of life in this population.

Adolescent↗
PubMed2002

Data collection methods for analyzing the quality of the dispensing in pharmacies.

OBJECTIVE: To review and discuss the advantages and limitations of the different data collection methods for analyzing the dispensing quality in community pharmacies. METHODS: A bibliographic search was carried out in MEDLINE (1980-2000). Articles with Medical Subject Heading (Mesh) "pharmacies" written in English and Spanish that evaluated the quality of dispensing (structure, process or outcome) were selected. RESULTS: Various data collection methods were observed. To analyze the quality of the structure, questionnaires and pharmacist interviews were used. To analyze the quality of the process, self-completed records, external observers and simulated clients were used. For analyzing the quality of the outcome, questionnaires, client interviews, and biologic samples were collected. CONCLUSIONS: The analysis of quality of structure can be useful as a first approach, however, this method may lack sensitivity. On the other hand, the analysis of outcome may be excessively complex and difficult to use, except for experimental or observational studies with large resources. Therefore, an analysis of the quality of the process is the best option. Methods utilizing external observers and simulated clients may best conjugate both internal and external validity.

Community Pharmacy Services↗
PubMed2003

Attenuated total reflectance Fourier transform mid-infrared spectroscopic quantification of sorbitol and sorbose during a Gluconobacter biotransformation process.

Mid-infrared spectroscopy (MIRS) was used to simultaneously detect and predict concentrations of D-sorbitol and L-sorbose during a Gluconobacter suboxydans biotransformation. Quantitative models for both these compounds were developed for the entire time-course of the process and validated externally using samples not included in the original modelling exercise, giving standard errors of prediction of 3.29 and 3.3% for sorbitol and sorbose, respectively, and a correlation coefficient close to 1.

Bioreactors↗
PubMed2003

QSAR analysis of the inhibition of recombinant CYP 3A4 activity by structurally diverse compounds using a genetic algorithm-combined partial least squares method.

PURPOSE: To develop a quantitative structure/activity relationship (QSAR) model for predicting drug-CYP 3A4 interactions. METHOD: The inhibitory effect of 53 structurally diverse drugs on the metabolism of 7-benzyloxy-4-trifluoromethyl coumarin (BFC) by recombinant CYP 3A4 was evaluated using a rapid microtiter plate assay. For each drug, a total of 220 two-dimensional topological indices were calculated using Molconn-Z software. Using a genetic algorithm-based partial least squares (GA-PLS) method, the desired descriptors were automatically selected to maximize the predictability of the IC50 values. RESULTS: The IC50 values of the drugs tested ranged from 9 nM to 2 mM. Based on the GA-PLS method, five principal components derived from 20 Molconn-Z descriptors were found to be effective for QSAR modeling. Interestingly, these descriptors suggested that the molecular size would be an important factor in determining drug-CYP 3A4 interactions. In the leave-one-out prediction, the rpred and the standard error of prediction (s) were 0.754 and 0.787, respectively. Even in an external validation, the predictions were in good agreement with experimental values (rpred = 0.744, s = 0.769, n = 9). CONCLUSIONS: The proposed model, in which two-dimensional topological descriptors were used as molecular descriptors, was able to predict drug-CYP 3A4 interactions with reasonable accuracy.

Algorithms↗
PubMed1998

Early Intervention Project: can its claims be substantiated and its effects replicated?

A comprehensive report to the National Institute of Health on the diagnosis, etiology, epidemiology, and treatment of autism indicated that early intervention has the potential of being an effective intervention (Bristol et al., 1996). In spite of this positive outlook, several research and methodological questions remain regarding time of treatment initiation, intensity of treatment and duration of treatment, random assignment, comparative treatment designs, and treatment integrity. Against this backdrop we consider the claims made by the Early Intervention Project (EIP; Lovaas, 1987, 1993; McEachin, Smith, & Lovaas, 1993). The EIP claims to produce recovery from autism in 47% of the cases and to greatly reduce its severity in an additional 42% of cases. This article evaluates the EIP against threats to internal and external validity and is found to suffer from a number of methodological problems. Based on rebuttals to criticisms of their program, the EIP authors seem unwilling to admit any methodological flaws in the sampling, design, and analysis of data of the EIP. It is recommended that parents and fair hearing officers adopt an attitude of healthy skepticism before proceeding to an unqualified endorsement of the EIP as a treatment for autism.

Adolescent↗
PubMedDate not supplied

Comparative binding energy analysis of haloalkane dehalogenase substrates: modelling of enzyme-substrate complexes by molecular docking and quantum mechanical calculations.

We evaluate the applicability of automated molecular docking techniques and quantum mechanical calculations to the construction of a set of structures of enzyme-substrate complexes for use in Comparative binding energy (COMBINE) analysis to obtain 3D structure-activity relationships. The data set studied consists of the complexes of eighteen substrates docked within the active site of haloalkane dehalogenase (DhlA) from Xanthobacter autotrophicus GJ10. The results of the COMBINE analysis are compared with previously reported data obtained for the same dataset from modelled complexes that were based on an experimentally determined structure of the DhlA-dichloroethane complex. The quality of fit and the internal predictive power of the two COMBINE models are comparable, but better external predictions are obtained with the new approach. Both models show a similar composition of the principal components. Small differences in the relative contributions that are assigned to important residues for explaining binding affinity differences can be directly linked to structural differences in the modelled enzyme-substrate complexes: (i) rotation of all substrates in the active site about their longitudinal axis, (ii) repositioning of the ring of epihalohydrines and the halogen substituents of 1,2-dihalopropanes, and (iii) altered conformation of the long-chain molecules (halobutanes and halohexanes). For external validation, both a novel substrate not included in the training series and two different mutant proteins were used. The results obtained can be useful in the future to guide the rational engineering of substrate specificity in DhlA and other related enzymes.

Binding Sites↗
PubMed2003

Development of a job-specific FCE protocol: the work demands of hospital nurses as an example.

Musculoskeletal disorders often result in employee disability leaves and sickness-related absenteeism in the workplace. Professional evaluations of an employee's capacity to work require additional support by means of Functional Capacity Evaluation (FCE) methods. However, most FCE methods assess general physical capacity and, because of fixed test procedures, testing times range between 4 and 6 h for up to several days. For return to work (vocational rehabilitation), the tests need to reflect the employees' specific work demands more precisely. This study aims to develop a job-specific FCE protocol on the Ergos Work Simulator for hospital nurses. In developing the contents of this specific protocol, hierarchical task analyses were performed with 20 nurses in four departments of a university medical center. A job-specific test protocol was developed that consisted of five steps. In this process, the original test protocol was analyzed first. Secondly, categorization of physical risk factors for work-related musculoskeletal disorders revealed 16 possible combinations of activity, posture, and load. Finally, duration and frequencies during one working day of these combinations were coupled to the Ergos test panels. The nurse-specific test protocol lasts 90 min. It was possible to develop a job-specific protocol, using on-site observations as the input. Compared to the original Ergos protocol, the external validity of the new job-specific protocol has improved: it simulates the functional capacity that nurses need to perform their job in a realistic way. The testing time of the original Ergos protocol is four times longer compared to the new job-specific protocol.

Computer Simulation↗
PubMed2004

Multivariate discrimination among cryptic species of the mite genus Chaetodactylus (Acari: Chaetodactylidae) associated with bees of the genus Lithurgus (Hymenoptera: Megachilidae) in North America.

Twenty-seven morphological characters from 111 heteromorphic deutonymphs of the mite genus Chaetodactylus Rondani (Acari: Chaetodactylidae) were analyzed. The mites were collected from four species of bees of the genus Lithurgus Berthold (Hymenoptera: Megachilidae) in continental North America. Principal component and canonical variates analyses on Darroch and Mosimann shape and size-and-shape variables revealed the presence of three cryptic species. Chaetodactylus gibbosi sp. n. (Florida) is geographically isolated from C. lithurgi sp. n. distributed in Texas, New Mexico, Arizona, Colorado, and Idaho. Sympatric C. lithurgi and C. abditus sp. n. (USA: Arizona, Mexico: Socorro Is.) are seasonally isolated in Arizona. Chaetodactylus gibbosi is associated with a single bee species, Lithurgus gibbosus Smith in Florida. The host range of C. lithurgi includes bees flying predominantly in the spring: L. apicalis Cresson, L. littoralis Cockerell, and western L. gibbosus. Chaetodactylus abditus sp. n. is associated with L. planifrons Friese and L. echinocacti Cockerell, flying predominantly in the fall in Arizona. No distinct groups separated by geographic locality or size were detected in any species. A six-variable model developed by the canonical variates analysis and estimated using jackknife resampling and external validation (n = 100) is capable of classifying the three species with 100% accuracy. Factors that influenced speciation of cryptic species of Chaetodactylus associated with Lithurgus are discussed. Based on morphological and geographical data and data on mite associates, the western and eastern populations of the bee L. gibbosus are distinct. Therefore, the taxonomic status of L. gibbosus s. lat. should be reevaluated.

Animals↗
PubMed2003

Computational models to predict blood-brain barrier permeation and CNS activity.

The blood-brain permeation of a structurally diverse set of 281 compounds was modeled using linear regression and a multivariate genetic partial least squares (G/PLS) approach. Key structural features affecting the logarithm of blood-brain partitioning (logBB) were captured through statistically significant quantitative structure-activity relationship (QSAR) models. These relationships reveal the importance of logP, polar surface area, and a variety of electrotopological indices for accurate predictions of logBB. The best models reveal an excellent correlation (r > 0.9) for a training set of 58 compounds. Likewise, the comparison of the average logBB values obtained from an ensemble of QSAR models with experimental values also verifies the statistical quality of the models (r > 0.9). The models provide good agreement (r approximately 0.7) between the predicted logBB values for 34 molecules in the external validation set and the experimental values. To further validate the models for use during the drug discovery process, a prediction set of 181 drugs with reported CNS penetration data was used. A >70% success rate is obtained by using any of the QSAR models in the qualitative prediction for CNS permeable (active) drugs. A lower success rate (approximately 60%) was obtained for the best model for CNS impermeable (inactive) drugs. Combining the predictions obtained from all the models (consensus) did not significantly improve the discrimination of CNS active and CNS inactive molecules. Finally, using the therapeutic classification as a guiding tool, the CNS penetration capability of over 2000 compounds in the Synthline database was estimated. The results were very similar to the smaller set of 181 compounds.

Blood-Brain Barrier↗
PubMed2004

New predictors for several ADME/Tox properties: aqueous solubility, human oral absorption, and Ames genotoxicity using topological descriptors.

In silico predictive models for aqueous solubility, human intestinal absorption (HIA), and Ames genotoxicity were developed principally using artificial neural net (ANN) analysis and topological descriptors. Approximately 10,000 compounds spread across three data sets were used in the construction of these quantitative-structure-activity/property-relationship (QSAR/QSPR) models. For aqueous solubility, 5,037 chemically diverse compounds were used to construct ANN-QSPRs for intrinsic aqueous solubility. When these robust models were applied to 938 compounds in external validation, they gave an r2 = 0.78 with 84% predicted within 1 log unit for these new chemical entities (NCEs). 417 therapeutic drugs were used in the development of an ANN-QSPR to predict for percent oral absorption (%OA). For validation testing on 195 new drugs, 92% of the compounds were predicted to within 25% of their reported %OA values, which ranged from 0% to 100%. Polar surface area and logP, the octanol-water partition coefficient, were found to be important descriptors in our QSPR model. Development of an ANN-QSAR as a genotoxicity predictor for S. typhimurium employed 2963 compounds including 290 therapeutic drugs. Validation results on 400 NCEs with the ANN-QSAR gave a concordance of 83% which rose to 91% when a confidence indicator was applied. With new drugs a concordance of 92% was reached, which increased to 97% when the reliably indicator was invoked.

Administration, Oral↗
PubMed2002

Periodontal microbiota and clinical periodontal status in a rural sample in southern Thailand.

We sought to determine (i) the association of subgingival bacterial profiles to clinical periodontal status in a population with limited access to dental care in Thailand, and (ii) the external validity of our earlier findings from a similar study in rural China. We examined 356 subjects, 30-39 yr old and 50-59 yr old, with respect to clinical periodontal status and subgingival plaque at maximally 14 sites per subject. Checkerboard hybridizations were used to analyse a total of 4343 samples. The prevalence of the 27 species investigated ranged between 87.2% and 100%. Discriminant analysis based on microbial profiles classified correctly 67.5% of all deep (> or = 5 mm) and 64.2% of all shallow sites, and 67.4% of all subjects with and 69.3% of all subjects without > or = 3 deep pockets. High colonization by 'red complex' bacteria was four times as likely (95% Confidence Limits (CL) 2.5-6.6) in subjects with > or = 10 sites with attachment loss of > or = 5 mm, and 4.3 times as likely (95% CL 2.6-7.1) in subjects with > or = 30 such sites. The data confirmed (i) the ubiquitous prevalence of the bacteria investigated in subjects with no regular access to dental care; and (ii) the high odds for periodontal pathology conferred by increased levels of specific periodontal bacteria.

Actinomyces↗
PubMed1996

The efficacy and effectiveness of psychotherapy relative to medications.

A recent survey by Consumer Reports (1994) found that people who received psychotherapy were generally pleased with their experience and that their satisfaction was unrelated to the type of treatment or the addition of medications. M.E.P. Seligman (1995) argued that these findings demonstrate the value of psychotherapy and suggested that such survey methodologies may be superior to randomized clinical trials in this regard because they study what occurs in actual clinical practice. Although such approaches provide important information, they are no substitute for controlled clinical trials when it comes to drawing causal inferences. However, the study does highlight the importance of defining outcome in the broadest possible fashion and of addressing the external validity of the findings obtained. Attention to such considerations has implications for the relative value of drugs and psychotherapy.

Combined Modality Therapy↗
PubMed2002

Building a practically useful theory of goal setting and task motivation. A 35-year odyssey.

The authors summarize 35 years of empirical research on goal-setting theory. They describe the core findings of the theory, the mechanisms by which goals operate, moderators of goal effects, the relation of goals and satisfaction, and the role of goals as mediators of incentives. The external validity and practical significance of goal-setting theory are explained, and new directions in goal-setting research are discussed. The relationships of goal setting to other theories are described as are the theory's limitations.

Goals↗
PubMed1998

Finding your marbles: does preschoolers' strategic behavior predict later understanding of mind?

The aim of this longitudinal study was to assess (a) stability of individual differences in preschoolers' executive function performance, (b) the external validity of 4 new simple executive function tasks, and (c) whether individual differences in early executive function performance could be used to predict later differences in theory of mind, or vice versa. Fifty children involved in an earlier study of relations between preschoolers' theory of mind, verbal ability, and executive function (C. Hughes, 1998) were followed up and tested 1 year later, using 1st- and 2nd-order false-belief tasks, a set of 4 simple executive function tasks, and a well-established executive test of planning: the Tower of London (T. Shallice, 1982). The results of the study support recent proposals (C. Hughes, 1996; J. Russell, 1996) that young children's understanding of mind is grounded in their growing competence in strategic planning and mental flexibility.

Age Factors↗