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PubMedDate not supplied

[Validation of the Italian version of the Self-report Insight Scale].

AIMS: To evaluate the psychometric properties of the Italian version of the Insight Scale (IS), self-report questionnaire assessing the awareness of psychiatric illness. The instrument contains two forms, the first A that enquires about the present status, and the second B that concerns past episodes of illness. METHOD: Factorial structure, internal consistency and concurrent validity (towards three selected items of the 24-item BPRS, Unusual thought content", Conceptual disorganization and Uncooperativeness) were studied on 80 chronic subjects affected by schizophrenia. Differences between acute and stabilised patients were investigated. Test-retest reliability was assessed in a sub-sample of 22 stable cases. RESULTS: The Italian IS showed satisfactory concurrent validity and reliability. Acute patients had lower scores than stabilised ones. Factorial analysis brought to the distinction between insight for need for care in the present and in the past, which seems both plausible and clinically-useful. CONCLUSION: The use of the IS Italian version may be encouraged as a valid insight self-report instrument. Sensitivity to change and predictive power concerning clinical and social outcome and adherence to treatment should be investigated.

Adult↗
PubMed1999

An overview of chemotherapeutic targets for antimalarial drug discovery.

The need for new antimalarials comes from the widespread resistance to those in current use. New antimalarial targets are required to allow the discovery of chemically diverse, effective drugs. The search for such new targets and new drug chemotypes will likely be helped by the advent of functional genomics and structure-based drug design. After validation of the putative targets as those capable of providing effective and safe drugs, targets can be used as the basis for screening compounds in order to identify new leads, which, in turn, will qualify for lead optimization work. The combined use of combinatorial chemistry--to generate large numbers of structurally diverse compounds--and of high throughput screening systems--to speed up the testing of compounds--hopefully will help to optimize the process. Potential chemotherapeutic targets in the malaria parasite can be broadly classified into three categories: those involved in processes occurring in the digestive vacuole, enzymes involved in macromolecular and metabolite synthesis, and those responsible for membrane processes and signalling. The processes occurring in the digestive vacuole include haemoglobin digestion, redox processes and free radical formation, and reactions accompanying haem release followed by its polymerization into haemozoin. Many enzymes in macromolecular and metabolite synthesis are promising potential targets, some of which have been established in other microorganisms, although not yet validated for Plasmodium, with very few exceptions (such as dihydrofolate reductase). Proteins responsible for membrane processes, including trafficking and drug transport and signalling, are potentially important also to identify compounds to be used in combination with antimalarial drugs to combat resistance.

Antimalarials↗
PubMed1985

The validity of type A behavior scales for employed women.

The purpose of this study was to test the validity of the Jenkins Activity Survey (JAS) and the Framingham Type A Scale (FTAS) for employed women using structured interview ratings (SI) as the validating criterion. The sample consisted of 149 white females ages 30-42 who were employed full time. Forty-five percent were classified as Type A. The JAS Type A Scale provided better agreement with the SI (57%) than the FTAS (49%). Eleven items from all four scales of the JAS in combination with four FTAS items were identified by discriminant analysis. Using the resulting equation, 76.5% of the women were classified correctly as Type A or not Type A. It was concluded that neither the standardized version of the JAS Type A Scale nor the FTAS has a satisfactory degree of concurrent validity for measuring this behavior pattern in employed women. Investigators are cautioned against using either instrument to measure Type A behavior in women without recognition of their limitations.

Adult↗
PubMed2001

Loss of serotonin oxidation as a component of the altered substrate specificity in the Y444F mutant of recombinant human liver MAO A.

To investigate the roles of tyrosyl residues located near the covalent 8alpha-S-cysteinyl FAD in monoamine oxidase A (MAO A) and to test the suggestion that MAO A and plant polyamine oxidase may have structural homology, tyrosyl to phenylalanyl mutants of MAO A at positions 377, 402, 407, 410, 419, and 444 were constructed and expressed in Saccharomyces cerevisiae. All mutant enzymes were expressed and exhibited lower specific activities as compared to WT MAO A using kynuramine as substrate. The lowest specific activities in this assay are exhibited by the Y407F and Y444F mutant enzymes. On purification and further characterization, these two mutants were found to each contain covalent FAD. Both mutant enzymes are irreversibly inhibited by the MAO A inhibitor clorgyline and exhibit binding stoichiometries of 0.54 (Y407F) and 0.95 (Y444F) as compared to 1.05 for WT MAO A. Y444F MAO A oxidizes kynuramine with a k(cat) <2% of WT enzyme and is greater than 100-fold slower in catalyzing the oxidation of phenylethylamine or of serotonin. In contrast, Y444F MAO A oxidizes p-CF(3)-benzylamine at a rate 25% that of WT enzyme. Steady state and reductive half-reaction stopped-flow data using a series of para-substituted benzylamine analogues show Y444F MAO A exhibits quantitative structure activity relationships (QSAR) properties on analogue binding and rates of substrate oxidation very similar to that exhibited by the WT enzyme (Miller and Edmondson (1999) Biochemistry 38, 13670): log K(d) = -(0.37 +/- ()()0.07)V(W)(x0.1) - 4.5 +/- 0.1; log k(red) = +(2.43 +/- 0.19)sigma + 0.17 +/- 0.05. The Y444F MAO A mutant also exhibits similar QSAR properties on the binding of phenylalkyl side chain amine analogues as WT enzyme: log K(i) = (4.37 +/- 0.51)E(S) + 1.21 +/- 0.77. These data show that mutation of Y444F in MAO A results in a mutant that has lost its ability to efficiently oxidize serotonin (its physiological substrate) but, however, exhibits unaltered quantitative structure-activity parameters in the binding and rate of benzylamine analogues. The mechanism of C-H abstraction is therefore unaltered. The suggestion that polyamine oxidase and monoamine oxidase may have structural homology appears to be valid as regards Y444 in MAO A and Y439 in plant polyamine oxidase.

Animals↗
PubMed2005

PostDOCK: a structural, empirical approach to scoring protein ligand complexes.

In this work we introduce a postprocessing filter (PostDOCK) that distinguishes true binding ligand-protein complexes from docking artifacts (that are created by DOCK 4.0.1). PostDOCK is a pattern recognition system that relies on (1) a database of complexes, (2) biochemical descriptors of those complexes, and (3) machine learning tools. We use the protein databank (PDB) as the structural database of complexes and create diverse training and validation sets from it based on the "families of structurally similar proteins" (FSSP) hierarchy. For the biochemical descriptors, we consider terms from the DOCK score, empirical scoring, and buried solvent accessible surface area. For the machine-learners, we use a random forest classifier and logistic regression. Our results were obtained on a test set of 44 structurally diverse protein targets. Our highest performing descriptor combinations obtained approximately 19-fold enrichment (39 of 44 binding complexes were correctly identified, while only allowing 2 of 44 decoy complexes), and our best overall accuracy was 92%.

Ligands↗
PubMedDate not supplied

Principles of good practice for decision analytic modeling in health-care evaluation: report of the ISPOR Task Force on Good Research Practices--Modeling Studies.

OBJECTIVES: Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies. Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice. This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies. METHODS: The task force was appointed with the advice and consent of the Board of Directors of ISPOR. Members were experienced developers or users of models, worked in academia and industry, and came from several countries in North America and Europe. The task force met on three occasions, conducted frequent correspondence and exchanges of drafts by electronic mail, and solicited comments on three drafts from a core group of external reviewers and more broadly from the membership of ISPOR. RESULTS: Criteria for assessing the quality of models fell into three areas: model structure, data used as inputs to models, and model validation. Several major themes cut across these areas. Models and their results should be represented as aids to decision making, not as statements of scientific fact; therefore, it is inappropriate to demand that models be validated prospectively before use. However, model assumptions regarding causal structure and parameter estimates should be continually assessed against data, and models should be revised accordingly. Structural assumptions and parameter estimates should be reported clearly and explicitly, and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses. CONCLUSIONS: Model-based evaluations are a valuable resource for health-care decision makers. It is the responsibility of model developers to conduct modeling studies according to the best practicable standards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built.

Benchmarking↗
PubMed2004

Properties of metabolic networks: structure versus function.

Biological data from high-throughput technologies describing the network components (genes, proteins, metabolites) and their associated interactions have driven the reconstruction and study of structural (topological) properties of large-scale biological networks. In this article, we address the relation of the functional and structural properties by using extensively experimentally validated genome-scale metabolic network models to compute observable functional states of a microorganism and compare the "structure versus function" attributes of metabolic networks. It is observed that, functionally speaking, the essentiality of reactions in a node is not correlated with node connectivity as structural analyses of other biological networks have suggested. These findings are illustrated with the analysis of the genome-scale biochemical networks of three species with distinct modes of metabolism. These results also suggest fundamental differences among different biological networks arising out of their representation and functional constraints.

Algorithms↗
PubMedDate not supplied

Korean version of the diagnostic interview for genetic studies: Validity and reliability.

The Diagnostic Interview for Genetic Studies (DIGS), developed in 1994 by the National Institute of Mental Health (NIMH), was translated into Korean and tested for reliability and diagnostic validity. Concurrent validity was tested using the Structured Clinical Interview for DSM-IV (SCID) and clinical diagnoses in 53 patients, most of whom had either schizophrenia or bipolar disorder. Inter-rater reliability was tested in 24 patients. Test-retest reliability was also tested in 17 patients. Overall and specific diagnostic validity for the Korean version of DIGS (DIGS-K) was excellent for most diagnoses. Inter-rater and test-retest reliability for overall and specific diagnoses also ranged from fair to excellent. For schizoaffective disorder, the test-retest reliability of DIGS-K was in a fair range, although the level was lower than that of other diagnoses. However, its diagnostic validity and inter-rater reliability was below fair range. In conclusion, DIGS-K appears to be a reliable interview for major psychiatric disorders.

Genetic Testing↗
PubMed2002

Comparative influence of forest management and habitat structural factors on the abundances of hollow-nesting bird species in subtropical Australian eucalypt forest.

We examined the impact of single-tree selective logging and fuel reduction burns on the abundance of hollow-nesting bird species at a regional scale in southeastem Queensland, Australia. Data were collected on species abundance and habitat structure of dry sclerophyll production forest at 36 sites with known logging and fire histories. Sixteen bird species were recorded with most being resident, territorial, obligate hollow nesters that used hollows that were either small (< 10 cm diameter) or very large (>18 cm diameter). Species densities were typically low, but combinations of two forest management and three habitat structural variables influenced the abundances of eight bird species in different and sometimes conflicting ways. The results suggest that habitat tree management for biodiversity in production forests cannot depend upon habitat structural characteristics alone. Management histories appear to have independent influence (on some bird species) that are distinguishable from their impacts on habitat structure per se. Rather than managing to maximize species abundances to maintain biodiversity, we may be better off managing to avoid extinctions of populations by identifying thresholds of acceptable fluctuations in populations of not only hollow-nesting birds but other forest dependent wildlife relative to scientifically valid forest management and habitat structural surrogates.

Animals↗
PubMed2000

Psychometric evaluation of the short form inventory of drinking situations (IDS-42) in a community-recruited sample of substance-abusing women.

PURPOSE: We investigated the psychometric properties (factor structure, internal consistency reliability, concurrent validity) of the Short Form Inventory of Drinking Situations (IDS-42) in women substance abusers. METHODS: A sample of 297 substance-abusing women was recruited from the community. The women completed the IDS-42 and the three-factor Drinking Motives Questionnaire (DMQ). RESULTS: Confirmatory factor analyses of IDS-42 items suggested a hierarchical structure for the scale. Eight factors (corresponding to Marlatt and Gordon's eight heavy drinking situations) provided the best model fit at the lower-order level, and three factors (i.e., Negatively Reinforcing vs. Positively Reinforcing vs. Temptation Situations) provided the best model fit at the higher-order level. Lower- and higher-order IDS-42 subscales were shown to possess adequate-to-high levels of internal consistency. The eight lower-order IDS-42 factors demonstrated excellent concurrent validity with conceptually similar DMQ subscale scores. Across the entire sample of female substance abusers, a higher frequency of heavy drinking was reported in Positively Reinforcing Situations and Unpleasant Emotions Situations, as compared to other heavy drinking situations. IMPLICATIONS: Results support the IDS-42's good psychometric properties and demonstrate its utility as a tool in identifying situation-specific antecedents to heavy drinking among women substance abusers.

Adult↗
PubMed2001

Validity and sensitivity to change of the extended Glasgow Outcome Scale in mild to moderate traumatic brain injury.

Using a structured outcome interview, this study addressed the validity and sensitivity to change of the Glasgow Outcome Scale (GOS) and the Extended GOS (GOSE) in a prospective study of patients who sustained mild (n = 30) to moderate (n = 13) traumatic brain injury (TBI) or general trauma (n = 44). The patients were recruited from the emergency center or inpatient units of Ben Taub General Hospital and invited to participate in follow-up examinations at 3 and 6 months. Using a series of functional outcome measures, assessment of affective status, and neuropsychological tests as criteria, the validity of the GOSE generally exceeded the GOS. Analysis of the outcome data for the patients who completed both the 3-month and 6-month assessments disclosed that the GOSE was more sensitive to change than the GOS. Comparison of the 3-month outcome data disclosed that the GOSE and GOS scores did not differ for the TBI and general trauma groups. These findings lend further support for utilization of the GOSE in clinical trials when it is based on a structured interview.

Adult↗
PubMed2006

Development and validation of the Edmonton Ankylosing Spondylitis Metrology Index.

OBJECTIVE: Assessment of spinal and hip mobility has been recommended by the Assessments in Ankylosing Spondylitis (AS) Working Group for clinical trials and record keeping, although suggested measures primarily reflect structural damage. Our objective was to validate a simple, 4-item composite measure of spinal and hip mobility, the Edmonton AS Metrology Index (EDASMI). METHODS: We assessed the EDASMI and the Bath AS Metrology Index (BASMI) using a total of 263 patients from 3 countries: Canada (n = 205), Australia (n = 29), and Colombia (n = 29). Intra- and interobserver reliability were assessed in a subset of 44 patients. Construct validity with respect to disease activity (Bath AS Disease Activity Index [BASDAI]), function (Bath AS Functional Index [BASFI]), and structural damage (modified Stoke AS Spinal Score [mSASSS]) was analyzed using correlation and hierarchical regression. Responsiveness was assessed in a subset of 33 patients who received either anti-tumor necrosis factor alpha therapy (n = 26) or pamidronate (n = 7) over 24 weeks. RESULTS: In contrast to the EDASMI, BASMI scores covered a limited range, with 70% of patients demonstrating a score < or =3 (range 0-10) and 4 of 5 individual measures demonstrating substantial floor effects. Both measures were highly reliable (intraclass correlation coefficient >0.90) and demonstrated similar construct validity (EDASMI correlated with disease duration [0.52], BASDAI [0.24], BASFI [0.61], Bath Ankylosing Spondylitis Radiology Index [0.79], mSASSS [0.75]; P < 0.001 for all). The change in EDASMI score was significant after 24 weeks of therapy (standardized response mean 0.40; P = 0.03), but change in the BASMI was not significant. CONCLUSION: The EDASMI is a simple, rapid, and reliable tool for the assessment of spinal mobility in AS that is responsive to therapeutic intervention.

Adult↗
PubMed1998

[Quality of the information collected during admission to a hospital geriatric service: importance of a structured medical record].

OBJECTIVES: The medical record (MR) is a key document for hospitalized patients. Several audits have however demonstrated that much important information is often missing in hospital MR. We conducted this survey with the aim of improving the quality of MR in a geriatric unit. PATIENTS AND METHODS: A structured MR was elaborated and implemented in order to guide and record the assessment of patients admitted in our geriatric ward. MR of 54 consecutive patients admitted after implementation of the structured MR were studied and compared to those of 108 consecutive patients admitted on the preceeding year (classical MR). Quality of data collected at admission was assessed using a 33-item guide, proposed by 3 experts in geriatric medicine unaware of the structured MR studies. For each item, a binary score (present/absent) and a precision score were used. A validation study was conducted using the same methods in another geriatric ward which has not participated to development of the structured charts MR studied. RESULTS: For most items studied, information was present in a significantly higher proportion in structured MR than in classical MR. Likewise, the precision score was significantly higher in structured MR. The validation survey found analogous results. CONCLUSION: Use of a structured MR significantly improves the quality of data collection at admission in geriatric units. This improvement appears to be related more to the use of the structured MR than the effect of developing a new tool.

Aged↗
PubMed1993

The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials.

OBJECTIVE: To develop a set of disease activity measures for use in rheumatoid arthritis (RA) clinical trials, as well as to recommend specific methods for assessing each outcome measure. This is not intended to be a restrictive list, but rather, a core set of measures that should be included in all trials. METHODS: We evaluated disease activity measures commonly used in RA trials, to determine which measures best met each of 5 types of validity: construct, face, content, criterion, and discriminant. The evaluation consisted of an initial structured review of the literature on the validity of measures, with an analysis of data obtained from clinical trials to fill in gaps in this literature. A committee of experts in clinical trials, health services research, and biostatistics reviewed the validity data. A nominal group process method was used to reach consensus on a core set of disease activity measures. This set was then reviewed and finalized at an international conference on outcome measures for RA clinical trials. The committee also selected specific ways to assess each outcome. RESULTS: The core set of disease activity measures consists of a tender joint count, swollen joint count, patient's assessment of pain, patient's and physician's global assessments of disease activity, patient's assessment of physical function, and laboratory evaluation of 1 acute-phase reactant. Together, these measures sample the broad range of improvement in RA (have content validity), and all are at least moderately sensitive to change (have discriminant validity). Many of them predict other important long-term outcomes in RA, including physical disability, radiographic damage, and death. Other disease activity measures frequently used in clinical trials were not chosen for any one of several reasons, including insensitivity to change or duplication of information provided by one of the core measures (e.g., tender joint score and tender joint count). The committee also proposes specific ways of measuring each outcome. CONCLUSION: We propose a core set of outcome measures for RA clinical trials. We hope this will decrease the number of outcomes assessed and standardize outcomes assessments. Further, we hope that these measures will be found useful in long-term studies.

Arthritis, Rheumatoid↗
PubMed2000

Cross-Validation Methods.

This paper gives a review of cross-validation methods. The original applications in multiple linear regression are considered first. It is shown how predictive accuracy depends on sample size and the number of predictor variables. Both two-sample and single-sample cross-validation indices are investigated. The application of cross-validation methods to the analysis of moment structures is then justified. An equivalence of a single-sample cross-validation index and the Akaike information criterion is pointed out. It is seen that the optimal number of parameters suggested by both single-sample and two-sample cross-validation indices will depend on sample size. Copyright 2000 Academic Press.

Journal Article↗
PubMed1998

Confirmatory factor analysis of the Task and Ego Orientation in Sport Questionnaire with cross-validation.

Although a number of factor analytic studies have been conducted on the factorial validity of the Task and Ego Orientation in Sport Questionnaire (TEOSQ), the results have been equivocal. To further substantiate its evidence of validity, this study cross-validated the measurement model using a rigorous structural equation modeling (SEM) approach. Data collected from a college student sample were first analyzed on a calibration sample (n = 439). Results confirmed the two-factor orthogonal structure representing the underlying task and ego orientations. The results were cross-validated on a validation sample (n = 439) using various SEM-based cross-validation procedures. Collectively, these findings support the construct validity of the TEOSQ as a measure of achievement goal orientation.

Achievement↗
PubMed2006

Structure of the 5' nontranslated region of the coxsackievirus b3 genome: Chemical modification and comparative sequence analysis.

Coxsackievirus B3 (CVB3) is a picornavirus which causes myocarditis and pancreatitis and may play a role in type I diabetes. The viral genome is a single 7,400-nucleotide polyadenylated RNA encoding 11 proteins in a single open reading frame. The 5' end of the viral genome contains a highly structured nontranslated region (5'NTR) which folds to form an internal ribosome entry site (IRES) as well as structures responsible for genome replication, both of which are critical for virulence. A structural model of the CVB3 5'NTR, generated primarily by comparative sequence analysis and energy minimization, shows seven domains (I to VII). While this model provides a preliminary basis for structural analysis, the model lacks comprehensive experimental validation. Here we provide experimental evidence from chemical modification analysis to determine the structure of the CVB3 5'NTR. Chemical probing results show that the theoretical model for the CVB3 5'NTR is largely, but not completely, supported experimentally. In combination with our chemical probing data, we have used the RNASTRUCTURE algorithm and sequence comparison of 105 enterovirus sequences to provide evidence for novel secondary and tertiary interactions. A comprehensive examination of secondary structure is discussed, along with new evidence for tertiary interactions. These include a loop E motif in domain III and a long-range pairing interaction that links domain II to domain V. The results of our work provide mechanistic insight into key functional elements in the cloverleaf and IRES, thereby establishing a base of structural information from which to interpret experiments with CVB3 and other picornaviruses.

5' Untranslated Regions↗
PubMed2026

Assessing Metal Ion Assignment Accuracy in Protein Data Bank Models via Elemental Spectroscopy.

Accurate representation of metal ions in macromolecular structures is critical for chemical interpretation, computational modeling, and machine-learning methods that rely on Protein Data Bank (PDB) entries. However, the elemental identity of metals modeled in crystallographic structures is often inferred indirectly and rarely validated experimentally. Here, we combine Particle Induced X-ray Emission (PIXE) and X-ray Fluorescence Spectroscopy (XRFS) to determine the elemental composition of protein samples used to generate 70 deposited metalloprotein crystal structures. By analyzing the original protein material employed for crystallization, but before the addition of crystallization buffer solutions, we assess whether the modeled metal ions in deposited structures are consistent with experimentally detectable elemental content. We find that in a majority of cases, the metals modeled in the corresponding PDB entries are inconsistent with the metals present in the protein samples before crystallization, or that additional metals are present but not represented in the structural models. Spectroscopic results were integrated with automated crystallographic validation metrics, including real-space Z-difference (RSZD) analysis and systematic rerefinement, to evaluate atomic-number mismatch at metal sites. PIXE and XRFS show strong agreement for dominant elemental signals and provide complementary, scalable approaches for identifying suspect metal assignments. This work does not address physiological or functional metalation but instead highlights a widespread data integrity issue in deposited macromolecular structures, PDB-wide. These results establish an experimentally corroborated link between elemental identity and crystallographic validation metrics, enabling the large-scale detection of chemically inconsistent annotations in structural databases used for computational modeling and machine learning.

Databases, Protein↗