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[Factorial structure of the BAKO 1-4. On the validation of the "Base competence for school years 1-4" test for determining phonological processing].

BACKGROUND: Phonological awareness in native German speaking school children in grades 1 through 4 can be tested using the BAKO 1-4. We raised the question whether BAKO 1-4 subtests probe different aspects of phonological processing. METHODS: Participants were 62 school children aged 7-12 years. Application of the BAKO 1-4 was performed during routine clinical testing. RESULTS: Statistical analysis indicated two factors with sufficient loading as latent variables. DISCUSSION: Our data indicate that two underlying variables constitute BAKO 1-4 test performance: the first involves "conscious phonological processing in a narrow sense", and the second involves decision making. Two subtests loading on factor 2 may be related to the decision making processes. This has to be kept in mind when applying the test to indecisive children.

Auditory Perceptual Disorders↗

Diagnostic reference frames for seizures: A validation study.

INTRODUCTION: We developed structured descriptions of signs and symptoms for specific seizure types (called Diagnostic Reference Frames-DRFs-by us) that can serve as a frame of reference in the process of classifying patients with epileptic seizures. In this study the validity of the DRFs for clinical use is evaluated and described. MATERIAL AND METHODS: In this study we use a decision support system based on the DRFs and using Bayes's rule for the validation of the DRFs. Patient's manifestations are entered in the decision support system and by successively applying Bayes's rule posterior probabilities are calculated. The DRFs with the highest posterior probability gives an indication of the classification of the seizure. The validation of the DRFs was performed by comparing the seizure type with the highest posterior probability with the classification of experienced epileptologists on a series of test cases with known epileptic seizures. In this way we assessed the accuracy of the DRFs in classifying patients with epileptic seizures. RESULTS: We included sixty-six patients in this efficacy study. The patients and/or their relatives described the manifestations occurring during a seizure. Sixty cases (91%) were correctly classified using the decision support system. DISCUSSION: The accuracy of 91 % indicates that the knowledge encoded in the DRFs for the included seizure types is valid. The next step is to test the DRFs in a clinical setting to evaluate the applicability in daily practice.

Adolescent↗

Validity of diagnosis using the French translation of the semi-structured interview for seizure classification.

PURPOSE: The purpose of this study was to assess the acceptability and validity of the French cross-cultural translation of a semistructured interview for seizure classification (SISC). We used the first revised version, the original of which was validated in 1990. METHODS: We administered the French SISC to a sample of 67 adults older than 15 years, comprising 17 controls and 50 patients with epilepsy (without provoked or isolated seizures). A cross-cultural translation was made from American English into French. Medical records were reviewed by epileptologists, who classified seizures, syndromes, and risk factors in accordance with the International League Against Epilepsy (ILAE) classifications. Agreement between interview- and physician-based diagnoses was assessed with a kappa coefficient (kappa) at each level of the recognized schemes for the classification of seizures (both broad and specific categories), syndromes, and risk factors. RESULTS: The sensitivity of the French SISC in diagnosing an epileptic seizure was 100%, with a specificity of 94%. Interview-based diagnoses agreed with those of physicians in 90% of patients for broad seizure categories [i.e., generalized or focal in origin (kappa = 0.74)]. When diagnoses agreed on focal origin, the agreement on seizure types-simple or complex-was 91% (kappa = 0.84). Among generalized seizures, the agreement was 73% (kappa = 0.60). Agreement on epilepsy syndromes was excellent for generalized epilepsy but moderate for focal epilepsy. Agreement on identified risk factors was 93%. CONCLUSIONS: The kappa coefficients demonstrated a good level of reliability. These results support the acceptability of this type of interview and the validity of the French version of the SISC.

Adolescent↗

Identification of the molecular defect in a family with spondyloepiphyseal dysplasia.

Spondyloepiphyseal dysplasias (SED) are a heterogeneous group of inherited disorders characterized by disproportionate short stature and pleiotropic involvement of the skeletal and ocular systems. Evidence has suggested that SED may result from structural defects in type II collagen. To confirm the validity of this hypothesis, the structure of the "candidate" type II collagen gene (COL2A1) has been directly examined in a relatively large SED family. Coarse scanning of the gene by Southern blot hybridization identified an abnormal restriction pattern in one of the affected members of the kindred. Analysis of selected genomic fragments, amplified by the polymerase chain reaction, precisely localized the molecular defect and demonstrated that all affected family members carried the same heterozygous single-exon deletion. As a consequence of the mutation, nearly 90 percent of the assembled type II collagen homotrimers are expected to contain one or more procollagen subunits harboring an interstitial deletion of 36 amino acids in the triple helical domain.

Amino Acid Sequence↗

A counterintuitive hypothesis about employment interview validity and some supporting evidence.

This study found mixed support for the hypothesis that the difference in criterion-related validity between unstructured and structured employment interviews is due solely to the greater reliability of structured interviews. Using data from prior meta-analyses, this hypothesis was tested in 4 data sets by using standard psychometric procedures to remove the effects of measurement error in interview scores from correlations with rated job performance and training performance. In the 1st data set. support was found for this hypothesis. However, in a 2nd data set structured interviews had higher true score correlations with performance ratings, and in 2 other data sets unstructured interviews had higher true score correlations. We also found that averaging across 3 to 4 independent unstructured interviews provides the same level of validity for predicting job performance as a structured interview administered by a single interviewer. Practical and theoretical implications are discussed.

Employee Performance Appraisal↗

Molecular modeling of the three-dimensional structure of dopamine 3 (D3) subtype receptor: discovery of novel and potent D3 ligands through a hybrid pharmacophore- and structure-based database searching approach.

The dopamine 3 (D3) subtype receptor has been implicated in several neurological conditions, and potent and selective D3 ligands may have therapeutic potential for the treatment of drug addiction, Parkinson's disease, and schizophrenia. In this paper, we report computational homology modeling of the D3 receptor based upon the high-resolution X-ray structure of rhodopsin, extensive structural refinement in the presence of explicit lipid bilayer and water environment, and validation of the refined D3 structural models using experimental data. We further describe the development, validation, and application of a hybrid computational screening approach for the discovery of several classes of novel and potent D3 ligands. This computational approach employs stepwise pharmacophore and structure-based searching of a large three-dimensional chemical database for the identification of potential D3 ligands. The obtained hits are then subjected to structural novelty screening, and the most promising compounds are tested in a D3 binding assay. Using this approach we identified four compounds with K(i) values better than 100 nM and eight compounds with K(i) values better than 1 microM out of 20 compounds selected for testing in the D3 receptor binding assay. Our results suggest that the D3 structural models obtained from this study may be useful for the discovery and design of novel and potent D3 ligands. Furthermore, the employed hybrid approach may be more effective for lead discovery from a large chemical database than either pharmacophore-based or structure-based database screening alone.

Algorithms↗

Comparison of the Objective Structured Clinical Examination with the performance of third-year medical students in surgery.

BACKGROUND: The purpose of this study was to investigate the validity of the Objective Structured Clinical Examination (OSCE) as an evaluation technique by comparing medical student performance on the OSCE with traditional forms of evaluation. SUBJECTS AND METHODS: We analyzed the performance of 129 third-year medical students in the 1997-1998 academic year on clinical evaluations, oral examinations, and NBME subject examinations, and on OSCE, which was not included in the final grade. RESULTS: The OSCE showed high correlation with the final grades received for the clerkship. Seventy-one percent of students receiving High Pass or Honors had high OSCE scores whereas 67% of students with low OSCE scores received poor or Defer grades. Pearson product-moment correlations demonstrated significant bivariate correlations with the other test parameters. CONCLUSIONS: This study demonstrates that the OSCE is similar to the traditional methods in evaluating general ability and is also able to evaluate clinical ability in a standardized manner.

Analysis of Variance↗

Refugee children from the Middle East.

OBJECTIVE: To map the frequency (prevalence) of torture victims among parents in asylum seeking Middle Eastern refugee families, to map the occurrence (prevalence) of experiences of war and other forms of organised violence among the children in these families, to map the occurrence (prevalence) of emotional symptoms and behavioural problems among the children, and to identify risk indicators and modifying factors for anxiety symptoms among the children. DESIGN: Interview with parents using a structured interview questionnaire developed for this study. Validated through a blinded semi-structured interview conducted with approximately 1/3 of the families. AUSPICES: The study has been carried out by the Rehabilitation and Research Centre for Torture Victims (RCT) in cooperation with the Danish Red Cross. MATERIAL: Structured interviews with parents regarding 311 children aged 3-15 from 149 families, all registered as asylum seekers from the Middle East between February 1, 1992 and April 30, 1993. The response was 90.4%. PRINCIPAL VARIABLES: Background (past-past)--social and demographic data; trauma complex (past)--war-related life circumstances (conditions) and experiences of war and other forms of organized violence such as loss, separation, direct exposure to violence and witnessing acts of violence (specific events and changes of life conditions); present life context (past-present)--family circumstances upon arrival in Denmark; effect (present)--the child's current psychological state. RESULTS: 28% of the parents (44% of the fathers and 13% of the mothers) had been tortured, to the effect that 51% of the children were part of a family including a survivor of torture. The most frequent specific types of violence-related events or circumstances were 'lived in a refugee camp outside the home country' (92%), 'lived under conditions of war' (89%) and 'been on the run with parents' (89%). Twenty percent of the children had lost one parent, and another 60% had been separated from one parent for more than a month. The highest prevalence of emotional symptoms were found within the anxiety dimension, as 67% of the children were assessed as being clinically anxious. The most important risk indicators for anxiety were 'lived in a refugee camp outside the home country', 'part of a torture surviving family', 'lack of opportunities for play with other children', 'beaten/kicked by an official', and 'loss of father'. Current parental behaviour was also an important risk indicator for anxiety, if the mother or father hit or punished the child more than was the case prior to arrival in Denmark. The most important anxiety-modifying factor was arrival in Denmark in the company of both parents. CONCLUSIONS: Asylum seeking refugee children from the Middle East have had many experiences of war and other forms of organised violence. The children frequently reacted with anxiety and with other symptoms of emotional instability. Prevalent anxiety symptoms correlated both with previous living conditions and present family situation. Living under prolonged conditions influenced by war and other forms of organised violence (prevalence) were found to a higher degree to be risk indicators for anxiety than were specific events or changes of life conditions (incidence).

Adolescent↗

The development of an age structured model for schistosomiasis transmission dynamics and control and its validation for Schistosoma mansoni.

Mathematical models are potentially useful tools to aid in the design of control programmes for parasitic diseases. In this paper, a fully age structured epidemiological model of human schistosomiasis is developed and parameterized, and used to predict trends in infection prevalence, intensity and prevalence of heavy infections over age and time during several rounds of mass and age targeted treatment. The model is validated against data from a Schistosoma mansoni control programme in Kenya.

Adolescent↗

Homologous modeling of the lysosomal protective protein/carboxypeptidase L: structural and functional implications of mutations identified in galactosialidosis patients.

The deficiency of the lysosomal protective protein/carboxypeptidase L (CARB L) causes the lysosomal storage disorder, galactosialidosis, characterized by neuraminidase and beta-galactosidase deficiencies in patients' cells. The three enzymes form a complex inside the lysosome, and the neuraminidase and beta-galactosidase deficiencies are secondary to CARB L deficiency. Sequence similarity and common enzymological properties suggest that the protomeric tertiary structure of CARB L is conserved within a family of serine carboxypeptidases which includes the yeast carboxypeptidase Y, killer expression I gene product and several plant carboxypeptidases. We used this homology to build a model of the CARB L structure based on the recently published X-ray atomic coordinates of the wheat carboxypeptidase II (CPDW-II) which shares 32% primary structure identity with CARB L. Small insertions and deletions were accommodated into the model structure by energy minimization using the DREIDING II force field. The C alpha atomic coordinates of the final CARB L model have a RMS shift of 1.01 A compared to the corresponding conserved residues in the CPDW-II template structure. The correct orientation of the homologous catalytic triad residues Ser150, His429 and Asp392, the potential energy calculations and the distribution of hydrophobic and hydrophillic residues in the structure all support the validity of the CARB L model. Most missense mutations identified in galactosialidosis patients were located in secondary structural elements except for the Tyr211-->Asn mutation which is in a loop. The other mutant residues have their side chains deeply buried in the central beta-sheet of the model structure except for the Phe412-->Val mutation which is located in the dimer interface. The predicted effects of specific mutations on CARB L structural stability correlates well with recently published transient expression studies of mutant CARB L (Shimmoto, M. et al., J. Clin. Invest., 91:2393-2399, 1993).

Amino Acid Sequence↗

Using two factor structures of the Mental Adjustment to Cancer (MAC) scale for assessing adaptation to breast cancer.

The validity and reliability of two factor structures of the Mental Adjustment to Cancer (MAC) scale for assessing coping style was assessed by examining the relationship between the subscales, psychological distress, and quality of life (QOL) among Stage II and Stage IV breast cancer patients in four phases. First, MANOVAs assessed differences in coping, distress, and QOL across disease stages. Second, for each MAC factor structure, canonical correlation analyses assessed the relationship between coping styles, distress, and QOL, for each disease-stage group separately. Third, structural equation modeling (SEM) assessed the relationship among coping styles, distress, and QOL for all participants. Finally, the internal consistency of both MAC factor structures was assessed using Chronbach's alpha. The results were as follows: (1) significant differences across disease stages were found for coping styles using either the Watson or the Schwartz MAC subscales, but there were no differences in levels of distress or QOL; (2) for both MAC factor structures, coping style was found to be highly related to emotional distress and QOL, however, the strengths of the correlations between individual coping styles and distress/QOL indicators varied across disease stages; (3) SEM indicated that coping style was significantly related to distress and QOL when stage of disease was not considered, and that coping style and indicators of distress/QOL are separate, but highly correlated factors, as opposed to a single latent construct; and, (4) the Watson MAC subscales showed slightly better internal consistency than the Schwartz MAC subscales. Taken together, these findings highlight: (i) the validity of both MAC factor structures for clinical and research use with American breast cancer patients; (ii) the role of coping style as a mediator between disease stage and psychological distress and QOL; and, (iii) the need for refinement of certain Watson and Schwartz subscales.

Adaptation, Psychological↗

Consensus based validation of membrane porins.

Porins are outermembrane beta-barrel proteins. They have varied biological functionality ranging from phage receptors, immunogenicity, pathogenicity to apoptosis. However, only a small number has been structurally and functionally characterised. A validation mechanism and a database of porins would be useful for target selection in proteomics and structural genomics work. Here we report a validation mechanism developed for membrane porins. A database server for porins, PRNDS, has been created containing experimentally proven porins and likely putative porins. Each porin is validated and ranked using a weighted scoring system developed based on six, structure and sequence based criteria. The server also predicts possible porins.

Amino Acid Sequence↗

A structured diagnostic interview for identification of primary alcoholism: a preliminary evaluation.

Forty alcoholic inpatient men were used to evaluate the test-retest reliability and the validity of a new structured diagnostic interview. The Alcohol Research Center (ARC) Intake Interview was constructed from the Schedule of Affective Disorders and Schizophrenia (SADS) parts I and II and from the Diagnostic Interview Schedule family history section by extracting information on diagnoses most likely to be seen in alcoholic patients and by expanding the data set with questions relevant to alcohol and drug use. The test-retest reliability for patients' primary and secondary diagnoses included a kappa of 1.00 for the comparison of interviewers A and B (100% agreement) and of .76 for interviewers A and C. The validity of ARC Intake Interview patient diagnoses as compared to the SADS demonstrated an overall agreement between 91 and 100%. Reliabilities for labeling of families as positive or negative for specific illness in any first-degree relatives revealed a kappa of 1.00; validities on family diagnoses ranged from 77 to 100%, with the ARC Intake Interview identifying more illness in families than the SADS. Although further evaluation of the ARC Intake Interview is needed, this instrument is recommended to investigators attempting to evaluate the clinical course and treatment needs among alcoholics, especially those patients presenting with multiple diagnoses.

Adult↗

The family profile: a new self-report instrument for family assessment.

The Family Profile is a new self-report family assessment instrument that is grounded in family theory and designed following a construct validation approach to instrument design that integrated theoretical concepts with test construction and empirical analysis. Development consisted of three component phases: rational theoretical design, empirical structural analysis, and psychometric validation. The first theoretical design phase resulted in a 231-item instrument with 13 construct scales. Structural analysis data were collected from a pilot sample of 160 patients selected from 6 family practice clinics in urban, suburban, and rural locations. After revision based on item and scale analysis, a 129-item instrument was administered to a random sample of 876 patients from family practices throughout Minnesota. Responses were analyzed for item- and scale-distribution characteristics, item-scale and scale-scale correlations, correlation with social desirability, factor analysis to confirm or disconfirm the existence of the theoretical dimensions, internal consistency reliability, and test-retest reliability. This analysis reduced the instrument to 90 items from all 13 postulated constructs that cluster into 6 main factors--Family Concordance, Family Discordance, Marital Strength, Active Involvement, Religiosity, and Parental Leadership. The Family Profile is also temporally stable and free from social desirability bias. Validation (construct and criterion) and normative data studies of various populations are in progress.

Family↗

Automatic differentiation of anatomical patterns in the human brain: validation with studies of degenerative dementias.

We compared voxel-based morphometry (VBM) with independent accurate region-of-interest (ROI) measurements of temporal lobe structures in order to validate the usefulness of this fully automated and unbiased technique in Alzheimer's disease (AD) and semantic dementia (SD). In AD, ROI analyses appear more sensitive to volume loss in the amygdalae, whereas VBM analyses appear more sensitive to right middle temporal gyrus and regional hippocampal volume loss. In SD, ROI analyses appear more sensitive to left middle and inferior temporal gyrus volume loss, whereas VBM appears more sensitive to regional hippocampal volume loss. In addition the significance of volume reductions was generally less in VBM owing to more stringent corrections for multiple comparisons. In conclusion, the automated technique detects a general trend of atrophy similar to that of expertly labeled ROI measurements in AD and SD, although there are discrepancies in the ranking of severity and in the significance of volume reductions that are more marked in AD.

Alzheimer Disease↗

Linear regression models for solvent accessibility prediction in proteins.

The relative solvent accessibility (RSA) of an amino acid residue in a protein structure is a real number that represents the solvent exposed surface area of this residue in relative terms. The problem of predicting the RSA from the primary amino acid sequence can therefore be cast as a regression problem. Nevertheless, RSA prediction has so far typically been cast as a classification problem. Consequently, various machine learning techniques have been used within the classification framework to predict whether a given amino acid exceeds some (arbitrary) RSA threshold and would thus be predicted to be "exposed," as opposed to "buried." We have recently developed novel methods for RSA prediction using nonlinear regression techniques which provide accurate estimates of the real-valued RSA and outperform classification-based approaches with respect to commonly used two-class projections. However, while their performance seems to provide a significant improvement over previously published approaches, these Neural Network (NN) based methods are computationally expensive to train and involve several thousand parameters. In this work, we develop alternative regression models for RSA prediction which are computationally much less expensive, involve orders-of-magnitude fewer parameters, and are still competitive in terms of prediction quality. In particular, we investigate several regression models for RSA prediction using linear L1-support vector regression (SVR) approaches as well as standard linear least squares (LS) regression. Using rigorously derived validation sets of protein structures and extensive cross-validation analysis, we compare the performance of the SVR with that of LS regression and NN-based methods. In particular, we show that the flexibility of the SVR (as encoded by metaparameters such as the error insensitivity and the error penalization terms) can be very beneficial to optimize the prediction accuracy for buried residues. We conclude that the simple and computationally much more efficient linear SVR performs comparably to nonlinear models and thus can be used in order to facilitate further attempts to design more accurate RSA prediction methods, with applications to fold recognition and de novo protein structure prediction methods.

Amino Acids↗

Modeling of the structural features of integral-membrane proteins reverse-environment prediction of integral membrane protein structure (REPIMPS).

The Profiles-3D application, an inverse-folding methodology appropriate for water-soluble proteins, has been modified to allow the determination of structural properties of integral-membrane proteins (IMPs) and for testing the validity of solved and model structures of IMPs. The modification, known as reverse-environment prediction of integral membrane protein structure (REPIMPS), takes into account the fact that exposed areas of side chains for many residues in IMPs are in contact with lipid and not the aqueous phase. This (1) allows lipid-exposed residues to be classified into the correct physicochemical environment class, (2) significantly improves compatibility scores for IMPs whose structures have been solved, and (3) reduces the possibility of rejecting a three-dimensional structure for an IMP because the presence of lipid was not included. Validation tests of REPIMPS showed that it (1) can locate the transmembrane domain of IMPs with single transmembrane helices more frequently than a range of other methodologies, (2) can rotationally orient transmembrane helices with respect to the lipid environment and surrounding helices in IMPs with multiple transmembrane helices, and (3) has the potential to accurately locate transmembrane domains in IMPs with multiple transmembrane helices. We conclude that correcting for the presence of the lipid environment surrounding the transmembrane segments of IMPs is an essential step for reasonable modeling and verification of the three-dimensional structures of these proteins.

Bacteriorhodopsins↗

The 12-item General Health Questionnaire (GHQ-12): translation and validation study of the Iranian version.

BACKGROUND: The objective of this study was to translate and to test the reliability and validity of the 12-item General Health Questionnaire (GHQ-12) in Iran. METHODS: Using a standard 'forward-backward' translation procedure, the English language version of the questionnaire was translated into Persian (Iranian language). Then a sample of young people aged 18 to 25 years old completed the questionnaire. In addition, a short questionnaire containing demographic questions and a single measure of global quality of life was administered. To test reliability the internal consistency was assessed by Cronbach's alpha coefficient. Validity was performed using convergent validity. Finally, the factor structure of the questionnaire was extracted by performing principal component analysis using oblique factor solution. RESULTS: In all 748 young people entered into the study. The mean age of respondents was 21.1 (SD = 2.1) years. Employing the recommended method of scoring (ranging from 0 to 12), the mean GHQ score was 3.7 (SD = 3.5). Reliability analysis showed satisfactory result (Cronbach's alpha coefficient = 0.87). Convergent validity indicated a significant negative correlation between the GHQ-12 and global quality of life scores as expected (r = -0.56, P < 0.0001). The principal component analysis with oblique rotation solution showed that the GHQ-12 was a measure of psychological morbidity with two-factor structure that jointly accounted for 51% of the variance. CONCLUSION: The study findings showed that the Iranian version of the GHQ-12 has a good structural characteristic and is a reliable and valid instrument that can be used for measuring psychological well being in Iran.

Adolescent↗