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PubMed1998

Predictive validity of cocaine, sedative, and alcohol dependence diagnoses.

This study examined the predictive validity of Structured Clinical Interview for DSM-III-R (Spitzer, Williams, Gibbon, & First, 1990) based substance dependence diagnoses (i.e., cocaine, sedative, and alcohol) for 518 opioid-dependent outpatients entering methadone maintenance. Patients were followed over 1 year of treatment, which involved daily methadone substitution supplemented by individual and group counseling. Urine specimens were tested randomly 1-4 times per month. Patients diagnosed with current cocaine, sedative, or alcohol dependence were more likely to use these drugs than were patients with past only or no dependence syndrome. Current cocaine dependence predicted early treatment dropout. The results demonstrate the predictive and discriminant validity of several substance dependence diagnoses common among patients in substance abuse or other psychiatric treatment settings.

Adult↗
PubMed1997

The AIMS2-SF: a short form of the Arthritis Impact Measurement Scales 2. French Quality of Life in Rheumatology Group.

OBJECTIVE: To develop a short form of the Arthritis Impact Measurement Scales 2 (AIMS2) questionnaire, preserving content validity as the priority criterion. METHODS: A 2-step reduction procedure was used: 1) Delphi technique, with 1 panel of patients and 1 panel of experts each selecting 1 set of items independently; and 2) nominal group technique, where members of both panels reached consensus on the final selection of items, using information derived from item analysis. Psychometric properties of the AIMS2-Short Form (AIMS2-SF) and AIMS2 were compared using data from a cohort of 127 rheumatoid arthritis patients who completed the AIMS2 twice prior to the initiation of methotrexate (MTX) treatment and 3 months post-initiation of MTX treatment. RESULTS: The 2 panels reached consensus on a 26-item AIMS2-SF (54.4% reduction from the AIMS2). Factor analysis showed preservation of the 5-component structure. Convergent validity (Physical and Symptom components with clinical variables: r = 0.24-0.59), test-retest reproducibility (intraclass correlation coefficient >0.7), and sensitivity to change at 3 months (standardized response mean 0.36-0.8, except Social Interaction component [0.08]) were very close to the values for the original AIMS2. CONCLUSION: The AIMS2-SF is a shorter version of the AIMS2 (i.e., available in 2-page format) and has psychometric properties similar to those of the AIMS2.

Activities of Daily Living↗
PubMed1998

Iditis: protein structure database.

The validation, enrichment and organization of the data stored in PDB files is essential for those data to be used accurately and efficiently for modelling, experimental design and the determination of molecular interactions. The Iditis protein structure database has been designed to allow the widest possible range of queries to be performed across all available protein structures. The Iditis database is the most comprehensive protein structure resource currently available, and contains over 500 fields of information describing all publicly deposited protein structures. A custom-written database engine and graphical user interface provide a natural and simple environment for the construction of searches for complex sequence- and structure-based motifs. Extensions and specialized interfaces allow the data generated by the database to used in conjunction with a wide range of applications.

Database Management Systems↗
PubMed1985

Epidemiology: reflections on testing the validity of psychiatric interviews.

Laboratory tests that validate psychiatric disorder are unavailable. Accordingly, the validity of structured diagnostic interviews such as the Diagnostic Interview Schedule have been assessed through a double-blind test-retest design. This approach compares the Diagnostic Interview Schedule to a clinician's assessment and evaluates its results by three statistics: sensitivity and specificity, for which the clinician's interview serves as the standard, and K, which measures concordance between the two interviews. This design is found wanting on several counts: the reinterview may be answered differently because of clinical change or because of its meaning to the respondent; the clinician's interview may be an erratic standard; and the statistics are affected by both prevalence and severity of disorder. Furthermore, the statistics may not predict the accuracy of prevalence estimates made by the interview or its ability to detect correlates of disorder. Some alternative approaches are suggested.

Clinical Trials as Topic↗
PubMed1978

Wechsler Memory Scale: a selective review of the literature.

Research on the Wechsler Memory Scale (WMS) is reviewed with respect to questions of its reliability, factor structure, construct validity, and utility. The relationship of Memory Quotient to Full Scale IQ is explored and the conditions under which disparity between the two scores may be clinically useful indicated. Despite its numerous limitations, the WMS has been a sensitive test of short-term verbal memory. As such, it may be helpful in identifying impairment of the dominant (left) temporal lobe and its medial hippocampal connections. The test is badly in need of re-standardization, however, and suggestions for improving the instrument are made.

Adult↗
PubMed1996

The effect of concentration on the structure of alpha-crystallin.

Several models have been proposed for arrangement of the subunits in alpha-crystallin. These include the contrasting proposals that subunits are arranged in three layers and that subunits assemble into micelle-like structures. The validity of the micelle model was investigated by examining the effects of variations in protein concentration on the surface tension, conductivity, molecular weight and conformation of alpha-crystallin. The data were compared with those obtained for bovine serum albumin (BSA) and sodium dodecyl sulphate (SDS). Measurements of surface tension were conducted in the range, 10 micrograms ml-1 to 130 mg ml-1, in low and high ionic strength buffers. An apparent point of inflection, independent of ionic strength, was seen in alpha-crystallin's surface tension at around 1.9 mg ml-1 (95 microM). The surface tension did not plateau beyond this point, as is the case with surfactants, but continued to decrease up to 130 mg ml-1. BSA exhibited similar surface tension properties with an apparent inflection at 0.9 mg ml-1 (13 microM). The conductivity of alpha-crystallin and BSA solutions increased smoothly with no sign of any transition up to 96 mg ml-1 and 60 mg ml-1, respectively. In contrast, SDS showed a clear transition in this property at the concentration corresponding to its CMC. The aggregation state of the alpha-crystallin aggregates was examined by comparing molecular masses and Stokes radii. The size of the protein remained uniform over a wide concentration range and was unaffected by variations in ionic strength. Protein conformation, which was monitored by examining the microenvironment of tryptophan residues, was also found to be independent of protein concentration. It is concluded that over the concentration range that was investigated, alpha-crystallin does not exhibit any of the properties associated with classical micelles formed from small amphiphilic molecules.

Animals↗
PubMed1999

Influence of internal dynamics on accuracy of protein NMR structures: derivation of realistic model distance data from a long molecular dynamics trajectory.

In order to study the effect of internal dynamics on the accuracy of NMR structures in detail, we generated NOE distance data from a long molecular dynamics trajectory of BPTI. Cross-relaxation rates were calculated from the trajectory by analysis of the appropriate proton-proton vector autocorrelation functions. A criterion for the convergence of correlation functions was developed, and the analysis was restricted to those correlation functions that had converged within the simulation time. Effective distances were determined from the calculated cross-relaxation rates. Internal dynamics affected the derived distances in a realistic way, since they were subject both to radial averaging (which increases the cross-relaxation rate) and angular averaging (which decreases the cross-relaxation rate). The comparison of the effective distances with average distance between the protons during the trajectory showed that for most the effects of angular and distance averaging essentially cancel out. For these distances, the effective distance derived from an NOE is therefore a very good estimate of the average distance, or the distance in the average structure. However, for about 10% of the distances, the effective distance was more than 10% larger than the average distance, while for about 5%, it was more than 10% smaller, in some cases by more than 2 A. Little correlation is observed between the effects on cross-relaxation rates to different protons of the same residue. The results of this analysis have implications for the way structures are calculated from NOE distance data. For many distances, the assumption of a rigid structure is valid, and large error bounds would result in the loss of too much information content. On the other hand, the error bounds very often employed are not wide enough for some of the effects seen in our study.

Animals↗
PubMed1995

A local lymph-node assay validation study of a structure-activity relationship model for contact allergens.

A structure-activity relationship model for prediction of contact allergenic potential of chemicals had previously been developed. The model had been shown to be able to classify known allergens and nonallergens using data on physicochemical and reactivity parameters of functional groups by discriminant two-value multiple regression analysis. To investigate the model, six selected chemicals which had not been previously investigated for allergenicity were studied with both the model and a murine local lymph-node assay. The same compounds were predicted to be allergens (3-bromo-2-coumaranone, 1-nitrocyclohexene and alpha-acryloyloxy-beta, beta-dimethyl-beta-butyrolactone) and nonallergens (1-carbethoxy-4-piperidone, 6,7-dimethoxy-2-tetralone and 9-acetylanthracene) by both the model and the local lymph-node assay.

Allergens↗
PubMed1989

Effect of neuroleptics on positive and negative symptoms and the deficit state.

The concept of negative symptoms tries to operationalize a deficit syndrome observed in schizophrenia, but also in other disorders. The instruments for the measurement developed so far are unclear in their dimensional structure and validity. Further methodological development is needed. A new scale for measuring negative symptoms was derived from the AMDP-system and applied to results of drug trials with clozapine, fluperlapine, and haloperidol. The three drugs were equally effective on negative symptoms of acute and chronic schizophrenics.

Antipsychotic Agents↗
PubMed1999

[Quality of life. Construct validation and the development of a modular system].

The construct Quality of Life (QoL) is investigated by metaanalysis of eight (inter)nationally validated questionnaires in a multicenter study. Data have been collected in a mentally healthy (n = 479), a depressed (n = 171) and a schizophrenic (n = 139) sample. Conventional psychometric criteria and a facet analytical methodology have been applied. The resulting questionnaire "Modular System for Quality of Life" (MSQoL) consists of a core module with 47 items (one "G-factor" and six subdimensions), which is sufficiently valid for all three samples. Additionally, there are four specific modules (demography, family, partnership, profession). No specific modules can be identified for the psychopathological subgroups. The validated radex structure for subjective QoL offers the opportunity for a cumulative research design and for adaptations to the actual setting.

Adolescent↗
PubMed1992

Development of a computer application for headache diagnosis: the Headache Diagnostic System.

A computer-assisted decision support system for headache classification and diagnosis is presented. The system provides: structured headache data collection, automated data quality control and management, and automated headache classification. The system is based upon headache classification and diagnostic criteria recently developed by the International Headache Society. Development, logical structure and validation of the system are discussed. The system is shown to provide a general improvement in headache classification reliability and has utility for validation and improvement of present headache classification criteria.

Adult↗
PubMed1996

Heteroligation of a mouse monoclonal IgE antibody (La2) with small molecules, analysed by computer-aided automated docking.

A mouse monoclonal anti-TNP IgE antibody (IgE-La2) was screened by a competitive-binding ELISA with a random pool of over 2000 small molecules, mostly drugs, drug derivatives and metabolites. Thirteen of these (naproxene, beta-carboxy-chi-naphthol, oxolinic acid, hymecromone, 8-aminoquinoline, beta-naphthylamine, chi-nitrilo-cinnamic acid, 1,5-diaminonaphthaline, prolonium iodide, diaspirin, 3,4,5-trimethoxy-cinnamic acid, cycrimine, hemimellitic acid) were found to bind as strongly, or stronger, to the antibody as the immunizing hapten. We have used a Monte Carlo search technique for simulated docking of the DNP and non-DNP ligands to a model of the Fv region of IgE(La2). The validity of structural predictions made by the AutoDock program were tested on IgG(ANO2), the three-dimensional structure of which had been obtained previously by X-ray crystallography and 2D-NMR. The rms differences between the experimentally determined and auto-docked complexes in the energetically most favored binding modes were 0.31-0.44 A. Evaluation of structures of IgE(La2)-ligand complexes [including 2,4-dinitrophenol (DNP), 16 DNP amino acids, and the 13 non-DNP ligands listed above] obtained by computer-aided automated docking, suggested the existence of two subsites within an approximately 12 x 18 A2 groove extending between the H and L CDRs. Some of the ligands (DNP-Glu, 8-aminoquinoline, prolonium-I, beta-naphthylamine) were found to bind exclusively to subsite 1, others (DNP-Ala, chi-nitrilo-cinnamic acid, hemimellitic acid, beta-carboxy-chi-naphthol) to subsite 2. The majority of DNP amino acids and other ligands (oxolinic acid, 3,4,5-trimethoxy-cinnamic acid, diaspirin, [R]-cycrimine) were found to occupy an overlapping area including subsites 1 and 2, while some of the compounds (DNP-Asn, DNP-Pro, hymecromone, 1,5-naphthylenediamine) were predicted to interact with either of these subsites with comparable probabilities. When all of the docked La2-ligand complexes were taken into account, five tyrosine residues (H33, L32, L91, L92, L96) were found to provide the majority (53.4%) of all observed contact points. Thus, a multitude of interactions with aromatic residues, and a combinatorial type of interaction within the binding region, seem to be the major factors to explain the mechanism of heteroligation by IgE(La2).

Amino Acid Sequence↗
PubMed1987

Reconstruction of NOESY maps. A requirement for a reliable conformational analysis of biomolecules using 2D NMR.

The modelling of the conformation of a biomolecule in solution is based mainly on the internuclear distances deduced from measurements of nuclear Overhauser effects (nOe) in NOESY correlation maps. The distances are then used as restraints in the energy minimization procedure, which leads to one or several optimized conformations. A general and safe technique for validating these structures with respect to the experimental data is here proposed: from the internuclear distances, the relaxation matrix can be computed under the assumption of a unique rotational correlation time. By stepwise integration of these relaxation equations, the NOESY maps can be accurately reconstructed for any mixing time. Because multi-spin effects are correctly taken into account, any difference between the experimental and theoretical maps can be easily interpreted in terms of conformation, and possible inconsistencies due to conformational averaging can be pointed out. The technique is illustrated for a bacterial lipopeptide, mycosubtilin, the spectrum of which is completely assigned.

Biopolymers↗
PubMed1995

Towards eradication of measles virus: global progress and strategy evaluation.

Despite an increase in global measles vaccine coverage from under 20% in 1980 to around 80% in 1990, measles remains a major cause of morbidity and mortality world-wide. This paper addresses a number of issues relating to efforts to control measles, namely, (i) at the global level, how might we assess the impact of measles vaccination on the incidence of infection and associated disease, and, (ii), at the strategic level, how can we utilise an understanding of the transmission dynamics of childhood viral infections to aid the design of optimal immunisation programmes? Based on WHO vaccine coverage data, and organising countries according to similarities in demographic and epidemiological parameters, an age-structured model of measles transmission is used to capture the non-linear dynamics of infection and mass vaccination and to generate projections of the impact of measles immunization world-wide. The results provide a crude indication of the percentage reduction in measles cases by year 2000 (compared with no immunization) and suggest an approximately 70% reduction in cases over all ages, and 77% reduction in cases under 5 years (where there is the greatest risk of case fatality); these suggest that WHO targets for 1995 are unlikely to be achieved. In the second part of the paper, examples are given to illustrate the usefulness of a modelling approach in evaluating measles immunization policy. The introduction of MMR vaccine in the UK in 1988 has resulted in measles incidence falling to an all time low and attention has turned to the requirements of elimination. A realistic age structured model, validated using extensive serological data, is used to compare the merits of single or two dose strategies. Based upon recent estimates of vaccine efficacy (90%) and coverage (92% by end of second year of life) it is suggested that a two-dose policy with a pre-school second dose given irrespective of vaccine history is required to prevent the build up of susceptibles to epidemic proportions in the longer term. In a second example, prompted by the success of the campaign approach to polio and measles elimination in Central and South America, simple models are used to explore and quantify the process by which pulse vaccination programmes (i.e. repeated application across a wide age range) act to control transmission.

England↗
PubMed1998

Incorporation of [3H]valproic acid into lipids in GT1-7 neurons.

Valproic acid (2-propylpentanoic acid, valproate, VPA), an 8-carbon, branched chain fatty acid, is effectively used in the treatment of mania and epilepsy. The biochemical mechanisms by which this drug has its therapeutic effects are not yet established. The purpose of this study was to partially characterize the incorporation of [3H]VPA into phospholipids of GT1-7 neurons, an immortalized hypothalamic cell line. GT1-7 neurons were grown to confluence in culture dishes, and then were incubated with various concentrations of [3H]VPA between 10 and 400 microg/mL for various times up to 20 hr. Total lipids were extracted and phospholipids were separated from neutral lipids using TLC. Our results indicate that [3H]VPA (10 microg/mL) was incorporated into phospholipids of GT1-7 neurons in a time-dependent and saturable manner over 300 min. Subsequent separation of the lipid fraction by TLC indicated that 44.4% of the radioactivity taken up by the cells was incorporated into phospholipids and neutral lipids. One of the phospholipids migrated with a slightly lower Rf value than authentic phosphatidylcholine. Our results show that the incorporation of VPA into phospholipids and glycerides was linear with VPA concentrations from 10 to 400 microg/mL. Finally, we synthesized 1-acyl-2-valproyl-sn-glycero-3-phosphocholine and validated its structure with nuclear magnetic resonance and electrospray mass spectrometry to verify the structure of this compound, confirming that this compound is structurally possible. We conclude that VPA is incorporated into lipids in GT1-7 neurons and discuss the possible effects of valproyl phospholipids on neuronal functional properties.

Anticonvulsants↗
PubMed1999

Chlorothalonil: lack of genotoxic potential.

Based upon analyses using a number of validated structure-activity relationship models, it is concluded that the carcinogenicity in rodents of chlorothalonil is not due to a genotoxic mechanism.

Animals↗
PubMed1983

An assessment of the evidence for the role of ribonucleoprotein particles in the maturation of eukaryote mRNA.

This article has sought to draw together, on the one hand, what is known of mRNA processing and its control and, on the other hand, what is known of the structure and validity of hnRNP and snRNP particles. At the same time, it has attempted to synthesize these two themes into a critical assessment of the evidence which suggests that the particles are intimately involved in processing. It cannot be said that the case is proven. The evidence is compelling but circumstantial. The last few years have seen the development of the first in vitro splicing systems (Weingartner and Keller, 1981; Goldenberg and Raskus, 1981; Kole and Weissman, 1982), the isolation of monoclonal antibodies to defined snRNP (Lerner et al., 1981a; Billings et al., 1982) and hnRNP proteins (Hugle et al., 1982), and the ability to use artificial lipid vesicles to transfer antisera (Lenk et al., 1982) and radioactive snRNA (Gross and Cetron, 1982) into cells. It is to be hoped that further refinements of these and other techniques will allow us to solve this, one of the major outstanding problems of molecular biology.

Animals↗
PubMed2000

[Informed consent at a primary care area].

OBJECTIVE: Assessment of the understanding and performance of informed consent by primary care doctors and people attending clinics (PAC) in Madrid Area 3. DESIGN: Descriptive cross-sectional study. SETTING: The 20 health centres in Madrid Area 3. PARTICIPANTS: Doctors and PAC in Area 3. MEASUREMENTS AND MAIN RESULTS: It was a structured survey, validated by a pilot study. 98.7% of doctors stated that they informed their patients about illnesses; 91.8% on the risks and benefits. 90.6% and 78.6%, respectively, of the PAC said they were informed. Although 86.8% (CI 83.7-89.9) of the PAC thought they understood the information transmitted well, only 61% (CI 53.4-68.6) of the doctors thought so. 60.4% of the doctors and 54.6% of the PAC thought that the doctors' decisions took into account the patient's view. This was also the preferred option of both groups (46.5% and 59.3%). 29% of the doctors preferred greater power of decision for the patients, and only 16.06% of the PAC. 91.6% (CI 89.1-94.1) of the PAC were satisfied with the information received. CONCLUSIONS: Doctors think they give information better than PAC think. Patients' understanding of the information is given a higher rating by the PAC than by the doctors. Decisions are habitually taken by the doctor, with the patient's views borne in mind. However, doctors would prefer patients to have greater decision-making power.

Adult↗