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PubMed1996

Life support courses: are they effective?

STUDY OBJECTIVE: To determine the effectiveness of life support courses for health care providers on the basis of one of three outcomes: (1) patient mortality and morbidity, (2) retention of knowledge or skills, and (3) change in practice behavior. METHODS: English-language articles from 1975 to 1992 were identified through MEDLINE and ERIC searches, bibliographies of articles, and current abstracts. Studies were considered relevant if they included a study population of life support providers, an intervention of any of the identified life support courses, and assessment of at least one of the three listed outcomes. Relevant studies were selected and validity scores were assigned to them by agreement of two independent reviewers, using a structured form to assess validity. Data on setting, methods, participants, intervention, and outcomes were then abstracted and verified. RESULTS: Seventeen of 67 identified studies pertaining to life support courses met the inclusion criteria. (1) All three mortality and morbidity studies indicated a positive impact, with an overall odds ratio of.28 (95% confidence interval [Cl], .22 to .37). (2) No net increase in scores was found in 5 of 8 studies of retention of knowledge and in 8 of 9 studies of skills retention. Two of three studies reporting refresher activities yielded positive effects on knowledge retention. Outcomes were not significantly different between groups taught with modular or didactic techniques. (3) Studies assessing behavioral outcome were methodologically weak. CONCLUSION: Among providers, retention of knowledge and skills acquired by participation in support courses is poor. However, refresher activities increase knowledge retention. Modular courses are as good as lectures for learning course material. There is evidence that use of the Advanced Trauma Life Support course has decreased mortality and morbidity. Further studies of patient outcome and provider behaviors are warranted.

Clinical Competence↗
PubMed1999

Sensitivity analysis of pharmacokinetic and pharmacodynamic systems: I. A structural approach to sensitivity analysis of physiologically based pharmacokinetic models.

Based on a frequency response approach to the sensitivity analysis of pharmacokinetic models, the concept of structural sensitivity is introduced. The core of this concept is the factorization of the system sensitivity into two multipliers. The first one, called structural sensitivity index, has an analytical form, which depends solely on the structure and connectivity of the system and does not depend on the drug administered or the factor perturbed. The second multiplier, the parameter sensitivity index, depends on the drug properties, the tissue of interest and the parameter perturbed, but is largely independent of the structure of the system. The structural and parametric sensitivity indices can be evaluated and analyzed separately. The most important feature of the proposed approach is that the conclusions drawn from the analysis of the structural sensitivity index are valid across all mammalian species, as the latter share a common anatomical and physiological structure. The concept of structural sensitivity is illustrated on the commonly used structure of the whole body physiologically based pharmacokinetic models by showing that the factorization of the sensitivity carried out arises naturally from the mechanism of the distribution of perturbations throughout the organism. The concept of structural sensitivity has interesting practical implications. It enables the formal proof of relationships and facts that have been observed previously. Moreover, the conclusions drawn introduce in fact a ranking of the tissues or subsystems with respect to their impact on the model outputs. From this ranking, direct recommendations regarding the design of experiments for whole-body physiologically based pharmacokinetic models are derived.

Animals↗
PubMed2003

Is the isolated ligand binding domain a good model of the domain in the native receptor?

Numerous studies have used the atomic level structure of the isolated ligand binding domain of the glutamate receptor to elucidate the agonist-induced activation and desensitization processes in this group of proteins. However, no study has demonstrated the structural equivalence of the isolated ligand binding fragments and the protein in the native receptor. In this report, using visible absorption spectroscopy we show that the electronic environment of the antagonist 6-cyano-7-nitro-2,3-dihydroxyquinoxaline is identical for the isolated protein and the native glutamate receptors expressed in cells. Our results hence establish that the local structure of the ligand binding site is the same in the two proteins and validate the detailed structure-function relationships that have been developed based on a comparison of the structure of the isolated ligand binding domain and electrophysiological consequences in the native receptor.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1985

Long range RNA-RNA interactions in the 30 S ribosomal subunit of E. coli.

We have attempted to identify long-range interactions in the tertiary structure of RNA in the E. coli 30 S ribosome. Native subunits were cleaved with ribonuclease and separated into nucleoprotein fragments which were deproteinized and fractionated into multi-oligonucleotide complexes under conditions intended to preserve RNA-RNA interactions. The final products were denatured by urea and heat and their constituent oligonucleotides resolved and sequenced. Many complexes contained complementary sequences known to be bound together in the RNA secondary structure, attesting to the validity of the technique. Other co-migrating oligonucleotides, not joined in the secondary structure, contained mutually complementary sequences in locations that allow base-pairing interaction without disrupting pre-existing secondary structure. In seven instances the complementary relationship was found to have been preserved during phylogenetic diversification.

Base Sequence↗
PubMed1995

Bicarbonate kinetics in humans: identification and validation of a three-compartment model.

A model of bicarbonate kinetics is crucial to a correct interpretation of experiments for measuring oxidation in vivo of carbon-labeled compounds. The aim of this study is to develop a compartmental model of bicarbonate kinetics in humans from tracer data by devoting particular attention to model identification and validation. The data base consisted of impulse-dose studies of 14C-labeled bicarbonate in nine normal subjects. The decay curve of specific activity of CO2 in expired air (saRCO2) was frequently sampled for 4-7 h. In addition, endogenous production of CO2, VCO2, was measured by indirect calorimetry. A model of data, i.e., an exponential model, analysis of decay curves of saRCO2 showed first that three compartments are necessary and sufficient to describe bicarbonate tracer kinetics. Compartmental models were then used as models of system. To correctly describe the input-output configuration, labeled CO2 flux in the expired air, phi RCO2 (= saRCO2.VCO2), has been used as measurement variable in tracer model identification. A mammillary three-compartment model with a respiratory and a nonrespiratory loss has been studied. Whereas there is good evidence that respiratory loss takes place in the central compartment, whether nonrespiratory loss is taking place in the central compartment or in one of the two peripheral compartments is uncertain. Thus three competing tracer models were considered. Using a model-independent analysis of data, based on the body activity variable, to calculate mean residence time in the system, we have been able to validate a specific model structure, i.e., with the two irreversible losses taking place in the central compartment. This validated tracer model was then used to quantitate bicarbonate masses in the system. Because there is uncertainty about where endogenous production enters the system, lower and upper bounds of masses of bicarbonate in the body are derived.

Bicarbonates↗
PubMed1993

Expression of human salivary histatin and cystatin/histatin chimeric cDNAs in Escherichia coli.

We have previously constructed recombinants encoding the full-length and truncated forms of cystatin-SN and expressed these in the Escherichia coli expression system pGEX-2T, which expresses foreign sequences as fusion proteins with glutathione S-transferase (GST). Recombinant cystatins were produced and purified in large quantities. The full-length recombinant cystatin-SN exhibited comparable biological activity and secondary structure to natural cystatin, validating the use of the full-length and mutant recombinant proteins for structure-function studies of salivary molecules. In this study, we have expressed histatin-1 cDNA in the pGEX-3X vector and cystatin-SN/histatin-1 or cystatin-SN/histatin-3 chimeric cDNAs in the pGEX-2T vector. Gene splicing by overlap extension (SOE), a PCR-based method, was used for generating the chimeric cDNAs. Each construct was analyzed by DNA sequencing, which showed the correct junctions and reading frames between the GST/histatin-1 and the GST/cystatin/histatin cDNAs. Expression of histatin and cystatin/histatin chimeras was induced by IPTG and the production of the fusion proteins monitored by SDS-PAGE/Coomassie blue staining and in the case of the GST/cystatin/histatin fusion proteins, also by Western blot using anti-cystatin antibody. The results of these studies showed that we have successfully constructed recombinants encoding the individual and chimeric salivary molecules and efficiently expressed these in E. coli expression system pGEX. Purification and characterization of recombinant histatin and cystatin-histatin hybrid proteins are presently ongoing.

Amino Acid Sequence↗
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↗
PubMed1991

EEG laterality in the era of structural brain imaging.

Bilateral EEG recording is a common practice when brain laterality needs to be assessed in cognitive neurophysiology and psychiatry research. Its precision and validity remain uncertain. With structural brain imaging methods, it is possible to examine EEG electrode placements according to the 10-20 system and the validity of inferences made on derived data. Frequent sources of placement errors are examined along with important factors that contribute to EEG imbalance. Examples are mentioned where asymmetries of EEG/ERP caused by cranial and parenchymal brain asymmetries may be mistaken for cognition-related laterality changes. Because external skull landmarks are not reliable predictors of cranial and parenchymal brain asymmetries, laterality assessment cannot be guaranteed by the 10-20 system. Consequently, a return, on a case-to-case basis, to nonstandard montages, assisted by structural brain imaging is seen as an acceptable alternative.

Brain↗
PubMed1996

The use of objective structured clinical examination (OSCE) for evaluation and instruction in graduate medical education.

This study had two purposes: determining the reliability and validity of the Objective Structured Clinical Examination (OSCE) in assessing performance by trainees at all levels, including medical students and chief residents; and estimating the impact of providing OSCE participants with immediate feedback about their performance. A comprehensive 210-min OSCE was administered to 53 surgical residents and 6 junior medical students. Faculty experts proctored all patient stations and provided immediate feedback to participants after the patient interaction segments (Part A). The participants then answered questions about the patients seen (Part B). The reliability of the OSCE was high (.91), identical to that of a previous resident OSCE with no feedback. The standard error of measurement for both parts was approximately 4%. At the 95% confidence interval, each participant's actual level of clinical performance (Part A) and clinical knowledge (Part B) could be estimated with an error of +/-8%. Participants showed significant differences in clinical performance (Part A, P < 0.01) and knowledge (Part B, P < 0.01) by level of training. Most participants (74%) rated the OSCE as an above average or outstanding educational method. The OSCE is a valid and reliable test of residents' clinical skills. Feedback to participants during the OSCE was positively received and did not perturb test reliability.

Clinical Competence↗
PubMedDate not supplied

Numerical simulation and experimental validation of blood flow in arteries with structured-tree outflow conditions.

Blood flow in the large systemic arteries is modeled using one-dimensional equations derived from the axisymmetric Navier-Stokes equations for flow in compliant and tapering vessels. The arterial tree is truncated after the first few generations of large arteries with the remaining small arteries and arterioles providing outflow boundary conditions for the large arteries. By modeling the small arteries and arterioles as a structured tree, a semi-analytical approach based on a linearized version of the governing equations can be used to derive an expression for the root impedance of the structured tree in the frequency domain. In the time domain, this provides the proper outflow boundary condition. The structured tree is a binary asymmetric tree in which the radii of the daughter vessels are scaled linearly with the radius of the parent vessel. Blood flow and pressure in the large vessels are computed as functions of time and axial distance within each of the arteries. Comparison between the simulations and magnetic resonance measurements in the ascending aorta and nine peripheral locations in one individual shows excellent agreement between the two.

Adult↗
PubMed2004

[French version of structured interviews for the Glasgow Outcome Scale: guidelines and first studies of validation].

OBJECTIVES: The Glasgow Outcome Scale (GOS) is the most widely used outcome measure after traumatic brain injury. The GOS's reliability is improved by a structured interview. The two aims of this paper were to present a French version of the structured interview for the five-point Glasgow Outcome Scale and the extended eight-point GOS (GOSE) and to study their validity. METHODS: The French version was developed using back-translation. Concurrent validity was studied by comparison with GOS/GOSE without structured interview. Inter-rater reliability was studied by comparison between assignments made by untrained head injury observers and trained head injury observers. Strength of agreement between ratings was assessed using the Kappa statistic. RESULTS: The French version and the guidelines for their use are given in the Appendix. Ratings were made for 25 brain injured patients and 25 relatives. Concurrent validity was good and inter-rater reliability was excellent. CONCLUSION: Using the structured interview for the GOS will give a more reliable assessment of the outcome of brain injured patients by French-speaking rehabilitation teams and a more precise assessment with the extended GOS.

Adolescent↗
PubMed2000

A high-resolution structure of a DNA-chromomycin-Co(II) complex determined from pseudocontact shifts in nuclear magnetic resonance.

BACKGROUND: The drug chromomycin-A(3) binds to the minor groove of DNA and requires a divalent metal ion for complex formation. (1)H, (31)P and (13)C pseudocontact shifts occurring in the presence of a tightly bound divalent cobalt ion in the complex between d(TTGGCCAA)(2) and chromomycin-A(3) have been used to determine the structure of the complex. The accuracy of the structure was verified by validation with nuclear Overhauser enhancements (NOEs) and J-coupling constants not used in the structure calculation. RESULTS: The final structure was determined to 0.7 A resolution. The structure was compared with a structure obtained in an earlier study using NOEs, in order to assess the accuracy of NOEs in giving global structural information for a DNA complex. Although some basic features of the structures agreed, they differed substantially in the fine structural details and in the DNA axis curvature generated by the drug. The distortion of base-pair planarity that was observed in the NOE structure was not seen in our structure. Differences in drug orientation and hydrogen bonding also occurred. The curvature and elongation of the DNA that was obtained previously was not found to occur in our study. CONCLUSIONS: The use of pseudocontact shifts has enabled us to obtain a high-precision global structure of the chromomycin-DNA complex, which provides an accurate template on which to consider targeting minor groove binding drugs. The effect of such binding is not propagated far along the helix but is restricted to a local kink in the axis that reverts to its original direction within four base pairs.

Antibiotics, Antineoplastic↗
PubMed2005

Clinical utility of the Defensive Functioning Scale in the assessment of depression.

The Defensive Functioning Scale (DFS) and Overall Defensive Functioning score (ODF) have been used as reliable and valid measures of defense structure when applied to clinical narratives. This study aims to replicate and extend positive clinical validity data for the ODF in the assessment of depression and examine the relationship between specific defense levels of the DFS and depressive symptoms. Sixty-nine outpatients who completed the Symptom Checklist 90-Revised and Personality Assessment Inventory were rated on the DFS by trained clinicians. Lower (more maladaptive) scores on the ODF were significantly related to the presence and severity of patient-reported depression symptoms. Furthermore, depression symptoms were significantly related to both the presence of low-level action defenses and an absence of higher-range defenses in the mental inhibitions-obsessional level. Findings from this study provide further support for the clinical application and relevance of the DFS system; support the theory of defensive processes falling into a hierarchy of adaptive functioning; and, because of a naturalistic setting, are highly generalizable to real-world practice.

Adult↗
PubMed2005

Validation of the holyoake codependency index.

Some clinicians working with families with alcohol or other drug problems continue to use the codependency model to guide their practice despite the limited empirical support for this approach. Research into codependency has been hampered by the lack of psychometrically sound instruments. The Holyoake Codependency Index (HCI; G. E. Dear & C. M. Roberts, 2000) is a 13-item self-report measure of codependent traits that has previously shown adequate to high reliability, initial evidence of construct validity, and an internal structure that is consistent across samples. In the 4 studies reported here, the internal structure of the HCI was confirmed using confirmatory factor analysis, and further evidence of construct validity was found in that the HCI subscales showed meaningful associations with other psychological and demographic variables.

Adult↗
PubMedDate not supplied

A pilot study of the use of objective structural clinical examinations for the assessment of ophthalmology education.

PURPOSE: A pilot study was carried out to evaluate the practicality, reliability, and validity of an objective structured clinical examination (OSCE) for assessing the clinical skills and abilities of specialists in ophthalmology. METHODS: Ten unfolded OSCE style, criterion referenced questions were asked to nine candidates to assess their clinical skills and abilities, as opposed to subject knowledge. Candidate and assessor reactions to the examination process were monitored and analyzed using participant observation and questionnaires administered immediately after the event. Relevant statistical techniques were applied to the results. RESULTS: A total of 89% of candidates passed the examination, with the pass boundary set at 70%. Candidates revealed themselves more successful in meeting clinical skill criteria (mean 77%) than clinical ability criteria (mean 72%). Candidates, assessors, and observers all expressed the view that the OSCE pilot had been a successful way of assessing clinical skills and abilities. CONCLUSIONS: OSCE style assessment is an effective and efficient means of assessing skills and abilities in clinical ophthalmology education.

Adult↗
PubMed1995

Psychometric characteristics and validity of the Dutch adaptation of the Buss-Durkee Hostility Inventory (the BDHI-D).

Data are presented on the factorial structure, internal consistency, and validity of the Dutch adaptation of the Buss-Durkee Hostility Inventory (the BDHI-D). Factor analyses of the responses of 463 subjects revealed two scales measuring Overt Aggression and Covert Aggression. The reliability of both subscales is good. Concordance with other self-report measures reveals satisfactory convergent and divergent validity.

Adolescent↗
PubMed2000

The ultrahigh resolution crystal structure of ribonuclease A containing an isoaspartyl residue: hydration and sterochemical analysis.

Crystals of the deamidated form of bovine pancreatic ribonuclease which contains an isoaspartyl residue in position 67 diffract to 0. 87 A at 100 K. We have refined the crystallographic model using anisotropic displacement parameters for all atoms to a conventional crystallographic residual R=0.101 for all observed reflections in the resolution range 61.0-0.87 A. The ratio observations/parameters is 7.2 for the final model. This structure represents one of the highest resolution protein structures to date and interestingly, it is the only example containing more than one molecule in the asymmetric unit with a resolution better than 1.0 A. The non-crystallographic symmetry has been used as a validation check of the geometrical parameters and it has allowed an estimate for an upper limit of errors associated with this high resolution model. In the present structure it was possible to obtain a more accurate picture of the active site whose electron density was not clearly interpretable in the previous 1.9 A resolution structure. In particular, the P1 site is alternatively occupied either by a sulphate anion or by a water molecule network. Most of hydrogen atoms were visible in the electron density maps, including those involved in C(alpha)-H(alpha).O interactions. Analysis of protein-solvent interactions has revealed the occurrence of an extensive cluster of water molecules, predominantly arranged in pentagonal fused rings and surrounding hydrophobic moiety of side-chains. Finally, in spite of the limited sample of residues, we have detected a clear dependence of backbone N-C(alpha)-C angle on residue conformation. This correlation can be fruitfully used as a valuable tool in protein structure validation.

Amides↗
PubMed2002

Alcohol urges in alcohol-dependent drinkers: further validation of the Alcohol Urge Questionnaire in an untreated community clinical population.

BACKGROUND: Alcohol craving is a key element of the alcohol dependence syndrome. However, there is a lack of consensus about the precise nature of craving and the most appropriate method of measurement. Alcohol urges measured by the Alcohol Urge Questionnaire showed a unidimensional structure and evidence of validity and reliability in a US clinical population. The main aim of this study was to establish the validity of the AUQ in an untreated UK clinical population, and its relationships to drinking and personality factors. SUBJECTS: All subjects (n = 80) were alcohol-dependent (DSM-IV) and presenting for pre-treatment assessment at a community alcohol team in South-west -London. METHOD: All subjects completed the AUQ, Severity of Alcohol Dependence -Questionnaire (SADQ), Spielberger's State Trait Anxiety Inventory (STAI) and Eysenck Personality Questionnaire (EPQ) and provided a breath specimen for alcohol analysis (BAL). RESULTS: Principal components analysis of AUQ revealed one factor which accounted for 69% of variance with high interitem correlations, and an alpha reliability of 0.93. AUQ was significantly correlated with SADQ, BAC, state and trait anxiety and negatively correlated with time since last drink. There were no significant correlations between AUQ and any of the EPQ subscales. SADQ was correlated with neuroticism, but not other EPQ subscales. A regression analysis showed that only SADQ, time since last drink and BAL were significant predictors of alcohol urges. CONCLUSIONS: This study confirmed the AUQ factor structure and provided further evidence for the validity of AUQ. The relationship between BAL and urges deserves further research. The results did not support the contention that -anxiety and personality factors predict urges when drinking-related variables, which also predict urges, are controlled for. The AUQ is a useful measure for clinical and experimental alcohol craving research.

Adult↗