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The validation of a diabetes patient knowledge test.

Diabetes knowledge tests, used in conjunction with measures of patient attitudes and behaviors, can provide a useful basis for assessing educational needs and designing appropriate instructional experiences. Accurate decisions require instruments that measure patient knowledge of diabetes and its management with high reliability and validity. Data obtained from more than 950 administrations of two parallel forms of a Diabetes Patient Knowledge Test have provided documentation of patient knowledge levels, insight into the effectiveness of educational programs, and support for ongoing program revisions. These data have also allowed study of the psychometric properties of the test instruments, including factor structure, reliability, and validity. Each test form has an overall reliability of 0.89 and the forms are of equal difficulty. Five subcomponents (factors) labeled "Carbohydrates," "Blood Sugar," "Basics," "Food Exchanges," and "Insulin Administration" are measured in the tests. Evidence of content, construct, concurrent, and discriminant validity has been demonstrated.

Blood Glucose↗

Initial validation of a test of spatial knowledge in anatomy.

The authors have developed HERCULES, a computer-based test designed to assess the spatial, non-verbal components of knowledge in anatomy. The test consists of two tasks, each requiring subjects to estimate the vertical level in the body of a set of color, cross-sectional images. In Task 1, subjects make the estimate based on a limited number of clues, where each clue is an anatomical structure that appears in the cross-section. In Task 2, subjects estimate the level based on a view of the cross-section with all structures shown. A validation study of this test using six images for each task was performed with preclinical medical students, fourth year medical students, and experienced teachers of anatomy as subjects. Results indicate that the exercise is at an appropriate level of difficulty and that a somewhat longer test than used in this study would be adequately reliable for use in actual assessment. The test appears to discriminate the expert faculty from more novice students and thus exhibits an aspect of validity that is very important in assessment exercises of this type.

Anatomy↗

The importance of larger data sets for protein secondary structure prediction with neural networks.

A neural network algorithm is applied to secondary structure and structural class prediction for a database of 318 nonhomologous protein chains. Significant improvement in accuracy is obtained as compared with performance on smaller databases. A systematic study of the effects of network topology shows that, for the larger database, better results are obtained with more units in the hidden layer. In a 32-fold cross validated test, secondary structure prediction accuracy is 67.0%, relative to 62.6% obtained previously, without any evolutionary information on the sequence. Introduction of sequence profiles increases this value to 72.9%, suggesting that the two types of information are essentially independent. Tertiary structural class is predicted with 80.2% accuracy, relative to 73.9% obtained previously. The use of a larger database is facilitated by the introduction of a scaled conjugate gradient algorithm for optimizing the neural network. This algorithm is about 10-20 times as fast as the standard steepest descent algorithm.

Algorithms↗

Development of a SAW duplexer with one-chip isolation circuits.

We propose new structures of one-chip type SAW duplexers where Tx and Rx SAW ladder filters as well as isolation networks are fabricated together on a single 36 degrees LiTaO(3) piezoelectric substrate. The new SAW duplexer can overcome the difficulty in fabrication of conventional SAW duplexers while providing the performance matching that of conventional duplexers. Validity of the structure is verified through numerical simulation and experiments.

Journal Article↗

Experimental resolution of early steps in protein folding: testing molecular dynamics simulations.

Time-resolved Tyr fluorescence spectroscopy coupled with a laser-induced temperature-jump (T-jump) was employed to follow the folding relaxation dynamics of the B-domain of Staphylococcal protein A. The single Tyr is located in helix 1 (H1) and is a sensitive probe of the structure of this helix and the overall helical bundle structure. The results from this study were compared to those from a complementary infrared T-jump study on this protein [Vu, D. M.; Myers, J. K.; Oas, T. G.; Dyer, R. B. Biochemistry 2004, 43, 3582]. Both methods detect a microsecond process that follows the cooperative relaxation of the helical bundle core. However, a fast process (10-7 s) that follows the relaxation of the individual helices was observed only with the infrared probe. Thus, fast formation of H1 is not observed, but rather H1 forms in the microsecond phase, concomitantly with the docking to (and stabilization by) the other two helices to form the helical bundle structure. This observation validates the results of several previous molecular dynamics simulations that predict H1 formation only in the final assembly of the helix bundle.

Computer Simulation↗

Continuity of care: validation of a new self-report measure for individuals using mental health services.

Continuity of care is a concern for individuals with persistent mental illness who need diverse services over time in response to multiple and changing needs. Efforts to study continuity have been hampered by lack of appropriate instruments. The Alberta Continuity of Services Scale--Mental Health is a newly developed, self-report scale that assesses continuity of care across settings and providers. This study examined the structure, reliability, and validity of the measure among users of community mental health programs. Findings were positive. Scores captured both positive and negative perceptions of care. Factor analyses elucidated 3 components of continuity--system access, interpersonal aspects, and care team function. Associations between the continuity scores and selected client and service use measures supported its validity. The tool holds promise for system monitoring, but would need refinements to create a shorter, conceptually clearer version. Also, performance among individuals with mild and very severe levels of mental illness needs to be evaluated.

Adult↗

Veterinary school admission interviews, part 1: literature overview.

An analysis of the admission interview used by schools in four health professions (veterinary medicine, allopathic medicine, optometry, and dentistry) portrays a largely similar approach to selection interviews: INTERVIEW USE: At least 80% of schools interview applicants. For schools that offer interviews, at least 40% of candidates are interviewed (a strong academic profile is the number one determinant of receiving an interview offer). The interview is one of the three most important selection tools used by schools. Less than 26% of schools fix the interview's weight in the selection process (fixed weights range from 31% to 35%). INTERVIEW PURPOSE AND CONTENT: The most common purposes of the interview are to (1) gather information, (2) make decisions, (3) verify information provided in other parts of the application, (4) recruit candidates, and/or (5) promote public relations. The most common characteristics and skills interviewers are interested in assessing are motivation for the profession, interpersonal skills, and communication skills. The desire to assess cognitive ability with the interview (>25% of schools) is surprising in view of the use of other selection tools (e.g., GPA). INTERVIEW FORMAT: Medical schools are more likely to offer two interviews per candidate, while optometry schools are more likely to offer one interview per candidate. Individual interviews (one interviewer, one candidate) are the predominant format among medical schools, while panel interviews (more than one interviewer, one candidate) are the most common format among optometry schools. The duration of the interview is 30 to 45 minutes. Interview questions most often address facts and knowledge, hypothetical situations, and the ability to meet program requirements. Most interviews do not meet the criteria for a structured interview, which has demonstrated greater validity and reliability than semi-structured or unstructured interviews. INTERVIEWERS: Interviewers are most likely to be health care faculty members (e.g., veterinarians at a veterinary school). Interviewers receive limited training. RECOMMENDATIONS FOR INCREASING INTERVIEW RELIABILITY AND VALIDITY: The purpose(s) of the interview must be clearly articulated so that the interview and interviewer training can be designed to achieve that purpose. Interview structure should be increased by developing a "job analysis" set of questions that is posed to all candidates and scored using behavioral anchors. Interviewers should receive more training in rater bias, listening skills, and interview structure. Panel interviews should be used to increase reliability. Interviewers should not have access to the candidate's application unless the interview is used to verify information. To increase the utility of the interview in the selection process, the weight of the interview in relation to other selection components should be determined.

Complementary Therapies↗

Solution structure of PMP-D2, a 35-residue peptide isolated from the insect Locusta migratoria.

The three-dimensional solution structure of PMP-D2, a 35 amino acid peptide isolated from the insect Locusta migratoria, has been determined from two-dimensional 1H NMR spectroscopy data. The structure calculations were performed from 222 NOE-derived interproton distances and 11 dihedral angles calculated from the JHN-H alpha coupling constants, using either a combination of distance geometry and restrained simulated annealing or by restrained simulated annealing alone. PMP-D2 contains three disulfide bridges that have been assigned from NMR data and structure calculations and independently confirmed using chemical and enzymatic methods. The core region of PMP-D2 adopts a compact globular fold, stabilized by hydrophobic interactions, which consists of a short three-stranded antiparallel beta-sheet involving residues 8-11, 15-19, and 25-29. Back-calculation of the NOESY spectra was used to validate the final structures. Analysis of the CD spectra of PMP-D2 under various conditions of ionic strength and in the presence of organic solvents demonstrates the high stability of this molecule. PMP-D2 was recently shown to inhibit Ca2+ currents. This activity is discussed based on the comparison of PMP-D2 three-dimensional structure with the recently established three-dimensional structure of the Ca2+ channel blocker omega-conotoxin GVIA.

Amino Acid Sequence↗

The admission interview: the validity question.

This study reports on the validity of a structured, standardized admission interview for dentistry. An entire class of 86 fourth-year dental students at The University of Iowa was studied, and the relationships between information from the interview, faculty ratings, and numerous dental and predental academic data were compared. Many correlations were found to be significant, which permitted technical description of three aspects of validity: concurrent, content, and construct. Reliability of both the instrument and the interview method were shown to affect validity.

Achievement↗

Effect of metal ion and water coordination on the structure of a gas-phase amino acid.

The mode of metal ion and water binding to the amino acid valine is investigated using both theory and experiment. Computations indicate that without water, the structure of valine is nonzwitterionic. Both Li(+) and Na(+) are coordinated to the nitrogen and carbonyl oxygen (NO coordination), whereas K(+) coordinates to both oxygens (OO coordination) of nonzwitterionic valine. The addition of a single water molecule does not significantly affect the relative energies calculated for the cationized valine clusters. Experimentally, the rates of water evaporation from clusters of Val.M(+)(H(2)O)(1), M = Li, Na, and K, are measured using blackbody infrared radiative dissociation. The dissociation rate from the valine complex is compared to water evaporation rates from model complexes of known structure. These results indicate that the metal ion in the lithiated and the sodiated clusters is NO-coordinated to nonzwitterionic valine, while that in the potassiated cluster has OO coordination, in full agreement with theory. The zwitterionic vs nonzwitterionic character of valine in the potassiated cluster cannot be distinguished experimentally. Extensive modeling provides strong support for the validity of inferring structural information from the kinetic data.

Cations, Monovalent↗

Psychometric evaluation of an inventory for assessment of parental rearing practices. A Dutch form of the EMBU.

The EMBU, an instrument which was designed to assess one's memories of parental rearing behaviour, was psychometrically evaluated. Principal component factor analysis of data of a mixed sample of 841 non-institutionalized phobic individuals revealed four factors which were termed Rejection, Emotional warmth, Over-protection and Favouring subject, thereby contributing to the convergent (cross-national) reliability and validity of the structural model of perceived parental behaviour. Besides the utilization of data from aforementioned phobic sample, the scales' internal consistency was assessed in data of five additional samples, which consisted of 277 'normals', 40 agoraphobics, 29 social phobics, 21 height phobics and 38 obsessive-compulsive neurotics, and found to be very satisfactory. In the normal and mixed phobic sample, validity measures were shown to be acceptable and to be independent of the parent's sex. Furthermore, findings suggested that the fact that retrospective data is being measured with the scales does not threaten the reliability and validity of gathered information due to faulty recall or falsified accounts.

Adolescent↗

X-ray crystallographic determination of a collagen-like peptide with the repeating sequence (Pro-Pro-Gly).

The crystal structure of the triple-helical peptide (Pro-Pro-Gly)10 has been re-determined to obtain a more accurate description for this widely studied collagen model and to provide a comparison with the recent high-resolution crystal structure of a collagen-like peptide containing Pro-Hyp-Gly regions. This structure demonstrated that hydroxyproline participates extensively in a repetitive hydrogen-bonded assembly between the peptide and the solvent molecules. Two separate structural studies of the peptide (Pro-Pro-Gly)10 were performed with different crystallization conditions, data collection temperatures, and X-ray sources. The polymer-like structure of one triple-helical repeat of Pro-Pro-Gly has been determined to 2.0 A resolution in one case and 1.7 A resolution in the other. The solvent structures of the two peptides were independently determined specifically for validation purposes. The two structures display a reverse chain trace compared with the original structure determination. In comparison with the Hyp-containing peptide, the two Pro-Pro-Gly structures demonstrate very similar molecular conformation and analogous hydration patterns involving carbonyl groups, but have different crystal packing. This difference in crystal packing indicates that the involvement of hydroxyproline in an extended hydration network is critical for the lateral assembly and supermolecular structure of collagen.

Collagen↗

Molecular modelling of the Dolichos biflorus seed lectin and its specific interactions with carbohydrates: alpha-D-N-acetyl-galactosamine, Forssman disaccharide and blood group A trisaccharide.

The three-dimensional structure of Dolichos biflorus seed lectin has been constructed using five legume lectins for which high resolution crystal structures were available. The validity of the resulting model has been thoroughly investigated. Final structure optimization was conducted for the lectin complexed with alpha GalNAc, providing thereby the first three-dimensional structure of lectin/GalNAc complex. The role of the N-acetyl group was clearly evidenced by the occurrence of a strong hydrogen bond between the protein and the carbonyl oxygen of the carbohydrate and by hydrophobic interaction between the methyl group and aromatic amino acids. Since the lectin specificity is maximum for the Forssman disaccharide alpha GalNAc(1-3) beta GalNAc-O-Me and the blood group A trisaccharide alpha GalNAc(1-3)[alpha Fuc(1-2)] beta Gal-O-Me, the complexes with these oligosaccharides have been also modelled.

ABO Blood-Group System↗

Development of alpha-keto-based inhibitors of cruzain, a cysteine protease implicated in Chagas disease.

Trypanosoma cruzi, a protozoan parasite, is the causative agent of Chagas disease, a major cause of cardiovascular disease in many Latin American countries. There is an urgent need to develop an improved therapy due to the toxicity of existing drugs and emerging drug resistance. Cruzain, the primary cysteine protease of T. cruzi, is essential for the survival of the parasite in host cells and therefore is an important target for the development of inhibitors as potential therapeutics. A novel series of alpha-ketoamide-, alpha-ketoacid-, alpha-ketoester-, and aldehyde-based inhibitors of cruzain has been developed. The inhibitors were identified by screening protease targeted small molecule libraries and systematically optimizing the P1, P2, P3, and P1' residues using specific structure-guided methods. A total of 20 compounds displayed picomolar potency in in vitro assays and three inhibitors representing different alpha-keto-based inhibitor scaffolds demonstrated anti-trypanosomal activity in cell culture. A 2.3A crystallographic structure of cruzain bound with one of the alpha-ketoester analogs is also reported. The structure and kinetic assay data illustrate the covalent binding, reversible inhibition mechanism of the inhibitor. Information on the compounds reported here will be useful in the development of new lead compounds as potential therapeutic agents for the treatment of Chagas disease and as biological probes to study the role that cruzain plays in the pathology. This study also demonstrates the validity of structure-guided approaches to focused library design and lead compound optimization.

Amides↗

A neural network based classification scheme for cytotoxicity predictions:Validation on 30,000 compounds.

Elimination of cytotoxic compounds in the early phases of drug discovery can save substantial amounts of research and development costs. An artificial neural network based approach using atomic fragmental descriptors has been developed to categorize compounds according to their in vitro human cytotoxicity. Fragmental descriptors were obtained from the Atomic7 linear logP calculation method implemented in Pallas PrologP program. We used cytotoxicity values obtained from an in-house screening campaign of a diverse set of 30,000 drug-like molecules. The training set included only the most and least toxic 12,998 compounds, however, cytotoxicity data for all compounds were used for validation. The proposed approach can be safely used for filtering out potentially cytotoxic candidates from the development pipeline before synthesis or assays during lead development or lead optimisation. The trained neural network misclassified less than 5% percent of the non-toxic and 9% of the toxic compounds.

Cell Line↗

Validation of a brief measure of posttraumatic stress disorder: the Distressing Event Questionnaire (DEQ).

The Distressing Event Questionnaire (DEQ) is a brief instrument for assessing posttraumatic stress disorder (PTSD) according to criteria provided in Diagnostic and Statistical Manual of Mental Disorders (4th ed.). The DEQ possesses high internal consistency and exhibited satisfactory short-term temporal stability in studies with Vietnam War combat veterans and battered women. In a sample of Vietnam War veterans and 4 separate samples of abused women (with histories of incest, rape, intimate partner abuse, or prostitution and abuse), the DEQ exhibited very good discriminative validity when judged against structured interview assessment of PTSD. The DEQ exhibited strong convergent validity with other PTSD measures and other indexes of adjustment and also exhibited strong convergent validity as a measure of PTSD across ethnic groups in both the veteran sample and the combined women's sample.

Adult↗

Depression in veterans of the first Gulf War and comparable military controls.

Depression is a common mental disorder associated with poor health outcomes. The purpose of this study is to examine the prevalence of depression, mental health comorbidity, illness variables, and quality of life in a sample of military veterans serving during the first Gulf War. The Iowa Gulf War Case Validation Study involved face-to-face evaluations in 1999--2002 of 602 military personnel--either deployed ("deployed veterans") or eligible but not deployed ("non-deployed veterans") to the Gulf. Subjects were sampled by conducting a series of case-control studies nested within a population-based survey of 4,886 military personnel. All subjects were interviewed using the Structured Clinical Interview for DSM-IV (SCID-IV), and a series of semi-structured interviews and validated questionnaires. Best estimate psychiatric diagnoses were assigned based on all available data. One-hundred-ninety-two (32%) of the 602 surveyed veterans met criteria for a current or lifetime depressive disorder (major depression, dysthymia, depressive disorder--not otherwise specified). Depressed non-deployed veterans were more likely to be female and to have served in the Air Force than depressed deployed veterans. There were few significant differences between the depressed deployed veterans and the depressed non-deployed veterans. Depressed deployed veterans had significantly higher lifetime rates of comorbid cognitive dysfunction (55% vs. 35%), and anxiety disorders (59% vs. 33%)--mainly accounted for by specific phobias (12% vs. 2%) and posttraumatic stress disorder (33% vs. 10%)--than did depressed non-deployed veterans. Lifetime substance use disorders were significantly more frequent in deployed veterans than non-deployed veterans (70% vs. 52%), particularly alcohol disorders (68% vs. 52%). There were no differences in rates of personality characteristics, family psychiatric history, stressors, hypochondriasis, and level of functioning between the two study groups showed no significant differences. Depressive illness is frequent in military samples, as it is in the general population. The prevalence, pattern of comorbidity, and illness features were similar in deployed veterans and non-deployed veterans, suggesting that the depression suffered by both groups of veterans is qualitatively comparable. The main difference between study, groups was that depressed deployed veterans had higher rates than depressed non-deployed veterans of comorbid anxiety disorders, hypothesized to be part of the stress-related syndromes seen in those who experience combat.

Adult↗

Utility of Butvar support film and methylamine tungstate stain in three-dimensional electron microscopy: agreement between stain and frozen-hydrated reconstructions.

A random conical tilt reconstruction of negatively stained Saccharomyces cerevisiae fatty acid synthase was used as a model to compute a three-dimensional reconstruction from untilted stain specimens of the molecules in multiple orientations using a three-dimensional projection alignment method. The resulting structure (24 A resolution) has a more uniform resolution than the initial structure and the handedness revealed in the random conical tilt method is preserved. In a similar approach, this model was used to compute a 21-A-resolution frozen-hydrated structure from untilted specimens of the molecules in multiple orientations. Even though the reconstructions are in close agreement, the stain structure appears to enhance the protein density associated with less robust features. These procedures significantly reduce the time and effort required to obtain a three-dimensional reconstruction from frozen-hydrated data with a resolution that is comparable to the best obtained by more laborious methods. The agreement between the stain and frozen-hydrated reconstructions affords convincing evidence concerning the validity of the structure and the information afforded by the two reconstructions significantly enhances the structural analysis of the molecule.

Coloring Agents↗