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Is cross-validation valid for small-sample microarray classification?

MOTIVATION: Microarray classification typically possesses two striking attributes: (1) classifier design and error estimation are based on remarkably small samples and (2) cross-validation error estimation is employed in the majority of the papers. Thus, it is necessary to have a quantifiable understanding of the behavior of cross-validation in the context of very small samples. RESULTS: An extensive simulation study has been performed comparing cross-validation, resubstitution and bootstrap estimation for three popular classification rules-linear discriminant analysis, 3-nearest-neighbor and decision trees (CART)-using both synthetic and real breast-cancer patient data. Comparison is via the distribution of differences between the estimated and true errors. Various statistics for the deviation distribution have been computed: mean (for estimator bias), variance (for estimator precision), root-mean square error (for composition of bias and variance) and quartile ranges, including outlier behavior. In general, while cross-validation error estimation is much less biased than resubstitution, it displays excessive variance, which makes individual estimates unreliable for small samples. Bootstrap methods provide improved performance relative to variance, but at a high computational cost and often with increased bias (albeit, much less than with resubstitution).

Algorithms↗

Application of the general health status questionnaire SF36 to patients with gastrointestinal dysfunction: initial validation and validation as a measure of change.

OBJECTIVE: To determine whether the Short Form (SF36) Health Status Survey is a valid measure of health status and health change for patients with irritable bowel syndrome (IBS). METHODS: The SF36 was self-administered by 116 patients with IBS at the commencement and end of a controlled clinical trial. Patients were recruited through two Sydney teaching hospitals and through private gastroenterologists during 1997 and treated with Chinese herbal medicine. RESULTS: The SF36 health concepts demonstrated internal consistency, construct validity and concurrent validity when applied to patients with significant bowel dysfunction. Patient scores on two health scales of the SF36 (bodily pain, general health) correlated significantly with the bowel symptom scores recorded by patients and gastroenterologists at the beginning and end of the trial period. Actively treated patients significantly improved their scores in four out of eight of the health scales of the SF36 and reported overall improvement compared with inactively treated patients. CONCLUSIONS: The SF36 is a valid measure of general health status in IBS patients, is sensitive to the presence of IBS, and is adequately sensitive to gastrointestinal change in IBS patients. IMPLICATIONS: While the SF36 general health measure is used by the Australian Bureau of Statistics and widely overseas, until recently no data have been available on the sensitivity of the SF36 to gastrointestinal dysfunction or numerous other disorders. The SF36 is not only sensitive to the presence of IBS, it also provides a useful adjunct to current methods of evaluating treatment outcomes for IBS, and potentially other disorders.

Adolescent↗

Cross-validation and discriminant validity of Adolescent Health Promotion Scale among overweight and nonoverweight adolescents in Taiwan.

This study used cross-validation and discriminant analysis to evaluate the construct and discriminant validity of Adolescent Health Promotion (AHP) scale between the overweight and nonoverweight adolescents in Taiwan. A cross-sectional survey method was used and 660 adolescents participated in this study. Cluster and discriminant analyses were used to analyze the data. Our findings indicate that the AHP is a valid and reliable scale to discriminate between the health-promoting behaviors of overweight and nonoverweight adolescents. For the total scale, cluster analyses revealed two distinct patterns, which we designated the healthy and unhealthy groups. Discriminate analysis supported this clustering as having good discriminant validity, as nonoverweight adolescents tended to be classified as healthy, while the overweight tended to be in the unhealthy group. In general, overweight adolescents practiced health-related behaviors at a significantly lower frequency than the nonoverweight. These included exercise behavior, stress management, life appreciation, health responsibility, and social support. These findings can be used to further develop and refine knowledge of adolescent overweight and related strategies for intervention.

Adolescent↗

Selection of test chemicals for the ECVAM international validation study on in vitro embryotoxicity tests. European Centre for the Validation of Alternative Methods.

The European Centre for the Validation of Alternative Methods (ECVAM) has sponsored a large international prevalidation and validation study of three embryotoxicity tests, involving embryonic stem cells, limb bud micromass cultures, and post-implantation whole-embryo cultures. The main objective of the study was to assess the performance of these in vitro tests in discriminating between non-embryotoxic, weakly embryotoxic and strongly embryotoxic compounds. An initial part of the study was to select 20 test substances for the formal validation trial, conducted under blind conditions. A database of in vivo and in vitro developmental toxicity test results was complied on 310 chemicals that had been used in previous validation studies, or suggested for such use, or that had good quality "segment II"-type in vivo data, or for which there were human data. From this database, a shortlist of about 30 candidates was constructed. Because the ECVAM study would not include metabolic activation, chemicals known to require activation for their developmental effects were excluded as candidates, although some known stable metabolites were included. Attempts were made: to include substances of diverse mechanism; to avoid overemphasis on pharmaceuticals; to avoid biologically inert substances as non-embryotoxicants; and to make the list different from those used previously. The candidates were of three categories: Class 3, strongly embryotoxic, was defined as developmentally toxic in all species tested, inducing multiple developmental effects, and with a high A/D ratio. Class 1, non-embryotoxic, was defined as not developmentally toxic at maternally toxic exposures, but which may show some minor embryo/fetal toxicity, which cannot be separated from maternal toxicity. Class 2, weakly embryotoxic, were chemicals of intermediate activity. From this candidate list, chemicals of known receptor (androgen, oestrogen, glucocorticoid, aryl hydrocarbon) mechanisms were excluded, on the basis that simple tests for such activity are already available. In addition, chemicals not freely available were excluded, and an emphasis on human data was applied. The final list of 20 chemicals was: Class 3--6-aminonicotinamide, 5-bromo- 2'-deoxyuridine, hydroxyurea, methylmercury chloride, methotrexate, all-trans-retinoic acid; Class 2--boric acid, dimethadione, lithium chloride, methoxyacetic acid, valproic acid (VPA), 2-propyl-4-pentynoic acid (4-yn-VPA), salicylic acid sodium salt; and Class 1--acrylamide, D-(+)-camphor, dimethyl phthalate, diphenhydramine hydrochloride, 2-ethyl-4- methylpentanoic acid (isobutyl-ethyl-VPA), Penicillin G sodium salt, saccharin sodium hydrate.

Animal Testing Alternatives↗

Clinical validity of the Mattis Dementia Rating Scale in detecting Dementia of the Alzheimer type. A double cross-validation and application to a community-dwelling sample.

OBJECTIVE: To assess the clinical validity of the Dementia Rating Scale (DRS) in detecting patients with dementia of the Alzheimer type (DAT). BACKGROUND: The DRS is widely used to evaluate cognitive functioning in older adults. Adequate normative data are unavailable; studies addressing the clinical validity of the DRS are limited by small sample sizes. DESIGN AND METHODS: Administered the DRS to 254 outpatients with DAT and 105 healthy elderly subjects. Performed (1) multiple regressions of demographic factors on the DRS and its subscales; (2) derivation of optimal DRS cutoff scores using receiver operating characteristic curves; (3) double cross-validation with stepwise logistic regressions; and (4) application of results to a community-dwelling sample. RESULTS: Age- and education-adjusted DRS scores were computed. The optimal DRS cutoff score for DAT of 129 or less revealed a sensitivity of 98% and a specificity of 97%. The logistic regressions resulted in a combination of the Memory and Initiation/Perseveration subscales that correctly classified 98% of all subjects, 92% of a subsample of 76 patients with mild DAT, and 100% of the 51 patients with autopsy-confirmed DAT. The resultant equation was then applied to a community-dwelling sample (238 healthy elderly subjects and 44 patients with DAT): 91% of patients and 93% of normal subjects were correctly classified. Of an additional 77 individuals with questionable DAT, 43 were classified as demented and 34 were classified as nondemented. CONCLUSIONS: The DRS is a clinically valid psychometric test for the detection of DAT. The Memory and Initiation/Perseveration subscales are its best discriminative indexes for an abbreviated version.

Aged↗

Verbal Concept Attainment Test: cross-validation and validation of a booklet form.

Conducted this study to cross-validate the Verbal Concept Attainment Test as a measure of potential value in neuropsychological assessment and to validate a booklet form of this test. Two samples of 75 patients referred for neuropsychological examination were studied. In both samples the pattern of relationship between the VCAT and a number of widely used neuropsychological measures closely paralleled the pattern reported in the initial validation study. The pattern of relationships with the booklet form was also very similar to the pattern of relationships between the neuropsychological measures and the Impairment Index from the Halstead-Reitan Battery. It was concluded that these data provided evidence of the stability of this test across samples and that the booklet form appeared to be an equally valid measure.

Adolescent↗

Who checks the checkers? Four validation tools applied to eight atomic resolution structures. EU 3-D Validation Network.

Eight protein crystal structures, which have been refined against X-ray diffraction data extending to atomic resolution, 1.2 A or better, were inspected using four different validation tools, PROCHECK, PROVE, SQUID and WHATCHECK. Two general questions were addressed. (1) Do the structures imply changes in "expected" stereochemical properties and are the target values used for restraints in the validation programs and the refinement protocol appropriate? (2) Can errors in models be detected and how reliable are the coordinates after refinement? Preliminary analysis by members of the network led to modifications both to the validation programs and to the refinement protocols. The results of the final analyses are reported here. Apparent discrepancies in cell dimensions were identified. Most stereochemical properties are shown to be more tightly clustered than for lower resolution analyses. In contrast the omega angle has a wider distribution. The validation software is generally available and can be accessed at servers listed at the end of the paper.

Bacterial Proteins↗

Relative validity of a food frequency questionnaire among tin miners in China: 1992/93 and 1995/96 diet validation studies.

OBJECTIVE: Diet validation research was conducted to compare the respondents' reporting of dietary intake in a food frequency questionnaire (FFQ) with intake reported in food recalls. Because the population received annual salary increments that could modify food intake, diet validation studies (DVSs) were conducted during two time intervals. DESIGN: A 99-item FFQ was administered by an interviewer twice in a 1-year interval, and responses to each FFQ item were compared with 28 days of interviewer-administered food recalls that were collected in four 1-week intervals during each season of 1992/93. The second validation study in 1995/96 had a similar design to the earlier one. SETTING: A prospective cohort study of lung cancer among tin miners in China was initiated in 1992, with dietary and other risk factors updated annually. SUBJECTS: Among a cohort of high risk tin miners for lung cancer, two different samples (n = 141 in 1992/93, and n = 113 in 1995/96) for each diet validation study were randomly selected from four mine units, that were representative of all worker units. RESULTS: Miners reported a significantly higher average frequency of intake of foods in the food recalls than the FFQ, with few exceptions. Deattenuated Pearson correlation coefficients of the frequency of food intake between the FFQ and food recalls were in the range of -0.40 to 0.72 in both studies, with higher positive correlations for beverages and cereal staples than for animal protein sources, vegetables, fruits and legumes. The percentage of individuals with exact agreement in the extreme quartiles of intake in the food recalls and FFQ ranged from 0 to 100% in both studies. CONCLUSIONS: Among Chinese miners, the range in correlations between the food recalls and the FFQ were due to: (i) market availability of foods during the food recall weeks compared to their annual reported intake in the FFQ; (ii) cultural perception of time; and (iii) differences in how the intake of mixed dishes and their multi-ingredient foods were reported in the recalls vs. the FFQ. The range in the percentage of agreement in the same quartiles and the changes in food intake over time may have implications for the analysis of the diet-disease relationship in this cohort.

Analysis of Variance↗

Development and validation of the Validity Indicator Profile.

The Validity Indicator Profile (VIP; Frederick, 1997) is a two-alternative forced choice (2AFC) procedure intended to identify when the results of cognitive and neuropsychological testing may be invalid because of malingering or other problematic response styles. The test consists of 100 problems that assess nonverbal abstraction capacity and 78 word-definition problems. The VIP attempts to establish whether an individual's performance in an assessment battery should be considered representative of his or her true overall capacities (valid or invalid). Performances classified as valid are classified as "compliant" and reflect a high effort to respond correctly. Performances classified as invalid are subclassified as "careless" (low effort to respond correctly), "irrelevant" (low effort to respond incorrectly), or "malingering" (high effort to respond incorrectly). The VIP development sample included 944 nonclinical participants and 104 adults undergoing neuropsychological evaluation. The cross-validation sample consisted of 152 nonclinical participants, 61 brain-injured adults, 49 individuals considered to be at risk for malingering, and 100 randomly generated VIP protocols. The nonverbal subtest of the VIP demonstrated an overall classification rate of 79.8%, with 73.5% sensitivity and 85.7% specificity. The verbal subtest of the VIP demonstrated an overall classification rate of 75.5%, with 67.3% sensitivity and 83.1% specificity.

Adolescent↗

Studying pretrial publicity effects: new methods for improving ecological validity and testing external validity.

Although research examining the effects of pretrial publicity (PTP) on individuals' appraisals of a defendant and verdict decision making generally has been found to be internally valid, the external validity has been questioned by some social scientists as well as lawyers and judges. It is often proposed that the verisimilitude (or ecological validity) ofthe research should be increased in the service of increasing external validity; however, increasing verisimilitude can be costly in terms of both time and money. It is proposed that the Internet is a viable means of conducting PTP research that allows high verisimilitude without high costs. This is demonstrated with a study in which we used the Internet to examine PTP effects in an actual trial as it was taking place. Successful use of the Internet to conduct experimental research in other areas of psychology and law is discussed, as well as the importance of future research examining whether independent variables interact with methods in ways that undermine the generalizability of research findings.

Adult↗

Comparing the predictive validity of DUI risk screening instruments: development of validation standards.

AIMS: This study compares the predictive efficacy of driving under the influence (DUI) screening instruments validated in previous studies, illustrates how variations in base rates of failure and selection ratios affect conclusions concerning the efficacy of different instruments, and develops evaluation standards to ensure valid comparisons of risk prediction instruments. DESIGN: The study: (1) examines a sample of 4815 DUI offenders to illustrate how variations in base rates of failure and selection ratios affect traditional measures of predictive efficacy, (2) uses such measures to compare the predictive efficacy of 10 instruments validated in previous studies, and (3) demonstrates the use of a measure of predictive efficacy which is relatively insensitive to the aforementioned variations. FINDINGS: While three instruments examined at specific cut-points consistently ranked highest on several measures of predictive efficacy, use of different evaluation standards produced substantively different conclusions regarding the efficacy of different instruments. Based on the analyses, standards for validation of risk prediction instruments were developed. CONCLUSIONS: The findings illustrate how failure to use equivalent standards have led to erroneous conclusions concerning the relative predictive efficacy of different risk prediction instruments. The standards developed in this study should facilitate equivalent comparisons of the predictive efficacy of risk prediction instruments.

Alcohol Drinking↗

Validation list no. 98. Validation of publication of new names and new combinations previously effectively published outside the IJSEM.

The purpose of this announcement is to effect the valid publication of the following new names and new combinations under the procedure described in the Bacteriological Code (1990 Revision). Authors and other individuals wishing to have new names and/or combinations included in future lists should send three copies of the pertinent reprint or photocopies thereof to the IJSEM Editorial Office for confirmation that all of the other requirements for valid publication have been met. It is also a requirement of IJSEM and the ICSP that authors of new species, new subspecies and new combinations provide evidence that types are deposited in two recognized culture collections in two different countries (i.e. documents certifying deposition and availability of type strains). It should be noted that the date of valid publication of these new names and combinations is the date of publication of this list, not the date of the original publication of the names and combinations. The authors of the new names and combinations are as given below, and these authors' names will be included in the author index of the present issue and in the volume author index. Inclusion of a name on these lists validates the publication of the name and thereby makes it available in bacteriological nomenclature. The inclusion of a name on this list is not to be construed as taxonomic acceptance of the taxon to which the name is applied. Indeed, some of these names may, in time, be shown to be synonyms, or the organisms may be transferred to another genus, thus necessitating the creation of a new combination.

Bacteria↗

Validation list no. 110. List of new names and new combinations previously effectively, but not validly, published.

The purpose of this announcement is to effect the valid publication of the following new names and new combinations under the procedure described in the Bacteriological Code (1990 Revision). Authors and other individuals wishing to have new names and/or combinations included in future lists should send three copies of the pertinent reprint or photocopies thereof to the IJSEM Editorial Office for confirmation that all of the other requirements for valid publication have been met. It is also a requirement of IJSEM and the ICSP that authors of new species, new subspecies and new combinations provide evidence that types are deposited in two recognized culture collections in two different countries (i.e. documents certifying deposition and availability of type strains). It should be noted that the date of valid publication of these new names and combinations is the date of publication of this list, not the date of the original publication of the names and combinations. The authors of the new names and combinations are as given below, and these authors' names will be included in the author index of the present issue and in the volume author index. Inclusion of a name on these lists validates the publication of the name and thereby makes it available in bacteriological nomenclature. The inclusion of a name on this list is not to be construed as taxonomic acceptance of the taxon to which the name is applied. Indeed, some of these names may, in time, be shown to be synonyms, or the organisms may be transferred to another genus, thus necessitating the creation of a new combination.

Bacteria↗

Validation list no. 113. List of new names and new combinations previously effectively, but not validly, published.

The purpose of this announcement is to effect the valid publication of the following new names and new combinations under the procedure described in the Bacteriological Code (1990 Revision). Authors and other individuals wishing to have new names and/or combinations included in future lists should send three copies of the pertinent reprint or photocopies thereof, or an electronic copy of the published paper, to the IJSEM Editorial Office for confirmation that all of the other requirements for valid publication have been met. It is also a requirement of IJSEM and the ICSP that authors of new species, new subspecies and new combinations provide evidence that types are deposited in two recognized culture collections in two different countries (i.e. documents certifying deposition and availability of type strains). It should be noted that the date of valid publication of these new names and combinations is the date of publication of this list, not the date of the original publication of the names and combinations. The authors of the new names and combinations are as given below, and these authors' names will be included in the author index of the present issue and in the volume author index. Inclusion of a name on these lists validates the publication of the name and thereby makes it available in bacteriological nomenclature. The inclusion of a name on this list is not to be construed as taxonomic acceptance of the taxon to which the name is applied. Indeed, some of these names may, in time, be shown to be synonyms, or the organisms may be transferred to another genus, thus necessitating the creation of a new combination.

Bacteria↗

Valid arguments? a consideration of the concept of validity in establishing the credibility of research findings.

Validity is an important concept in establishing the credibility of research findings. However, the current debate about the criteria used to substantiate claims for the validity of research evidence is largely based on a set of distinctions between qualitative and quantitative methodology which are outdated and misleading. This paper argues that validity is an epistemological concept, whose application depends upon some fundamental positions taken about the nature of truth, representation and scientific methodology. There remain important, unresolved questions about the meaning and application of the concept of validity which have a crucial bearing on what criteria are used to establish the credibility of research evidence.

Philosophy↗

Validation of professional licensure examinations. Professions theory, test design, and construct validity.

Although the unitary view of test validity has gained support recently, it has real limitations where professional licensing examinations are concerned. A strategy for validation of professional licensure tests requires modifying conventional approaches in three ways. First, a theory of professions must be incorporated into the test development process so as to acknowledge the social character of professions. Second, the importance of test design in the validation of licensing tests should be enhanced. Third, the concept of construct validation must be expanded to accommodate the special features of content that inhere to professional licensure testing. Methods for accomplishing these three things are described and the implications of these and other views discussed.

Cognition↗

Research validity scales for the NEO-PI-R: development and initial validation.

The purpose of this investigation was to develop a set of research validity scales for use with the NEO Personality Inventory-Revised (NEO-PI-R; Costa & McCrae, 1992b). In study 1 we used the existing NEO-PI-R item pool to select items for three validity scales: positive presentation management, negative presentation management, and inconsistency. Several iterative item and scale analyses were conducted, using multiple criteria for item selection. These analyses resulted in 10-item scales. In Study 2, the internal consistency, interscale relationships, and normative characteristics were examined in a separate sample of working adults. In Study 3, the validity of the scales was examined by contrasting five sets of NEO-PI-R protocols: from a separate sample of working adults, from a sample of 100 NEO-PI-R protocols with randomly produced responses, and from three samples of undergraduates completing the NEO-PI-R under different instructional sets. Analyses revealed that both the research validity scales and the NEO-PI-R domain scales were sensitive to group differences. issues relating to the appropriate use of the scales are discussed.

Journal Article↗

Concurrent validity of the MacAndrew Alcoholism Scale: mixed-group validation.

The concurrent validity of the MacAndrew Alcoholism Scale (MAC) was assessed using the mixed-group validation procedure described by Dawes and Meehl (1966). Using mixed groups consisting of different proportions of individuals likely to become alcoholic, classified according to their family histories of probable alcohol abuse, the proportions of subjects exceeding various MAC cutting scores were observed. Depending upon the base rates that were assumed, validity coefficients ranging from .82 to 1.02 were obtained when a MAC cutting score of 24 was used. These values are comparable to concurrent validity estimates obtained using known alcoholics.

Adult↗