Evaluation of a Digene-recommended algorithm for human papillomavirus low-positive results present in a "retest zone"

The Digene Hybrid Capture 2 (hc2) high-risk human papillomavirus (HPV) DNA test (Digene, Gaithersburg, MD) is widely used for triage of women with atypical squamous cells of undetermined significance. Results in a "retest zone" (weakly positive tests) are repeated up to 2 times according to the Digene-recommended algorithm.We studied 56 cervical samples in the retest zone. Specimens were tested by a multiplex polymerase chain reaction (PCR)-based genotyping assay, and relevant cytopathologic results were reviewed. Digene results were compared with a reference standard that combined PCR genotyping and cytopathology results. The first repeated Digene assay yielded a sensitivity of 85.2% and a specificity of 62.1% with false-positive and false-negative rates of 40.0% and 15.4%, respectively. The 22 negative samples underwent a second retest and 18 (82%) were negative by the reference standard. The combined first and second retest sensitivity, specificity, and predictive values remained unchanged from the first retest alone.Repeating specimens in the retest zone is necessary, but a second retest does not offer advantages over the first retest.     

Practice effects and the use of alternate forms in serial neuropsychological testing.

Accurate understanding of practice characteristics, performance stability, and error on neuropsychological tests is essential to both valid clinical assessment and maximization of signal detection for clinical trials of cognitive enhancing drugs. We examined practice effects in 28 healthy adults. As part of a larger study using donepezil and simulating a Phase I trial, participants were randomized into: placebo, no-treatment and donepezil. Donepezil results are presented elsewhere. Neuropsychological tests were administered in a fixed order for 6 weeks, with alternate forms available for most tests. Despite alternate forms, ANOVAs revealed significant improvements for the pooled control group (placebo and no-treatment) on all tests except Letter Number Sequencing and Trails B. Learning occurred principally in the first three to four sessions. PASAT and Stroop interference showed the greatest learning. Thus, serial assessment with alternate forms may attenuate retest effects on some tests, but continued learning occurs on novel tests or those in which an advantageous test-taking strategy can be identified. Alternate forms and baseline practice sessions may help control early, rapid improvements in clinical trials.     

Implications of short-term retest effects for the interpretation of longitudinal change

Although within-person comparisons allow direct assessments of change, some of the observed change may reflect effects associated with prior test experience rather than the processes of primary interest. One method that might allow retest effects to be distinguished from other influences of change involves comparing the pattern of results in a longitudinal study with those in a study with a very short retest interval. Three short-term retest studies with moderately large samples of adults are used to provide this type of reference information about the magnitude of change, test-retest correlations, reliabilities of change, and correlations of the change in different cognitive variables with each other, and with other types of variables.     

Treatment assessment of learning disabled children: is there a role for frequently repeated neuropsychological testing?

Test/retest practice effects among learning disabled (LD) and non-learning disabled (NLD) children were examined using the Halstead Category Test. Two experimental paradigms were performed. The first compared subjects on successive trials. The second paradigm used a control group to compare second trial performance of the experimental group with first trial performance of the controls. Both paradigms provide evidence of the relative inability of LD children to profit from practice. It is suggested that neuropsychological data can be used for short term test/retest as one indication of the efficacy of treatment intervention for learning disabled children without the practice effect being a significantly confounding variable.     

D-cycloserine enhances memory consolidation in the plus-maze retest paradigm

Prior undrugged exposure to the elevated plus-maze (EPM) alters future behavioral strategy as well as responsivity to conventional anxiolytic agents. This EPM retest phenomenon appears to be dependent upon learning the spatial configuration of the maze on initial exposure and, in particular, the location of the relatively safe enclosed arms. As posttraining administration of the glycineB receptor partial agonist, D-cycloserine (DCS), has been shown to enhance the consolidation of many forms of memory, we have examined the effects of this compound on the EPM retest effect in male mice. The results of Experiment 1 confirmed that 5 min undrugged exposure to the EPM completed abolishes the anxiolytic efficacy of chlordiazepoxide (CDP; 15 mg/kg) on 24 hr retest. In Experiment 2, posttraining administration of DCS (7.5 and 15 mg/kg), but not CDP (15 mg/kg) or DCS (30 mg/kg), significantly and selectively increased time spent in the enclosed arms (and reciprocally decreased open arm exploration) on 24 hr retest, a finding consistent with an enhancement of consolidation. Experiment 3 used a modified EPM retest protocol to assess the effects of posttraining DCS (15 mg/kg) on behavioral responses to CDP (15 mg/kg) challenge on 24 hr retest. Using a 1-min prior exposure regimen that did not compromise the anxiolytic efficacy of CDP in control mice, the results showed that posttraining administration of DCS abolished the anxiolytic response to CDP challenge. These data strongly suggest that the EPM retest effect involves glycineB/NMDA receptor-dependent neuroplasticity. Further studies will be required to identify the neural circuitry involved.     

The "atypical" mycobacteria: recognition and disease association

Although techniques based on immunologic or chromatographic analyses have been described for identifying mycobacteria in clinical laboratories, most microbiologists continue to rely on a series of specialized physiological and biochemical tests for this purpose. The recognition of additional significant species over the past decade has required the addition of more tests to the battery used for mycobacterial identification. This paper will review briefly the taxonomic status of species likely to be encountered in clinical specimens and the most useful tests for characterizing them. Strategies will be presented for using these tests in the most efficient way to provide optimal resolution of taxa without use of an unreasonably large battery of tests. A brief survey of techniques that may become more practical in the future will also be included.     

Selective neurotoxic amygdala lesions in monkeys disrupt reactivity to food and object stimuli and have limited effects on memory

Monkeys with bilateral neurotoxic amygdala lesions and normal monkeys were administered tests of emotional reactivity, recognition memory, and reward association memory. There were 3 main findings. First, monkeys with amygdala lesions performed differently than normal monkeys on initial administrations of the emotional reactivity tests and on retests that were given 21-23 months after surgery. Second, they performed like normal monkeys on tests of recognition memory. Third, they were initially impaired on a test of reward association memory, but they were not impaired on a retest that was given 16 months after surgery. These findings underscore the role of the amygdala in aspects of emotional reactivity and reward association memory, but not in recognition memory. In addition, at least some of the behavioral effects of amygdala damage can be long lasting.     

Unreliability of IgE/IgG4 antibody testing as a diagnostic tool in food intolerance

BACKGROUND: Some clinicians link chronic disease in certain patients to 'food intolerance'. This is currently diagnosed by exclusion dieting, a time-consuming and tedious technique. It has been claimed that IgE/IgG4 antibody testing is a rapid and valid method of determining food intolerance. OBJECTIVE: To determine the test/retest reliability of IgE/IgG4 antibody testing as a diagnostic tool. METHODS: Blinded testing of duplicate blood samples from nine patients with suspected food intolerance was undertaken by tertiary referral centre using the services of a commercial laboratory. The proportions of consistent and inconsistent results for tests of 95 different foods were analysed. RESULTS: Test/retest reliability was low. Even though the study method systematically overestimated kappa, this value never exceeded 0.51, regardless of the statistical model used. All but one patient had a greater number of inconsistent results than had been prespecified as an unacceptable level of disagreement. In one case, 50 out of 95 test results were inconsistent on retest. CONCLUSIONS: We found no evidence that IgE/IgG4 antibody testing as performed by this laboratory is a reliable diagnostic tool.     

A rapid assay for evaluation of antiviral activity against coxsackie virus B3, influenza virus A, and herpes simplex virus type 1

In order to identify new potential antiviral drugs, small amounts of extracts or compounds have to be examined for cytotoxicity and antiviral activity in primary screening using a rapid, easy, inexpensive, and highly standardised test system. In this study, high-throughput cytopathic effect (CPE) inhibitory assays were established for coxsackie virus B3 on HeLa Ohio cells, influenza virus A on Madin-Darby canine kidney cells, and herpes simplex virus type 1 (HSV-1) on green monkey kidney cells that meet these requirements. The cytotoxic and the antiviral effects were quantified using a crystal violet uptake assay allowing automated handling of large numbers of candidate agents. To ensure comparable results with plaque reduction assays, the 50 and 90% plaque inhibitory concentrations of guanidine, amantadine, and phosphonoformic acid were used to standardise the anti-coxsackie virus B3, anti-influenza virus A, and anti-HSV-1 tests, respectively. The strong correlation between the antiviral activity determined by CPE-inhibitory assays and plaque reduction assay was further proved for other antivirals. In summary, low amounts of large numbers of compounds may be tested inexpensively and standardised within 24 h (coxsackie virus B3 and influenza virus A) or 48 h (herpes simplex virus type 1) post-infection using CPE inhibitory assays.     

Three patterns of brain damage of the WAIS.

Compared four groups of matched Ss (40 each) in order to examine different subtest patterns of brain damage on the WAIS, using F-tests and age mean profiles. The groups were: Normals, diffuse cortical degeneration, right and left hemisphere damage. The results indicated three patterns: (1) a normal pattern; (2) a diffuse degenerative and right hemisphere pattern; and (3) a left hemisphere pattern. The diffuse degenerative results were not significantly different from the right hemisphere results. The left hemisphere pattern had no large verbal vs. performance differences. These patterns appear to be produced by the interaction of three brain damage effects: (1) a general effect; (2) a right hemisphere effect; and (3) a left hemisphere effect. Verbal tests are both "hold" and left hemisphere tests, while three Performance Tests are "don't hold" and right hemisphere tests. The WAIS requires other specific tests of brain damage for an adequate assessment of brain damage.     

Sugar "allergy" and children's behavior

Sixteen children whose behavior was said to become aggressive, overly active, loud, and noncompliant when ingesting sugar were tested. Sugar-free home diet was maintained and an "open" challenge to a large dose (3 g/kg) of candy bar sucrose was given. Subsequent behavior was noted by actometer, quantitative playroom observation using several standard behavioral tests, and ability to do maze drawings. No significant changes were found on the open challenge test. A slight change from baseline was noted in seven cases on three or four behavioral parameters. Five of these children agreed to a double-blind challenge test utilizing lemon-flavored slushes of sucrose, honey, tapioca starch, or aspartame, administered after a standard lunch free of sucrose. One child reacted to both sucrose and honey and another child reacted only to sucrose. These two children were challenged a second time. The child who reacted to honey again did so according to actometer readings, but this time not by Stony Brook test. To sugar, he reacted only at the 70-minute Stony Brook. The other child reacted to placebo instead of sucrose when rechallenged. The results indicate that high doses of sugar are not related to abnormal behavior. "Open" challenge was sufficient to rule out such a relationship in most instances. A repeated double-blind challenge confirmed the absence of a sugar effect in cases showing initial possibility of response.     

Tests of Association Between Quantitative Traits and Haplotypes In A Reduced-Dimensional Space

Candidate gene association tests are currently performed using several intragenic SNPs simultaneously, by testing SNP haplotype or genotype effects in multifactorial diseases or traits. The number of haplotypes drastically increases with an increase in the number of typed SNPs. As a result, large numbers of haplotypes will introduce large degrees of freedom in haplotype‐based tests, and thus limit the power of the tests. In this study we propose using the principal component method to reduce the dimension, and then construct association tests on the lower‐dimensional space to test the association between haplotypes and a quantitative trait using population‐based samples. The proposed method allows ambiguous haplotypes. We use simulation studies to evaluate the type I error rate of the tests, and compare the power of the proposed tests with that of the tests without dimension reduction, and the tests with dimension reduction by merging rare haplotypes. The simulation results show that the proposed tests have correct type I error rates and are more powerful than other tests in most cases considered in our simulation studies.     

Assessing cognitive change in Parkinson's disease: development of practice effect-corrected reliable change indices.

Serial assessments of cognitive functioning in individuals with Parkinson's disease (PD) are commonly used for the detection of incident dementia and neurobehavioral changes associated with treatments using neuromodulation (e.g., deep brain stimulation) and pharmacological agents (e.g., cholinesterase inhibitors). This study provides test-retest stability, expected practice effects, and practice-corrected reliable change indices for several commonly used neuropsychological tests from 62 older adults with mostly mild PD who underwent repeat evaluations approximately 17 months apart. At the group level, results showed adequate test-retest reliability (Spearman's rho range=0.24-0.86) and generally small practice effects (Cohen's d range=0.00-0.50). Application of reliable change indices using 90% confidence intervals showed the expected number of individuals (generally 10% or fewer) with statistically meaningful improvements (range=0-12%) or declines (range=2-8%) in cognitive performance at retest. Limitations discussed include ceiling effects at test baseline, sample homogeneity, interpretative cautions, and generalizability of study results. These data may be useful to researchers and clinicians interested in determining the statistical significance of changes in cognitive test performance in persons with PD over a 1- to 2-year interval.     

Effect sizes, statistical power and sample sizes in "the Japanese Journal of Psychology"

This study analyzed the statistical power of research studies published in the "Japanese Journal of Psychology" in 2008 and 2009. Sample effect sizes and sample statistical powers were calculated for each statistical test and analyzed with respect to the analytical methods and the fields of the studies. The results show that in the fields like perception, cognition or learning, the effect sizes were relatively large, although the sample sizes were small. At the same time, because of the small sample sizes, some meaningful effects could not be detected. In the other fields, because of the large sample sizes, meaningless effects could be detected. This implies that researchers who could not get large enough effect sizes would use larger samples to obtain significant results.     

Relationship between age and IQ among fragile X males: a multicenter study

Longitudinal decline in IQ among fragile X males was reported recently. However, there are problems in retesting IQ that may affect scores. Two such factors are intertest time interval and score obtained on the first test. To determine the generality of IQ score changes, we examined 101 fragile X males from 6 centers. To ensure high test-retest reliability, only results from Stanford-Binet and Wechsler tests were used. Thus there were retest scores from 60 subjects. Test-retest reliability between first and last scores was very good (r = 0.85) and comparable to those seen in nonfragile X mentally retarded individuals. Also computed were z-scores of differences in IQ scores. The z-score differences were distributed about a mean at 1 SD below the expected zero value. Eighteen subjects showed statistically significant decreases in IQ, 6 showed statistically significant increases, while 5 showed the same scores. Z-score differences were not correlated with type of residence or elapsed intertest interval, but were negatively correlated with first score obtained, indicating a regression-to-the-mean effect. Using a multiple regression analysis, we found first score obtained, age tested, and age retested significant predictors of score differences, accounting for 19% of the total variance. These results suggest that factors previously identified as affecting retest scores have a smaller effect than originally thought. It is suspected that decline in IQ is associated with dynamic neurological processes and needs to be investigated further.     

"Side effects" of ECT are mainly depressive phenomena and are independent of age

BACKGROUND: The aetiology of reported side effects of electroconvulsive therapy (ECT) is unclear. We examined the interaction of depression and age on adverse neuropsychological and putative side effects of ECT. METHOD: Inpatients (N=81; median age 70 years) with major depression were assessed prospectively pre-ECT, immediately post-ECT and 1-3 years later. Patients were administered the Hamilton Rating Scale for Depression (HRSD), the Global Assessment of Functioning scale (GAF) and neuropsychological tests from the Wechsler Memory Scale. Side effects and total burden scores were rated pre- and post-treatment. RESULTS: HRSD and GAF scores improved with treatment after ECT, but the prevalence and total burden of side effects were unchanged. Side effect burden was related to depression level before and after ECT. Improvement in depression correlated with reduction in side effect burden. There was a significant decline in side effect burden after controlling for change in depression. Patients' scores on neuropsychological measures did not appear to change after ECT or between pre-ECT and follow-up. Re-analysis, allowing for age, chronicity of depression, medication use and development of dementia, did not alter the findings. LIMITATIONS: lack of a control group, lack of information on ECT technique, incomplete data sets and limited neuropsychological testing. CONCLUSIONS: ECT, an effective treatment for depression, does not cause significant side effects or neuropsychological impairment, which are more likely to be depressive phenomena. ECT appears to be safe for old (> or =65 years) and very old (> or =75 years) patients, who do not appear to be more susceptible to adverse effects.     

Effect of repeated administration of a neuropsychological battery in the elderly.

Our study explored the magnitude of practice effect in repeated administration of NP measures that tap different cognitive domains in normal elderly subjects (N = 122) between ages 57 and 85, who were evaluated over three annual testing probes. Results revealed that WAIS-R PIQ, serial recall of words, WMS visual memory, and memory for logical passages (immediate and delayed) are likely to improve on the retest due to practice effect in individuals below age 75, whereas test-retest changes in older people show a different pattern. Implications of age-specific changes on retest for differential diagnosis of dementia in clinical practice were considered.     

Improving biobank consent comprehension: a national randomized survey to assess the effect of a simplified form and review/retest intervention

PurposeTo determine the individual and combined effects of a simplified form and a review/retest intervention on biobanking consent comprehension.MethodsWe conducted a national online survey in which participants were randomized within four educational strata to review a simplified or traditional consent form. Participants then completed a comprehension quiz; for each item answered incorrectly, they reviewed the corresponding consent form section and answered another quiz item on that topic.ResultsConsistent with our first hypothesis, comprehension among those who received the simplified form was not inferior to that among those who received the traditional form. Contrary to expectations, receipt of the simplified form did not result in significantly better comprehension compared with the traditional form among those in the lowest educational group. The review/retest procedure significantly improved quiz scores in every combination of consent form and education level. Although improved, comprehension remained a challenge in the lowest-education group. Higher quiz scores were significantly associated with willingness to participate.ConclusionEnsuring consent comprehension remains a challenge, but simplified forms have virtues independent of their impact on understanding. A review/retest intervention may have a significant effect, but assessing comprehension raises complex questions about setting thresholds for understanding and consequences of not meeting them.Genet Med advance online publication 13 October 2016     

On the “Dependence” of “Independent” Group EEG Sources; an EEG Study on Two Large Databases

The aim of this work is to study the coherence profile (dependence) of robust eyes-closed resting EEG sources isolated by group blind source separation (gBSS). We employ a test–retest strategy using two large sample normative databases (N = 57 and 84). Using a BSS method in the complex Fourier domain, we show that we can rigourously study the out-of-phase dependence of the extracted components, albeit they are extracted so as to be in-phase independent (by BSS definition). Our focus on lagged communication between components effectively yields dependence measures unbiased by volume conduction effects, which is a major concern about the validity of any dependence measures issued by EEG measurements. We are able to show the organization of the extracted components in two networks. Within each network components oscillate coherently with multiple-frequency dynamics, whereas between networks they exchange information at non-random multiple time-lag rates.     

Low intensity training, inactivity and resumed training in sedentary men

The effects of a low intensity training regimen, consisting of two 7-week periods with an interspersed 8-week inactivity period were investigated in 16 sedentary men. A follow-up was made on 7 subjects after 38 additional weeks' training. Systemic as well as local effects were studied using exercise tests and leg muscle biopsies. The two 7-week training periods both resulted in a 6% increase in Vo2 max and a lowered heart rate during submaximal work. No persisting training effects were detected by exercise tests after inactivity. In skeletal muscle, however, striking differences in enzyme activity pattern and ultrastructure were observed between the two periods, indicating that some training effect of importance for muscle metabolic adaptation might have persisted during inactivity. It is suggested that such an effect might be associated with the local oxygen supply. During the 38-week training period there was a large increase in muscle metabolic capacity, but no change in maximal oxygen uptake. This separation of systemic and local training effects indicates a lack of a direct causal relationship between muscle metabolic potential and max imal oxygen uptake. It is suggested that the elevated muscle oxidative capacity is of importance for an increased endurance capacity.