Manipulation of attention in highly and low hypnotizable individuals: a study on verbal priming

This study investigated the effects of manipulation of attention on verbal priming in highly (Highs) and low (Lows) hypnotizable individuals. Priming was evaluated via the word-stem completion task (WSCT). The experimental paradigm consisted of one condition in full-attention and in two conditions with colored words in which attention was directed, respectively, only to the color and to both color and word. No significant differences between Highs and Lows were found in none of the three attentional conditions. However, during encoding in full-attention, Highs showed shorter reaction times (RTs) than Lows. This is in accord with previous evidence of faster simple and choice RTs in Highs than in Lows, and suggests hypnotizability-related differences in arousal, likely driven by a different cognitive control activity. Also, Highs' self-report of interference of color-naming on word-reading suggests possible differences between Highs and Lows in cognitive activity related to mental effort.     

Clinical validation of a blood-based classifier for diagnostic evaluation of asymptomatic individuals with pulmonary nodules

Background

The number of pulmonary nodules detected in the US is expected to increase substantially following recent recommendations for nationwide CT-based lung cancer screening. Given the low specificity of CT screening, non-invasive adjuvant methods are needed to differentiate cancerous lesions from benign nodules to help avoid unnecessary invasive procedures in the asymptomatic population. We have constructed a serum-based multi-biomarker panel and assessed its clinical accuracy in a retrospective analysis of samples collected from participants with suspicious radiographic findings in the Prostate, Lung, Chest and Ovarian (PLCO) cancer screening trial.

Methods

Starting with a set of 9 candidate biomarkers, we identified 8 that exhibited limited pre-analytical variability with increasing clotting time, a key pre-analytical variable associated with the collection of serum. These 8 biomarkers were evaluated in a training study consisting of 95 stage I NSCLC patients and 186 smoker controls where a 5-biomarker pulmonary nodule classifier (PNC) was selected. The clinical accuracy of the PNC was determined in a blinded study of asymptomatic individuals comprising 119 confirmed malignant nodule cases and 119 benign nodule controls selected from the PLCO screening trial.

Results

A PNC comprising 5 biomarkers: CEA, CYFRA 21-1, OPN, SCC, and TFPI, was selected in the training study. In an independent validation study, the PNC resolved lung cancer cases from benign nodule controls with an AUC of 0.653 (p < 0.0001). CEA and CYFRA 21-1, two of the markers included in the PNC, also accurately distinguished malignant lesions from benign controls.

Conclusions

A 5-biomarker blood test has been developed for the diagnostic evaluation of asymptomatic individuals with solitary pulmonary nodules.

     

Polymorphism of the serotonin receptor (5-HTR2A) gene and verbal fluency in normalcy and schizophrenia

To study the effect of the serotonergic brain system on verbal fluency (i.e., the ability to rapidly extract necessary words from the vocabulary), the T102C polymorphism of the serotonin receptor type 2A (5-HTR2A) gene was tested for association with verbal fluency in 108 patients with schizophrenia or schizotypic disorders and 97 mentally healthy individuals. A significant association was observed only in male schizophrenics (N = 67), with homozygotes A2A2 having lower verbal fluency. The results did not support the association between the 5-HTR2A polymorphism and verbal fluency in normalcy, and agree with the assumed contribution of genotype A2A2 to the severity of schizophrenia.     

A novel and simple method of screening compounds for interaction with DNA: A validation study

We report the development of a simple, cost-effective assay for detecting compounds that have the ability to interact with and modify DNA. Potential uses for the assay lie in the areas of early genotoxicity testing of drug candidates, anticancer and antibiotic drug discovery, environmental monitoring and testing in the food, beverage and cosmetics industries. At present the assay has been used to assess direct-acting compounds only and it is yet to be established whether the assay is compatible with bio-activation. The methodology is based on the oxidative reaction of potassium permanganate with pyrimidine bases, which have become perturbed and more reactive by the agent under test. Results are recorded by use of UV/vis spectroscopy. The adaptation to a multi-well plate format provides the capacity for high throughput utilizing small amounts of compounds. Over 100 compounds, comprising different classes of DNA-binding chemicals as well as non-binding controls, have been put through the assay and the results compared with existing genotoxicity testing data from other methods. The assay has shown to be predictive of the results of other genotoxicity testing methods. We have found that the method is overall predictive of 71% of Ames bacterial reverse-mutation test results (where data are given) encompassing both negative and positive results.     

The use of reconstructed human epidermis for skin absorption testing: Results of the validation study

A formal validation study was performed, in order to investigate whether the commercially-available reconstructed human epidermis (RHE) models, EPISKIN, EpiDerm and SkinEthic, are suitable for in vitro skin absorption testing. The skin types currently recommended in the OECD Test Guideline 428, namely, ex vivo human epidermis and pig skin, were used as references. Based on the promising outcome of the prevalidation study, the panel of test substances was enlarged to nine substances, covering a wider spectrum of physicochemical properties. The substances were tested under both infinite-dose and finite-dose conditions, in ten laboratories, under strictly controlled conditions. The data were subjected to independent statistical analyses. Intra-laboratory and inter-laboratory variability contributed almost equally to the total variability, which was in the same range as that in preceding studies. In general, permeation of the RHE models exceeded that of human epidermis and pig skin (the SkinEthic RHE was found to be the most permeable), yet the ranking of substance permeation through the three tested RHE models and the pig skin reflected the permeation through human epidermis. In addition, both infinite-dose and finite-dose experiments are feasible with RHE models. The RHE models did not show the expected significantly better reproducibility, as compared to excised skin, despite a tendency toward lower variability of the data. Importantly, however, the permeation data showed a sufficient correlation between all the preparations examined. Thus, the RHE models, EPISKIN, EpiDerm and SkinEthic, are appropriate alternatives to human and pig skin, for the in vitro assessment of the permeation and penetration of substances when applied as aqueous solutions.     

Analysis of energy saving lamps for use by photosensitive individuals

Due to European legislation, the British government has begun the phase out of incandescent bulbs, to be replaced by energy-saving alternatives. The alternatives that are available on the market are Compact Fluorescent Lamps (CFL), Energy-Efficient Halogens (EEH) and Light Emitting Diodes (LED). Whilst previous research has shown that CFLs emit UVC, UVB and UVA, there is conflicting data available on whether double enveloped CFLs are a safer alternative to single enveloped CFLs for individuals suffering from photosensitivity. The emission spectra of 106 single enveloped CFLs and 65 double enveloped CFLs were measured. There were 17 different models of single enveloped CFLs, including lamps from 6 different manufacturers (ranging from 8-20 W) and 9 models of double enveloped CFLs from 6 different manufacturers (7-15 W). In addition, the emission spectra of 53 LEDs and 56 EEHs were also analysed. The LEDs consisted of 8 different models, from 3 manufacturers, spanning between 2.5 and 12 W. There were 11 models of EEH from 6 different manufacturers with wattages ranging from 28-70 W. In order to reduce sample bias, some bulbs were provided by the lighting industry federation and others were purchased randomly from local retailers. The results validate previous research in that considerable variation exists in the UV emitted from CFLs. This variation in UV levels is true, not only within different makes and models but also, surprisingly, within a box of 8 seemingly identical bulbs supplied by a single manufacturer. It was concluded that double enveloped CFLs do reduce the levels of UVC and UVB and therefore are a safer alternative for photosensitive individuals. However, as some double enveloped CFLs and EEHs do emit UVA at levels that provoke a reaction in the skin of UVA sensitive individuals, newly emerging LEDs that have minimal UV levels may provide a safer alternative.     

The appropriate use of regression equations for the estimation of segmental inertia parameters

Linear regression equations are commonly used in conjunction with experimental data to provide linear relationships between quantities which are dimensionally distinct. In many cases theoretical relationships between such quantities are known and can be used as a basis for non-linear regression equations. This study compares linear and non-linear approaches for estimating the segmental moments of inertia from anthropometric measurements using the data of Chandler et al. [Chandler et al. (1975) Investigation of inertial properties of the human body. AMRL Technical Report 74-137, Wright Patterson Air Force Base. OH.] Right limb data were used to derive the equations while left limb data were used as a cross-validation sample to evaluate the inertia estimates calculated from the equations. For the limb segments the standard error estimates had average values of 21% for the linear equations and 13% for the non-linear equations. Data on a 10 yr-old boy was used to compare the two approaches outside the sample range. The mean percentage residuals were 286% for the linear equations and 20% for the non-linear equations. A set of non-linear equations is provided.     

A note on appropriate use of statistical tests of mutation rates from ordered groups

Recently it was found that the frequency of familial dysautonomia (FD) carriers in Ashkenazi Jews (AJ) was higher in AJ of Polish descent compared to AJ of non-Polish descent. The study population was classified into groups ranging from no to full Polish origin. The statistical procedure used to compare the frequencies of FD carriers did not incorporate this intrinsic ordering of individuals by degree of Polish ancestry. In this paper we describe a test designed to utilize this information and show that it is more powerful than the standard test of equality of proportions. In particular, the p value of the trend test on their data is noticeably lower (0.003) than 0.012 found by the standard test, providing stronger evidence for a relationship between allele frequency and Polish descent.     

Androgens and autistic traits: A study of individuals with congenital adrenal hyperplasia

Testosterone promotes male-typical neural and behavioral development in non-human mammals. There is growing evidence that testosterone exerts similar influences on human development, although the range of behaviors affected is not completely known. This study examined the hypothesis that autistic traits are increased following prenatal exposure to abnormally high levels of testosterone caused by congenital adrenal hyperplasia (CAH). Sixty individuals with CAH (34 female, 26 male) and 49 unaffected relatives (24 female, 25 male) completed the Autism Spectrum Quotient (AQ). Females with CAH scored significantly higher than unaffected females on total AQ score, largely due to enhanced scores on subscales measuring social skills and imagination. These results suggest that prenatal exposure to high levels of testosterone influences some autistic traits and that hormonal factors may be involved in vulnerability to autism.     

Dynamics of acoustical evoked potentials on a background of habituation to verbal stimulus in persons with different individual anxiety levels

Changes in the amplitude and the latencies of peak P300 of acoustical evoked potential on a background of the verbal stimulus novelty loss were used for determination of the brain activity specifity in individuals with various anxiety levels. The increase of the peak P300 latency of acoustical evoked potential on a background of trace processes arising after habituation was determined. This parameter did not depend on an anxiety level. However, the latency change depended on the attentional level to a submitted signal. The peak P300 amplitude in the right temporal cortex field was connected with the anxiety level--there was a growth of amplitude on a habituation background with the low anxious subjects, and with the highly anxious people the changes of this parameter were not observed. The anxiety level has rendered influence to dehabituation reaction. Dehabituation is observed with the low-anxiety subjects.     

National validation study of a cellulose sponge wipe-processing method for use after sampling Bacillus anthracis spores from surfaces

This work was initiated to address the gaps identified by Congress regarding validated biothreat environmental sampling and processing methods. Nine Laboratory Response Network-affiliated laboratories participated in a validation study of a cellulose sponge wipe-processing protocol for the recovery, detection, and quantification of viable Bacillus anthracis Sterne spores from steel surfaces. Steel coupons (645.16 cm(2)) were inoculated with 1 to 4 log(10) spores and then sampled with cellulose sponges (Sponge-Stick; 3M, St. Paul, MN). Surrogate dust and background organisms were added to the sponges to mimic environmental conditions. Labs processed the sponges according to the provided protocol. Sensitivity, specificity, and mean percent recovery (%R), between-lab variability, within-lab variability, and total percent coefficient of variation were calculated. The mean %R (standard error) of spores from the surface was 32.4 (4.4), 24.4 (2.8), and 30.1 (2.3) for the 1-, 2-, and 4-log(10) inoculum levels, respectively. Sensitivities for colony counts were 84.1%, 100%, and 100% for the 1-, 2-, and 4-log(10) inocula, respectively. These data help to characterize the variability of the processing method and thereby enhance confidence in the interpretation of the results of environmental sampling conducted during a B. anthracis contamination investigation.     

The use of spun columns in the purification of double-stranded cDNA appropriate for tailing

A reliable estimation of the efficiency of adding homopolymeric tails to double-stranded cDNA molecules by terminal deoxynucleotidyl transferase is extremely important in the construction of cDNA libraries. Appreciable differences in transformation efficiency result when the homopolymer tails to be annealed are of inadequate length. We report here that the use of a Sephadex G-50 spun column to remove oligo(dT)12-18 frequently coprecipitating in ethanol with the cDNA results in a more dependable estimation of tail lengths.     

A four-state cross bridge model for muscle contraction. Mathematical study and validation

A mathematical model of contracting skeletal muscle is studied. The model is composed by an elastic element (SE) in series with a contractile element (CE) that describes the cross bridge kinetics with a formulation derived by that proposed by Eisenberg and Hill (1978). An analytical study of the system of nonlinear partial differential equations of the model allows the existence and the uniqueness of the solution to be proved. A suitable approach to the numerical solution is defined and a series of numerical tests are performed. These tests lead to select an appropriate set of parameters and allow to compare model predictions and experimental observations on frog skeletal muscle. Work partially supported by M.P.I., by CNR through I.A.N. of Pavia and by HUSPI Project     

A study on the degree of relationship between two individuals

The paper studies the likely degree of relationship between two individuals who could possibly be half sibs. The possible common ancestor was dead, which further complicated the problem. The model used was devised by Thompson [in Rao and Chakraborty (eds): Handbook of Statistics, North-Holland, Amsterdam, 1991] and establishes a correspondence between the possible degree of relationship and certain feasible probability distributions on the number of identical by descent genes. Two statistical approaches are considered: the classical one, in which the maximum likelihood estimation for the parameters of Thompson's model are obtained, and the Bayesian one, in which the test of the hypothesis of half sibs is accompanied by a robustness study.     

Design and validation of a dynamic flow perfusion bioreactor for use with compliant tissue engineering scaffolds

In tissue engineering, flow perfusion bioreactors can be used to enhance nutrient diffusion while mechanically stimulating cells to increase matrix production. The goal of this study was to design and validate a dynamic flow perfusion bioreactor for use with compliant scaffolds. Using a non-permanent staining technique, scaffold perfusion was verified for flow rates of 0.1-2.0 mL/min. Flow analysis revealed that steady, pulsatile and oscillatory flow profiles were effectively transferred from the pump to the scaffold. Compared to static culture, bioreactor culture of osteoblast-seeded collagen-GAG scaffolds led to a 27-34% decrease in cell number but stimulated an 800-1200% increase in the production of prostaglandin E(2), an early-stage bone formation marker. This validated flow perfusion bioreactor provides the basis for optimisation of bioreactor culture in tissue engineering applications.