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PubMed2002

The joint modeling of a longitudinal disease progression marker and the failure time process in the presence of cure.

In this paper we present an extension of cure models: to incorporate a longitudinal disease progression marker. The model is motivated by studies of patients with prostate cancer undergoing radiation therapy. The patients are followed until recurrence of the prostate cancer or censoring, with the PSA marker measured intermittently. Some patients are cured by the treatment and are immune from recurrence. A joint-cure model is developed for this type of data, in which the longitudinal marker and the failure time process are modeled jointly, with a fraction of patients assumed to be immune from the endpoint. A hierarchical nonlinear mixed-effects model is assumed for the marker and a time-dependent Cox proportional hazards model is used to model the time to endpoint. The probability of cure is modeled by a logistic link. The parameters are estimated using a Monte Carlo EM algorithm. Importance sampling with an adaptively chosen t-distribution and variable Monte Carlo sample size is used. We apply the method to data from prostate cancer and perform a simulation study. We show that by incorporating the longitudinal disease progression marker into the cure model, we obtain parameter estimates with better statistical properties. The classification of the censored patients into the cure group and the susceptible group based on the estimated conditional recurrence probability from the joint-cure model has a higher sensitivity and specificity, and a lower misclassification probability compared with the standard cure model. The addition of the longitudinal data has the effect of reducing the impact of the identifiability problems in a standard cure model and can help overcome biases due to informative censoring.

Journal Article↗
PubMed2007

A comparison of adaptive allocation rules for group-sequential binary response clinical trials.

In clinical trials to compare two or more treatments with dichotomous responses, group-sequential designs may reduce the total number of patients involved in the trial and response-adaptive designs may result in fewer patients being assigned to the inferior treatments. In this paper, we combine group-sequential and response-adaptive designs, extending recent work on sample size re-estimation in trials to compare two treatments with normally distributed responses, to analogous binary response trials. We consider the use of two parameters of interest in the group-sequential design, the log odds ratio and the simple difference between the probabilities of success. In terms of the adaptive sampling rules, we study two urn models, the drop-the-loser rule and the randomized Pólya urn rule, and compare their properties with those of two sequential maximum likelihood estimation rules, which minimize the expected number of treatment failures. We investigate two ways in which adaptive urn designs can be used in conjunction with group-sequential designs. The first method updates the urn at each interim analysis and the second method continually updates the urn after each patient response, assuming immediate patient responses. Our simulation results show that the group-sequential design, which uses the drop-the-loser rule, applied fully sequentially, is the most effective method for reducing the expected number of treatment failures and the average sample number, whilst still maintaining the nominal error rates, over a range of success probabilities.

Clinical Trials as Topic↗
PubMed2003

Adapter-tagged competitive PCR (ATAC-PCR)--a high-throughput quantitative PCR method for microarray validation.

Adapter-tagged competitive PCR (ATAC-PCR) is an advanced version of competitive quantitative PCR that is characterized by the addition of unique adapters to cDNA derived from each sample RNA. Using multiple adapters, we can accurately measure the relative expression ratios of many samples, with a calibration curve obtained from internal standards included in the same reaction. ATAC-PCR can identify differences in gene expression as small as twofold, even from very small amounts of sample RNA. This technique is suitable for confirming results obtained with cDNA microarrays or differential display, and it can process more than a thousand of genes per day when used in conjunction with a capillary DNA sequencer.

Animals↗
PubMed1985

Effect of manipulative variables on the accuracy of crown wax patterns.

An instrument was developed to carve wax patterns in a reproducible manner. The methods of wax application to the die and wax removal during carving were similar to routine laboratory procedures. The wax patterns were invested in stone with the dies on which they were prepared, and sectioned to allow the determination of their adaptation on sectioned samples. Shrinkage of wax patterns on dies was found to create a marginal gap at shoulders and bevels. Further shrinkage observed after removal from the die was attributed to relaxation of elastic stresses in the wax. Carving of bevels improved adaptation to the die for samples with large gaps at the shoulder. This improved adaptation can be attributed to plastic deformation in the wax bevel. Remodeling of pattern margins was found to improve adaptation to the die, especially if carried out after the pattern was removed and replaced on the die. Remodeling the margin should involve heating with a spatula of a narrow band of wax around the margin up to the axial die wall over the entire shoulder width.

Chemical Phenomena↗
PubMed1995

[The effect of virginiamycin on rumen fermentation in vitro after adaptation of donors to the inoculum].

Virginiamycin is an antibiotic active against grampositive bacteria in the alimentary tract, which is also suitable for supplementation of diets of growing and finishing ruminants. The aim of this work was to specify the effect of virginiamycin on some parameters of rumen fermentation in vitro with inoculi taken from wethers adapted or non-adapted to the virginiamycin intake. Incubations were performed anaerobically at 39 degrees C in serum bottles closed with Bunsen valves. Virginiamycin was added at 0 or 10 mg/l to the rumen fluid diluted with McDougall buffer. Virginiamycin significantly decreased production and utilization of lactic acid, production of methane and decomposition of casein when rumen fluid was taken from non-adapted wethers. Most of its effects disappeared when rumen fluid was sampled from wethers adapted to the virginiamycin intake (100 mg per head daily for 2 months). Adaptation of wethers to virginiamycin was further confirmed by analyses of the rumen fluid which was used for inoculation of in vitro cultures. Molar percentages of acetate, propionate, butyrate and valerate were the same before and after the adaptation. Therefore it can be concluded that the effects of virginiamycin on rumen parameters are not stable and its addition to ruminant diets cannot be recommended, with exception of the milk nutrition period. In the last experiment the stability of virginiamycin in the rumen fluid of adapted wethers was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1997

Rapid RNA isolation without the use of commercial kits: application to small tissue samples.

We describe an adapted version of the Chomczynski and Sacchi [Anal Biochem (1987) 162:156-159] RNA isolation procedure that can be performed in less than 1 h on small (<15 mg) tissue samples, using commonly available reagents. Our modifications included: (1) one rather than two precipitation steps in the aqueous phase with 99% ethanol and (2) elimination of the 1-h incubation step at -20 degrees C. Our adaptations resulted in RNA yield (microg/mg of tissue) and purity (260/280 nm ratios) comparable to those of the original procedure. Furthermore, the isolated RNA was successfully utilized in reverse transcriptase-polymerase chain reaction assays, suggesting that it was essentially free of carry-over contaminants that could inhibit enzymatic reactions. When tested on tissue sample sizes of 7-12 mg, our adapted procedure allowed the recovery of enough total RNA for use in techniques such as Northern blot analysis. Our modified technique is therefore an inexpensive alternative to commercially available kits when isolating good-quality RNA from very small tissue samples, such as those obtained from needle biopsies.

Animals↗
PubMed2006

Measurement properties of the Fagerström Test for nicotine dependence adapted for use in an adolescent sample.

This study uses confirmatory factor analysis to test the factor structure of a modified version of the Fagerström Test for Nicotine Dependence (FTND) in an adolescent sample. Specifically, we test the fit of a two-factor model specification as well as a single-factor solution. This study uses methods that are appropriate to the categorical nature of the items making up the FTND and is the first study to examine the measurement properties of the FTND in a large adolescent sample. Both the two-factor and single-factor model specifications achieved acceptable model fit. It should be noted that these study results speak to the dimensionality of the FTND and not to the dimensionality of a general nicotine dependence construct in adolescents.

Adolescent↗
PubMed2006

A Monte Carlo sampling method of amino acid sequences adaptable to given main-chain atoms in the proteins.

We have developed a computational method of protein design to detect amino acid sequences that are adaptable to given main-chain coordinates of a protein. In this method, the selection of amino acid types employs a Metropolis Monte Carlo method with a scoring function in conjunction with the approximation of free energies computed from 3D structures. To compute the scoring function, a side-chain prediction using another Metropolis Monte Carlo method was performed to select structurally suitable side-chain conformations from a side-chain library. In total, two layers of Monte Carlo procedures were performed, first to select amino acid types (1st layer Monte Carlo) and then to predict side-chain conformations (2nd layers Monte Carlo). We applied this method to sequence design for the entire sequence on the SH3 domain, Protein G, and BPTI. The predicted sequences were similar to those of the wild-type proteins. We compared the results of the predictions with and without the 2nd layer Monte Carlo method. The results revealed that the two-layer Monte Carlo method produced better sequence similarity to the wild-type proteins than the one-layer method. Finally, we applied this method to neuraminidase of influenza virus. The results were consistent with the sequences identified from the isolated viruses.

Amino Acid Sequence↗
PubMedDate not supplied

[Defense mechanisms in soldiers during the period of adaptation to the military environment].

An important role during the adaptation period to the military service in the first three months have the defense mechanisms, which belong to the adaptive functioning of an organism. The aim of this study was to determine the defense mechanisms of soldiers in adaptation to the military environment. The sample consisted of 144 adapted (group A) and 400 nonadapted (group NA) soldiers. The applied instruments were: Social-demographic questionnaire and DSQ-40 (Defense Style Questionnaire--short form). The results of this study show that soldiers of NA group use immature defense mechanisms and soldiers of group A use mature defense mechanisms. A significant correlation existed between soldiers of groups A and NA in the use of: mature defense style (p < 0.01), humor (p < 0.005) and sublimation (p < 0.001). It was concluded that there was a relationship between maturity of defense mechanisms and level of adaptation to the military service and factors of the family environment.

Adaptation, Psychological↗
PubMed1993

51Cr-release assay adapted to a 96-well format sample reading.

The application of the Matrix 96, a direct beta counter, to monitor cell-mediated lympholysis assays (CML) was investigated. Until now, the gamma rays emitted from 51Cr, released in the supernatant of the sample following lysis of targets by effector cells, were read in gamma counters using individual tubes for each sample. The Matrix 96 has been designed to count 96 wells simultaneously for assays performed in 96-well microplates. Aliquots of supernatants were spotted on a 96-well disposable metal spotting plate and dried prior to reading in the Matrix 96. A tight correlation was observed between the counts obtained in the Matrix 96 and a gamma counter, which indicates that the detection of electron capture beta particles emitted from 51Cr was as accurate as reading gamma rays from the same isotope. Both methods confirmed the minimal level of cytotoxicity mediated by unstimulated lymphocytes and the high levels of nonspecific cytolytic activity mediated by lymphokine-activated killer (LAK) cells against several tumor cell lines.

Beta Particles↗
PubMed2002

7-ketocholesterol in human and adapted milk formulas.

In the last few years, a variety of experimental and clinical studies concerning the formation, metabolism, and cellular effects of cholesterol oxidation products (COPs) have been carried out. Nevertheless, a substantial lack of knowledge exists regarding the possible intake of these compounds by the newborn through human and/or adapted formula milk. As far as the pathological role of COPs is concerned, exhaustive studies have shown that since dietary COPs are cytotoxic and atherotoxic, they may lead to adverse effects on health. The aim of this study was to investigate the possible development of cholesterol oxidation in adapted formula and in human milk by comparing the main cholesterol oxidation biomarker (7-ketocholesterol) concentration in both. To do so, the total (bonded and free) 7-ketocholesterol content was measured in ten fresh human mature milk samples and in ten milk adapted formula samples by high performance liquid chromatography and diode array detection. The 7-ketocholesterol human milk content (0.7+/-0.3) was often below the quantifiable limit (0.5 microg/g of extracted lipids) while 7-ketocholesterol adapted milk concentrations were often above (3.6+/-4.0) this limit. The 7-ketocholesterol content of adapted formula samples was significantly higher as compared to human milk samples (P<0.05). This is the first study to provide data concerning the concentrations of cholesterol oxides in human milk and in formula milk. Our results clearly suggest that the manufacturing technologies employed and the nutrient extractive sources play a crucial role in the development of cholesterol oxides in the end product. Careful surveillance has to be paid in order to avoid alteration of bioactive properties of nutrients and/or development of potentially toxic derivative compounds.

Cholesterol↗
PubMed2001

On sample size and inference for two-stage adaptive designs.

Proschan and Hunsberger (1995, Biometrics 51, 1315-1324) proposed a two-stage adaptive design that maintains the Type I error rate. For practical applications, a two-stage adaptive design is also required to achieve a desired statistical power while limiting the maximum overall sample size. In our proposal, a two-stage adaptive design is comprised of a main stage and an extension stage, where the main stage has sufficient power to reject the null under the anticipated effect size and the extension stage allows increasing the sample size in case the true effect size is smaller than anticipated. For statistical inference, methods for obtaining the overall adjusted p-value, point estimate and confidence intervals are developed. An exact two-stage test procedure is also outlined for robust inference.

Biometry↗
PubMed1995

Effect of spatial sampling on grating resolution and letter identification.

The purpose of the study was to determine whether spatial sampling has equivalent effects on visual performance for grating and letter stimuli, two optotypes that are frequently used in the clinical assessment of visual function. Test targets consisted of five-bar square-wave gratings, spatial D6 (sixth derivative of a Gaussian) patterns, or individual Sloan letters, presented for 255 ms in the center of an adapting field. Spatial sampling was introduced by replacing random regions of the targets with occluding elements that had the same luminance as the adapting field, so that only random samples of the test target were visible on each trial. The occluding elements consisted of 4 x 4, 8 x 8, or 16 x 16 pixel arrays (subtending 0.67, 1.33, and 2.67 arcmin, respectively), and the percentage of the test target that remained unoccluded ranged from 3% to 100%. Visual acuity and contrast sensitivity for the spatially sampled targets were measured in two visually normal subjects. Results were compared with the predicted effect of the reduction in effective contrast that was introduced by the sampling paradigm. For grating stimuli the effect of spatial sampling was equivalent to the reduction in effective stimulus contrast produced by the sampling, regardless of occluding-element size. For letter stimuli the reduction in effective stimulus contrast predicted most, but not all, of the loss of visual acuity and contrast sensitivity for sampled targets, and the deficit in performance increased when larger occluding elements were used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Adaptation of sweeteners in water and in tannic acid solutions.

Repeated exposure to a tastant often leads to a decrease in magnitude of the perceived intensity; this phenomenon is termed adaptation. The purpose of this study was to determine the degree of adaptation of the sweet response for a variety of sweeteners in water and in the presence of two levels of tannic acid. Sweetness intensity ratings were given by a trained panel for 14 sweeteners: three sugars (fructose, glucose, sucrose), two polyhydric alcohols (mannitol, sorbitol), two terpenoid glycosides (rebaudioside-A, stevioside), two dipeptide derivatives (alitame, aspartame), one sulfamate (sodium cyclamate), one protein (thaumatin), two N-sulfonyl amides (acesulfame-K, sodium saccharin), and one dihydrochalcone (neohesperidin dihydrochalcone). Panelists were given four isointense concentrations of each sweetener by itself and in the presence of two concentrations of tannic acid. Each sweetener concentration was tasted and rated four consecutive times with a 30 s interval between each taste and a 2 min interval between each concentration. Within a taste session, a series of concentrations of a given sweetener was presented in ascending order of magnitude. Adaptation was calculated as the decrease in intensity from the first to the fourth sample. The greatest adaptation in water solutions was found for acesulfame-K, Na saccharin, rebaudioside-A, and stevioside. This was followed by the dipeptide sweeteners, alitame and aspartame. The least adaptation occurred with the sugars, polyhydric alcohols, and neohesperidin dihydrochalcone. Adaptation was greater in tannic acid solutions than in water for six sweeteners. Adaptation of sweet taste may result from the desensitization of sweetener receptors analogous to the homologous desensitization found in the beta adrenergic system.

Adult↗
PubMed1997

The mechanisms for detecting compressively sampled gratings.

Contrast thresholds for sine-wave gratings are raised when the gratings are compressively sampled into a set of narrow bright bars on a dark background, even though this method of sampling preserves the mean luminance and contrast of the grating. Burr et al. [(1985). Vision Research, 25, 717-727] suggested threshold elevation was due to localized luminance adaptation to the sample bars, whose average peak luminance necessarily increased when fewer bars per cycle were present. Previously, we reported results using decrement-bar compressively sampled gratings (CSGs), which consist of dark sample bars on a bright background, which favoured the local luminance adaptation hypothesis (Kingdom & Rainville, 1995). Here we report experiments that suggest that this hypothesis is untenable. Using increment-bar CSGs (bright sample bars on a dark background) we found that raising background luminance while holding sample bar luminance constant reduced thresholds by as much as a factor of ten. This suggests that it is the contrast of the bars, rather than their luminance, which determines thresholds. Further experiments showed that CSG detection was facilitated by unsampled grating pedestals, and thresholds were elevated when the fundamental was physically cancelled. This implied that CSGs were detected by the same mechanisms as the unsampled gratings from which they are derived. Finally, we provide evidence for the involvement of a dynamic gain control component for increment-bar CSG detection.

Contrast Sensitivity↗
PubMed2000

Quantification of group 5 grass pollen allergens in house dust.

BACKGROUND: It is widely known and accepted that grass pollen is a major outdoor cause of hay fever. However, it is of virtual importance for grass pollen allergic patients with symptoms all the year round to know the concentration of grass pollen allergens in their homes. OBJECTIVE: The main objective of this study was to quantify the amount of grass pollen allergen in mass units (microg Phl p 5) in dust settled indoors and to detect the distribution of allergenic activity in different sampling locations of homes. Furthermore, we studied the seasonal fluctuation of allergen content in dust samples. METHODS: We adapted the two site binding assay for detection of group 5 grass pollen allergens in samples from randomly selected homes in Hamburg (n = 371), Erfurt (n = 396), Hettstedt (n = 353), Zerbst (n = 289) and Bitterfeld (n = 226), Germany. Dust samples were collected from floor of living room (LR), bedroom (BR) or children's room (CR) and mattress (MA) during period of June 1995 to August 1998. The amount of the major grass group 5 allergens was detected in microg/g dust. RESULTS: Phl p 5 was detected in 67% of the samples analysed (n = 4760). The range was between undetectable (< 0.03 microg/g dust) and 81 microg/g dust. Phl p 5 levels were significantly higher in the dust from LR (geometric mean 0.117 microg/g dust) or BR/CR floors (geometric mean 0.098 microg/g dust) than in mattresses (geometric mean 0.043 microg/g dust). We observed seasonal fluctuation of indoor Phl p 5 levels with peak in June but also annual differences. Thus Phl p 5 content indoors reflects also the different quantities of pollen counts of annual courses. During pollination period we found two times higher Phl p 5 levels (0.172 microg/g dust, P < 0.001) than outside of grass pollination season (0.095 microg/g dust). The indoor Phl p 5 levels outside of season seem to be independent of pollination before. We suppose that settled pollen grains or allergenic material from outdoor particles carried indoors via footwear and clothes accumulates in house dust. CONCLUSION: Although we not known how the allergens in settled dust are equilibrated with those in the air, the considerable high level of Phl p 5 in indoor dust even during periods when no grass pollen is present in the atmosphere may be an important cause of pollen-allergy symptoms outside of season.

Air Pollution, Indoor↗