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Magnetization transfer characteristics in atherosclerotic plaque components assessed by adapted binomial preparation pulses.

Increasing the contrast between atheromatous plaque components is a major issue in cardiovascular MRI research. It would allow one to identify unstable plaque by differentiating the lipid core associated with vulnerability, from the fibrous cap, considered as a factor of stability. T2 and diffusion-weighted imaging have already provided satisfying results. Magnetization transfer (MT) between restricted protons Hr and free-water protons Hf could achieve a different contrast related to collagen and lipoprotein macromolecules present in the fibrous cap and lipid core, respectively. The purpose of this work was to evaluate in vitro the MT effect produced by adapted T2-selective 1-3-3-1 binomial pulses on isolated samples of atheromatous arteries at 3 T. A method based on simulation was used in order to improve the MT specificity: it is shown that 50% 1-3-3-1 pulses (the percentage indicating the level of Hr saturation) allow an estimation of T2r, the Hr T2. Using this technique, magnetization transfer was observed for the first time in atherosclerotic plaque components, an effect more pronounced for the fibrous cap and media than for the lipid core and adventitia. The T2r estimation gave values ranging from 20 to 25 micros for the four samples. This preliminary study provides a basis for establishing an MT imaging sequence of atheromatous arteries, by using 50% 1-3-3-1 pulses calibrated for saturating protons with a 20 micros T2. This MT protocol should be further compared to T2 and diffusion-weighted imaging.

Arteriosclerosis↗

Joining genetic linkage maps using a joint likelihood function.

We present an efficient method to join genetic maps derived from different crosses, which is especially appropriate for dominant markers. In contrast to the "JoinMap" algorithm, which estimates information about recombination in a given cross from the LOD values and then combines estimates among crosses assuming a binomial sampling distribution, we construct a joint likelihood function that combines information across all crosses, to obtain a joint estimate of recombination. Simulations indicated that the difference between these two approaches is small when codominant markers are used, but that the joint likelihood approach shows substantially improved estimates when dominant or a mixture of dominant and codominant markers are used. This is because the joint likelihood implicitly finds the optimal weights among different classes of data, while the former method does not accurately predict the information from crosses involving dominant markers. Application of our method is illustrated by the construction of a linkage map for Linanthus using both backcrosses and the F2 of a cross between Linanthus jepsonii and L. bicolor, assayed with amplified fragment length polymorphisms (AFLP).

Chromosome Mapping↗

Accuracy of the Bernoulli equation for estimation of pressure gradient across stenotic Blalock-Taussig shunts: an in vitro and numerical study.

Accurate assessment of the pressure gradient (PG) across a modified Blalock-Taussig (mBT) shunt is important in planning for staging to a cavopulmonary anastomosis for many patients with cyanotic congenital heart disease. The mBT shunt Doppler velocity has been used in the simplified echo Bernoulli equation to predict this PG with variable results. The purpose of this investigation is to provide analysis of the flow dynamics through stenotic mBT shunts and to assess the accuracy of Doppler techniques in determining PGs and the presence and location of stenosis. Three-dimensional models of mBT shunts were created, with and without stenosis. In vitro and computational fluid dynamic flow experiments were carried out. In vitro experiments demonstrated that the Doppler-measured PG underestimated catheter-measured PG in the mBT shunt with diffuse stenosis. In nonstenotic mBT and those that had outlet and inlet stenosis, the Doppler-measured PG showed underestimation of catheter PG at low PG and generally improved estimation at higher PG. In the mBT shunt model with inlet stenosis, there was slight overestimation at higher PG. Numerical simulations provide an "observation window" into events occurring in and around mBT shunts showing that the hemodynamics vary significantly. Changing hemodynamic processes are at work through stenotic mBT shunts causing variations in overestimation and underestimation of catheter-measured PG using the simplified echo Bernoulli equation. Our results have relevance to the assessment of patients with mBT shunts, helping to explain some of the discrepancies that investigators have found in the past.

Binomial Distribution↗

Short-term binding of fibroblasts to fibronectin: optical tweezers experiments and probabilistic analysis.

The biophysical properties of the interaction between fibronectin and its membrane receptor were inferred from adhesion tests on living cells. Individual fibroblasts were maintained on fibronectin-coated glass for short time periods (1-16 s) using optical tweezers. After contact, the trap was removed quickly, leading to either adhesion or detachment of the fibroblast. Through a stochastic analysis of bond kinetics, we derived equations of adhesion probability versus time, which fit the experimental data well and were used to compute association and dissociation rates (k+ = 0.3-1.4 s(-1) and koff = 0.05-0.25 s(-1), respectively). The bond distribution is binomial, with an average bond number < or = 10 at these time scales. Increasing the fibronectin density (100-3000 molecules/microm2) raised k+ in a diffusion-dependent manner, leaving koff relatively unchanged. Increasing the temperature (23-37 degrees C) raised both k+ and koff, allowing calculation of the activation energy of the chemical reaction (around 20 kBT). Increasing the compressive force on the cell during contact (up to 60 pN) raised k+ in a logarithmic manner, probably through an increase in the contact area, whereas koff was unaffected. Finally, by varying the pulling force to detach the cell, we could distinguish between two adhesive regimes, one corresponding to one bond, the other to at least two bonds. This transition occurred at a force around 20 pN, interpreted as the strength of a single bond.

3T3 Cells↗

Effect of roadway geometrics and environmental factors on rural freeway accident frequencies.

This paper explores the frequency of occurrence of highway accidents on the basis of a multivariate analysis of roadway geometrics (e.g. horizontal and vertical alignments), weather, and other seasonal effects. Based on accident data collected in the field, a negative binomial model of overall accident frequencies is estimated along with models of the frequency of specific accident types. Interactions between weather and geometric variables are proposed as part of the model specifications. The results of the analysis uncover important determinants of accident frequency. By studying the relationship between weather and geometric elements, this paper offers insight into potential measures to counter the adverse effects of weather on highway sections with challenging geometrics.

Accidents, Traffic↗

The relationship between truck accidents and geometric design of road sections: Poisson versus negative binomial regressions.

This paper evaluates the performance of Poisson and negative binomial (NB) regression models in establishing the relationship between truck accidents and geometric design of road sections. Three types of models are considered: Poisson regression, zero-inflated Poisson (ZIP) regression, and NB regression. Maximum likelihood (ML) method is used to estimate the unknown parameters of these models. Two other feasible estimators for estimating the dispersion parameter in the NB regression model are also examined: a moment estimator and a regression-based estimator. These models and estimators are evaluated based on their (i) estimated regression parameters, (ii) overall goodness-of-fit, (iii) estimated relative frequency of truck accident involvements across road sections, (iv) sensitivity to the inclusion of short road sections, and (v) estimated total number of truck accident involvements. Data from the Highway Safety Information System are employed to examine the performance of these models in developing such relationships. The evaluation results suggest that the NB regression model estimated using the moment and regression-based methods should be used with caution. Also, under the ML method, the estimated regression parameters from all three models are quite consistent and no particular model outperforms the other two models in terms of the estimated relative frequencies of truck accident involvements across road sections. It is recommended that the Poisson regression model be used as an initial model for developing the relationship. If the overdispersion of accident data is found to be moderate or high, both the NB and ZIP regression models could be explored. Overall, the ZIP regression model appears to be a serious candidate model when data exhibit excess zeros, e.g. due to underreporting. However, the interpretation of the ZIP model can be difficult.

Accidents, Traffic↗

The effect of firm characteristics on truck accidents.

This paper expands an earlier analysis of the effect of firm characteristics and safety practices on truck accident rates. The sample size has been increased from 13,000 to 75,500. Negative binomial regressions are used in preference to the Poisson technique used previously. The current analysis confirms previous results, but provides important new insights into the safety implications of being a private carrier and hauling hazardous materials and the effect of having been in business for many years.

Accidents, Traffic↗

Speed limitation and motorway casualties: a time series count data regression approach.

The paper deals with the effect of a lowered speed limit on the number of accidents in which there are fatalities, injuries and vehicle damage on Swedish motorways. Two models extending the Poisson and negative binomial count data models are used for estimation. The extended models account for both overdispersion and potential dependence between successive counts. The inferences of the parameters depend on the assumed form of overdispersion. It is found that the speed limit reduction has decreased the number of accidents involving minor injuries and vehicle damage. Furthermore, the models allowing for serial correlation are shown to have the best ex ante forecasting performance.

Accidents, Traffic↗

An abstract to concrete shift in the development of biological thought: the insides story.

For more than a century, theorists of cognitive development have embraced some form of the thesis that cognitive development proceeds from concrete to abstract knowledge. In contrast to this view, we suggest an abstract to concrete shift in the development of biological thought. In five studies we examine children's expectations for what could be inside animals and machines and we find that children of all ages respond systematically, revealing abstract expectations for how the insides of animals and machines should differ. By 8 years, children seem to have more concrete expectations for the nature of insides, and are substantially more accurate than preschoolers. More broadly, we suspect that an abstract to concrete progression may capture important features of how knowledge develops in the realm of biological thought and in many other areas of understanding as well.

Age Factors↗

Exact power calculations when the dependent variable is a single proportion and the number of events is small.

This paper presents methods for calculating the exact power to reject the null hypothesis that an observed event rate is significantly lower than a clinically relevant alternative event rate or that the confidence interval is less than a specified range when the hypothesis will be tested using exact binomial confidence intervals. SAS programs that perform the calculations are presented and the results are compared with power calculations using the normal approximation. The method can be extended to studies involving paired comparisons but, in that case, it does not appear to provide a significant advantage over normal approximation methods.

Algorithms↗

Quickbasic program for exact and mid-P confidence intervals for a binomial proportion.

Computation of the exact confidence interval for a binomial proportion is tedious and requires iterative computer techniques. A Quickbasic program for the IBM PC computer is described that accomplishes the confidence interval calculation accurately, quickly, and with no limits placed on the confidence level, or the size of the numerator or denominator. If desired, the mid-P confidence interval can be computed. The compiled program takes one second on the IBM PC 386/33 without a math co-processor.

Algorithms↗

Mucin-containing lozenges in the treatment of intraoral problems associated with Sjögren's syndrome. A double-blind crossover study in 42 patients.

Irreversible hyposalivation is a common sequela of Sjögren's syndrome and may lead to a decreased quality of the patient's life. The aim of this study was to evaluate the efficacy and therapeutic value of mucin-containing lozenges in reducing patients' complaints of hyposalivation. In a double-blind crossover trial in 42 patients with Sjögren's syndrome, the efficacy and therapeutic value of both a mucin-containing and placebo lozenge were assessed by means of self-administered questionnaires, which had to be completed before and after the use of each type of lozenge for a period of 2 weeks. Seventy-six percent of the patients preferred the mucin lozenge, 10% preferred the placebo, and 14% had no preference. In reducing patients' complaints, sucking the mucin lozenge resulted in a larger improvement of the total pattern of complaints and the sensation of oral dryness, and in a longer moistening of the oral cavity than the placebo. Oral functioning was improved after the use of the placebo, and the patients reported the taste of the placebo to be better than the mucin lozenge. From the responses it was concluded that the use of the mucin lozenges can be recommended in the treatment of oral symptoms of xerostomia.

Adult↗

Contribution to the theoretical study of the Doppler half-time method for the measurement of the cross-sectional area of the mitral valve.

The acceleration term is included in the expression of the Bernoulli equation and an application of this formalism to the study of the Doppler measured mitral flow velocity is discussed. Based on calculation of the time-to-time variation of the parameters involved, a possible theoretical explanation of the pressure half-time method for the measurement of the cross-sectional area of the mitral valve is given.

Binomial Distribution↗

Reactions to other corticosteroids in patients with positive patch test reactions to budesonide.

BACKGROUND: Corticosteroid cross-reactions have been classified into four well-defined groups. A previous study of patch test reactions to other corticosteroids in patients allergic to hydrocortisone failed to conform to these groups. It was suggested that substitution at the C6 and C9 positions of the corticosteroid was the most important determinant of a further reaction. OBJECTIVE: Our aim was to analyze multiple positive patch tests to corticosteroids in patients sensitized to budesonide to confirm our earlier findings. METHODS: Forty-six patients with positive patch tests to budesonide were patch-tested to 17 other topical corticosteroids. The results were examined by a generalized linear model and a chi-square test. RESULTS: Substitution of the corticosteroid at the C6 and C9 positions significantly reduced the number of reactions. A different substitution at the C16 and C17 positions was less important, and that at the C21 position was of no significance. CONCLUSIONS: Patients sensitized to budesonide are most likely to react to other non-C6 and non-C9 substituted corticosteroids.

Adrenal Cortex Hormones↗

The use of health services in the management of wound infection.

This study focuses on the use of health services by patients (n = 1100) with a wound infection that warranted compensation in Finland during 1988-1990, under the no-fault insurance scheme instituted in 1987. The use of services covered the basic hospitalization for the operation and the extra use of outpatient and inpatient services. On average, the initial hospital stay for the basic operation was 9.2 days, but the patients required, on average, 33.2 extra hospital days and 3.9 extra outpatient visits. The infection was detected after discharge in 62% of the cases. The probability of any outpatient visits increased (P < 0.05) if the initial hospital stay was short, if the infection was detected after discharge and if the patient was still receiving compensation. The number of extra visits increased if the operation took place in the public sector, if the infection was detected after discharge, if the patient was still receiving compensation and the older the patient was. The probability of any extra days increased if the operation was non-orthopaedic, if it was non-elective, with more than one preoperative day, if the infection was detected in hospital and if the patient was still receiving compensation. The number of extra days increased if the operation was non-elective, if the infection was detected in hospital, if the patient was still receiving compensation, the older the patient and the longer the initial hospital stay.

Aged↗

Exact repeated confidence intervals for Bernoulli parameters in a group sequential clinical trial.

This paper presents methods for constructing exact repeated confidence intervals (RCIs) for the success probability, p, of a single Bernoulli treatment and for the difference of success probabilities, delta = p1-p2, of two independent Bernoulli treatments in the context of a group sequential clinical trial. These RCIs calculated at each interim analysis are useful for evaluating the data in light of all the information available rather than relying on rigid stopping criteria used by repeated significance tests. Extensions to construction of RCIs for the relative risk p = p1/p2 and odds ratio psi = p1(1-p2)/p2(1-p1) are indicated.

Antineoplastic Combined Chemotherapy Protocols↗

A comparison of preoperative and postoperative naproxen sodium for suppression of postoperative pain.

Using a within-subject, crossover experimental design, this study compared the efficacies of a nonsteroidal anti-inflammatory drug, naproxen sodium, 550 mg, administered either 30 minutes preoperatively or 30 minutes postoperatively to 36 patients undergoing the removal of impacted third molar teeth. Pain intensity was assessed postoperatively for 8 hours. Treatment with naproxen sodium, 550 mg, 30 minutes following completion of surgery was just as effective as presurgical administration in controlling postoperative pain. Administration of naproxen sodium in the immediate postoperative period may be indicated for optimum postoperative analgesia for patients in whom preoperative oral intake is contraindicated.

Adolescent↗

Mixed oligo designer (MOD), a computer program to aid planning of automated, mixed oligodeoxyribonucleotide synthesis for mutagenesis experiments.

A computer program, MOD (mixed oligo designer), which aids in planning site-directed mutagenesis experiments using highly substituted oligodeoxyribonucleotides (oligos), is described. The program calculates the relationship between the degree of oligo substitution and the mutation frequency, in order to achieve an optimal level of mutagenesis. The program can be used on a wide variety of computers and runs under a number of different operating systems.

Algorithms↗