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PubMed1999

Constructing confidence intervals for cost-effectiveness ratios: an evaluation of parametric and non-parametric techniques using Monte Carlo simulation.

The statistic of interest in most health economic evaluations is the incremental cost-effectiveness ratio. Since the variance of a ratio estimator is intractable, the health economics literature has suggested a number of alternative approaches to estimating confidence intervals for the cost-effectiveness ratio. In this paper, Monte Carlo simulation techniques are employed to address the question of which of the proposed methods is most appropriate. By repeatedly sampling from a known distribution and applying the different methods of confidence interval estimation, it is possible to calculate the coverage properties of each method to see if these correspond to the chosen confidence level. As the results of a single Monte Carlo experiment would be valid only for that particular set of circumstances, a series of experiments was conducted in order to examine the performance of the different methods under a variety of conditions relating to the sample size, the coefficient of variation of the numerator and denominator of the ratio, and the covariance between costs and effects in the underlying data. Response surface analysis was used to analyse the results and substantial differences between the different methods of confidence interval estimation were identified. The methods, both parametric and non-parametric, which assume a normal sampling distribution performed poorly, as did the approach based on simply combining the separate intervals on costs and effects. The choice of method for confidence interval estimation can lead to large differences in the estimated confidence limits for cost-effectiveness ratios. The importance of such differences is an empirical question and will depend to a large extent on the role of hypothesis testing in economic appraisal. However, where it is suspected that the sampling distribution is skewed, normal approximation methods produce particularly poor results and should be avoided.

Computer Simulation↗
PubMed2003

Numerical and exact solutions for continuum of alleles models.

Two results are presented for problems involving alleles with a continuous range of effects. The first result is a simple yet highly accurate numerical method that determines the equilibrium distribution of allelic effects, moments of this distribution, and the mutational load. The numerical method is explicitly applied to the mutation-selection balance problem of stabilising selection. The second result is an exact solution for the distribution of allelic effects under weak stabilising selection for a particular distribution of mutant effects. The exact solution is shown to yield a distribution of allelic effects that, depending on the mutation rate, interpolates between the "House of Cards" approximation and the Gaussian approximation. The exact solution is also used to test the accuracy of the numerical method.

Alleles↗
PubMed2003

Major bleeding complications in cardiopulmonary resuscitation: the place of thrombolytic therapy in cardiac arrest due to massive pulmonary embolism.

OBJECTIVE: Thrombolytic therapy in patients with massive pulmonary embolism (MPE) and prolonged cardiopulmonary resuscitation (CPR) is subject to debate. This study was performed to determine whether (1) thrombolytic treatment increases the risk of bleeding complications, (2) if the risk of bleeding is influenced by the duration of CPR and if (3) thrombolytic therapy improves outcome. DESIGN: Retrospective cohort study. SETTING: Emergency department of a tertiary care university hospital. PATIENTS AND METHODS: Sixty-six patients with cardiac arrest (CA) due to MPE admitted between July 1993 and December 2001. Thirty-six patients received thrombolysis (TL) and were compared with 30 patients without thrombolytic therapy. Bleeding complications were assessed by clinical evidence or autopsy. RESULTS: Major bleeding complications appear to occur more frequently in patients treated with thrombolytics (9/36 (25%) vs. 3/30 (10%)) even though the difference was statistically not significant (P=0.15). It appears that CPR duration >10 min has no adverse impact on major bleeding complications. No difference in the rate of major bleeding complications between thrombolyzed patients who had a CPR duration of </=10 or >10 min could be observed (2/8 (25%) vs. 7/28 (25%), P=0.99). In thrombolyzed patients a return of spontaneous circulation could be achieved more frequently (24/36 (67%) vs.13/30 (43%) in controls, P=0.06) and survival after 24 h was higher (19/36 (53%) vs. 7/30 (23%), P=0.01). Survival to discharge was also higher in the TL group (7/36 (19%) vs. 2/30 (7%)), but not statistically significant (P=0.15). CONCLUSION: Although severe bleeding complications tend to occur more frequently in patients undergoing TL, the benefit of this treatment might outweigh the risk of bleeding.

Adolescent↗
PubMed2003

Theoretical evidence that more microtubules reach the cortex at the pole than at the equator during anaphase in sea urchin eggs.

Astral microtubules are rapidly elongated during anaphase and telophase in sea urchin eggs. The number of microtubules extending to the cell surface was calculated with a computer. For the calculations, microtubules were assumed to radiate from the astral center uniformly over angles. Although microtubules from two asters freely overlapped around the equator, the number per the unit area, i.e. the surface density, was larger in the polar region than in the equatorial region. The ratio of the theoretically calculated numbers in the two regions was close to the ratio obtained from the ultrastructural observations by Asnes and Schroeder in 1979. When counted in the longitudinal section including two astral centers, the microtubule number was a little larger in the equatorial region than in the polar region. However, the numbers do not represent the surface density because the two-dimensional section contains only a small portion of all the microtubules spreading in the three-dimensional space. The fluorescence image for tubulin, in most cases, provides the microtubule distribution in the longitudinal section. Therefore, from such an image, we cannot judge whether the surface density of astral microtubules is larger at the pole or at the equator.

Anaphase↗
PubMed2006

Ramsay-curve item response theory (RC-IRT) to detect and correct for nonnormal latent variables.

Popular methods for fitting unidimensional item response theory (IRT) models to data assume that the latent variable is normally distributed in the population of respondents, but this can be unreasonable for some variables. Ramsay-curve IRT (RC-IRT) was developed to detect and correct for this nonnormality. The primary aims of this article are to introduce RC-IRT less technically than it has been described elsewhere; to evaluate RC-IRT for ordinal data via simulation, including new approaches for model selection; and to illustrate RC-IRT with empirical examples. The empirical examples demonstrate the utility of RC-IRT for real data, and the simulation study indicates that when the latent distribution is skewed, RC-IRT results can be more accurate than those based on the normal model. Along with a plot of candidate curves, the Hannan-Quinn criterion is recommended for model selection.

Area Under Curve↗
PubMed2004

Enhancing scatterplots with smoothed densities.

MOTIVATION: Scatterplots of microarray data generally contain a very large number of dots, making it difficult to get a good impression of their distribution in dense areas. RESULTS: We present a fast and simple algorithm for two-dimensional histogram smoothing, to visually enhance scatterplots. AVAILABILITY: Functions for Matlab and R are available from the corresponding author.

Algorithms↗
PubMed2006

Simulation of the measured ionisation-cluster distributions of alpha-particles in nanometric volumes of propane.

In the last years, the probability of the formation of ionisation clusters by primary alpha particles at 5.4 MeV in nanometric volumes of propane (20.6 and 24.0 nm in a material of density 1.0 g cm(-3)) was studied experimentally and by Monte Carlo simulation. Calculations were performed taking into account the single electron detection efficiency of the track-nanodosimetric counter, which was estimated on the base of Monte Carlo calculations of electron transport inside the detector. Now a new evaluation of the efficiency has been performed, pointing out a value lower than previously estimated. Besides, the efficiency of the counter in resolving temporally the collected electrons has been calculated, together with its effect on the measured distribution. On the base of these evaluations, a new comparison has been performed between measurements and calculations, pointing out a better agreement than previously reported.

Alpha Particles↗
PubMed1978

A field and circuit thermodynamics for integrative physiology. II. Power and communicational spectroscopy in biology.

This paper continues the development begun in Part I (15), to show in what way it is meaningful to reduce biological phenomena to physical theory at any level of organization. The appropriate level-independent physics is comprised of thermostatics, thermodynamics of irreversible processes, statistical mechanics, and nonlinear mechanics. Generalized, these approaches lead to a spectroscopic description of the constellation of periodic processes that constitute the living states. The spectroscopic description is here applied also to the inputs received by living systems, from lethal, high-energy, nuclear particles and radiation to low-energy communicational signals that make up languages understandable at the various levels in an hierarchical system. The concept of language is then itself generalized, showing how the empirical relation discovered by Zipf can be derived from a thermodynamic basis. It is demonstrated that certain linguistic and statistical-mechanical distribution functions can be related. Applications of the field thermodynamic approach to two problems in transport phenomena are given in APPENDIX I; applications of field thermodynamics to language and communication are given in APPENDIX II.

Biological Transport↗
PubMed2004

Synchronous cultures from the baby machine. A model for animal cells.

A baby-machine system that produces newborn Escherichia coli cells from cultures immobilised on a membrane was developed many years ago in an attempt to attain optimal synchrony with minimal disturbance of steady-state growth, and a model designed to characterise the nature and quality of the synchrony of such cells in a quantitative manner has been published. The baby machine has now been adapted for animal cells, and the present article is an attempt to modify the model to include these cells as well. The model consists of five elements, giving rise to five adjustable parameters (and a proportionality constant): a major, essentially synchronous group of cells with ages distributed normally about zero; a minor, random component from a steady-state population on the membrane that had undergone only very little age selection during the elution process; a fixed background count, to allow for the signals recorded by the electronic particle counter produced by debris and electronic noise; a time-shift, to account for differences between time of cell division and end of sample collection; and the coefficient of variation of the interdivision-time distribution, taken to be reciprocal-normal. It is this last feature, a reciprocal-normal rather than a Pearson type III interdivision-time distribution, that distinguishes this version of the model from its predecessor. The model is fitted by unconstrained non-linear least-squares to data from three different leukemia cell lines. The standard errors of the parameters are quite small in all cases, making their estimates highly significant; the quality of the fit is striking. The five parameters of the model can be divided into two nuisance parameters, two that are associated with the methodology and one that describes an inherent property of the cell itself; it turns out that both methodology parameters are zero in all three data sets studied. We also discuss the partition of the transition-time dispersion between the age distribution of the newborn cells and the age distribution of dividing cells and show that a reliable estimate of the corresponding parameters requires an experiment that extends over at least two and a half doubling times.

Animals↗
PubMed1999

Cataract and retinal detachment in patients with severe atopic dermatitis who were withdrawn from the use of topical corticosteroid.

Many patients with severe atopic dermatitis (AD) in Japan are afflicted with persistent erythema of the face (atopic red face) that is not only resistant to topical corticosteroid, but often becomes worse with its use. During a three-year period (1991-1993), we treated 79 inpatients with severe AD by a combination of careful daily skin care, use of emollients, and exclusion of exacerbating factors. Occular complications before and after treatment were examined in these cases. After withdrawal of topical corticosteroid, almost all of the patients showed a temporary worsening of their skin condition. Immediately thereafter, their occular symptoms did not change. Cataract was found in 20 cases (25.3%), and retinal detachment in 9 (11.4%). After 2 months, 11 cases of cataract and 5 cases of retinal detachment in the peripheral retina were observed. However, these incidences were similar to the numbers reported in Japan during conventional treatment with topical corticosteroid. The development of cataract or retinal detachment had no relationship to serum IgE levels, personal history of respiratory atopy, the duration of topical corticosteroid use on the face, or treatment with systemic corticosteroid. Our observations suggest that patients who habitually tap or rub their faces strongly tend to develop cataract or retinal detachment at a statistically significant higher frequency. Patients with AD should have ophthalmologic examinations every one to two months for at least one year after a facial oozing attack or withdrawal of corticosteroid.

Administration, Topical↗
PubMed1984

Population and social security projections for Bangladesh.

The author presents population projections for Bangladesh using data from the 1981 census, U.N. sources, and other official and nonofficial sources. "Confidence intervals for year 1986 and year 2001 populations for Bangladesh are developed. Rural-urban shifts in population are analyzed through Markov chains, and reveal a significant projected redistribution to urban areas. A study is presented of the actuarial cost of a potential social security program designed to meet the financial needs of an increasing set of urban dwellers.... Aggregate projected contributions and benefits for the years 1975, 2005, 2015, and 2025 illustrate the possible program."

Asia↗