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The use of the bootstrap statistical method for the pharmacoeconomic cost analysis of skewed data.

In pharmacoeconomics, the comparison of the costs of 2 different drugs used for the same treatment is of great interest. The problem is especially challenging when the drugs are likely to produce costly adverse effects in a small number of patients, which is often the case. The data are then skewed and traditional statistical methods to analyse the difference in the mean costs produced by 2 treatments may be inappropriate. The bootstrap method is presented as an alternative approach. A pharmacoeconomic cost-analysis example is presented and used throughout this article.

Costs and Cost Analysis↗

Syntactic bootstrapping in children with specific language impairment.

Syntactic bootstrapping was assessed in six children with normally developing language (NL) and six children with specific language impairment (SLI), ages 6 and 8, respectively. Children earned normal range non-verbal IQs and were matched by raw scores on a test of sentence comprehension. They were asked to listen to sentences containing novel verbs and to act out the meanings with toys. The SLI children earned reliably lower scores, but their errors suggested processing limitations rather than deficits in syntactic representation.

Child↗

Bootstrap finance: the art of start-ups.

Entrepreneurship is more popular than ever: courses are full, policymakers emphasize new ventures, managers yearn to go off on their own. Would-be founders often misplace their energies, however. Believing in a "big money" model of entrepreneurship, they spend a lot of time trying to attract investors instead of using wits and hustle to get their ideas off the ground. A study of 100 of the 1989 Inc. "500" list of fastest growing U.S. start-ups attests to the value of bootstrapping. In fact, what it takes to start a business often conflicts with what venture capitalists require. Investors prefer solid plans, well-defined markets, and track records. Entrepreneurs are heavy on energy and enthusiasm but may be short on credentials. They thrive in rapidly changing environments where uncertain prospects may scare off established companies. Rolling with the punches is often more important than formal plans. Striving to adhere to investors' criteria can diminish the flexibility--the try-it, fix-it approach--an entrepreneur needs to make a new venture work. Seven principles are basic for successful start-ups: get operational fast; look for quick break-even, cash-generating projects; offer high-value products or services that can sustain direct personal selling; don't try to hire the crack team; keep growth in check; focus on cash; and cultivate banks early. Growth and change are the start-up's natural environment. But change is also the reward for success: just as ventures grow, their founders usually have to take a fresh look at everything again: roles, organization, even the very policies that got the business up and running.

Capital Financing↗

Bootstrap methods for sex determination from the os coxae using the ID3 algorithm.

This study presents a method for identifying small subsets of morphological attributes of the skeletal pelvis that have consistently high reliability in assigning the sex of unknown individuals. An inductive computer algorithm (ID3) was applied to a bootstrapped training set/test set design in which the model was developed from 70% of the sample and tested on the remaining 30%. Relative accuracy of sex classification was evaluated for seven subsets of 31 morphological features of the adult os coxae. Using 115 ossa coxarum selected from the Terry Collection, a selected suite of the three most consistently diagnostic attributes averaged 93.1% correct classification of individuals by sex over ten trials. Attribute suites developed collaboratively with three well known skeletal experts averaged 87.8, 91.3, and 89.6% correct. The full set of 31 attributes averaged 90.0% accuracy. We demonstrate a small set of three criteria, selected and ordered by ID3, that is more accurate than other combinations, and suggest that ID3 is a useful approach for developing identification systems.

Algorithms↗

The evolution of chiropractic orthopedists: a bootstrapping of clinical skills.

Spanning half of the chiropractic century, the development of the American Board of Chiropractic Orthopedists (ABCO) is a story of an educational bootstrapping that originated from the concerns of practicing field chirporactors. In the post World War II era, a need was determined to develop various principles and procedures of orthopedics in relation to chiropractic practice. Innovative chiropractors sought to promote greater levels of diagnostic precision within the profession by creating a post graduate program to teach advanced methods of physical and neuromusculoskeletal examination and treatment. Various specialty societies emerging after the 1947 creation of the professionally owned, non-profit Los Angeles College of Chiropractic provided a humble beginning for the task. Eventually, with its roots in the National Chiropractic Association, the ABCO and its predecessors were successful in enhancing the education of practicing doctors, instituting similar programs in chiropractic college curricula, contributing papers to chiropractic literature and providing groundwork for early chiropractic research pertaining to musculoskeletal disorders.

Chiropractic↗

Cluster significance testing using the bootstrap.

Many of the statistical methods currently employed to analyze fMRI data depend on a response template. However, the true form of the hemodynamic response, and thereby the response template, is often unknown. Consequently, cluster analysis provides a complementary, template-free method for exploratory analysis of multidimensional fMRI data sets. Clustering algorithms currently being applied to fMRI data separate the data into a predefined number of clusters (k). A poor choice of k will result in erroneously partitioning well-defined clusters. Although several clustering algorithms have been successfully applied to fMRI data, techniques for statistically testing cluster separation are still lacking. To address this problem we suggest a method based on Fisher's linear discriminant and the bootstrap. Also introduced in this paper is a measure based on the projection of multidimensional data from two clusters onto the vector, maximizing the ratio of the between- to the within-cluster sums of squares. The resulting one-dimensional distribution may be readily visualized and used as a heuristic for estimating cluster homogeneity. These methods are demonstrated for the self-organizing maps clustering algorithm when applied to event-related fMRI data.

Algorithms↗

Design as bootstrapping. On the evolution of ICT networks in health care.

OBJECTIVES: This paper assumes that in addressing major challenges related to telemedicine as networks enabling huge improvements of heath services we need to move beyond complexity and rather focus on the very nature of such networks. METHODS: The results of this paper are based on an interpretive analysis of three case studies involving telemedicine, i.e. broadband networks in minimal invasive surgery, EDI infrastructures and telemedicine in ambulances. RESULTS AND CONCLUSION: The well-known concept of "critical mass" focuses on the number of users as a significant factor of network growth. We argue however, that we should not only consider the size of the network, but also the heterogeneity of its elements. In order to discuss heterogeneity along several dimensions, we find Granovetter's and Schelling's models of diversity in individual preferences helpful. In addition to the heterogeneity of the individual users, we discuss heterogeneity related to use areas and situation, to technologies, etc. The interdependencies and possible conflicts between these dimensions are discussed, and we suggest "bootstrapping" as a concept to guide the navigation/exploitation in/of these dimensions.

Ambulances↗

Comparison of preprocessing procedures for oligo-nucleotide micro-arrays by parametric bootstrap simulation of spike-in experiments.

OBJECTIVE: Due to scarcity of calibration data for microarray experiments, simulation methods are employed to assess preprocessing procedures. Here we analyze several procedures' robustness against increasing numbers of differentially expressed genes and varying proportions of up-regulation. METHODS: Raw probe data from oligo-nucleotide microarrays are assumed to be approximately multivariate normally distributed on the log scale. Chips can be simulated from a multivariate normal distribution with mean and variance-covariance matrix estimated from a real raw data set. A chip effect induces strong positive correlations. In reverse, sampling from a normal distribution with strong correlation variance-covariance matrix generates data exhibiting a chip effect. No explicit model of chip-effect is needed. Differences can be artificially spiked-in according to a given distribution of effect sizes. Thirty preprocessing procedures combining background correction, normalization, perfect match correction and summarization methods available from the BioConductor project were compared. RESULTS: In the symmetrical setting "50% differentially expressed genes, 50% of which up-regulated" background correction reduces bias, but inflates low intensity probe variance as well as the mean squared error of the estimates. Any normalization reduces variance and increases sensitivity with no clear winner. Asymmetry between up and down regulation causes bias in the effect-size estimate of non-differentially expressed genes. This markedly inflates the false positive discovery rates. Variance stabilizing normalization (VSN) behaved best. CONCLUSION: A simple parametric bootstrap was used to simulate oligo-nucleotide micro-array raw data. Current normalization methods inflate the false positive rate when many genes show an effect in the same direction.

Computer Simulation↗

Testing separate families of segregation hypotheses: bootstrap methods.

Aspects of the statistical modeling and assessment of hypotheses concerning quantitative traits in genetics research are discussed. It is suggested that a traditional approach to such modeling and hypothesis testing, whereby competing models are "nested" in an effort to simplify their probabilistic assessment, can be complimented by an alternative statistical paradigm - the separate-families-of-hypotheses approach to segregation analysis. Two bootstrap-based methods are described that allow testing of any two, possibly non-nested, parametric genetic hypotheses. These procedures utilize a strategy in which the unknown distribution of a likelihood ratio-based test statistic is simulated, thereby allowing the estimation of critical values for the test statistic. Though the focus of this paper concerns quantitative traits, the strategies described can be applied to qualitative traits as well. The conceptual advantages and computational ease of these strategies are discussed, and their significance levels and power are examined through Monte Carlo experimentation. It is concluded that the separate-families-of-hypotheses approach, when carried out with the methods described in this paper, not only possesses some favorable statistical properties but also is well suited for genetic segregation analysis.

Alleles↗

Circannual bootstrapping complements pattern discrimination in the assessment of endocrine markers for an expansive personality (EP).

The bootstrap distribution of the difference in the circannual mesor of DHEA-S, TSH and LH between healthy adult women of a lowly or highly expansive personality, assessed by scale 9 of an abbreviated Minnesota Multiphasic Personality Inventory, validates the potential classifying role of these hormones, originally singled out by methods of pattern discrimination.

Adult↗

Bootstrapping and added data discriminate, at low blood pressures, neuroendocrine risk of developing mesor-hypertension.

Under room-restricted conditions in a clinical research center, blood pressure and circulating aldosterone and TSH, sampled along 24-h and seasonal scales, reveal differences between small groups of young adult clinically healthy women at high or low risk of developing a high blood pressure. In view of the small sample sizes, data on additional age groups were added and both the original and the extended samples were further analyzed by bootstrapping. Monte Carlo procedures thus applied support the validity of the rhythm-stage-dependent endocrine and blood pressure differences as a function of the risk of developing a high blood pressure.

Aldosterone↗

A bootstrap model for the proximodistal pattern formation in vertebrate limbs.

For the sequential determination of proximodistal structures during the outgrowth of vertebrate limbs, a 'bootstrap'-mechanism is proposed: by increasing feedback of more distally determined cells onto the production of a morphogen at the apical ectodermal ridge a successive increase of the morphogen concentration is achieved during outgrowth. The model accounts for the formation of a progress-zone at the limb tip, for the correct regeneration after truncation, for the presence and absence of proximodistal intercalation after certain graft experiments in amphibian limbs, for the tendency with which distal structures form in proximal position after certain experimental manipulations and for the intimate coupling of the anteroposterior and the proximodistal axes.

Amphibians↗

Dependence of vancomycin clearance on renal function via regression and bootstrap methods.

BACKGROUND: Frequently, the estimation of vancomycin on the basis of renal function is too rough because the unknown parameters of a regression function between the vancomycin clearance (CL) and the creatinine clearance (ClCR) are based on small sample sizes. OBJECTIVE: In this study we aim to compare linear and nonlinear regression, spline interpolation and nonlinear kernel estimation for defining the relationship between measured Cl and ClCR. METHOD: We used data from published papers and appropriate numerical methods. The variability and accuracy of the estimated regression functions were determined from bootstrap methods and kernel density estimators. Tests to prove the usually assumed linearity of the regression were carried out and the influence of patient age and weight on Cl was determined. RESULTS: A linear relationship reported by several authors earlier has been determined as ClVAN = 0.763 ClCR + 2.715, (ml/min) (Cl = 0.011 ClCR + 0.055, (ml/min/ kg)). CONCLUSION: Nonparametric regression analysis shows that a nonlinear approximately parabolic function could fit the relationship between Cl and ClCR in the present case somewhat better than a linear function.

Anti-Bacterial Agents↗