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PubMed1975

Analytical approach for depth dose calculations (60Co beams with fixed source-target distance).

A method is described to calculate depth dose distribution to a principal plane using analytical formulas for 60Co teletherapy units and constant source-to-target distance. The formulas were derived from experimental measurements taking into consideration the obliquity of the beam. For the purposes of dose calculation the beam was divided into primary and scattered components. A computer program incorporating the formulas was developed for an IBM 360/67 computer. Dose distributions computed and obtained from experimental measurements were in good agreement. The computer program is now in use for treatment planning, including rotational techniques.

Cobalt Radioisotopes↗
PubMed1994

Radially restricted linear energy transfer for high-energy protons: a new analytical approach.

Radially restricted linear energy transfer (LET) is a basic physical parameter relevant to radiation biology and radiation protection. In this report a convenient method is presented for the analytical computation of this quantity without the need for complicated simulation. The method uses the energy-restricted LET L delta, as recently redefined in a 1993 ICRU draft document and supplements it by a relatively simple term that represents the energy of fast delta rays lost within distance r from the track core. The method provides a better fit than other models and is valid over the entire range of radial distance from track center to the maximum radial distance traveled by the most energetic secondary electrons. Lr computed by this approach differs only a few percent from the values obtained from explicit Monte Carlo simulations. The concept applies equally to heavy ions and to electrons.

Linear Energy Transfer↗
PubMed1997

Analytic approaches to longitudinal caries data in adults.

The objective of this paper is to consider current methods for analyzing longitudinal caries data in adults. To illustrate these methods, we used data from the Piedmont dental study, a prospective investigation of the oral health of older adults. Longitudinal dental data sets comprise repeated observations of an outcome (often clustered within randomly selected primary sampling units), and a set of covariates for each of many subjects, in whom clustering can occur as a result of measuring teeth, or surfaces, within people. One objective of statistical analysis is to predict the outcome variable as a function of the covariates, while accounting for the correlation among the repeated observations for a given subject and the effect of clustering within subjects, as well as between subjects within primary sampling units, such as communities, schools, hospitals, or other such units. We considered two statistical approaches: generalized estimating equations and survey regression models. We also examined the impact of varying diagnostic criteria for caries estimation between epidemiologists and clinicians. One approach is to perform the usual time(x) exam score minus time0 score analysis for the baseline and final examinations, while an alternative is to analyze trends among interim examinations. Finally, because caries studies in which the onset of the disease is the endpoint face the problem of censoring due to subject attrition and/or tooth loss, we recommend the incidence density (time-to-event) analytic strategy to address this problem. This approach was found to be most suitable for longitudinal studies of older adults since it accounts for the time each surface remains at risk for the event of interest, making use of interim exam data until the moment the subject and/or the tooth are no longer available for examination. We also included a discussion on biases that occur upon application of the usual methods of estimating caries experience in missing teeth and crowns, which often ignore the classification error in the estimation. We propose a method to adjust for misclassification of the M-component of the DMFS index. In the case where one can observe true reversals or remineralization of caries lesions, we recommend an adjustment formula to account for reversals that are most likely due to examiner misclassification. We provide examples to demonstrate the applicability of the methods for covariates subject to outcome misclassification.

Adult↗
PubMed2005

Management of the patient with suspected temporal arteritis a decision-analytic approach.

OBJECTIVE: To perform a decision analysis of temporal arteritis (TA) to guide clinicians in the interpretation of diagnostic testing and choice of therapy. DESIGN: Computer-based decision analytic model. METHODS: A 785-node decision tree was created that reflects common testing and therapeutic options for a patient with suspected TA. A comprehensive literature search was then performed. From this search, point estimates and distributions for pooled probabilities and utilities were derived using inverse variance weighting and random effects techniques. Employing utility analysis, this decision model selects the diagnostic/therapeutic pathway resulting in the greatest utility for any user-defined set of patient characteristics on presentation. MAIN OUTCOME MEASURE: Using utility analysis, the diagnostic/therapeutic pathway that results in the least expected disutility is selected as the optimal course of action. RESULTS: The choice of diagnostic testing depends on several factors, including patient age, symptoms, and clinical findings. These factors can be used to calculate the pretest probability of TA being present. The optimal selection of diagnostic tests (laboratory or biopsy) depends on the pretest probability of disease. A temporal artery biopsy is recommended under most circumstances, with the choice of a unilateral versus bilateral biopsy depending upon blood test results and calculated pretest probability. A few scenarios exist in which blood tests alone can rule in or rule out TA without the need for biopsy. Empiric steroid therapy is almost never recommended. CONCLUSIONS: In TA, both the disease and its treatment are hazardous for the patient. Clinicians should have a very low threshold to initiate a diagnostic workup for TA. Physicians are often uncertain when a temporal artery biopsy is indicated and whether to perform a unilateral or bilateral biopsy. Often, the pathway chosen is not evidence based. Although the biopsy has long been considered the gold standard for diagnosis, it is invasive and less than 100% sensitive. The decision whether to undertake unilateral or bilateral biopsies is difficult, and our decision model delineates a method for choosing.

Age Distribution↗
PubMed1982

An analytical approach to single photon emission computed tomography with the attenuation effect.

The problem of transverse plane reconstruction from an ensemble of projections is considered in its general formulation and an analytically exact solution to the attenuated tomographic operator is proposed. Such a technique, called the regularizing iterative method (RIM), allows the introduction of a priori knowledge on the size and shape of the activity distribution and in principle on the exact attenuation distribution. The relaxation factor used is so named because it provides noise filtering for a small number of iterations. The effectiveness of RIM was studied in the single photon emission computed tomography (SPECT) problem with the aim of correcting for attenuation before quantitative study. Its application involves the use of a rotating scintillation camera connected to a mini-computer system. Various mathematical and physical phantoms were studied, and a satisfactory attenuation correction was always obtained in the final image with an improvement in the contrast and signal-to-noise ratio. Preliminary clinical studies on liver transverse sections seems to indicate an improvement in deep lesion detectability, compared with images obtained by the filtered (Ramp) back projection technique.

Models, Structural↗
PubMed1994

A multilevel data-analytic approach for evaluation of relationships between daily life stressors and symptomatology: patients with irritable bowel syndrome.

Four statistical strategies were used to evaluate whether occurrence of daily stressors increases lower gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS) patients. Across-subject concurrent correlations between weekly stress and symptoms were positive but casually ambiguous and obscured between- and within-subject and occasion relationships. Multiple regressions assessing (weekly and daily) relations showed that prior symptoms predicted subsequent symptoms but that prior and concurrent daily stress had no consistent effects. Idiographic correlations also showed little evidence for a relationship between stress and symptoms. Daily stress did not appear to increase GI symptoms in IBS patients on a general basis. Daily recording methodology, in conjunction with within-subject analytic strategies, is proposed as an innovative approach to examine relations between stress and physical symptomatology.

Adult↗
PubMed2006

Analytical approach to determine ticlopidine in post-mortem blood.

A new and sensitive method to determine ticlopidine in whole human blood using proadifen as the internal standard (IS) is described. The analyte and IS were extracted by solid-phase extraction using Oasis HLB cartridges, and the extracts were analyzed by gas chromatography-electron impact ionisation-mass spectrometry (GC/EI-MS). Calibration curves were established daily in spiked blood samples using a non-linear calibration model, between 0.01 and 4.5 microg/mL. The correlation coefficients were higher than 0.995. Precision and accuracy fulfilled the internationally accepted criteria (coefficients of variation were less than 9%, and the measured concentrations were within +/-7% of the true value). Limits of detection and quantitation were respectively, 3 and 10 ng/mL. No interfering substances were detected by analysis of 10 blank blood samples of different origin. Mean recovery, calculated at three concentration levels, was 71%. Because of its simplicity and speed, the proposed method can be applied in the determination of this inhibitor of platelet aggregation in whole blood samples, and is suitable for application in toxicology routine analysis.

Chromatography, Gas↗
PubMed2004

Psychometric structure of a comprehensive objective structured clinical examination: a factor analytic approach.

PROBLEM STATEMENT AND BACKGROUND: While the psychometric properties of Objective Structured Clinical Examinations (OSCEs) have been studied, their latent structures have not been well characterized. This study examines a factor analytic model of a comprehensive OSCE and addresses implications for measurement of clinical performance. METHODS: An exploratory maximum likelihood factor analysis with a Promax rotation was used to derive latent structures for the OSCE. RESULTS: A model with two correlated factors fit the data well. The first factor was related to Physical Examination and History-Taking was labeled as information gathering, while the second factor was related to Differential Diagnosis/Clinical Reasoning, and Patient Interaction and was labeled as reasoning and information dissemination. Case Management did not contribute to either factor. The factors accounted for a total 61.6% of the variance in the skills variables. CONCLUSIONS: Recognizing the psychometric components of OSCEs may support and enhance the use of OSCEs for measuring clinical competency of medical students.

Clinical Competence↗
PubMed2005

Analytical approaches for transplant research, 2004.

This article provides detailed explanations of the methods frequently employed in outcomes analyses performed by the Scientific Registry of Transplant Recipients (SRTR). All aspects of the analytical process are discussed, including cohort selection, post-transplant follow-up analysis, outcome definition, ascertainment of events, censoring, and adjustments. The methods employed for descriptive analyses are described, such as unadjusted mortality rates and survival probabilities, and the estimation of covariant effects through regression modeling. A section on transplant waiting time focuses on the kidney and liver waiting lists, pointing out the different considerations each list requires and the larger questions that such analyses raise. Additionally, this article describes specialized modeling strategies recently designed by the SRTR and aimed at specific organ allocation issues. The article concludes with a description of simulated allocation modeling (SAM), which has been developed by the SRTR for three organ systems: liver, thoracic organs, and kidney-pancreas. SAMs are particularly useful for comparing outcomes for proposed national allocation policies. The use of SAMs has already helped in the development and implementation of a new policy for liver candidates with high MELD scores to be offered organs regionally before the organs are offered to candidates with low MELD scores locally.

Data Interpretation, Statistical↗
PubMed1999

Analytical approach to the stochastic FitzHugh-Nagumo system and coherence resonance.

We consider the FitzHugh-Nagumo system under the influence of white Gaussian noise in the excitable regime. We present an analytical approximation in the limit of fast activator time scale. Marginal probability densities of a reduced system and dynamical quantities such as the pulse rate are found and the mean interspike interval and its relative standard deviation are investigated. The latter quantities allow a quantitative description of the phenomenon of coherence resonance, as comparisons with simulations show.

Action Potentials↗
PubMed2000

Multiple maxima of likelihood in phylogenetic trees: an analytic approach.

Maximum likelihood (ML) is a widely used criterion for selecting optimal evolutionary trees. However, the nature of the likelihood surface for trees is still not sufficiently understood, especially with regard to the frequency of multiple optima. Here, we initiate an analytic study for identifying sequences that generate multiple optima. We concentrate on the problem of optimizing edge weights for a given tree or trees (as opposed to searching through the space of all trees). We report a new approach to computing ML directly, which we have used to find large families of sequences that have multiple optima, including sequences with a continuum of optimal points. Such data sets are best supported by different (two or more) phylogenies that vary significantly in their timings of evolutionary events. Some standard biological processes can lead to data with multiple optima, and consequently the field needs further investigation. Our results imply that hill-climbing techniques as currently implemented in various software packages cannot guarantee that one will find the global ML point, even if it is unique.

Evolution, Molecular↗
PubMed2003

Analytical approach to the drift of the tips of spiral waves in the complex Ginzburg-Landau equation.

In this paper, we investigate the motion of spiral waves in the complex Ginzburg-Landau equation (CGLE) analytically and numerically. We find that the tip of the spiral wave drifts primarily in the direction of the electric field and there is a smaller component of the drift that is perpendicular to the field when a uniform field is applied to the system. The velocity of the tip is uniform and its component along the electric field is equal to the strength of the field. When the CGLE system is driven by white noise, a diffusion law for the vortex core of the spiral wave is derived at long time explicitly. The diffusion constant is found to be D=T/C(2), in which T is the noise strength and C is the core asymptotic factor of the spiral wave. When the external force is a simple oscillation we find that the tip of the spiral wave drifts if the frequency of the external force is the same as that of the system. Our analytical results are verified using numerical simulations.

Journal Article↗
PubMed1999

Discovery of cancer susceptibility genes: study designs, analytic approaches, and trends in technology.

Determining the genetic causes of cancers has immense public health benefits, ranging from prevention to earlier detection and treatment of disease. Although a number of cancer susceptibility genes have been successfully identified, design and analytic issues remain that challenge the current paradigm of gene discovery. Some examples are the definition and measurement of cancer phenotype, the use of intermediate end points, the choice of sample (e.g., affected relative pairs versus large extended pedigrees), the choice of analytic method [e.g., parametric logarithm of the odds (LOD) score method versus model-free methods], and the influence of gene-environment interaction on linkage analysis. Furthermore, association methods, based on either the traditional case-control study design or family-based controls, are popular choices to evaluate candidate genes or screen for linkage disequilibrium. Finally, the study design and analytic methods for gene discovery are determined to some extent by what genomic technology is feasible within the laboratory. Many of the main issues related to gene discovery, as well as trends in genomic technology that will impact on gene discovery, are discussed from the perspective of their strengths and weaknesses, pointing to areas in need of further work.

Genes↗
PubMed2005

Comparison of a spatial perspective with the multilevel analytical approach in neighborhood studies: the case of mental and behavioral disorders due to psychoactive substance use in Malmo, Sweden, 2001.

Most studies of neighborhood effects on health have used the multilevel approach. However, since this methodology does not incorporate any notion of space, it may not provide optimal epidemiologic information when modeling variations or when investigating associations between contextual factors and health. Investigating mental disorders due to psychoactive substance use among all 65,830 individuals aged 40-59 years in 2001 in Malmö, Sweden, geolocated at their place of residence, the authors compared a spatial analytical perspective, which builds notions of space into hypotheses and methods, with the multilevel approach. Geoadditive models provided precise cartographic information on spatial variations in prevalence independent of administrative boundaries. The multilevel model showed significant neighborhood variations in the prevalence of substance-related disorders. However, hierarchical geostatistical models provided information on not only the magnitude but also the scale of neighborhood variations, indicating a significant correlation between neighborhoods in close proximity to each other. The prevalence of disorders increased with neighborhood deprivation. Far stronger associations were observed when using indicators measured in spatially adaptive areas, centered on residences of individuals, smaller in size than administrative neighborhoods. In neighborhood studies, building notions of space into analytical procedures may yield more comprehensive information than heretofore has been gathered on the spatial distribution of outcomes.

Adult↗
PubMed2000

Prostate cancer staging: should MR imaging be used?--A decision analytic approach.

PURPOSE: To determine the appropriate use of magnetic resonance (MR) imaging for preoperative staging of prostate cancer. MATERIALS AND METHODS: Literature review was performed by using the principles of evidence-based medicine and medical technology assessment. A decision analytic model was used to compare (a) the strategy that radical prostatectomy is performed on the basis of clinical staging with (b) the strategy that extracapsular disease detected at MR imaging contraindicates radical prostatectomy in patients who were considered surgical candidates on the basis of clinical staging. RESULTS: After review of the literature, expert panel opinion did not recommend MR staging. No studies in which therapeutic efficacy was addressed were found. The decision analytic model indicated that the strategy including MR staging decreased costs (MR imaging, $10,568; radical prostatectomy, $11,669) and resulted in almost equal life expectancy (MR imaging, 12.59 years; radical prostatectomy, 12.60 years) and quality-adjusted life-years ([QALYs] MR imaging, 12.53; radical prostatectomy, 12.52). Results of sensitivity analyses demonstrated that the MR strategy was both more effective and less costly if the prior probability of extracapsular disease was at least 39% when considering QALY and 50% when considering unadjusted life expectancy. CONCLUSION: It is not yet conclusively determined whether preoperative MR staging is appropriate, but results of decision analysis suggest that MR staging is cost-effective for men with moderate or high prior probability of extracapsular disease.

Contraindications↗
PubMed2001

Is the relationship between population density and body size consistent across independent studies? A meta-analytical approach.

The Energetic Equivalence Rule (EER) is a controversial issue in ecology. This rule states that the amount of energy that each species uses per unit of area is independent of its body size. Here, we perform a meta-analytical procedure to combine and compare the slopes of population density and body size relationships across independent studies of mammals and birds. We then compared a distribution of 50,000 bootstrap combined slopes with the expected slope (b = -0.75) under the EER. The combined slopes obtained for mammals and birds separately were -0.755 and -0.321, respectively. The homogeneity hypothesis (i. e. within studies the slopes differ by no more than would be expected due sampling variation) was rejected in both cases. So, EER cannot be supported since the use of an exponent of -0.75 is, in fact, an oversimplification. Significant heterogeneity of slopes within each group (mammals and birds) is an indicator of inferential problems related with variation in body size, spatial scale, the regression model adopted and phylogenetic relationships among species. So, we consider that questions regarding the estimation and validity of slopes is the next challenge of density-body size relationship studies.

Analysis of Variance↗
PubMed2000

Stress distribution in the temporomandibular joint affected by anterior disc displacement: a three-dimensional analytic approach with the finite-element method.

The purpose of this study was to investigate the influences of anterior disc displacement on TMJ loading during maximum clenching by use of finite-element analysis. Based on a young human dry skull, an analytic model of the mandible including the TMJ was developed. In addition to the standard model with normal disc-condyle relation, two models were designed to simulate various degrees of anterior disc displacement. In the standard model, compressive stresses were induced in the anterior, middle and lateral areas on the condyle and glenoid fossa, whereas tensile stresses were observed in the posterior and medial regions. In the models with anterior disc displacement, compressive stresses were recognized in all the areas of TMJ components excluding the bilaminar zone. Shear stresses in the articular disc and bilaminar zone significantly increased in most areas. In conclusion, stress distributions in the TMJ with a normal disc position was substantially different from those with anterior disc displacement, suggesting that the progress in disc displacement may have some association with the nature of stress distributions in the TMJ, in the articular disc in particular.

Bite Force↗
PubMed1990

Analytical approaches to the study of monoclonal antibody stability.

The stability of two purified monoclonal antibodies, MN12 and WT31, was investigated. The monoclonal antibodies were incubated for 32 days at different pH values (ranging from 3.0 to 10.0) at 4 and 37 degrees C. Various analytical methods were used to assess changes in physicochemical properties of the proteins. The monoclonal antibodies were more susceptible to degradation at 37 degrees C than at 4 degrees C. At low pH irreversible precipitation occurred. Decomposition of the proteins was enhanced at increasing pH values in the alkaline range. This was concluded from mouse IgG-specific and antigen-specific enzyme-linked immunosorbent assays, flow cytometry, analytical gel permeation chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isoelectric focusing, and immunoblotting. No substantial change in the apparent affinity constant of MN12 was observed, as determined by an affinity enzyme-linked immunosorbent assay. Fluorescence spectra, fluorescence polarization values, and fluorescence quenching parameters of MN12 and WT31 were not substantially affected, indicating that no major irreversible conformational changes had occurred. It was concluded that each of the techniques used has only limited value for stability assessment of monoclonal antibodies and, hence, that the application of several analytical techniques is essential to gain insight into monoclonal antibody stability.

Animals↗