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PubMed2002

Impact of cardiac catheterization-percutaneous coronary intervention timing on inhospital mortality.

BACKGROUND: It is more convenient and less costly to perform percutaneous coronary interventions (PCIs) in the catheterization laboratory after catheterization, but there is some doubt as to whether it is harmful to patients. Other studies on this topic have been hampered by small sample sizes and an inability to separate patients who underwent PCI after catheterization in the same admission from patients who underwent PCI in a subsequent admission. METHODS: Data from New York's PCI registry were used to develop a statistical model that predicted inhospital mortality based on preprocedural patient characteristics and the timing of the PCI (at same time as catheterization [combined procedure] or in the same admission as catheterization, but not at the same time [staged procedure]). The difference in mortality for the timing options was compared after adjusting for patient risk factors. RESULTS: Patients undergoing combined catheterization and PCI were more likely to have undergone a previous PCI and less likely to have had chronic obstructive pulmonary disease, renal failure, a history of congestive heart failure, carotid disease, or diabetes than patients who underwent a staged procedure. After adjustment for patient risk, there were no significant differences in mortality for the 2 timing options (OR 1.14, P =.38 for combined vs staged procedures). However, patients who underwent combined procedures who had congestive heart failure in the same admission or who had Canadian Cardiovascular Society class IV had odds ratios significantly higher than congestive heart failure patients who underwent staged procedures (OR = 1.59, P =.04 and OR = 1.64, P =.04, respectively). CONCLUSIONS: Combined procedures appear to have mortality as low as staged procedures on average, but are less effective for some groups of high-risk patients.

Aged↗

PubMed2005

De novo cis-regulatory module elicitation for eukaryotic genomes.

Transcription regulation is controlled by coordinated binding of one or more transcription factors in the promoter regions of genes. In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. The number of sites and distances between the sites, however, vary greatly in a module. We propose a statistical model to describe the underlying cluster structure as well as individual motif conservation and develop a Monte Carlo motif screening strategy for predicting novel regulatory modules in upstream sequences of coregulated genes. We demonstrate the power of the method with examples ranging from bacterial to insect and human genomes.

Base Sequence↗

PubMed2002

Soft and hard classification by reproducing kernel Hilbert space methods.

Reproducing kernel Hilbert space (RKHS) methods provide a unified context for solving a wide variety of statistical modelling and function estimation problems. We consider two such problems: We are given a training set [yi, ti, i = 1, em leader, n], where yi is the response for the ith subject, and ti is a vector of attributes for this subject. The value of y(i) is a label that indicates which category it came from. For the first problem, we wish to build a model from the training set that assigns to each t in an attribute domain of interest an estimate of the probability pj(t) that a (future) subject with attribute vector t is in category j. The second problem is in some sense less ambitious; it is to build a model that assigns to each t a label, which classifies a future subject with that t into one of the categories or possibly "none of the above." The approach to the first of these two problems discussed here is a special case of what is known as penalized likelihood estimation. The approach to the second problem is known as the support vector machine. We also note some alternate but closely related approaches to the second problem. These approaches are all obtained as solutions to optimization problems in RKHS. Many other problems, in particular the solution of ill-posed inverse problems, can be obtained as solutions to optimization problems in RKHS and are mentioned in passing. We caution the reader that although a large literature exists in all of these topics, in this inaugural article we are selectively highlighting work of the author, former students, and other collaborators.

Classification↗

PubMed1999

Cycles and trends in cod populations.

Year-to-year fluctuations in fish stocks are usually attributed to variability in recruitment, competition, predation, and changes in catchability. Trends in abundance, in contrast, are usually ascribed to human exploitation and large-scale environmental changes. In this study, we demonstrate, through statistical modeling of survey data (1921-1994) of cod from the Norwegian Skagerrak coast, that both short- and long-term variability may arise from the same set of age-structured interactions. Asymmetric competition and cannibalism between cohorts generate alternating years of high and low abundance. Intercohort interactions also resonate the recruitment variability so that long-term trends are induced. The coupling of age-structure and variable recruitment should, therefore, be considered when explaining both the short- and long-term fluctuations displayed by the coastal cod populations. Resonant effects may occur in many marine populations that exhibit this combination of traits.

Age Factors↗

PubMed2000

Importance of replication in microarray gene expression studies: statistical methods and evidence from repetitive cDNA hybridizations.

We present statistical methods for analyzing replicated cDNA microarray expression data and report the results of a controlled experiment. The study was conducted to investigate inherent variability in gene expression data and the extent to which replication in an experiment produces more consistent and reliable findings. We introduce a statistical model to describe the probability that mRNA is contained in the target sample tissue, converted to probe, and ultimately detected on the slide. We also introduce a method to analyze the combined data from all replicates. Of the 288 genes considered in this controlled experiment, 32 would be expected to produce strong hybridization signals because of the known presence of repetitive sequences within them. Results based on individual replicates, however, show that there are 55, 36, and 58 highly expressed genes in replicates 1, 2, and 3, respectively. On the other hand, an analysis by using the combined data from all 3 replicates reveals that only 2 of the 288 genes are incorrectly classified as expressed. Our experiment shows that any single microarray output is subject to substantial variability. By pooling data from replicates, we can provide a more reliable analysis of gene expression data. Therefore, we conclude that designing experiments with replications will greatly reduce misclassification rates. We recommend that at least three replicates be used in designing experiments by using cDNA microarrays, particularly when gene expression data from single specimens are being analyzed.

DNA, Complementary↗

PubMed2004

Biological control of house flies Musca domestica and stable flies Stomoxys calcitrans(Diptera: Muscidae) by means of inundative releases of Spalangia cameroni(Hymenoptera: Pteromalidae).

The efficacy of the pupal parasitoid Spalangia cameroni Perkins as a biological control agent was tested against house flies Musca domestica Linnaeus and stable flies Stomoxys calcitrans (Linnaeus) in one dairy cattle and two pig installations in Denmark. Weekly releases of S. cameroni from April through to September-October 1999 and 2000 resulted in significant suppressions of house fly populations to below nuisance level, whereas no effect on stable flies was found. Parasitism was significantly higher in the release years compared to the control years, but was below 25% averaged over the fly season for each farm. A statistical model based on a functional relationship between the innate capacity of increase of the two fly species and three explanatory variables (air temperature, fly density and parasitism) provided a fairly good fit to data with the abundances of house flies and stable flies explained mostly by temperature, but intra- and interspecific competition, and parasitism had a significant effect as well. Overall, the model was capable of explaining 14% and 6.6% of the total variation in data for house fly and stable fly, respectively. Spalangia cameroni was the predominant parasitoid to emerge from exposed house fly pupae, but from mid summer onwards Muscidifurax raptor Girault & Sanders (Hymenoptera: Pteromalidae) was also quite common. The study indicated that biological control of house flies can be an efficient alternative to chemical control.

Agriculture↗

PubMed2000

Long-term vestibulo-ocular reflex changes in patients with vestibular ablation.

Long-term changes in the parameters of the vestibulo-ocular reflex (VOR) were evaluated using recently developed multilevel statistical modelling techniques in a group of patients who had undergone ablative inner ear procedures. Data from 84 patients were available for study. The most dramatic recovery in the VOR occurred during the first 60 postoperative days, however, slow changes continued, levelling off at about 120 days. While frequency was a highly significant predictor of outcomes in all parameters, age showed significant predictive value only to phase measures (p = 0.006) and gender had no effect. Sum gain at the lowest frequency tested remained below the 5th percentile and at the higher frequencies remained below the 50th percentile for normal subjects. Phase decreased exponentially, but remained above the 95th percentile for normal subjects, except at the highest frequency where it remained above the 50th percentile. DC bias decreased exponentially, dropping to the 50th percentile by day 146. Asymmetry stayed between the 50th and 95th percentile, except at the highest frequency, where it was at the 50th percentile by day 125.

Female↗

PubMedDate not supplied

Detection of excess disease near an exposure point: a case study.

Many studies have evaluated the likelihood of adverse health effects associated with environmental contamination from point source exposures. Two statistical measures used in these studies are the ratio, R, of the observed to the expected number of cases occurring in the area containing the point and the average distance, D, between the cases and the point. This paper estimates the probability of detecting an association between disease and exposure when one actually exists (power) for R and D for several specific and plausible statistical models. Results are presented in the context of rare diseases such as congenital malformations. The practical implications of using these measures for the evaluation of risk of disease in environmental epidemiologic investigations are discussed.

California↗

PubMed2004

Predicting drug clearance from recombinantly expressed CYPs: intersystem extrapolation factors.

1. Recombinantly expressed human cytochromes P450 (rhCYPs) have been underused for the prediction of human drug clearance (CL). 2. Differences in intrinsic activity (per unit CYP) between rhCYP and human liver enzymes complicate the issue and these discrepancies have not been investigated systematically. We define intersystem extrapolation factors (ISEFs) that allow the use of rhCYP data for the in vitro-in vivo extrapolation of human drug CL and the variance that is associated with interindividual variation of CYP abundance due to genetic and environmental effects. 3. A large database (n = 451) of metabolic stability data has been compiled and used to derive ISEFs for the most commonly used expression systems and CYP enzymes. 4. Statistical models were constructed for the ISEFs to determine major covariates in order to optimize experimental design to increase prediction accuracy. 5. Suggestions have been made for the conduct of future studies using rhCYP to predict human drug clearance.

Algorithms↗

PubMed1997

Ultrasound diagnosis of soft-tissue tumours in the hand and forearm. A prospective study.

PURPOSE: The aim of this prospective investigation was to evaluate the accuracy of certain ultrasound characteristics in diagnosing 5 common types of soft-tissue tumour in the hand and forearm. MATERIAL AND METHODS: The study comprised 50 soft-tissue tumours, diagnosed by ultrasonography or histopathology as belonging to one of 5 soft-tissue tumour groups. The reported ultrasound diagnoses and the histopathological results were compared, and their sensitivity was calculated. A statistical model was applied to the prospective material. The first and second diagnostic alternatives were calculated for each specific tumour and for the whole prospective material. In the second part of this study, the prospective material was combined with a retrospective material of 96 tumours from a previous study. The combined material was analysed and the accuracy of the first and second diagnostic alternatives for each tumour and for the whole material was calculated. RESULTS: The sensitivity for the prospective material was 84%. The correct diagnosis predicted by the model for the combined material was 56% for the first alternative and 79% when the second alternative was included. CONCLUSION: Ultrasonography is useful in the diagnosis of soft-tissue tumours of the hand.

Adult↗

PubMed1995

Statistical description of nucleic acid secondary structure folding.

A simple statistical model describing the folding of nucleic acids is proposed. For long sequences the real configuration of the secondary structure is a quasi equilibrium state that cannot be characterised by minimal free energy. This is because the time required to achieve complete thermal equilibrium considerably exceeds the life-time of the molecule. The formation of the secondary structure is represented as a random walk process in the space of all possible molecular configurations. The quasi equilibrium structure is obtained by successive linking and disruptions of helix segments with probabilities determined by the rate constants of corresponding unimolecular reactions. The probabilities of configurations consisting of all possible compatible helices are calculated. Structures of some t-RNAs and ribosomal RNAs are analysed.

Algorithms↗

PubMed1999

Estimating maximum concentrations for open path monitoring along a fixed beam path.

Researchers have applied open path optical sensing techniques to a variety of workplace and environmental monitoring problems. Usually these data are reported in terms of a path-average (or path-integrated) concentration. When assessing potential human exposures along a beam path, this path-average value is not always informative, since concentrations along the path can vary substantially from the beam average. The focus of this research is to arrive at a method for estimating the upper-bound in contaminant concentrations over a fixed open beam path. The approach taken here uses a statistical model to estimate an upper-bound concentration based on a combination of the path-average and a measure of the spatial variability computed from point samples along the beam path. Results of computer simulations and experimental testing in a controlled ventilation chamber indicate that the model produced conservative estimates for the maximum concentration along the beam path. This approach may have many applications for open path monitoring in workplaces or wherever maximum concentrations are a concern.

Humans↗

PubMed2001

Quantitative structure-retention relationships for gas chromatographic retention indices of alkylbenzenes with molecular graph descriptors.

Quantitative structure-retention relationships (QSRR) represent statistical models that quantify the connection between the molecular structure and the chromatographic retention indices of organic compounds, allowing the prediction of retention indices of novel, not yet synthesized compounds, solely from their structural descriptors. Using multiple linear regression, QSRR models for the gas chromatographic Kováts retention indices of 129 alkylbenzenes are generated using molecular graph descriptors. The correlational ability of structural descriptors computed from 10 molecular matrices is investigated, showing that the novel reciprocal matrices give numerical indices with improved correlational ability. A QSRR equation with 5 graph descriptors gives the best calibration and prediction results, demonstrating the usefulness of the molecular graph descriptors in modeling chromatographic retention parameters. The sequential orthogonalization of descriptors suggests simpler QSRR models by eliminating redundant structural information.

Alkylation↗

PubMed2001

Data visualisation for time series in environmental epidemiology.

BACKGROUND: Data visualisation has become an integral part of statistical modelling. METHODS: We present visualisation methods for preliminary exploration of time-series data, and graphical diagnostic methods for modelling relationships between time-series data in medicine. We use exploratory graphical methods to better understand the relationship between a time-series reponse and a number of potential covariates. Graphical methods are also used to examine any remaining information in the residuals from these models. RESULTS: We applied exploratory graphical methods to a time-series data set consisting of daily counts of hospital admissions for asthma, and pollution and climatic variables. We provide an overview of the most recent and widely applicable data-visualisation methods for portraying and analysing epidemiological time series. DISCUSSION: Exploratory graphical analysis allows insight into the underlying structure of observations in a data set, and graphical methods for diagnostic purposes after model-fitting provide insight into the fitted model and its inadequacies.

Computer Graphics↗

PubMed2003

Alternative statistical approaches to identifying dementia in a community-dwelling sample.

Little attention has been paid to examining the extent to which alternative statistical models may facilitate identification of persons with dementia. Using a sub-sample of the Duke Established Populations for Epidemiologic Studies of the Elderly, two analytical approaches were compared: logistic regression (which focuses on identifying specific characteristics predictive here of dementia), and recursive partitioning methods using tree-based models (which permit identification of the characteristics of those groups with high dementing disorder). In the stepwise multiple logistic regression model which included as potential predictors, gender, age, history of chronic health conditions, scales of basic and instrumental activities of daily living (IADL), and cognitive status, only IADL and cognitive status were significant predictors, with cognitive status the single most important factor. The classification tree approach, which permits identification of the characteristics of those groups with particularly high dementia rates, identified cognitive status as the most important criterion for dementia (as did logistic regression analysis). Among those without cognitive impairment, older age was a risk factor, confirming findings consistently reported in the literature. Among the cognitively impaired, IADL was an important risk factor. Those with five or more IADL problems were further classified into two risk groups, based on number of ADL problems. While classification tree analysis encourages identification of groups at risk, logistic regression encourages targeting of specific characteristics.

Activities of Daily Living↗

PubMedDate not supplied

Identifying the determinants of viable microorganisms in the air and bulk metalworking fluids.

Exposure assessment was conducted for an epidemiologic study of the respiratory effects of exposure to metalworking fluids (MWF). As part of the study, airborne microorganisms were collected with a two-stage microbial impactor, and a sample of the bulk soluble MWF was collected from each machine sump, as well as information about the work environment. These data were then used to develop multivariate statistical models of the determinants bulk MWF and airborne microbial levels. Microbial concentrations in the bulk MWF ranged from 5 x 10(4) to 5 x 10(10) colony-forming units (CFU)/mL, with a geometric mean of 3.4 x 10(7) CFU/mL. The geometric mean airborne microbial level was 182 CFU/m3 (for particles size <8 microm) with a range of 1 to 8,308 CFU/m3. In modeling the determinants of bulk microorganisms, fluid-related factors were the most important characteristics associated with microbial levels, followed by process-related and environmental factors. The final full multivariate model predicted a significant reduction in bulk microbial levels by increasing pH of the fluid and reducing the amount of tramp oil leaking into the fluid. For the airborne microbial models, process-related factors were the major characteristics associated with microbial levels, followed by factors related to worker activities and environmental factors. The final full multivariate model predicted a significant control of airborne microorganisms by increasing worker distance from the machine, reducing the number of machines within 10 feet of the worker, decreasing the bulk microbial levels, and adding machine enclosures. These models can be used to prioritize nonbiocidal interventions to control microbial contamination of the bulk MWF and the air.

Air Microbiology↗

PubMedDate not supplied

A method for estimation of bias and variability of continuous gas monitor data: application to carbon monoxide monitor accuracy.

A method is presented for the evaluation of the bias, variability, and accuracy of gas monitors. This method is based on using the parameters for the fitted response curves of the monitors. Thereby, variability between calibrations, between dates within each calibration period, and between different units can be evaluated at several different standard concentrations. By combining variability information with bias information, accuracy can be assessed. An example using carbon monoxide monitor data is provided. Although the most general statistical software required for these tasks is not available on a spreadsheet, when the same number of dates in a calibration period are evaluated for each monitor unit, the calculations can be done on a spreadsheet. An example of such calculations, together with the formulas needed for their implementation, is provided. In addition, the methods can be extended by use of appropriate statistical models and software to evaluate monitor trends within calibration periods, as well as consider the effects of other variables, such as humidity and temperature, on monitor variability and bias.

Bias↗

PubMed2003

Measuring behaviours and perceptions: Rasch analysis as a tool for rehabilitation research.

Variables present in an individual, for example, independence, pain, balance, fatigue, depression and knowledge, cannot be measured directly (hence the term "latent" variables). They are usually assessed by measuring related behaviours, defined by sets of standardized items. The homogeneity of the different items, and proportionality of raw counts to measure, can only be postulated. In 1960 Georg Rasch proposed a statistical model that complied with the fundamental assumptions made in measurements in physical sciences. It allowed for the transformation of the cumulative raw scores (achieved by a subject across items, or by an item across subjects) into linear continuous measures of ability (for subjects) and difficulty (for items). These 2 parameters, only, govern the probability that "pass" rather than "fail" occurs. The discrepancies between model-expected scores (continuous between 0 and 1) and observed scores (discrete, either 0 or 1) provide indexes of inconsistency of individual subjects, items and classes of subjects. In subsequent years the same principles were extended to rating scales, with items graded on more than 2 levels, and to "many-facet" contexts where, beyond items and subjects, multiple raters, times of administration, etc. converge in determining the observed scores. Rasch modelling has increasing application in rehabilitation medicine. New scales with unprecedented metric validity (including internal consistency and reliability) can be built. Existing scales can be improved or rejected on a sound theoretical basis. In clinical trials the consistency and the linearity of measures of either subjects or raters can be validly matched with those of physical and chemical measures. The stability of the item difficulties across time, cultures, diagnostic groups and time of administration can be estimated, thus making it possible to compare homogeneous measures or foster diagnostic procedures on the reasons for differential item functioning.

Activities of Daily Living↗