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PubMed2001

Potential bias in NMR relaxation data introduced by peak intensity analysis and curve fitting methods.

We present an evaluation of the accuracy and precision of relaxation rates calculated using a variety of methods, applied to data sets obtained for several very different protein systems. We show that common methods of data evaluation, such as the determination of peak heights and peak volumes, may be subject to bias, giving incorrect values for quantities such as R1 and R2. For example, one common method of peak-height determination, using a search routine to obtain the peak-height maximum in successive spectra, may be a source of significant systematic error in the relaxation rate. The alternative use of peak volumes or of a fixed coordinate position for the peak height in successive spectra gives more accurate results, particularly in cases where the signal/noise is low, but these methods have inherent problems of their own. For example, volumes are difficult to quantitate for overlapped peaks. We show that with any method of sampling the peak intensity, the choice of a 2- or 3-parameter equation to fit the exponential relaxation decay curves can dramatically affect both the accuracy and precision of the calculated relaxation rates. In general, a 2-parameter fit of relaxation decay curves is preferable. However, for very low intensity peaks a 3 parameter fit may be more appropriate.

Bias↗

PubMed1988

Selective intraoperative cholangiography. A case for its use on an anatomic basis.

The routine use of intraoperative cholangiography has vastly improved the results of common duct exploration by reducing the number of negative explorations. The controversy surrounding the use of routine versus selective intraoperative cholangiography has centered on the incidence of unsuspected common-duct stones. A prospective study was designed to examine both preoperative clinical data and intraoperative anatomical information to determine criteria that would identify patients who would not require cholangiography. One hundred consecutive patients undergoing cholecystectomy were included in the study. When considering patients without preoperative clinical data suspicious for common duct stones three anatomical conditions were identified in which common duct stones would not be present: cystic duct less than 3 mm; smallest stone size greater than 6 mm; a single stone. Using intraoperative criteria as a basis for cholangiography, 44 per cent of patients without clinical suspicion of common duct stones would be spared an intraoperative cholangiogram. It is the authors' opinion that the addition of anatomic findings to preoperative clinical data can further reduce or eliminate the risk of unsuspected stones while sparing a large number of patients the risk and expense of routine intraoperative cholangiography and possible negative duct exploration.

Adult↗

PubMed2006

A simple imputation method for longitudinal studies with non-ignorable non-responses.

Missing data are a common problem in longitudinal studies in the health sciences. Motivated by data from the Muscatine Coronary Risk Factor (MCRF) study, a longitudinal study of obesity, we propose a simple imputation method for handling non-ignorable non-responses (i.e., when non-response is related to the specific values that should have been obtained) in longitudinal studies with either discrete or continuous outcomes. In the proposed approach, two regression models are specified; one for the marginal mean of the response, the other for the conditional mean of the response given non-response patterns. Statistical inference for the model parameters is based on the generalized estimating equations (GEE) approach. An appealing feature of the proposed method is that it can be readily implemented using existing, widely-available statistical software. The method is illustrated using longitudinal data on obesity from the MCRF study.

Algorithms↗

PubMed2003

PEAKS: powerful software for peptide de novo sequencing by tandem mass spectrometry.

A number of different approaches have been described to identify proteins from tandem mass spectrometry (MS/MS) data. The most common approaches rely on the available databases to match experimental MS/MS data. These methods suffer from several drawbacks and cannot be used for the identification of proteins from unknown genomes. In this communication, we describe a new de novo sequencing software package, PEAKS, to extract amino acid sequence information without the use of databases. PEAKS uses a new model and a new algorithm to efficiently compute the best peptide sequences whose fragment ions can best interpret the peaks in the MS/MS spectrum. The output of the software gives amino acid sequences with confidence scores for the entire sequences, as well as an additional novel positional scoring scheme for portions of the sequences. The performance of PEAKS is compared with Lutefisk, a well-known de novo sequencing software, using quadrupole-time-of-flight (Q-TOF) data obtained for several tryptic peptides from standard proteins.

Amino Acid Sequence↗

PubMed2001

Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a spatial reference system.

The transverse temporal gyrus of Heschl contains the human auditory cortex. Several schematic maps of the cytoarchitectonic correlate of this functional entity are available, but they present partly conflicting data (number and position of borders of the primary auditory areas) and they do not enable reliable comparisons with functional imaging data in a common spatial reference system. In order to provide a 3-D data set of the precise position and extent of the human primary auditory cortex, its putative subdivisions, and its topographical intersubject variability, we performed a quantitative cytoarchitectonic analysis of 10 brains using a recently established technique for observer-independent definition of areal borders. Three areas, Te1.1, Te1.0, and Te1.2, with a well-developed layer IV, which represent the primary auditory cortex (Brodmann area 41), can be identified along the mediolateral axis of the Heschl gyrus. The cell density was significantly higher in Te1.1 compared to Te1.2 in the left but not in the right hemisphere. The cytoarchitectonically defined areal borders of the primary auditory cortex do not consistently match macroanatomic landmarks like gyral and sulcal borders. The three primary auditory areas of each postmortem brain were mapped to a spatial reference system which is based on a brain registered by in vivo magnetic resonance imaging. The integration of a sample of postmortem brains in a spatial reference system allows one to estimate the spatial variability of each cytoarchitectonically defined region with respect to this reference system. In future, the transfer of in vivo structural and functional data into the same spatial reference system will enable accurate comparisons of cytoarchitectonic maps of the primary auditory cortex with activation centers as established with functional imaging procedures.

Adult↗

PubMed2002

Software design for analysis of multichannel intracardial and body surface electrocardiograms.

Analysis of multichannel ECG recordings (body surface maps (BSMs) and intracardial maps) requires special software. We created a software package and a user interface on top of a commercial data analysis package (MATLAB) by a combination of high-level and low-level programming. Our software was created to satisfy the needs of a diverse group of researchers. It can handle a large variety of recording configurations. It allows for interactive usage through a fast and robust user interface, and batch processing for the analysis of large amounts of data. The package is user-extensible, includes routines for both common and experimental data processing tasks, and works on several computer platforms. The source code is made intelligible using software for structured documentation and is available to the users. The package is currently used by more than ten research groups analysing ECG data worldwide.

Algorithms↗

PubMed1995

Approximate entropy (ApEn) as a complexity measure.

Approximate entropy (ApEn) is a recently developed statistic quantifying regularity and complexity, which appears to have potential application to a wide variety of relatively short (greater than 100 points) and noisy time-series data. The development of ApEn was motivated by data length constraints commonly encountered, e.g., in heart rate, EEG, and endocrine hormone secretion data sets. We describe ApEn implementation and interpretation, indicating its utility to distinguish correlated stochastic processes, and composite deterministic/ stochastic models. We discuss the key technical idea that motivates ApEn, that one need not fully reconstruct an attractor to discriminate in a statistically valid manner-marginal probability distributions often suffice for this purpose. Finally, we discuss why algorithms to compute, e.g., correlation dimension and the Kolmogorov-Sinai (KS) entropy, often work well for true dynamical systems, yet sometimes operationally confound for general models, with the aid of visual representations of reconstructed dynamics for two contrasting processes. (c) 1995 American Institute of Physics.

Journal Article↗

PubMed2025

HighDimMixedModels.jl: Robust high-dimensional mixed-effects models across omics data.

High-dimensional mixed-effects models are an increasingly important form of regression in which the number of covariates rivals or exceeds the number of samples, which are collected in groups or clusters. The penalized likelihood approach to fitting these models relies on a coordinate descent algorithm that lacks guarantees of convergence to a global optimum. Here, we empirically study the behavior of this algorithm on simulated and real examples of three types of data that are common in modern biology: transcriptome, genome-wide association, and microbiome data. Our simulations provide new insights into the algorithm's behavior in these settings, and, comparing the performance of two popular penalties, we demonstrate that the smoothly clipped absolute deviation (SCAD) penalty consistently outperforms the least absolute shrinkage and selection operator (LASSO) penalty in terms of both variable selection and estimation accuracy across omics data. To empower researchers in biology and other fields to fit models with the SCAD penalty, we implement the algorithm in a Julia package, HighDimMixedModels.jl.

Algorithms↗

PubMedDate not supplied

Primary care for women. Comprehensive assessment of the respiratory system.

This article reviews the anatomy and physiology of the respiratory system and provides techniques for the physical assessment and data collection for common respiratory complaints in women. The pertinent historical, physical examination, and laboratory data for asthma, pneumonia, bronchitis, cough, and tuberculosis are also presented. This article is the first of two articles on primary care for women with respiratory complaints; the subsequent article will address primary care management of common respiratory conditions.

Female↗

PubMed1996

How common is low back pain in the Nordic population? Data from a recent study on a middle-aged general Danish population and four surveys previously conducted in the Nordic countries.

STUDY DESIGN: Data were obtained in a Danish cross-sectional postal survey and compared with information from four methodologically similar studies conducted in some of the Nordic countries between 1977-1985. OBJECTIVES: The objectives were to estimate the lifetime cumulative incidence and the 1-year period prevalence of low back pain in the general population, to study whether there are any differences in the occurrence of low back pain according to age and sex, and to investigate whether low back pain is on the increase. SUMMARY OF BACKGROUND DATA: The prevalence of low back pain commonly is thought to be high, but estimates differ considerably between studies. It is also not known whether low back pain is more common in men or women or in certain age groups, and it is unclear whether the prevalence of low back pain has increased in the past years. METHODS: Prevalence estimates were established in a current study, and results then were adjusted to suit the age and sex criteria of four previous studies. RESULTS: Between 60-65% of 30- to 50-year-old men and women living in the Nordic countries reported at least one incident of low back pain during their lifetime, based on the information from four studies with a total sample size of 3513. The most likely 1-year period prevalence estimate is between 44-54%, based on two studies and a total sample of 2035 individuals. There was no consistent evidence favoring higher figures with increasing age or relating to any of the genders. No clearly observed time-related trend was noted. CONCLUSIONS: When data were examined from five methodologically similar studies on the 30- to 50-year-old Nordic population, there was reasonable consistency of prevalence figures. Thus, approximately 66% report having had low back pain at least sometime during their lifetime and approximately 50% sometime during the preceding year, with no significant differences relating to age or sex. The best method to investigate whether low back pain is on the increase might be through replicate studies.

Adult↗

PubMed2004

Genetic evidence concerning the origins of South and North Ossetians.

Ossetians are a unique group in the Caucasus, in that they are the only ethnic group found on both the north and south slopes of the Caucasus, and moreover they speak an Indo-European language in contrast to their Caucasian-speaking neighbours. We analyzed mtDNA HV1 sequences, Y chromosome binary genetic markers, and Y chromosome short tandem repeat (Y-STR) variability in three North Ossetian groups and compared these data to published data for two additional North Ossetian groups and for South Ossetians. The mtDNA data suggest a common origin for North and South Ossetians, whereas the Y-haplogroup data indicate that North Ossetians are more similar to other North Caucasian groups, and South Ossetians are more similar to other South Caucasian groups, than to each other. Also, with respect to mtDNA, Ossetians are significantly more similar to Iranian groups than to Caucasian groups. We suggest that a common origin of Ossetians from Iran, followed by subsequent male-mediated migrations from their Caucasian neighbours, is the most likely explanation for these results. Thus, genetic studies of such complex and multiple migrations as the Ossetians can provide additional insights into the circumstances surrounding such migrations.

Chromosomes, Human, Y↗

PubMed1998

Influences of progeny test programs on genetic evaluations of young sires.

Our purpose was to examine differences among AI progeny test programs in their effectiveness in identifying elite young sires for milk and protein. Data were from 6238 Holstein sires in five animal model evaluations of the USDA from January 1995 to February 1997. Bulls were required to be < or = 8 yr of age and to have > or = 10 daughters in production at the time of the evaluation. Bulls in AI programs were placed in nine groups based on affiliation with major AI organizations; from these nine groups, bulls with daughters averaging < 150 DIM and bulls sampled in > 100 herds were placed in two separate groups. Bulls sampled in organizations with controller numbers > or = 30 and bulls that had no connection to a sampling organization formed two additional groups. We also classified bulls by sampling codes of the National Association of Animal Breeders. A model predicting daughter yield deviation included effects of organization or sampling code, parent average (free of progeny information), and the interaction of organization or sampling method and parent average. When all data were used, a common intercept for milk was appropriate for all sampling methods, but the slopes differed (R2 = 0.44). Neither a common intercept nor a common slope was appropriate for protein. When data were restricted to the nine major organizations, a common intercept and slope were appropriate for milk, and R2 decreased to 0.14. A common intercept and slope were found for protein, and R2 decreased to 0.15. We detected no important differences in response to pedigree selection among progeny-testing methods used by major organizations that provide semen, but a difference was detected among the sampling codes of the National Association of Animal Breeders.

Animals↗

PubMed2005

The use of common ontologies and controlled vocabularies to enable data exchange and deposition for complex proteomic experiments.

Controlled vocabularies provide a roadmap through complex biological data. Proteomic data is increasing in volume and is currently poorly served by public repositories due to the large number of different formats in which the data is generated and stored. The Human Proteome Organization Proteome Standards Initiative is establishing standards for data transfer and deposition. These standards utilize ontologies and controlled vocabularies to describe experimental procedures and common processes such as sample preparation This paper will discuss the development of such ontologies by the user community and their current utilization in the fields of protein:proein interactions and mass spectrometry.

Computational Biology↗

PubMed1997

Testing for treatment related trend with partially exchangeable clustered data.

When testing for treatment related effect, it is common to focus on data that describe some primary response, even though an experiment might yield data on secondary, less conspicuous effects. An example of such an experiment can be found in developmental toxicity studies, where a primary response might be the presence of skeletal malformation in a fetus, and a secondary effect might be reduced weight. In such studies, weight reduction may occur not only among malformed fetuses, but also among normal fetuses. In this paper, we use a likelihood ratio procedure to construct treatment related trend tests for developmental experiments with such outcomes. We assume that within each cluster, data are partially exchangeable and we use the presence or absence of malformations as categorical covariates. Two models are considered for the covariance structures: In the general model, partially exchangeable covariance matrices are used for each cluster within dose groups. In the homogeneous model, a common exchangeable covariance matrix is used for all clusters. Maximum likelihood estimates (MLEs) of unknown parameters in the general model are obtained by directly maximizing the log-likelihood function through careful numerical consideration, while MLEs of parameters of teh homogeneous model are obtained through an iterative procedure. Two applications to developmental toxicity data are described.

Abnormalities, Drug-Induced↗

PubMed1999

Willingness to pay as a measure of the benefits of mental health care.

BACKGROUND: Decision-makers would benefit from being able to plan and evaluate mental health care interventions or programmes on the basis of costs and consequences that are measured in the same unit of measurement (money being the most convenient). Monetized quantification of the consequences of alternative interventions could be subsequently incorporated into cost-benefit allocation decisions. AIM: This paper provides an overview of the policy and research context within which willingness-to-pay survey techniques are located, together with a review of the main approaches used to date. We also highlight key issues in the application of these techniques and indicate areas of mental health research and policy that could benefit from their introduction. METHOD: Willingness-to-pay survey techniques are reviewed, and issues concerning their validity and application in the context of cost-benefit analyses of mental health policies are discussed. DISCUSSION: Different survey methods are available for generating willingness-to-pay data, the most common being the contingent valuation approach. An assessment of the validity of data generated by these alternative techniques is vital in order to ensure that they are consistent with the notion of economic preferences and values. IMPLICATIONS: The generation of valid and meaningful data on the monetized value of mental health outcomes would provide decision-makers with an improved evidence-based framework for resource allocation.

Journal Article↗

PubMed1992

Selection bias in using data from one population to another: common pitfalls in the interpretation of medical literature.

The prevalence, course and prognosis of diseases in patients referred to tertiary medical centers frequently differ from those treated in primary care settings. Extrapolation of findings from one population to another may therefore be unwarranted. Other factors that contribute to misinterpretation of medical literature include failure to distinguish statistical from clinical significance and advocacy of medical interventions prior to adequate clinical trials.

Epidemiology↗

PubMed2006

Child sociodemographic characteristics and common psychiatric diagnoses in medicaid encounter data: are they valid?

This study describes the rate that Medicaid encounter data on gender, race/ethnicity, and diagnosis matched information in the medical record, among a statewide sample of Medicaid children who received ongoing care for attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), and major depression (MD) in outpatient specialty mental health clinics in 1998-1999. The match rate for gender was 99%; and for race/ethnicity it was 71.8%, 90.5%, and 89.7% for Caucasian, African American, and Hispanic children, respectively. Misidentified Caucasian children were more likely to be recorded as African American or Hispanic than misidentified minority children to be recorded as Caucasian. Diagnosis match rates were high (ADHD: 98%, CD: 89%, MD: 89%). If the California Department of Mental Health relied solely on Medicaid encounter data, misclassification of African American or Hispanic children as Caucasian could produce an underestimate of their service use.

Adolescent↗

PubMed2006

Pharmacotherapy of attention-deficit hyperactivity disorder in children and adolescents: update on new stimulant preparations, atomoxetine, and novel treatments.

This article reviews data on the safety, tolerability, and efficacy of the extended-delivery stimulant preparations and atomoxetine, including nine methylphenidate formulations, five amphetamine formulations, and one norepinephrine reuptake inhibitor, now indicated for treatment of attention-deficit hyperactivity disorder (ADHD). Six of the nine methylphenidate formulations, three of the five compounds, and the norepinephrine reuptake inhibitor are long-acting, potentially once-daily agents. Data on treatment of common adverse events are described, and data on investigational treatments of ADHD are reviewed.

Adolescent↗