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Managing research data with self-documenting files.

Processing biomedical research data is frequently complex due to the evolutionary nature of experiments and the requisite modification of analysis software. For the past several years we have been evolving a set of software tools designed to improve our ability to respond to evolving experimental designs. These tools allow the investigator to easily manipulate the research data and specify desired data transformations at run time. Coupling of analysis software to research data files is dependent on data files that are commented in a manner similar to that used in programming languages. The resulting annotated data files are self-documenting, and their use facilitates visual interpretation of displayed data as well as automatic processing of subsets of data. Here we present a formal description of a self-documenting file and describe several software tools that facilitate processing of biomedical research data.

Electronic Data Processing↗

[Application of Arai's experimental spectral distribution data].

A new spectral distribution data file is set up by handling Arai's experimental data of spectral distribution, through the procession of interpolation and fitting. The distance of wavelength is 0.002 nm. The data file is applied to our FPM program and then to the analysis of refractory steels GH131. Correlation between theoretical and measured intensities is good. Results of theoretical influence coefficient method and fundamental parameter method are consistent with certified values; the relative error is smaller than 1% to Cr and Ni. The results show the accuracy is improved and the application range of FP and SFP is enlarged.

English Abstract↗

A strategic planning model for multihospital systems.

Strategic planning and marketing for regional multihospital systems requires aids far greater in scope than those needed by single institutions. In the first place, planners for a regional system must be able to determine effects of its actions throughout the region, taking into account competitive interactions among a large number of institutions. This requires a much greater degree of sophistication than is usually found at the level of the single institution. Moreover, this greater sophistication cannot be bought at the expense of speed or demands on the time of the decisionmakers, nor can it be achieved through more sophisticated managerial skills. The aids must also be able to handle expeditiously a far larger volume of inquiry. Those two considerations shaped the design of the Multihospital Strategic Planning Model. Because of its comprehensiveness, the ease with which management can use it, and the speed with which it can answer a large volume of questions, it has become a permanent part of the ongoing corporate-level planning and marketing activities of the Maryland Health Care System in Baltimore. The planning staff can quickly analyze a wide variety of "What if?" questions by making selected changes--on an objective or a subjective basis--in the data files that represent the input variables of the system. By storing such changes in new data files, the staff can piggyback future "What if?" questions onto those asked in the past. The system includes on-line software to change data and create new files. Designed in an interactive mode, the system may be used by the planning staff, in the planning office, at any time.

Adolescent↗

Increased throughput in quantitative bioanalysis using parallel-column liquid chromatography with mass spectrometric detection.

The feasibility of quantitative bioanalysis by parallel-column liquid chromatography in conjunction with a conventional single-source electrospray mass spectrometer has been investigated using plasma samples containing a drug and its three metabolites. Within a single chromatographic run time, sample injections were made alternately onto each of two analytical columns in parallel at specified intervals, with a mass spectrometer data file opened at every injection. Thus, the mass spectrometer collected data from two sample injections into separate data files within a single chromatographic run time. Therefore, without sacrificing the chromatographic separation or the selected reaction monitoring (SRM) dwell time, the sample throughput was increased by a factor of two. Comparing the method validation results obtained using the two-column system with those obtained using the corresponding conventional single-column approach, the methods on the two systems were found to be equivalent in terms of accuracy and precision. The parallel-column system is simple and can be implemented using existing laboratory equipment with no additional capital outlays. A parallel-column system configured in this manner can be used not only for the within-a-run analysis of two samples containing two different sets of chemical entities, but also for the within-a-run analysis of two samples containing the same set of chemical entities.

Chromatography, Liquid↗

Community environment and women's health outcomes: contextual data.

OBJECTIVES: This report presents some illustrative data and analyses from the Contextual Data File for the 1995 National Survey of Family Growth (NSFG). Data are shown by the woman's race and Hispanic origin, and selected characteristics of the community in which she lived. METHODS: Cycle 5 of the NSFG was based on in-person interviews with a national sample of 10,847 women 15-44 years of age in the United States in 1995. The interview included questions on the woman's births, marriages, contraceptive use, and characteristics such as her race and education. Measures of the characteristics of the woman's neighborhood were added to the interview data. RESULTS: This report shows that several simple measures of the social and economic status (SES) and resources of the woman's community of residence are closely associated with outcomes such as delayed childbearing, unwanted births, current marital status, the use of male or female contraceptive sterilization, breast-feeding, vaginal douching, and cigarette smoking. CONCLUSIONS: It is well-documented that the outcomes studied in this report are closely associated with individual characteristics such as age, race, education, and household income. But this report shows that these outcomes are also related to characteristics of the communities in which the individuals live. Researchers are encouraged to use the NSFG Contextual Data File to study these relationships further.

Adolescent↗

RADARS, a bioinformatics solution that automates proteome mass spectral analysis, optimises protein identification, and archives data in a relational database.

RADARS, a rapid, automated, data archiving and retrieval software system for high-throughput proteomic mass spectral data processing and storage, is described. The majority of mass spectrometer data files are compatible with RADARS, for consistent processing. The system automatically takes unprocessed data files, identifies proteins via in silico database searching, then stores the processed data and search results in a relational database suitable for customized reporting. The system is robust, used in 24/7 operation, accessible to multiple users of an intranet through a web browser, may be monitored by Virtual Private Network, and is secure. RADARS is scalable for use on one or many computers, and is suited to multiple processor systems. It can incorporate any local database in FASTA format, and can search protein and DNA databases online. A key feature is a suite of visualisation tools (many available gratis), allowing facile manipulation of spectra, by hand annotation, reanalysis, and access to all procedures. We also described the use of Sonar MS/MS, a novel, rapid search engine requiring 40 MB RAM per process for searches against a genomic or EST database translated in all six reading frames. RADARS reduces the cost of analysis by its efficient algorithms: Sonar MS/MS can identifiy proteins without accurate knowledge of the parent ion mass and without protein tags. Statistical scoring methods provide close-to-expert accuracy and brings robust data analysis to the non-expert user.

Amino Acid Sequence↗

Eligibility for the Medicare buy-in programs, based on a survey of income and program participation simulation.

Medicare buy-in programs are designed to reduce out-of-pocket expenses of beneficiaries with modest income and assets. This article provides estimates of the size of the Medicare beneficiary population eligible for the Qualified Medicare Beneficiary (QMB) program, the Specified Low-Income Medicare Beneficiary (SLMB) program, and the Qualified Individual-1 (QI-1) program. The buy-in programs use the same resource limits (twice those used in the Supplemental Security Income (SSI) program) but different thresholds for determining income eligibility. The QMB program uses 100 percent of the poverty line as the cutoff, QI-1 covers persons above 120 percent but at or below 135 percent of the poverty line, and the SLMB program is in between. Making informed judgments about the rate of participation in the buy-in programs and the need for outreach requires an accurate estimate of the size of the eligible population. If that population is underestimated, policymakers might come to unduly optimistic conclusions about current buy-in participation. In contrast, an overestimate may make current participation seem too low. If policymakers react to an upwardly biased estimate of the eligible population by increasing outreach, they are bound to be disappointed by the results of that effort. Estimates of the eligible population from past studies of the QMB and SLMB programs range from 5.1 million to 9.1 million. In the absence of new information, it is difficult to judge the accuracy of those estimates because the methodologies had substantial shortcomings that might bias the results. The most common shortcomings include the lack of high-quality, monthly income data and the lack of information on assets from the same data file that was used to estimate participation and income eligibility for Medicare. The current study uses the most recently available (as of August 2000) Survey of Income and Program Participation (SIPP) file that is matched to the Social Security Administration's (SSA's) administrative records. The data file covers 1995 information. Estimates were also obtained using 1991 data to assess the sensitivity of eligibility estimates to the year chosen. The SIPP has several major advantages over other data sources because it contains relevant, high-quality information on both income and assets for establishing financial eligibility for the buy-in programs. First, the SIPP collects detailed and conceptually appropriate information on monthly, rather than annual, income and therefore has more complete information about income than do other surveys. As a result, SIPP-based estimates of poverty are substantially lower than estimates based on the Current Population Survey. Second, the SIPP also collects information on assets at the individual level. Thus, the survey provides enough detail to measure the major income and asset exclusions directly. Finally, the SIPP data are matched to SSA administrative records: Medicare eligibility can therefore be accurately measured, and self-reported data on Social Security and SSI benefits can be replaced with more accurate monthly information. Our 1995 simulation estimates that approximately 4.8 million persons in the U.S. noninstitutionalized population were eligible for the QMB program and an additional 1.6 million for the SLMB program. The total--roughly 6.5 million--is within the range of estimates from past studies but is closer to the lower end, suggesting that the eligible population is smaller than was previously believed. When the estimated QI-1 eligible population of 0.9 million is added, the total for the three buy-in programs is 7.4 million. Because the QI-1 program did not exist in 1995, only the estimated 6.5 million QMBs and SLMBs would actually have been eligible to receive benefits. The 7.4 million figure represents the 1995 Medicare beneficiaries who would be eligible for buy-in under program rules for 2000. Adjusting that number to account for increases in the Medicare population between 1995 and 1999 yields an estimated eligible population of 7.8 million in 1999. Compared with other elderly Medicare recipients, eligible elderly QMBs and SLMBs have poorer health, more functional limitations, and higher rates of health care use. Thus, not only are their income resources relatively limited, but their need for potentially expensive medical care is also greater. Similar differences were not found in health, functional limitations, and health care use among disabled participants in the QMB and SLMB programs. Our estimates imply that about 2.5 million noninstitutionalized individuals were eligible for but not enrolled in the QMB and SLMB programs in 1999. That finding suggests that fewer eligibles may be available for targeting by outreach efforts than was previously believed. Outreach may be more difficult than it would be with a larger eligible population. (ABSTRACT TRUNCATED)

Adolescent↗

Qmd-plot: a graphical utility for rapid preliminary analysis of time series of fluctuating data, developed in the context of molecular dynamics simulations.

Qmd-plot is a utility to obtain rapid information about past or on-going simulations, or real-time data collections, in the form of graphs of recorded variables (x, y, ...), as x-y plots or as a function of simulated or real time. Time series records in the data file must be named. Variable names and their locations in the data file are initially unknown to the program, but are identified in a first scan, in which header records are located on the basis of a predefined key (that can be changed interactively). The names of the time series are then presented in an interactive menu, from which the user can repeatedly specify a graph to be viewed. Qmd-plot has been developed in the context of molecular dynamics simulations. We give examples of time series and x-y plots made from output of the sigma program. Qmd-plot code is a Java application; source and class files can be obtained free from the authors.

Journal Article↗

Computer programs to facilitate the estimation of time-dependent drug effects on ion channels.

The programs I-VOC and I-ROC have been designed to facilitate the analysis of drug effects on currents through ion channels in the cell membrane, measured by means of voltage-clamp. They are written in Igor Pro (WaveMetrics) and read exported files or raw data files generated by the Pulse (HEKA Electronic) or pClamp (Axon Instruments) programs. With I-VOC, the sweeps of current through voltage-operated ion channels can be quantified within six time ranges, and current run-down can be corrected for after the currents are fitted during the control period. Linear leak current can be subtracted even when the P/n method is not used. The results are plotted and tabulated. With I-ROC, an analogous program, receptor-operated currents can be quantified, the peak current or rate of desensitization can be fitted and run-down corrected for. Chart-like data can be converted to a sweep-like format. Several procedures are incorporated for rapid graphical data presentation. These programs accelerate and improve the estimation of drug effects on ion channels.

Animals↗

A microcomputer-based system for processing 31-phosphorus nuclear magnetic resonance spectra from studies of cardiac metabolism in immature hearts.

We designed an interactive microcomputer-based digital data processing system for analysis of 31-phosphorus nuclear magnetic resonance (31P-NMR) spectra from studies of cardiac metabolism in immature and neonatal hearts. This system included a digitizing tablet (Kurta Series Two), a microcomputer (IBM PC XT) and a graphics plotter (Hewlett-Packard 7470A) used in conjunction with a Nicolet 1280 NMR signal processing computer. We obtained 31P spectra from isolated perfused rabbit hearts with a Nicolet NT-200 4.7 Tesla superconducting NMR spectrometer operated in the pulsed Fourier transform mode. The small size of the hearts resulted in increased noise in spectra and demanded comparison of methods used to quantitate changes in inorganic phosphorus, phosphocreatine and ATP during ischemic stress. We performed microcomputer operations and interfacing functions with a software package written in BASIC. This system simplified documentation, data filing and statistical data processing. Our microcomputer system displayed and made hard copies of digitized spectra and results of analyses. Errors in data entry were rectified directly with this program. Consistent data reduction improved the precision of the physiological results and reduced the influence of noise on 31P spectra from neonatal hearts weighing about 0.5 g. The system flexibility extends its application to NMR spectra analysis for other in vivo organ systems, and signal processing in other biological research.

Animals↗

Increased risk of heart disease and stroke among foreign-born females residing in the United States.

BACKGROUND: Although the number of foreign-born people residing in the United States is at its highest point in 80 years, a mortality analysis of the foreign born has not been conducted since 1989. This article provides an update of mortality rates among the foreign born in the United States and, in particular, examines mortality rates from heart disease among foreign-born females. METHODS: We calculated mortality rates for U.S.-born and foreign-born people for all causes-ischemic heart disease, stroke, neoplastic disease, hypertensive diseases, diabetes, accidents, infectious disease, and chronic obstructive pulmonary disease-for 1997. Death data were obtained from the 1997 Multiple Cause of Death data file, and population data were obtained from the 1997 Current Population Survey. RESULTS: While all-cause, age-adjusted mortality rates for foreign-born people are significantly lower than for native-born people, deaths due to ischemic heart disease and stroke are significantly higher among foreign-born females than native-born females (161.63 and 58.24 deaths, respectively, per 100,000 foreign-born females vs 122.01 and 49.39 deaths per 100,000 native-born females). CONCLUSIONS: Foreign-born females appear to be at greater risk of death from ischemic heart disease and stroke than native-born females. Future research efforts are needed to determine which foreign-born groups are most at risk for heart disease and stroke so that targeted prevention efforts can be initiated.

Adolescent↗

Ten years of Swiss National IVF Register FIVNAT-CH. Are we making progress?

In 2001, analysis of Swiss data collected since 1993 included 1001 treatment cycles with IVF, 2217 treatment cycles with intracytoplasmic sperm injection and 2160 treatment cycles with frozen-thawed embryos or zygotes. IVF cycle number has remained constant over the past 10 years, now representing only 18% of the total. ICSI treatment cycles have plateaued since 2001. Altogether, patients receive 1.56 treatment cycles per year, nearly constant since 1995. Mean maternal age has increased from 33.9 to 35.7 years, while mean number of recovered oocytes has increased by 1.3. Considerable improvement was seen in clinical pregnancy rate after 'fresh' treatment cycles since 2000. Mean number of replaced embryos in 'fresh' treatment cycles has fallen to below 2.5 since 1996, long before the legal imposition of the three-embryo transfer limit in 2001, and is still decreasing without affecting the consistent twin pregnancy rate of 19%. The frequency of ovarian hyperstimulation syndrome has increased three-fold. External audits have reduced the mean number of errors per data file by half, and increased the number of correct files by 20%. Data collected over this 10-year period show that despite the introduction of a restrictive law and increasing mean maternal age, the overall clinical pregnancy rate has continued to improve.

Adult↗

Fatal and nonfatal unintentional injuries in adult women, United States.

OBJECTIVES: Although we know that injury death rates are lower for women than for men at all ages, we still have a long way to go in exploring the impact of unintentional injuries on women's lives. This paper reviews the leading causes of unintentional injury death and nonfatal injuries for adult women. It also explores selected activities of the Division of Unintentional Injury Prevention (CDC's National Center for Injury Prevention). METHODS: Data come from the Web-based Injury Statistics Query and Reporting System (WISQARS). Mortality data for the system come from the National Center for Health Statistics (CDC's annual mortality data files). Nonfatal injury data for the system come from the National Electronic Injury Surveillance System (NEISS). RESULTS: Unintentional injuries are the leading cause of death for women ages 18-34 and the eighth leading cause of death for adult women overall. In 2001, 31,400 adult women died as a result of unintentional injuries. Incidents related to motor vehicle traffic were the leading cause of unintentional injury death for women aged 18-74 years. Falls were the leading cause of unintentional injury deaths among women aged 75 years and older. In 2002, unintentional injuries accounted for over 8.6 million emergency department visits for adult women. The leading cause of nonfatal unintentional injury for adult women aged 25 years and older was fall related. CONCLUSIONS: Unintentional injury creates an enormous burden on the lives of women. Moving forward in reducing the burden of unintentional injury requires assessing and understanding the impact of these injuries on the lives of women. Further work is needed to develop a strong context and framework for research and dissemination.

Accidental Falls↗

The ins and outs of DNA fingerprinting the infectious fungi.

DNA fingerprinting methods have evolved as major tools in fungal epidemiology. However, no single method has emerged as the method of choice, and some methods perform better than others at different levels of resolution. In this review, requirements for an effective DNA fingerprinting method are proposed and procedures are described for testing the efficacy of a method. In light of the proposed requirements, the most common methods now being used to DNA fingerprint the infectious fungi are described and assessed. These methods include restriction fragment length polymorphisms (RFLP), RFLP with hybridization probes, randomly amplified polymorphic DNA and other PCR-based methods, electrophoretic karyotyping, and sequencing-based methods. Procedures for computing similarity coefficients, generating phylogenetic trees, and testing the stability of clusters are then described. To facilitate the analysis of DNA fingerprinting data, computer-assisted methods are described. Finally, the problems inherent in the collection of test and control isolates are considered, and DNA fingerprinting studies of strain maintenance during persistent or recurrent infections, microevolution in infecting strains, and the origin of nosocomial infections are assessed in light of the preceding discussion of the ins and outs of DNA fingerprinting. The intent of this review is to generate an awareness of the need to verify the efficacy of each DNA fingerprinting method for the level of genetic relatedness necessary to answer the epidemiological question posed, to use quantitative methods to analyze DNA fingerprint data, to use computer-assisted DNA fingerprint analysis systems to analyze data, and to file data in a form that can be used in the future for retrospective and comparative studies.

DNA Fingerprinting↗

GeneLink: a database to facilitate genetic studies of complex traits.

BACKGROUND: In contrast to gene-mapping studies of simple Mendelian disorders, genetic analyses of complex traits are far more challenging, and high quality data management systems are often critical to the success of these projects. To minimize the difficulties inherent in complex trait studies, we have developed GeneLink, a Web-accessible, password-protected Sybase database. RESULTS: GeneLink is a powerful tool for complex trait mapping, enabling genotypic data to be easily merged with pedigree and extensive phenotypic data. Specifically designed to facilitate large-scale (multi-center) genetic linkage or association studies, GeneLink securely and efficiently handles large amounts of data and provides additional features to facilitate data analysis by existing software packages and quality control. These include the ability to download chromosome-specific data files containing marker data in map order in various formats appropriate for downstream analyses (e.g., GAS and LINKAGE). Furthermore, an unlimited number of phenotypes (either qualitative or quantitative) can be stored and analyzed. Finally, GeneLink generates several quality assurance reports, including genotyping success rates of specified DNA samples or success and heterozygosity rates for specified markers. CONCLUSIONS: GeneLink has already proven an invaluable tool for complex trait mapping studies and is discussed primarily in the context of our large, multi-center study of hereditary prostate cancer (HPC). GeneLink is freely available at http://research.nhgri.nih.gov/genelink.

Alleles↗

Development of a predictive model for ross river virus disease in Brisbane, Australia.

This paper describes the development of an empirical model to forecast epidemics of Ross River virus (RRV) disease using the multivariate seasonal auto-regressive integrated moving average (SARIMA) technique in Brisbane, Australia. We obtained computerized data on notified RRV disease cases, climate, high tide, and population sizes in Brisbane for the period 1985-2001 from the Queensland Department of Health, the Australian Bureau of Meteorology, the Queensland Department of Transport, and Australian Bureau of Statistics, respectively. The SARIMA model was developed and validated by dividing the data file into two data sets: the data between January 1985 and December 2000 were used to construct a model, and those between January and December 2001 to validate it. The SARIMA models show that monthly precipitation (beta = 0.004, P = 0.031) was significantly associated with RRV transmission. However, there was no significant association between other climate variables (e.g., temperature, relative humidity, and high tides) and RRV transmission. The predictive values in the model were generally consistent with actual values (root mean square percentage error = 0.94%). Therefore, this model may have applications as a decision supportive tool in disease control and risk-management planning programs.

Alphavirus Infections↗

A population-based study of neonatal seizures in Fayette County, Kentucky.

This population-based, retrospective cohort study of neonatal seizures included all neonates born to residents of Fayette County, Kentucky, from 1985 to 1989. We ascertained potential cases by computer search of hospital-based medical record systems, Kentucky Center for Health Statistics birth certificate data files, and National Center for Health Statistics multiple-cause-of-death mortality data files. Medical records for potential cases were abstracted, and relevant portions were reviewed independently by three neurologists using prospectively determined case-selection criteria. Seizures occurred in 58 of 16,428 neonates (3.5/1,000 live births). An additional 15 neonates had possible seizures, for a combined risk of 4.4/1,000 live births. Neonatal seizure risk varied inversely with birth weight: 57.5/1,000 live births among very low birth weight infants (< 1,500 grams) compared with 4.4/1,000 for infants with moderately low birth weight (1,500 to 2,499 grams), 2.8/1,000 for those with normal birth weight (2,500 to 3,999 grams), and 2.0/1,000 for those with high birth weight (4,000 or more grams). Risk varied among the four hospitals in the county with obstetric units, the university hospital having the highest risk. Risk did not differ by race or gender. A Cox proportional hazards model confirmed the results of the simpler univariate analyses. Differences in birth weight of the subpopulations served by each hospital accounted for much but not all the differences in hospital-specific risk.

Cohort Studies↗