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PubMed2001

A body image scale for use with cancer patients.

Body image is an important endpoint in quality of life evaluation since cancer treatment may result in major changes to patients' appearance from disfiguring surgery, late effects of radiotherapy or adverse effects of systemic treatment. A need was identified to develop a short body image scale (BIS) for use in clinical trials. A 10-item scale was constructed in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Study Group and tested in a heterogeneous sample of 276 British cancer patients. Following revisions, the scale underwent psychometric testing in 682 patients with breast cancer, using datasets from seven UK treatment trials/clinical studies. The scale showed high reliability (Cronbach's alpha 0.93) and good clinical validity based on response prevalence, discriminant validity (P<0.0001, Mann-Whitney test), sensitivity to change (P<0.001, Wilcoxon signed ranks test) and consistency of scores from different breast cancer treatment centres. Factor analysis resulted in a single factor solution in three out of four analyses, accounting for >50% variance. These results support the clinical validity of the BIS as a brief questionnaire for assessing body image changes in patients with cancer, suitable for use in clinical trials.

Age Factors↗
PubMed2001

Comparison of intron-containing and intron-lacking human genes elucidates putative exonic splicing enhancers.

Of the rules used by the splicing machinery to precisely determine intron-exon boundaries only a fraction is known. Recent evidence suggests that specific short sequences within exons help in defining these boundaries. Such sequences are known as exonic splicing enhancers (ESE). A possible bioinformatical approach to studying ESE sequences is to compare genes that harbor introns with genes that do not. For this purpose two non-redundant samples of 719 intron-containing and 63 intron-lacking human genes were created. We performed a statistical analysis on these datasets of intron-containing and intron-lacking human coding sequences and found a statistically significant difference (P = 0.01) between these samples in terms of 5-6mer oligonucleotide distributions. The difference is not created by a few strong signals present in the majority of exons, but rather by the accumulation of multiple weak signals through small variations in codon frequencies, codon biases and context-dependent codon biases between the samples. A list of putative novel human splicing regulation sequences has been elucidated by our analysis.

Alternative Splicing↗
PubMedDate not supplied

Safety, permanency, and in-home services: applying administrative data.

This article describes the construction and use of safety and permanency indicators, two aspects of a full set of indicators that also includes child well-being and family functioning. The indicators were constructed from Philadelphia's Family and Child Tracking System and were used to examine the city's Services to Children in their Own Home (SCOH) program. Cohort datasets were constructed through the use of extract files, and two independent data file construction algorithms were employed to calibrate the accuracy of the data construction process. The primary unit of analysis was the "family" spell in SCOH services. Contextual variables included family structure, race, and service intensity. The indicators associated with SCOH spells included reports of maltreatment after service, founded maltreatment after service, and out-of-home placement after service. Event history techniques were used to conduct the data analysis. Baseline indicator data for Philadelphia are presented, and future uses for such data are discussed.

Child↗
PubMed1996

NMR spectral quantitation by principal-component analysis. II. Determination of frequency and phase shifts.

This paper extends the use of principal-component analysis in spectral quantification to the estimation of frequency and phase shifts in a single resonant peak across a series of spectra. The estimated parameters can be used to correct the spectra accordingly, resulting in more accurate peak-area estimation. Further, the removal of the variations in phase and frequency cause by instrumental and experimental fluctuations makes it possible to determine more accurately the remaining variations, which bear biological significance. The procedure is demonstrated on simulated data, a 3D chemical-shift-imaging dataset acquired from a cylinder of inorganic phosphate (Pi), and a set of 736 31P NMR in vivo spectra taken from a kinetic study of rate muscle energetics. In all cases, the procedure rapidly and automatically identifies the frequency and phase shifts present in the individual spectra. In the kinetic study, the procedure is used twice, first to adjust the phase and frequency of a reference peak (phosphocreatine) and then to determine the individual frequencies of the Pi peak in each of the spectra which further can be used for estimation of pH changes during the experiment.

Computer Simulation↗
PubMed1999

B-SPID: an object-relational database architecture to store, retrieve, and manipulate neuroimaging data.

We propose a hardware and software architecture to respond to crucial problems in the neuroimaging field: storage, retrieval, and processing of large datasets. The B-SPID project, here discussed, concerns the processing of neuroimages and attached components stored in an object-relational multimedia database management system (DBMS). Advanced bioinformation concepts are exploited in this project such as large scale data storage, high level graphical user interfaces and 3D graphical processing and display of data. Our database implementation is based on standard programming components, runs on several UNIX platforms and is written to be evolutive. Queries on this database are designed to obtain and display from neuroimaging data several types of results (pictures, text, or 3D graphical shapes) on heterogeneous systems.

Brain Mapping↗
PubMed1999

Molecular phylogeny and evolutionary history of the tit-tyrants (Aves: Tyrannidae).

Tit-tyrants of the genus Anairetes presently consist of six species; five inhabit various regions along the Andean cordillera of South America and one is endemic to the Juan Fernandez Islands off the coast of Chile. Data from mtDNA ND2 and Cyt b sequences were used to construct a phylogeny for all Anairetes species as well as Uromyias agilis, a closely related genus, and Stigmatura as an outgroup, to determine their relationships and history of radiation in South America. Results strongly supported the following paired relationships: A. nigrocristatus-A. reguloides, A. flavirostris-A. alpinus, and A. parulus-A. fernandezianus. This dataset, however, could not resolve basal nodes; therefore relationships among these pairs remains obscure. Moreover the genus Uromyias, controversially separated on morphological criteria from Anairetes, fell within the Anairetes clade, although its exact position could not be ascertained with confidence. The molecular data indicate that this group probably radiated within the past 2 million years, concomitant with highly accentuated cycles of global climatic change. Certain high altitude areas within the Andes may have been stable during global climatic changes and may have served as refugia during the Plio-Pleistocene.

Animals↗
PubMed1994

Comparison of chemotherapy and bone marrow transplants using two independent clinical databases.

Comparing the outcome of chemotherapy and bone marrow transplants in the absence of a randomized trial is difficult but necessary for diseases where small numbers of patients make such trials difficult if not impossible. To address this issue for adults with acute lymphoblastic leukemia in first remission, we created an empirical database using two separate datasets, one from the International Bone Marrow Transplant Registry and the other from two multicenter chemotherapy studies. Prior to combining the datasets, a study protocol was developed to define inclusion criteria, outcomes to be compared and statistical methods. The main problems of a non-randomized comparison are biases potentially introduced by differences in baseline composition of the two cohorts and differences in time-to-treatment. The source of the latter bias is different distributions of waiting times between achieving complete remission and receiving post-remission therapy. Several techniques to control these biases were evaluated; each gave qualitatively similar results. These methods can easily be applied to other clinical situations where randomized trials are not available.

Adolescent↗
PubMed2002

Profound effect of normalization on detection of differentially expressed genes in oligonucleotide microarray data analysis.

BACKGROUND: Oligonucleotide microarrays measure the relative transcript abundance of thousands of mRNAs in parallel. A large number of procedures for normalization and detection of differentially expressed genes have been proposed. However, the relative impact of these methods on the detection of differentially expressed genes remains to be determined. RESULTS: We have employed four different normalization methods and all possible combinations with three different statistical algorithms for detection of differentially expressed genes on a prototype dataset. The number of genes detected as differentially expressed differs by a factor of about three. Analysis of lists of genes detected as differentially expressed, and rank correlation coefficients for probability of differential expression shows that a high concordance between different methods can only be achieved by using the same normalization procedure. CONCLUSIONS: Normalization has a profound influence of detection of differentially expressed genes. This influence is higher than that of three subsequent statistical analysis procedures examined. Algorithms incorporating more array-derived information than gene-expression values alone are urgently needed.

Animals↗
PubMed1985

The classification of subjects with joint complaints on incomplete biochemical and haematological datasets.

We performed a retrospective study on 163 subjects suffering from rheumatic fever (16), rheumatoid arthritis (36), lupus erythematosus (17), gout (21), arthrosis (50) and osteomyelitis (23). The number of variables evaluated was 39. These were all of a general biochemical and haematological nature. A feature reduction resulted in sixteen variables that matched well with those known from the literature. Linear discriminant analysis yielded poor results in classifying the six disease categories (with 18 variables 61.8%). A reduction to three disease categories improved the classification results remarkably. This, and the excellent discriminating power between patients and the reference group, shows that the selected variables are illustrative only for general clinical pictures, such as infection, and not for the desired differential diagnosis.

Arthritis, Rheumatoid↗
PubMed2003

Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome.

The rate of the sudden infant death syndrome (SIDS) among American Indian infants in the Northern Plains is almost 6 times higher than in U.S. white infants. In a study of infant mortality among Northern Plains Indians, we tested the hypothesis that receptor binding abnormalities to the neurotransmitter serotonin (5-HT) in SIDS cases, compared with autopsied controls, occur in regions of the medulla oblongata that contain 5-HT neurons and that are critical for the regulation of cardiorespiration and central chemosensitivity during sleep, i.e. the medullary 5-HT system. Tritiated-lysergic acid diethylamide binding to 5-HT(1A-D) and 5-HT2 receptors was measured in 19 brainstem nuclei in 23 SIDS and 6 control infants using tissue receptor autoradiography. Binding in the arcuate nucleus, a part of the medullary 5-HT system along the ventral surface, in the SIDS infants (mean age-adjusted binding 7.1 +/- 0.8 fmol/mg tissue, n = 23) was significantly lower than in controls (mean age-adjusted binding 13.1 +/- 1.6 fmol/mg tissue, n = 5) (p = 0.003). Binding also demonstrated significant diagnosis x age interactions (p < 0.04) in 4 other nuclei that are components of the 5-HT system. These data suggest that medullary 5-HT dysfunction can lead to sleep-related, sudden death in affected SIDS infants, and confirm the same binding abnormalities reported by us in a larger dataset of non-American Indian SIDS and control infants. This study also links 5-HT abnormalities in the arcuate nucleus with exposure to adverse prenatal exposures, i.e. cigarette smoking (p = 0.011) and alcohol (p = 0.075), during the periconceptional period or throughout pregnancy. Prenatal exposure to cigarette smoke and/or alcohol may contribute to abnormal fetal medullary 5-HT development in SIDS infants.

Age Factors↗
PubMed2001

Design and analysis of trials with quality of life as an outcome: a practical guide.

Health Related Quality of Life (HRQoL) measures are becoming more frequently used in clinical trials, as both primary and secondary endpoints. Investigators are now asking statisticians for advice on how to plan (e.g., sample size) and analyze studies using HRQoL measures. HRQoL measures such as the SF-36 are usually measured on an ordered categorical (ordinal) scale. In the designing stages and when analyzing, the scales are often scored and the scores treated as if they were continuous and normally distributed. However the ordinal scaling of HRQoL measures leads to problems in determining sample size, and conventional parametric methods of estimation and hypothesis testing may not be appropriate for such outcomes. We present practical guidelines for the design and analysis of trials with HRQoL measures as outcomes. We used conventional statistical methods (i.e., t-tests and multiple regression), various ordinal regression models (proportional odds, continuation ratio, polytomous and stereotype) and bootstrap methods to analyze an HRQoL dataset. To illustrate the various methods we used HRQoL data on the SF-36 Role Limitations Emotional dimension for two groups of patients with leg ulcers. The bootstrap, t-test, and multiple regression methods gave similar results. The various ordinal regression models also gave similar results. If the HRQoL measure has a large number of ordered categories, most of which are occupied, and the underlying scale really is continuous but measured imperfectly by an instrument with a limited number of discrete values, then an informal rule of thumb is that this discrete scale should be treated as continuous if it has seven or more categories and as ordinal otherwise.

Algorithms↗
PubMed2001

Use of narrative analysis for comparisons of the causes of fatal accidents in three countries: New Zealand, Australia, and the United States.

OBJECTIVES: To investigate the utility of narrative analysis of text information for describing the mechanism of injury and to compare the patterns of the mechanism of injury for work related fatalities in three countries. METHODS: Three national collections of data on work related fatalities were used in this study including those for New Zealand, 1985-94 (n=723), for Australia, 1989-92 (n=1,220), and for the United States, 1989-92 (16,383). The New Zealand and Australian collections used the type of occurrence standard code for the mechanism of injury, however the United States collection did not. All three databases included a text description of the circumstances of the fatality so a text based analysis was developed to enable a comparison of the mechanisms of injury in each of the three countries. A test set of 200 cases from each country dataset was used to develop the narrative analysis and to allow comparison of the narrative and standard approaches to mechanism coding. RESULTS: The narrative coding was more useful for some types of injury than others. Differences in coding the narrative codes compared with the standard code were mainly due to lack of sensitivity in detecting cases for all three datasets, although specificity was always high. The pattern of causes was very similar between the two coding methods and between the countries. Hit by moving objects, falls, and rollovers were among the five most common mechanisms of workplace fatalities for all countries. More common mechanisms that distinguished the three countries were electrocutions for Australia, drowning for New Zealand, and gunshot for the United States. CONCLUSION: Narrative analysis shows some promise as an alternative approach for investigating the causes of fatalities.

Accidents, Occupational↗
PubMed1999

A new multiparameter flow cytometer: optical and electrical cell analysis in combination with video microscopy in flow.

BACKGROUND: Flow cytometers, which are commercially available, do not necessarily meet all demands of actual biomedical research. This is the case for the investigation of mechanisms involved in cell volume regulation, which requires electrical volume measurement and ratiometric multichannel fluorescence analysis for the simultaneous assessment of different physiologic parameters (intracellular pH and the intracellular concentration of calcium ions, etc). METHODS AND RESULTS: We describe the construction of a new nonsorting flow cytometer designed for the simultaneous acquisition of seven parameters including fluorescence signals, forward and perpendicular light scatter, cell volume according to the electrical Coulter principle, and flow cytometric imaging. The instrument is equipped with three different light sources. A tunable argon-ion laser generates efficient excitation of the most standard fluorescent probes in the visible spectral range, and an arc lamp provides the means for ultraviolet excitation at low cost. Because of the spatial filtering by the excitation and detection optics, two independent sets of dual fluorescence measurements can be performed, a prerequisite for flexible ratiometric fluorescence analysis. A flow video microscope integrated into the optical system optionally generates either brightfield or phase images of selected flowing particles. Only particles whose individual datasets meet predefined gating conditions are imaged in real time. To avoid smear effects, the motion of the object to be imaged (speed approximately 8 m/s) is frozen on the target of a CCD camera by flash illumination. For this purpose, a high radiance gas discharge lamp with 25-mJ electric pulse energy provides an illumination time of 18 ns (full width half maximum). Test results obtained from latex spheres and cells are shown. CONCLUSIONS: Test results indicate that our instrument can perform Coulter measurements in combination with flexible optical analysis. Moreover, integration of an adapted video microscope into a flow cytometer is an approach to overcome the gap between flow and image cytometry.

Animals↗
PubMed1997

A population needs assessment profile for dementia.

The Tayside Profile for Dementia Planning is an instrument designed to obtain data for population needs assessment and planning. It provides a brief tool to collect a minimum dataset by non-specialists. Third-party informants-informal carers or involved professionals-are used as data sources. The key concept is the use of a descriptive profile rather than a summative score or categorization. The profile consists of a set of needs indicators, information on current service response and demographic and background data. Key levels of dependency are measured by time interval dependency. Validity, reliability, acceptability and usability are satisfactory, with the crucial exception that informal carers and professionals appear to perceive needs differently. Further research is needed to assess which type of informant provides the more useful data.

Caregivers↗
PubMed2002

Publishing large proteome datasets: scientific policy meets emerging technologies.

Currently, there are various approaches to proteomic analyses based on either 2D gel or HPLC separation platforms, generating data of different formats, structures and types. Identification of these separated proteins or peptide fragments is typically achieved by mass spectrometry (MS) measurements that use either accurate mass measurements or fragmentation (MS-MS) information. Integrating the information generated from these different platforms is essential if proteomics is to succeed. A further challenge lies in generating standards that can accept the hundreds-of-thousands of mass spectra produced per analysis based on threshold or probability measurements. Finally, peer review and electronic publication processes will be crucial to the dissemination and use of proteomic information. Merging the policy requirements of data-intensive research with information technology will enable scientists to gain real value from global proteomics information.

Chromatography, Liquid↗
PubMed1999

Quantification of 99Tcm-HMPAO brain SPET in two series of healthy volunteers using different triple-headed SPET configurations: normal databases and methodological considerations.

We evaluated the methodological issues underlying the assessment of normal confidence intervals, as used in clinically based region-of-interest (ROI) semi-quantification of 99Tcm-HMPAO brain SPET. At two different centres equipped with high-resolution, triple-headed gamma cameras, HMPAO SPET scans were performed on two groups of 24 and 15 healthy volunteers respectively. Together with an operator-defined analysis (ODA), a semi-automated analysis (SAA) was conducted on the normal datasets in one centre. Tests of intra- and inter-observer variability were performed. Repeat scans were performed within 72 h after the first to analyse short-term regional inter-study variations. The overall regional uptake showed significant differences in most regions between both normal datasets. Intra-observer and inter-observer reproducibility were on average within 4% for the ODA, while for the SAA it was less than 1%. Inter-study variations were excellent for both centres, ranging from -4% to +3% for most regions studied. The variability in clinical brain perfusion studies largely depends on the reproducibility of the data analysis technique. A semi-automated approach shows clear advantages over an entirely operator-defined approach. Intra-subject repeat studies show enough stability for use as reliable baseline measurements in the construction of a normal database or to allow activation studies with high sensitivity.

Adult↗
PubMed1997

Evaluation of a novel infrared range vibration-based descriptor (EVA) for QSAR studies. 1. General application.

A novel molecular descriptor (EVA) based upon calculated infrared range vibrational frequencies is evaluated for use in QSAR studies. The descriptor is invariant to both translation and rotation of the structures concerned. The method was applied to 11 QSAR datasets exhibiting both a range of biological endpoints and various degrees of structural diversity. This study demonstrates that robust QSAR models can be obtained using the EVA descriptor and examines the effect of EVA parameter changes on these models; recommendations are made as to the appropriate choice of parameters. The performance of EVA was found to be comparable in statistical terms to that of CoMFA, despite the fact that EVA does not require the generation of a structural alignment. Models derived using semiempirical (MOPAC AM1 and PM3) and AMBER mechanics calculated normal mode frequencies are compared, with the overall conclusion that the semiempirical methods perform equally well and both outperform the AMBER-based models.

Computer Simulation↗
PubMed1999

Comparison of alternative methods for assessing injury severity based on anatomic descriptors.

BACKGROUND: There is mounting confusion as to which anatomic scoring systems can be used to adequately control for trauma case mix when predicting patient survival. METHODS: Several Abbreviated Injury Scale (AIS) and International Classification of Disease Clinical (ICD-9CM)-based methods of scoring severity were compared by using data from the Pennsylvania Trauma Outcome Study. By using a design dataset, the probability of survival was modeled as a function of each score or profile. Resulting coefficients were used to derive expected probabilities in a test dataset; expected and observed probabilities were then compared by using standard measures of discrimination and calibration. RESULTS: The modified Anatomic Profile, Anatomic Profile, and New Injury Severity Score outperformed the International Classification of Disease-based Injury Severity Score. This finding remains true when AIS values are obtained by means of a conversion from International Classification of Disease to AIS. CONCLUSION: Results support the integrity of the AIS and argue for its continued use in research and evaluation. The modified Anatomic Profile, Anatomic Profile, and New Injury Severity Score, however, should be used in preference to the Injury Severity Score as an overall measure of severity.

Humans↗