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PubMed1985

Prothrombin time proficiency testing: a robust grading method.

A robust two-way analysis of variance technique was applied to determine simultaneously the effects of method and thromboplastin on prothrombin time. A new approach to outlier detection for two-way analysis of variance was used. Focusing on the underlying error structure improved the uniformity of the grading procedure in the hematology proficiency testing program of the New York State Department of Health. The logarithm-transformed scale produced constancy of error variance and resulted in uniformity of the acceptable spread of data. The common variance was lower than that obtained by previous methods and allowed for a narrower acceptable range of reported prothrombin times by reducing the inflated standard deviation, thus improving the efficiency of the grading procedure. For proficiency testing, no advantage was found in the use of either a common thromboplastin or freeze-dried, coumadinized patient plasmas rather than artificially depleted commercial plasmas, except for special purposes.

Automation↗
PubMed1979

Consequences of experimental mitral insufficiency induced by chordotomy.

In mitral insufficiency induced by chordotomy in dogs beside the common diagnostic data the values for tissue perfusion indicative of myocardial microcirculation have been studied. Unexpectedly, a decrease of subendocardial circulation was found; this reduced circulation manifested itself with alterations such as changes in mitochondrial structure, increased quantity of subsarcolemic sarcoplasma, and degenerative symptoms.

Animals↗
PubMed1978

LATCH at the Washington Hospital Center, 1967-1975.

Immediate access to needed information is essential if medical personnel are to provide quality health care. At the Washington Hospital Center, Literature Attached to Charts, LATCH, was created in 1967 to provide the required information quickly. As a collection of a few relevant articles attached to the patient's chart, it supplies current literature on some aspect of the patient's illness. Following an account of the program's inception, an analysis of 1,935 LATCH requests for the years 1968--1975 reveals that new physicians, that is, interns and first-year residents, requested LATCHes most often. Requests in areas of internal medicine were the most common. The data also show that the program has been well received by its users. LATCH has affected the medical library in several ways. The program has been partially responsible for increases in staff, in the number of journal subscriptions, and in the number of literature searches requested. The program has also brought about greater access to the collection via the card catalog. An important effect has been the tremendous development of professional expertise in the staff preparing the LATCH.

Humans↗
PubMed1993

Protein secondary structure prediction using two-level case-based reasoning.

We have developed a two-level case-based reasoning architecture for predicting protein secondary structure. The central idea is to break the problem into two levels: first, reasoning at the object (protein) level, and using the global information from this level to focus on a more restricted problem space; second, decomposing objects into pieces (segments), and reasoning at the internal structures level; finally, synthesizing the pieces back to the objects. The architecture has been implemented and tested on a commonly used data set with 69.3% predictive accuracy. It was then tested on a new data set with 67.3% accuracy. Additional experiments were conducted to determine the effects of using different similarity matrices.

Amino Acid Sequence↗
PubMed1994

Building a children's health network: city-wide computer linkages among heterogeneous sites for pediatric primary care.

For many infants and children in our cities, quality of care and health status outcomes suffer due to poor continuity and coordination among ambulatory care sites. Despite proximity to technologically-advanced secondary and tertiary institutions, primary care services for children are fragmented, multiple-site use is common, and data flow among providers serving the same patients is primitive. Preventive and acute health care is often incomplete or redundant, and aggregate information for public health purposes is insufficient. This paper focuses on the development of a city-wide computer-based pediatric health care network to improve provider decision-making and follow-through, parent role in their children's care, and community-wide data. A process of building consensus for a regional system is presented, addressing issues of establishing a uniform data base, coordination among heterogeneous institutions, system development, confidentiality, and integration with public health reporting and planning functions.

Child↗
PubMed1994

["Revolution psychoses" in 1989 and their catamnesis].

In the submitted paper the author deals in detail with patients hospitalized in two large Moravian sanatoria on account of psychotic disorders in the development of which events of November 1989 played some part. The author sought in these patients common anamnestic data, analyzed the psychopathological picture of the disease and finally subjected all the patients to a three-year catamnestic follow-up. The results were compared with several publications dealing with the same subject. The author had, however, the advantage of a longer follow-up and more extensive sources of information, whereby she made also use of contact in writing with former patients. The achieved results were processed by statistical methods, compared also in parts of the group classified by age and sex. In the presented paper only the most interesting data are given. The most positive conclusion is the fact that 31.43% of the group had no longer any psychic complaints, 81.63% of the group work (and another 6.06% returned to work after invalidization). With one exception all patients or their doctors evaluate the present situation at least as satisfactory.

Adolescent↗
PubMed1993

Recent advances in understanding maternal and fetal responses to exercise.

In the past decade, physical health fitness has become increasingly more important in the lives of women of child-bearing age. Many have made regular, and sometimes vigorous commitments to exercise programs. In 1985, the American College of Obstetricians and Gynecologists (ACOG) developed a set of guidelines for women who plan to exercise during pregnancy. Recommendations were based on available, but somewhat limited, scientific data and common sense. Since that time, researchers have learned a significant amount of new information about how a pregnant woman and her fetus respond to aerobic activity. The objective of this communication is to review recent investigations in this area. Specific topics include a) maternal responses to exercise, b) fetal responses to maternal exercise, c) animal research models, and d) pregnancy and physical conditioning. Our objectives are to present information that will a) stimulate new and innovative research designs for exercise and pregnancy studies, and b) add significantly to our knowledge and ability to develop safe and effective exercise programs for women who wish to remain physically active throughout a normal-term pregnancy.

Animals↗
PubMed1993

Early diagnosis of smoldering acute lymphoblastic leukemia using immunological marker analysis.

During a period of 9 years, we performed immunological marker analysis in 164 children with acute lymphoblastic leukemia. In four children the diagnosis acute leukemia could not be established by cytomorphological analysis of bone marrow and peripheral blood samples at initial presentation. In two of these four children a hypoplastic bone marrow was found, whereas the bone marrow of the other two children was normocellular. Using double immunological marker analysis, we detected high frequencies of CD10+, TdT+ cells in bone marrow (range: 18-53%) as well as peripheral blood (range: 0.04-19.5%). In control bone marrow and peripheral blood samples from healthy children, the frequency of CD10+, TdT+ cells does not exceed 10% and 0.03%, respectively. Based on the immunological data, a common acute lymphoblastic leukemia (ALL) was suspected. In addition, chromosome analysis revealed a high hyperdiploid (> 50 chromosomes) karyotype in three patients and t(9;22) in one patient. At 18 to 68 days after initial presentation, an ALL was diagnosed according to cytomorphological criteria in all four patients. At that time the percentage of CD10+, TdT+ cells in bone marrow and peripheral blood had increased significantly. One patient could be monitored frequently from initial presentation onwards. First a decline in the percentage of CD10+, TdT+ cells was found, although treatment consisted only of red blood cell transfusion and antibiotics. Subsequently the percentage of CD10+, TdT+ cells gradually increased until the morphological ALL diagnosis. These results illustrate that CD10, TdT double immunological marker analysis is a useful tool for early diagnosis of smoldering ALL in patients with a suspicious bone marrow, even when the bone marrow is hypoplastic.

Adolescent↗
PubMed1995

A desk top computer program for visualized statistical analysis of lesional images in intracerebral hemorrhage.

Statistically identified information on the relationships between the sites of lesions in intracerebral hemorrhage (ICH), risk factors such as a smoking or drinking habit, anamnesis, and biochemical data through blood tests will extend assistance to neuromedical clinicians on their daily clinical duties. It will provide them with a useful guide to determine the method of treatment. Also, it will be a basic research material for their clinical studies on diagnosis, progress, or prognosis in ICH. In order to obtain such statistics with the help of the computer, we need to have a computationally effective image database system. As is generally known, medical image data especially requires a great amount of storage; high-speed processing techniques are therefore also needed to deal with such data effectively. In addition, it is desired that we have outputs from the analysis edited with well-visualized effect, using 3D computer graphics, etc. These are why most existing image processing systems have been designed to work on comparatively large-scale computers. So far as we know, it is hard to find a practical and inexpensive personal computer-based application system for visualized statistical analysis of lesional images in ICH. We have developed a desk top computer-based program for statistical analysis of lesional image data of ICH. With this system, we can organize a medical image database that consists of the personal data of patients with ICH (sex, age, occupation, diagnosis, symptoms, part of physical disorder, etc.), risk factors, anamnesis (cerebral apoplexy, hypertension, hypotension, corpulence, diabetes, hyperlipidemia, atrial fibrillation, valvular endocarditis, etc.), biochemical data of blood, and lesional image data from CT or MRI. This system consists of the following components: 1) database management, 2) information retrieval (IR), 3) lesional image processing, 4) statistical analysis, and 5) prognostic prediction. The images are drawn manually on prescribed data sheets by tracing CT or MRI films and are read through the image scanner; then the compressed data of the digitized images is recorded in the database. Each recorded image data consists of the following two components: the frame image that corresponds to the contour of tissues of interest on the corresponding sliced section, and the actual image that corresponds to the lesion itself. In our system, these two images are separately stored and managed so that we can effectively perform subsequent image analysis. Other variables in the database (risk factors, anamnesis, etc.) are mainly used as search keys for making the aggregate of image data by the IR subsystem. In any aggregate, its elements, namely image data, have common medical background descriptions with the search keys. These aggregates can be used as input for the lesional image processing subsystem. With this subsystem, we can obtain the accumulated distribution of frequencies within a specified range of any sliced section, display planar color maps and profiles associated with the distribution, reconstruct it in 3D form, perform transformations of 3D images (zooming, enhancement, rotation, etc.), and test the significant difference of frequencies between any two different sites. We have been making practical use of this system to find the neurological relationship between the symptom (dysarthria, and paralysis of upper/lower limbs) and the site of lesion with cerebral infarction in pons. This study is quite important since the distributions of pyramidal tract related to the above symptom in pons are not well-known compared to those in cerebral cortex, internal capsule, or cerebral peduncle. With our system, we have obtained several findings expected to be helpful for this study. However, since this study is still in the initial phases, we will only present the outcome as a working example of our system. Our system was originally developed for analyzing lesional images with ICH. However, it could

Cerebral Hemorrhage↗
PubMed1996

Inter-rater reliability and review of the VA unresolved narratives.

To better understand how VA clinicians use medical vocabulary in every day practice, we set out to characterize terms generated in the Problem List module of the VA's DHCP system that were not mapped to terms in the controlled-vocabulary lexicon of DHCP. When entered terms fail to match those in the lexicon, a note is sent to a central repository. When our study started, the volume in that repository had reached 16,783 terms. We wished to characterize the potential reasons why these terms failed to match terms in the lexicon. After examining two small samples of randomly selected terms, we used group consensus to develop a set of rating criteria and a rating form. To be sure that the results of multiple reviewers could be confidently compared, we analyzed the inter-rater agreement of our rating process. Two rates used this form to rate the same 400 terms. We found that modifiers and numeric data were common and consistent reasons for failure to match, while others such as use of synonyms and absence of the concept from the lexicon were common but less consistently selected.

Medical Records Systems, Computerized↗
PubMed1997

An epidemiological study of diagnostic and therapeutic strategies in office practice patients with subacute or chronic pain in the thoracic or low back. Comparison of practices in primary care and rheumatology settings.

UNLABELLED: There is a paucity of epidemiological data on diagnostic and therapeutic practices in office practice patients with subacute or chronic pain in the thoracic or low back. STUDY OBJECTIVE: to describe diagnostic and therapeutic strategies used in such patients. PATIENTS AND METHODS: descriptive, prospective, two-month epidemiological study in 50 general practitioners and 50 rheumatologists. Each physician was asked to provide data on the demographics, clinical features, history of spinal disease, investigations, prior treatments and treatments prescribed on D0 and D30 in two patients with low back pain and two with thoracic back pain, of one to 12 months' duration. RESULTS: A total of 352 patients were included. In the 217 patients with low back pain, including 107 women and 110 men, duration of the pain was 4.3 +/- 0.2 months and mean age was 49.6 +/- 1 years; 67% of these patients were economically active and 22% were retired; 59% were recruited by rheumatologists. In the thoracic back pain group, there were 135 patients, including 82 women (61%) and 53 men, with a mean duration of pain of 3.8 +/- 0.3 months and a mean age of 47.7 +/- 1.4 years; 60% were economically active and 22% were retired; 49% were recruited by rheumatologists. A history of conservatively-treated low or thoracic back pain was reported for 95.4% of patients in the low back pain group and 94% in the thoracic back pain group. Of the patients with low back pain, 6.3% had had spinal surgery. Investigations were as follows: roentgenograms in 85% of low back pain and 75% of thoracic back pain patients, computed tomography in 11% and 5.8%, magnetic resonance imaging in 2% and 1% and laboratory tests in 14% and 20%. Ninety-one per cent of low back pain and 84% of thoracic back pain patients were already under therapy on D0. Ninety-six per cent of patients overall were given a prescription at the end of the D0 visit, for a nonsteroidal antiinflammatory drug or an analgesic in 80% of low back pain and 63% of thoracic back pain patients, for muscle relaxants in 62% and 69%, for drugs aimed at preventing gastric side effects in 19% and 9.5%, for myotonic agents in 10% and 8% and for sedatives in 5% and 11%. A local steroid injection was given to 20% of low back pain patients. Twenty-four per cent of low back pain and 14% of thoracic back pain patients missed days of work (mean, 11 +/- 1.7 days and 13 +/- 4.6 days, respectively). Physical therapy was prescribed to 36% of low back pain and 27% of thoracic back pain patients and a lumbar support belt to 17% of low back pain patients. On D30, the pain had abated in 86% of low back pain and 89% of thoracic back pain patients and complete freedom from pain was reported by 28% and 32% of patients in these two groups, respectively. Treatments prescribed on D30 were physical therapy (43% and 31%), analgesics (40% and 36%) muscle relaxants (25% and 30%), and nonsteroidal antiinflammatory drugs (23% and 12%). Conclusion. This preliminary study provides data on common practices in subacute and chronic low back and back pain and may prove useful for health care cost estimations.

Acute Disease↗
PubMed1997

Drug interactions among commonly used medications. Chart simplifies data from critical literature review.

OBJECTIVE: To simplify risk assessment, we have developed a way to present critically appraised drug interaction information through a chart. DATA SOURCES: Fifty drugs most frequently prescribed by Canadian family physicians and 16 drugs and substances that frequently interact with these drugs were the basis for a literature review. Drug interaction textbooks and MEDLINE (from 1966 to 1994) were searched for documented interactions. Reports of additive effects and animal or in vitro studies were excluded. STUDY SELECTION: All reports of interactions were evaluated for clinical effect, clinical significance, and quality of evidence. SYNTHESIS: Of the 464 drug-drug or drug-substance pairs evaluated, 387 (83.4%) demonstrated an interaction, 59 (12.7%) documented no effect, and 18 (3.9%) pairs had conflicting evidence. Five percent of interactions were of major clinical significance; only 1.3% were of major clinical significance and supported by good-quality evidence. By using symbols, colours, and legends in a "grid-map" format, a large amount of drug interaction information was reduced to a single-page chart suitable for a desk reference or wall mounting. CONCLUSIONS: Our chart organizes a large amount of drug interaction information in a format that allows for rapid appreciation of outcome, clinical significance, and quality of evidence.

Canada↗
PubMed2025

Optimizing genetic ancestry adjustment in DNA methylation studies: a comparative analysis of approaches.

BACKGROUND: Genetic ancestry is an important factor to account for in DNA methylation studies because genetic variation influences DNA methylation patterns. One approach uses principal components (PCs) calculated from CpG sites that overlap with common SNPs to adjust for ancestry when genotyping data is not available. However, this method does not remove technical and biological variations, such as sex and age, prior to calculating the PCs. The first PC is therefore often associated with factors other than ancestry. METHODS: We developed and adapted the adapted EpiAnceR+ approach, which includes (1) residualizing the CpG data overlapping with common SNPs for control probe PCs, sex, age, and cell type proportions to remove the effects of technical and biological factors, and (2) integrating the residualized data with genotype calls from the SNP probes (commonly referred to as rs probes) present on the arrays, before calculating PCs and evaluated the clustering ability and relationship to genetic ancestry. RESULTS: The PCs generated by EpiAnceR+ led to improved clustering for repeated samples from the same individual and stronger associations with genetic ancestry groups predicted from genotype information compared to the original approach. EpiAnceR+ also outperformed the use of DNA methylation PCs or surrogate variables for ancestry adjustment. CONCLUSIONS: We show that the EpiAnceR+ approach improves the adjustment for genetic ancestry in DNA methylation studies. EpiAnceR+ can be integrated into existing R pipelines for commercial methylation arrays, such as 450 K, EPIC v1, and EPIC v2. The code is available on GitHub ( https://github.com/KiraHoeffler/EpiAnceR ).

DNA Methylation↗
PubMed2006

Selection of differentially expressed genes in microarray data analysis.

One common objective in microarray experiments is to identify a subset of genes that express differentially among different experimental conditions, for example, between drug treatment and no drug treatment. Often, the goal is to determine the underlying relationship between poor versus good gene signatures for identifying biological functions or predicting specific therapeutic outcomes. Because of the complexity in studying hundreds or thousands of genes in an experiment, selection of a subset of genes to enhance relationships among the underlying biological structures or to improve prediction accuracy of clinical outcomes has been an important issue in microarray data analysis. Selection of differentially expressed genes is a two-step process. The first step is to select an appropriate test statistic and compute the P-value. The genes are ranked according to their P-values as evidence of differential expression. The second step is to assign a significance level, that is, to determine a cutoff threshold from the P-values in accordance with the study objective. In this paper, we consider four commonly used statistics, t-, S- (SAM), U-(Mann-Whitney) and M-statistics to compute the P-values for gene ranking. We consider the family-wise error and false discovery rate false-positive error-controlled procedures to select a limited number of genes, and a receiver-operating characteristic (ROC) approach to select a larger number of genes for assigning the significance level. The ROC approach is particularly useful in genomic/genetic profiling studies. The well-known colon cancer data containing 22 normal and 40 tumor tissues are used to illustrate different gene ranking and significance level assignment methods for applications to genomic/genetic profiling studies. The P-values computed from the t-, U- and M-statistics are very similar. We discuss the common practice that uses the P-value, false-positive error probability, as the primary criterion, and then uses the fold-change as a surrogate measure of biological significance for gene selection. The P-value and the fold-change can be pictorially shown simultaneously in a volcano plot. We also address several issues on gene selection.

Data Interpretation, Statistical↗
PubMed1986

Evolution of enterovirus 70 in nature: all isolates were recently derived from a common ancestor.

The data of large RNase T1-resistant oligonucleotide mapping of enterovirus 70 (EV 70) previously reported (Takeda et al., Virology 134, 375-388, 1984) were subjected to further genetical analysis to estimate the evolutionary rate of genome RNA of EV 70 and to clarify the phylogenetic relationship among isolates. A proportion of common spots between strains decreased as the year elapsed and eventually, only seven spots were common to all the 16 isolates tested, indicating that the substitution is scattered throughout the genome. On the other hand, some specific sets of spots were conserved among geographically or epidemiologically related strains. Base sequence variation of the isolates was deduced according to Aaronson et al. (Nucleic Acids Res. 10, 237-246, 1982) from pariwise comparison of the common spots and used as a genetic distance between them. The base substitution rate of virus genome was estimated by regression analysis of the genetic distance of the isolates against the sampling time. A fairly constant and rapid rate was obtained; it was 1.83 X 10(-3)/base/year. Based on the substitution rate, genetic distance and sampling time of the strains, the phylogenetic tree of EV 70 was constructed using Unweighted Pair Group Method Using Arithmetic Averages (UPGMA) (Nei, Molecular Population Genetics and Evolution, North Holland, Amsterdam, 1975). The tree supports the previous hypothesis that evolution of EV 70 started from a single common ancestor. The time of its emergence was estimated to be 1967 +/- 15 months. The virus branched into many strains early during the first pandemic and has evolved in a divergent fashion, yielding genetically polymorphic viruses in the world.

Biological Evolution↗
PubMed1996

A simple method for the removal of mains interference from pre-recorded electrophysiological data.

MOTIVATION: A common problem with electrophysiological recording is the contamination of the signal of interest with interference generated at mains frequency. Standard filtering techniques are often inappropriate because the signal of interest has components spectrally close to the mains frequency. RESULTS: A digital subtraction method is described for removing mains frequency interference from pre-recorded data. The data are first digitized with a sample rate that is some direct multiple of mains frequency. Next a 20 ms (for UK mains frequency) data set is constructed containing the average interference pattern. This is subtracted from each 20 ms window of the raw data. Finally, the mean value of the interference is added back to the raw data to restore the DC component. AVAILABILITY: A Windows program which implements the method for the EGAA data acquisition system (R.C.Electronics, Santa Barbara, CA) is available from the author. CONTACT: wjh@st-andrews.ac.uk

Action Potentials↗
PubMed1993

Potential problems in estimating the male-to-female mutation rate ratio from DNA sequence data.

It is commonly believed that the rate of mutation is much higher in males than in females because the number of germ-cell divisions per generation is much larger in males than in females. However, the precise magnitude of the male-to-female mutation rate ratio (alpha m) remains unknown. Recently there have been efforts to estimate alpha m by using DNA sequence data from different species. We have studied the potential problems in such an approach. We found that the rate of synonymous substitution varies about fivefold among X-linked genes, as large as the variation among autosomal genes. This large variation makes the assumption of selective neutrality of synonymous changes dubious, so one should be cautious in using the synonymous rates in X-linked and autosomal genes to estimate alpha m. A similar difficulty was also observed in using nonhomologous intron sequences to estimate alpha m. Contrary to the expectation that X-linked sequences should evolve more slowly than autosomal sequences, the Alu repeat in the last intron of the X-linked zinc finger gene has evolved faster than the four autosomal Alu repeats used in this study. It appears that the best way to estimate alpha m is to use homologous sequences. However, such sequences may be involved in gene conversion events. In fact, we found evidence that the Y-linked and X-linked zinc finger genes have been involved in multiple conversion events during primate evolution. Thus, the possibility of gene conversion should be considered when using homologous sequences to estimate alpha m.

Animals↗