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At least 145 records · Page 8Linked to original sources
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↗
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↗
PubMed1989

Diverse prognosis in metastatic breast cancer: who should be offered alternative initial therapies?

In an attempt to clarify appropriate treatment options for women with stage IV breast cancer, we studied the survival experience of a large dataset of patients treated on Cancer and Leukemia Group B (CALGB) protocols. The study, restricted to women who had had no prior chemotherapy for metastatic disease, demonstrated a surprisingly poor prognosis, with an estimated median survival of 1.6 years and only 26% alive at 3 years. Analysis of prognostic factors permitted the identification of subsets with even shorter survival, such as women with estrogen receptor negative tumor in more than one metastatic site and prior adjuvant chemotherapy. We feel that an evaluation of intensive investigational treatment approaches, such as trials using autologous bone marrow transplantation, is justified for most stage IV breast cancer patients, in view of their poor prognosis.

Biomarkers, Tumor↗
PubMed1994

From terminology to terminology services.

Terminologies have traditionally been considered as static datasets held in books or databases. The GALEN Terminology Server presents a prototype for a new view of terminologies delivered as a set of functions and services provided to other applications. This facilitates their development and integration as part of a strategy for sharing and re-using information and knowledge. The essential features of the Terminology server are the functions which it can perform; questions which it can answer and statements which it can be told. The GALEN Terminology Server supports these operations through a modular architecture and uniform applications programming interface which allows client applications to ignore the internal structure and simply use the Server for terminological, coding, and linguistic functions.

Computer Systems↗
PubMed2000

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial of the National Cancer Institute: history, organization, and status.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is enrolling 148,000 men and women ages 55-74 at ten screening centers nationwide with balanced randomization to intervention and control arms. For prostate cancer, men receive a digital rectal examination and a blood test for prostate-specific antigen. For lung cancer, men and women receive a posteroanterior view chest X-ray. For colorectal cancer, men and women undergo a 60-cm flexible sigmoidoscopy. For ovarian cancer, women receive a blood test for the CA125 tumor marker and transvaginal ultrasound. Members of the control arm continue with their usual care. Follow-up in both groups will continue for at least 13 years from randomization to assess health status and cause of death. The primary endpoint is mortality from the four PLCO cancers, which accounts for about 53% of all cancer deaths in men and 41% of cancer deaths in women in the United States each year. Blood specimens are collected from screened participants, buccal cell DNA from controls, and histology slides from cases; these are maintained in a biorepository. Participants complete a baseline questionnaire (covering health status and risk factors) and a dietary questionnaire. More than 12,000 participants were enrolled in the pilot phase (concluded in September 1994). Changes in the eligibility criteria followed. As of April 2000, enrollment exceeded 144,500. Data are scanned into designated on-site computers for uploading by participant identification number to the coordinating center for quality checks, archival storage, and preparation of analysis datasets for use by the National Cancer Institute (NCI). Scientific direction is provided by NCI scientists, trial investigators, external consultants, and an independent data safety and monitoring board. Performance and data quality are monitored via data edits, site visits, random record audits, and teleconferences. The PLCO trial is formally endorsed by the American Cancer Society and has been ranked by the American Urological Association as one of the most important prostate cancer studies being conducted. Special efforts to enroll black participants are cosponsored by the U.S. Centers for Disease Control and Prevention.

Aged↗
PubMed2001

yMGV: a database for visualization and data mining of published genome-wide yeast expression data.

The yeast Microarray Global Viewer (yMGV) is an on-line database providing a synthetic view of the transcriptional expression profiles of Saccharomyces cerevisiae genes in most of the published expression datasets. yMGV displays a one-screen graphical representation of gene expression variations for each published genome-wide experiment, allowing quick retrieval of experimental conditions affecting expression of this gene. yMGV also provides tools to isolate groups of genes sharing similar transcription profiles in a defined subset of experiments. Additionally, yMGV furnishes a set of statistical tools for critical assessment of published data. We therefore believe that yMGV is an efficient tool that affords a quick and comprehensive overview of microarray data and generates new gene classifications. As of 20 March 2001 the yMGV database contains 6 000 000 measurements, representing genome-wide expression comparisons of 932 experiments from 39 microarray publications. The yMGV interface is available at http://transcriptome.ens.fr/ymgv/.

Computational Biology↗
PubMed1995

Analysis of the CD3 gene region and type 1 diabetes: application of fluorescence-based technology to linkage disequilibrium mapping.

The CD3 gene region on chromosome 11q23 has been implicated in susceptibility to type 1 (insulin-dependent) diabetes mellitus. Using semi-automated fluorescence-based technology, we have undertaken association and linkage analysis of a dinucleotide microsatellite in the CD3 delta (CD3D) gene. We have also performed a large case-control analysis of a restriction fragment length polymorphism (RFLP) in the CD3 epsilon (CD3E) gene, 26 kb from CD3D. We found no evidence for the previously reported association between the 8 kb allele of the RFLP and disease in a UK dataset of 403 diabetic patients and 446 nondiabetic controls. Furthermore, the use of the transmission/disequilibrium test (TDT) showed no evidence of linkage or association to type 1 diabetes at either marker locus. We conclude that the CD3 gene region does not contribute significantly to IDDM susceptibility. We have successfully applied semi-automated, fluorescence-based technology to undertake association analysis on the CD3D microsatellite. Moreover, by analysing 94 other dinucleotide repeat markers, we conclude that fluorescence-based methodology can generally be applied to large-scale, semi-automated association studies with most microsatellite markers.

Adolescent↗
PubMed1996

A clinical evaluation of flurbiprofen LAT and piroxicam gel: a multicentre study in general practice.

A prospective, randomized, multicentre, open, crossover study of the comparative efficacy, tolerability and acceptability of two topical nonsteroidal anti-inflammatory drug (NSAID) therapies, flurbiprofen local-action transcutaneous (LAT) patch (40 mg b.d.) and piroxicam gel (3 cm, 0.5% q.d.s), was conducted in general practice in the UK in 137 men and women with soft-tissue rheumatism of the shoulder or elbow (e.g. epicondylitis, tendinitis, bursitis and adhesive capsulitis). Patients received one therapy for 4 days before crossing over to the other NSAID for a further 4 days, followed by 6 days of their preferred therapy. Clinical assessment of severity of pain, tenderness and overall clinical condition was carried out at baseline and after 4, 8 and 14 days. Patients self-assessed the severity of pain during the day and at night, and also the quality of their sleep during each treatment phase. More patients showed a greater improvement in all of the clinical assessments of efficacy following treatment with flurbiprofen LAT during the crossover phase. There was a statistically significant reduction in the severity of pain, the principal measure of efficacy, in favour of flurbiprofen LAT: 42% of patients showed greater improvement with flurbiprofen LAT compared with 26% who showed a greater improvement with piroxicam gel (p = 0.012; n = 131, intent-to-treat). Eligible dataset (n = 126) analysis revealed statistically significant differences in favour of flurbiprofen LAT in the severity of lesion tenderness (p = 0.03) and the overall change in clinical condition (p = 0.04) compared with baseline status. Superior efficacy for flurbiprofen LAT was also indicated in the patients' assessment at the end of the crossover phase (day 8), at which 69% chose to continue treatment with flurbiprofen LAT compared with only 31% of patients who chose piroxicam gel (n = 126; p < 0.001). There were, in addition, statistically significant differences in favour of flurbiprofen LAT in assessments for night pain (p < 0.001), quality of sleep (p = 0.004) and the patients' overall opinion of treatment (p < 0.001). Both treatments were well tolerated with a low incidence of mainly local adverse events. These results showed that flurbiprofen LAT had a greater efficacy than piroxicam gel, and was also preferred by patients in the treatment of painful soft-tissue rheumatism of the shoulder and elbow.

Administration, Cutaneous↗
PubMed1999

Transparent image access in a distributed picture archiving and communications system: the Master Database broker.

A distributed design is the most cost-effective system for small-to medium-scale picture archiving and communications systems (PACS) implementations. However, the design presents an interesting challenge to developers and implementers: to make stored image data, distributed throughout the PACS network, appear to be centralized with a single access point for users. A key component for the distributed system is a central or master database, containing all the studies that have been scanned into the PACS. Each study includes a list of one or more locations for that particular dataset so that applications can easily find it. Non-Digital Imaging and Communications in Medicine (DICOM) clients, such as our worldwide web (WWW)-based PACS browser, query the master database directly to find the images, then jump to the most appropriate location via a distributed web-based viewing system. The Master Database Broker provides DICOM clients with the same functionality by translating DICOM queries to master database searches and distributing retrieval requests transparently to the appropriate source. The Broker also acts as a storage service class provider, allowing users to store selected image subsets and reformatted images with the original study, without having to know on which server the original data are stored.

CD-ROM↗
PubMed1999

Tetanus toxoid and congenital abnormalities.

OBJECTIVE: To study the human teratogenic potential of tetanus vaccination during pregnancy. METHODS: Pair analysis of cases with congenital abnormalities and matched healthy controls was performed in the large population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1994. RESULTS: Of 35 727 pregnant women who had babies without any defects in the study period (control group), 33 (0.09%) were vaccinated with tetanus. Of 21563 pregnant women who had offspring with congenital abnormalities, 25 (0.12%) had tetanus vaccination. This difference was not significant (P = 0.39). The case-control pair analysis confirmed the safety of tetanus vaccination during pregnancy, particularly in the second and third months of gestation, i.e. during the critical period for congenital abnormalities. CONCLUSION: Tetanus vaccination during pregnancy appears not be teratogenic to the fetus. Thus, there is no contraindication, if the use of tetanus toxoid is necessary during pregnancy.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Scientific and cost-effectiveness criteria in selecting batteries of short-term tests.

The scientific and cost-effectiveness criteria introduced in this paper can be applied to published datasets and current and proposed batteries of short-term tests. The reports in the current volume will provide a wealth of additional material for such evaluations, but more systematically obtained information will be necessary to assess both the internal and external validity of these tests. Individual tests and batteries of tests should be standardized, employ positive controls, generate results capable of quantitative analyses that may make dichotomous classification as "positive" and "negative" obsolete, be interpreted in light of mechanisms of action, and be cost-effective on a grand scale. For regulatory purposes our long-term goal should be to replace the whole animal lifetime bioassay with an appropriate and cost-effective set of short-term tests.

Animals↗
PubMed1992

Distributed data analysis in a multicenter study: the CARDIA Study.

Unlike distributed data entry, which is used in many large epidemiologic studies and multicenter clinical trials, distributed data analysis is a relatively new concept. This paper reports on the usefulness of such a system in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA distributes the entire examination dataset to participating centers soon after completion of each round of data collection. The process was designed to encourage more numerous, diverse, and rapid publications, and to allow for more efficient use of the manpower and expertise in centers. Responsibilities of the coordinating center have changed from a conventional coordinating center but remain substantial due to the need for collating, monitoring, verifying, and documenting the distributed data analysis (DDA) system. DDA is successful from the standpoint of implementation and operation--21 manuscripts representing work analyzed at six participating centers had been submitted for publication within 3.5 years of the completion of the baseline examination.

Adolescent↗
PubMed1999

Seamless multiresolution display of portable wavelet-compressed images.

Image storage, display, and distribution have been difficult problems in radiology for many years. As improvements in technology have changed the nature of the storage and display media, demand for image portability, faster image acquisition, and flexible image distribution is driving the development of responsive systems. Technology, such as the wavelet-based multiresolution seamless image database (MrSID) portable image format (PIF), is enabling image management solutions that address the shifting "point-of-care." The MrSID PIF employs seamless, multiresolution technology, which allows the viewer to determine the size of the image to be viewed, as well as the position of the viewing area within the image dataset. In addition the MrSID PIF allows control of the compression ratio of decompressed images. This capability offers the advantage of very rapid image recall from storage devices and portability for rapid transmission and distribution using the internet or wide-area networks. For example, in teleradiology, the radiologist or other physician desiring to view images at a remote location has full flexibility in being able to choose a quick display of an overview image, a complete display of a full diagnostic quality image, or both without compromising communication bandwidth. The MrSID algorithm will satisfy Joint Photographic Experts Group (JPEG) 2000 standards, thereby being compatible with future versions of the Digital Imaging and Communications in Medicine (DICOM) standard for image data compression.

Algorithms↗
PubMed2001

Discovering common stem-loop motifs in unaligned RNA sequences.

Post-transcriptional regulation of gene expression is often accomplished by proteins binding to specific sequence motifs in mRNA molecules, to affect their translation or stability. The motifs are often composed of a combination of sequence and structural constraints such that the overall structure is preserved even though much of the primary sequence is variable. While several methods exist to discover transcriptional regulatory sites in the DNA sequences of coregulated genes, the RNA motif discovery problem is much more difficult because of covariation in the positions. We describe the combined use of two approaches for RNA structure prediction, FOLDALIGN and COVE, that together can discover and model stem-loop RNA motifs in unaligned sequences, such as UTRs from post-transcriptionally coregulated genes. We evaluate the method on two datasets, one a section of rRNA genes with randomly truncated ends so that a global alignment is not possible, and the other a hyper-variable collection of IRE-like elements that were inserted into randomized UTR sequences. In both cases the combined method identified the motifs correctly, and in the rRNA example we show that it is capable of determining the structure, which includes bulge and internal loops as well as a variable length hairpin loop. Those automated results are quantitatively evaluated and found to agree closely with structures contained in curated databases, with correlation coefficients up to 0.9. A basic server, Stem-Loop Align SearcH (SLASH), which will perform stem-loop searches in unaligned RNA sequences, is available at http://www.bioinf.au.dk/slash/.

Algorithms↗
PubMed1995

Commentary and opinion: III. Some nonontological and functionally unconnected views on current issues in the analysis of PET datasets.

Strother et al. (1995) and Friston (1995) both raise important issues and provide useful reviews of various aspects of PET data analysis. Statisticians would not assume that any single piece of methodology would answer all questions about a type of data in a variety of experimental and observational contexts. The fundamental importance of hypothesis-driven inference, based on well designed experiments, cannot be overestimated for its ability to progress scientific understanding in an orderly manner. However, hypothesis-generating experiments are also vital in their own right. In practice, we generally do not have the luxury of both types of experiment, and we should note Strother et al.'s comment on the importance of extracting as much information as possible from each dataset. Friston (1995) also sees formal testing methods and exploratory methods such as principal components analysis as complementary. The correct approach would therefore seem to be (a) to select methods for formal and exploratory data analysis from the rich existing tool kit of statistical procedures, (b) to modify these as necessary to deal with special PET problems such as multiplicity, (c) to be aware of the assumptions underlying the methods being used and to investigate the problems that can arise if these assumptions fail to hold, (d) to appreciate the complexity of both PET data and of the potential questions that can be asked of it, and (e) to be aware of the limitations of any statistical analysis and the need for caution in interpreting conclusions not based on any predefined hypothesis.

Analysis of Variance↗