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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↗

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↗

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↗

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↗

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↗

DMARD use in early rheumatoid arthritis. Lessons from observations in patients with established disease.

The concept of early and aggressive therapy of rheumatoid arthritis (RA) has been well documented in the past years. It includes immediate DMARD institution after diagnosis, the use of the most effective DMARDs, and rapid switching of regimens if a level of disease activity close to remission is not achieved. In this review we briefly explore to what degree this new concept has been implemented in routine clinical care. Based on an observational dataset comprising 3342 DMARD courses, we present evidence of a change in DMARD patterns in newly diagnosed RA patients towards a higher prescription rate of more aggressive drugs like methotrexate (MTX), as well as a decreasing lag time until MTX was instituted in RA patients over the years. One consequence of recent changes in therapeutic strategies is that comparative analyses of formerly versus recently employed DMARDs will be considerably biased in observational studies. By contrast to changes in DMARD usage, survey data show neither a shortening of referral time nor a change in the approach to diagnose early RA. These data indicate a need for more dissemination of the early arthritis concept.

Adult↗

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↗

Neural network based automated algorithm to identify joint locations on hand/wrist radiographs for arthritis assessment.

Arthritis is a significant and costly healthcare problem that requires objective and quantifiable methods to evaluate its progression. Here we describe software that can automatically determine the locations of seven joints in the proximal hand and wrist that demonstrate arthritic changes. These are the five carpometacarpal (CMC1, CMC2, CMC3, CMC4, CMC5), radiocarpal (RC), and the scaphocapitate (SC) joints. The algorithm was based on an artificial neural network (ANN) that was trained using independent sets of digitized hand radiographs and manually identified joint locations. The algorithm used landmarks determined automatically by software developed in our previous work as starting points. Other than requiring user input of the location of nonanatomical structures and the orientation of the hand on the film, the procedure was fully automated. The software was tested on two datasets: 50 digitized hand radiographs from patients participating in a large clinical study, and 60 from subjects participating in arthritis research studies and who had mild to moderate rheumatoid arthritis (RA). It was evaluated by a comparison to joint locations determined by a trained radiologist using manual tracing. The success rate for determining the CMC, RC, and SC joints was 87%-99%, for normal hands and 81%-99% for RA hands. This is a first step in performing an automated computer-aided assessment of wrist joints for arthritis progression. The software provides landmarks that will be used by subsequent image processing routines to analyze each joint individually for structural changes such as erosions and joint space narrowing.

Algorithms↗

Long terminal repeat retrotransposons of Mus musculus.

BACKGROUND: Long terminal repeat (LTR) retrotransposons make up a large fraction of the typical mammalian genome. They comprise about 8% of the human genome and approximately 10% of the mouse genome. On account of their abundance, LTR retrotransposons are believed to hold major significance for genome structure and function. Recent advances in genome sequencing of a variety of model organisms has provided an unprecedented opportunity to evaluate better the diversity of LTR retrotransposons resident in eukaryotic genomes. RESULTS: Using a new data-mining program, LTR_STRUC, in conjunction with conventional techniques, we have mined the GenBank mouse (Mus musculus) database and the more complete Ensembl mouse dataset for LTR retrotransposons. We report here that the M. musculus genome contains at least 21 separate families of LTR retrotransposons; 13 of these families are described here for the first time. CONCLUSIONS: All families of mouse LTR retrotransposons are members of the gypsy-like superfamily of retroviral-like elements. Several different families of unrelated non-autonomous elements were identified, suggesting that the evolution of non-autonomy may be a common event. High sequence similarity between several LTR retrotransposons identified in this study and those found in distantly-related species suggests that horizontal transfer has been a significant factor in the evolution of mouse LTR retrotransposons.

Animals↗

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↗

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↗

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↗

Clinical quality needs complex adaptive systems and machine learning.

The vast increase in clinical data has the potential to bring about large improvements in clinical quality and other aspects of healthcare delivery. However, such benefits do not come without cost. The analysis of such large datasets, particularly where the data may have to be merged from several sources and may be noisy and incomplete, is a challenging task. Furthermore, the introduction of clinical changes is a cyclical task, meaning that the processes under examination operate in an environment that is not static. We suggest that traditional methods of analysis are unsuitable for the task, and identify complexity theory and machine learning as areas that have the potential to facilitate the examination of clinical quality. By its nature the field of complex adaptive systems deals with environments that change because of the interactions that have occurred in the past. We draw parallels between health informatics and bioinformatics, which has already started to successfully use machine learning methods.

Artificial Intelligence↗

Identification of tryptic peptides from large databases using multiplexed tandem mass spectrometry: simulations and experimental results.

Multiplexed tandem mass spectrometry (MS/MS) has recently been demonstrated as a means to increase the throughput of peptide identification in liquid chromatography (LC) MS/MS experiments. In this approach, a set of parent species is dissociated simultaneously and measured in a single spectrum (in the same manner that a single parent ion is conventionally studied), providing a gain in sensitivity and throughput proportional to the number of species that can be simultaneously addressed. In the present work, simulations performed using the Caenorhabditis elegans predicted proteins database show that multiplexed MS/MS data allow the identification of tryptic peptides from mixtures of up to ten peptides from a single dataset with only three "y" or "b" fragments per peptide and a mass accuracy of 2.5 to 5 ppm. At this level of database and data complexity, 98% of the 500 peptides considered in the simulation were correctly identified. This compares favorably with the rates obtained for classical MS/MS at more modest mass measurement accuracy. LC multiplexed Fourier transform-ion cyclotron resonance MS/MS data obtained from a 66 kDa protein (bovine serum albumin) tryptic digest sample are presented to illustrate the approach, and confirm that peptides can be effectively identified from the C. elegans database to which the protein sequence had been appended.

Algorithms↗

Identifying residues in natural organic matter through spectral prediction and pattern matching of 2D NMR datasets.

This paper describes procedures for the generation of 2D NMR databases containing spectra predicted from chemical structures. These databases allow flexible searching via chemical structure, substructure or similarity of structure as well as spectral features. In this paper we use the biopolymer lignin as an example. Lignin is an important and relatively recalcitrant structural biopolymer present in the majority of plant biomass. We demonstrate how an accurate 2D NMR database of approximately 600 2D spectra of lignin fragments can be easily constructed, in approximately 2 days, and then subsequently show how some of these fragments can be identified in soil extracts through the use of various search tools and pattern recognition techniques. We demonstrate that once identified in one sample, similar residues are easily determined in other soil extracts. In theory, such an approach can be used for the analysis of any organic mixtures.

Benzopyrans↗

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↗

Detection of differentially expressed proteins in early-stage melanoma patients using SELDI-TOF mass spectrometry.

Tumor progression is a dynamic sequence of events that involves specific protein changes. We hypothesized that Surface Enhanced Laser Desorption/Ionization (SELDI) mass spectrometric analysis of sera from patients with AJCC stage I and II melanoma with negative loco-regional lymph nodes could identify potential melanoma-associated protein biomarkers of disease recurrence. Serum specimens were collected from 49 patients who developed recurrence (n = 25) or remained free of recurrence (n = 24) without evidence of disease following complete resection (AJCC stage I and II). Follow-up was longer than 5 years. Serum proteins were denatured and applied onto two protein chip chemistry surfaces (weak cationic WCX2; metal-binding, IMAC3-Cu). SELDI ProteinChip mass spectrometry was then performed. SELDI data were analyzed, protein peak clustering and classification were performed, and a supervised classification algorithm was employed to classify the dataset. Multiple protein peaks ranging from 3.3 to 30 kDa were identified between patients with recurrence and those without recurrence, and the expression pattern differences of three proteins were used to generate the discriminating classification tree. The biomarkers were expressed with a high degree of reproducibility. In this early characterization study, melanoma recurrence was predicted with a sensitivity of 72% (18/25) and a specificity of 75% (18/24). This novel pilot study revealed three proteins that accurately identified patients who developed recurrence after curative resection of primary melanoma.

Adult↗

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↗