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The United Kingdom Heart Valve Registry.

The United Kingdom Heart Valve Registry project began in 1986 following discussions between the Department of Health (DOH) and the Society of Cardiothoracic Surgeons of the United Kingdom and Ireland. The intention was to establish a computerized database for valve replacement operations carried out in the UK Health Service cardiac units. This paper describes the experience gained over the first five years of this project. Around 30,000 patients were entered in the registry between 1986 and 1990. All Uk Health Service cardiac surgical units contribute their data, which is processed by the central Registry Office. The accuracy of the mortality data is ensured by tracking the registered patients through the Office of Population Census and Surveys (OPCS). The pattern of valve replacement surgery over the period 1986-90 revealed several interesting trends. Although the number of procedures remained static at around 5,000 valve transplants per year, the number of aortic replacements increased and the number of mitrals decreased. The use of prosthetic valves increased from 54% in 1986 to over 70% in 1990. The mean age of the patients increased from 58.31 years in 1986 to 60.97 years in 1990, with over 22% of the valve replacement operations in 1990 being performed on patients over 70 years of age. The five year survival rate for patients over 70 years at the time of the valve implant is significantly lower than for patients under 70 years (p < 0.005).

Aged↗

[Ways of improvement of the accuracy of arterial pressure oscillometry].

The history of the auscultation method of arterial pressure (AP) measurement dates back to more than century ago. Nevertheless, the problem of the accuracy of measurement is still on the agenda. Standards of the accuracy of measurements and data processing are subjects of regular revision and update. The accuracy and reliability of AP monitoring in complex clinical cases are competitive advantages important for manufacturers of medical monitors. A new Triton ElectronicS module for AP measurements based on original technology and results of its testing are considered in this work. An original algorithm of the module operation provides an opportunity for more accurate and convenient monitoring, particularly in case of disordered hemodynamics.

Arteries↗

Determination of adefovir in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study.

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated to determine the concentrations of adefovir [9-(2-phosphonylmethoxyethyl)adenine, PMEA] in human plasma. After one-step protein precipitation of plasma samples by methanol, adefovir was analyzed by LC/MS/MS using positive electrospray ionization. Chromatography was performed on a C18 column. The extraction recoveries of adefovir were found to be 85.1-89.3%. Adefovir was stable under routine laboratory conditions. A minimal matrix effect resulting in a slight ionization enhancement of adefovir (<10.9%) was observed, which did not markedly affect the behavior of the calibrations curves and accuracy and precision data. The method had a chromatographic run time of 7.8 min and a linear calibration curve over the concentration range 1.5-90 ng/mL for adefovir. The lower limit of quantification of the method was 1.5 ng/mL. The intra- and inter-day precision was less than 8.4%. These results indicated that this LC/MS/MS method has high selectivity and efficiency, and acceptable accuracy, precision and sensitivity. The validated LC/MS/MS method has been successfully used in a pharmacokinetic study in healthy volunteers treated with oral adefovir dipivoxil at 10 and 20 mg.

Adenine↗

Race, racism, and epidemiological surveys.

Many studies of clinical populations have reported significant differences between whites and blacks in prevalence rates of mental disorders. However, data from the Epidemiologic Catchment Area study indicate only modest differences. The author describes factors in the treatment experiences of black and white patients that may lead researchers to find questionable disparities in prevalence rates. These factors include racial differences in treatment-seeking behavior, likelihood of involuntary commitment, representation in research samples, presentation of psychiatric symptoms and resulting diagnoses, and accuracy of psychological tests as well as disparities in treatment. The author suggests guidelines for improving research methods and designs, including documenting the ethnic composition of samples and using structured diagnostic assessments, so that unintended inequalities can be identified, addressed, and monitored and the accuracy of prevalence data among blacks can be improved.

Adolescent↗

Comparison of different fluorescence fluctuation methods for their use in FRET assays: monitoring a protease reaction.

We compare the accuracy of a variety of Fluorescence Fluctuation Spectroscopy (FFS) methods for the study of Förster Resonance Energy Transfer (FRET) assays. As an example, the cleavage of a doubly labeled, FRET-active peptide substrate by the protease Trypsin is monitored and analyzed using methods based on fluorescence intensity, Fluorescence Correlation Spectroscopy (FCS) and Fluorescence Intensity Distribution Analysis (FIDA). The presented fluorescence data are compared to High-Pressure Liquid Chromatography (HPLC) data obtained from the same assay. The HPLC analysis discloses general disadvantages of the FRET approach, such as incomplete labeling and the need for aliquots. However, the simultaneous use of two photon detectors monitoring the fluorescence signal of both labels significantly improves the analysis. In particular, the two global analysis tools Two-Dimensional Fluorescence Intensity Distribution Analysis (2D-FIDA) and Two-Color Global Fluorescence Correlation Spectroscopy (2CG-FCS) highlight the potential of a combination of FFS and FRET. While conventional FIDA and FCS auto- or cross-correlation analysis leaves the user with drawbacks inherent in two-color and FRET applications, these effects are overcome by the global analysis on the molecular level. Furthermore, it is advantageous to analyze the unnormalized as opposed to the normalized correlation data when combining any fluorescence correlation method with FRET, since the analysis of the unnormalized data introduces more accuracy and is less sensitive to the experimental drawbacks.

Algorithms↗

Construction of a physical and preliminary genetic map of Aeromonas hydrophila JMP636.

A physical and preliminary genetic map of the Aeromonas hydrophila JMP636 chromosome has been constructed. The topology of the genome was predicted to be circular as chromosomal DNA did not migrate from the origin during PFGE unless linearized by S1 nuclease. Cleavage of the chromosome with PacI and PmeI produced 23 and 14 fragments, respectively, and enabled calculation of the genome size at 4.5 Mb. Digestion of the chromosome with I-CeuI produced 10 fragments, indicating that 10 rrl (23S) genes were likely to be present. Hybridizations between DNA fragments generated with PacI, PmeI and I-CeuI were used to initially determine the relationship between these segments. To accurately map genes previously characterized from JMP636, the suicide vector pJP5603 was modified to introduce restriction sites for PacI and PmeI, producing pJP9540. Following cloning of genes into this vector and recombinational insertion into the JMP636 chromosome, PacI and PmeI cleavage determined the location of genes within macrorestriction fragments with the additional bands produced forming hybridization probes. From the data generated, it was possible to form a physical map comprising all the fragments produced by PacI and PmeI, and assign the contig of I-CeuI fragments on this map. The preliminary genetic map defines the location of six loci for degradative enzymes previously characterized from JMP636, while the locations of the 10 sets of ribosomal genes were assigned with less accuracy from hybridization data.

Aeromonas hydrophila↗

Reassessment of measuring total iron binding capacity in acute iron overdose.

OBJECTIVE: To evaluate recent data that suggest that total iron binding capacity (TIBC) is not a reliable laboratory parameter in assessing acute iron overdose. DATA SOURCES: A MEDLINE search of the literature with a fan search of relevant articles. STUDY SELECTION AND DATA EXTRACTION: Laboratory, human, and animal studies on the measurement and relevance of TIBC in acute iron poisoning were reviewed. These data were analyzed in light of the current guidelines for use of TIBC in assessing iron poisoning. DATA SYNTHESIS: There are significant data to suggest that the sensitivity of TIBC in acute iron poisoning is unacceptable. This lack of sensitivity is also reflected in the poor positive predictive value of TIBC. The specificity and negative predictive value are higher but not without error. One survey of 500 laboratories reported a coefficient of variation for TIBC of 16 percent (95 percent confidence interval), suggesting unacceptable accuracy. CONCLUSIONS: These data suggest that TIBC may not be a reliable laboratory parameter in assessing acute iron poisoning. Studies are needed to develop a reliable analytical procedure for TIBC and to correlate TIBC with clinical outcomes in acute iron poisonings.

Clinical Trials as Topic↗

Physician-patient interaction in reproductive counseling.

OBJECTIVE: To review the scientific and clinical bases for effective patient counseling in contraceptive care. DATA SOURCES: All articles and chapters in the Annotated Bibliography of Doctor Patient Communication of the Task Force on Doctor and Patient of the American Academy on Physician and Patient were searched and included. This is an expert-derived data base based on MEDLINE review from 1969 to 1994 and including expert-selected additions from PsychLit and a variety of other social science data bases, books, and reviews. METHODS OF STUDY SELECTION: Expert consensus was used from the Committee on Bibliography of the American Academy on Physician and Patient. TABULATION, INTEGRATION, AND RESULTS: The doctor-patient interaction is the main determinant of the accuracy and completeness of patient data, diagnostic accuracy, efficiency in the encounter, compliance, patient understanding of problems, and patient and physician satisfaction. Yet this critical skill is inadequately taught and practiced, with serious consequences for patient care and physician job satisfaction. Use of the 14 structural elements (preparing the environment, preparing oneself, observation, greeting, introduction, detecting and overcoming barriers to communication, surveying problems, negotiating a priority problem, developing a narrative thread, establishing the life context of the patient, establishing a safety net, presenting findings and options, negotiating plans, and closing) and three functions (gathering information, developing a therapeutic relationship, and patient education) and their associated behaviors improves encounter results significantly. Other helpful activities are patient activation, facilitating partnership, review of findings and plans, eliciting and responding to patients' attitudes and emotions about contraception and fertility, and use of empathy and positive regard. CONCLUSIONS: The use of scientifically derived, empirically validated interview skills substantially improves outcomes in contraceptive and other patient education and counseling. Use of appropriate structure and functions of the encounter, patient participation and partnership, review of patient understanding and reactions, and relating to the patients' attitudes and emotions about the subject each improve the outcomes of contraceptive care.

Contraception↗

Normalization of multicolor fluorescence in situ hybridization (M-FISH) images for improving color karyotyping.

BACKGROUND: Multiplex or multicolor fluorescence in situ hybridization (M-FISH) is a recently developed cytogenetic technique for cancer diagnosis and research on genetic disorders. By simultaneously viewing the multiply labeled specimens in different color channels, M-FISH facilitates the detection of subtle chromosomal aberrations. The success of this technique largely depends on the accuracy of pixel classification (color karyotyping). Improvements in classifier performance would allow the elucidation of more complex and more subtle chromosomal rearrangements. Normalization of M-FISH images has a significant effect on the accuracy of classification. In particular, misalignment or misregistration across multiple channels seriously affects classification accuracy. Image normalization, including automated registration, must be done before pixel classification. METHODS AND RESULTS: We studied several image normalization approaches that affect image classification. In particular, we developed an automated registration technique to correct misalignment across the different fluor images (caused by chromatic aberration and other factors). This new registration algorithm is based on wavelets and spline approximations that have computational advantages and improved accuracy. To evaluate the performance improvement brought about by these data normalization approaches, we used the downstream pixel classification accuracy as a measurement. A Bayesian classifier assumed that each of 24 chromosome classes had a normal probability distribution. The effects that this registration and other normalization steps have on subsequent classification accuracy were evaluated on a comprehensive M-FISH database established by Advanced Digital Imaging Research (http://www.adires.com/05/Project/MFISH_DB/MFISH_DB.shtml). CONCLUSIONS: Pixel misclassification errors result from different factors. These include uneven hybridization, spectral overlap among fluors, and image misregistration. Effective preprocessing of M-FISH images can decrease the effects of those factors and thereby increase pixel classification accuracy. The data normalization steps described in this report, such as image registration and background flattening, can significantly improve subsequent classification accuracy. An improved classifier in turn would allow subtle DNA rearrangements to be identified in genetic diagnosis and cancer research.

Algorithms↗

Quantitative phase-contrast flow MRI measurements in the presence of a second vessel closely positioned to the examined vessel.

PURPOSE: To examine the influence of the truncated sampling of k-space data on the accuracy of phase-contrast (PC) flow quantifications in the presence of nearby vessels. MATERIALS AND METHODS: Computer simulations were performed along with some experimental validations on a flow phantom and a normal subject. RESULTS: The accuracy of the PC flow quantification decreased when a second vessel was positioned closely to the examined vessel. The effect strongly depended on the peak flow velocity in the second vessel relative to the velocity encoding (venc) level of the MRI acquisition, and on the position and area of the second vessel. CONCLUSION: Due to the truncated sampling of the k-space data, signal leaked from nearby vessels and distorted the PC flow quantification in the examined vessel. The presented results suggest specific experimental conditions to minimize this flow quantification error.

Blood Flow Velocity↗

Spline-based image-to-volume registration for three-dimensional electron microscopy.

This paper presents an algorithm based on a continuous framework for a posteriori angular and translational assignment in three-dimensional electron microscopy (3DEM) of single particles. Our algorithm can be used advantageously to refine the assignment of standard quantized-parameter methods by registering the images to a reference 3D particle model. We achieve the registration by employing a gradient-based iterative minimization of a least-squares measure of dissimilarity between an image and a projection of the volume in the Fourier transform (FT) domain. We compute the FT of the projection using the central-slice theorem (CST). To compute the gradient accurately, we take advantage of a cubic B-spline model of the data in the frequency domain. To improve the robustness of the algorithm, we weight the cost function in the FT domain and apply a "mixed" strategy for the assignment based on the minimum value of the cost function at registration for several different initializations. We validate our algorithm in a fully controlled simulation environment. We show that the mixed strategy improves the assignment accuracy; on our data, the quality of the angular and translational assignment was better than 2 voxel (i.e., 6.54 angstroms). We also test the performance of our algorithm on real EM data. We conclude that our algorithm outperforms a standard projection-matching refinement in terms of both consistency of 3D reconstructions and speed.

Algorithms↗

Complex signals in the genomic 3' nontranslated region of bovine viral diarrhea virus coordinate translation and replication of the viral RNA.

The genomes of positive-strand RNA viruses strongly resemble cellular mRNAs. However, besides operating as a messenger to generate the virus-encoded proteins, the viral RNA serves also as a template during replication. A central issue of the viral life cycle, the coordination of protein and RNA synthesis, is yet poorly understood. Examining bovine viral diarrhea virus (BVDV), we report here on the role of the variable 3'V portion of the viral 3' nontranslated region (3'NTR). Genetic studies and structure probing revealed that 3'V represents a complex RNA motif that is composed of synergistically acting sequence and structure elements. Correct formation of the 3'V motif was shown to be an important determinant of the viral RNA replication process. Most interestingly, we found that a proper conformation of 3'V is required for accurate termination of translation at the stop-codon of the viral open reading frame and that efficient termination of translation is essential for efficient replication of the viral RNA. Within the viral 3'NTR, the complex 3'V motif constitutes also the binding site of recently characterized cellular host factors, the so-called NFAR proteins. Considering that the NFAR proteins associate also with the 5'NTR of the BVDV genome, we propose a model where the viral 3'NTR has a bipartite functional organization: The conserved 3' portion (3'C) is part of the nascent replication complex; the variable 5' portion (3'V) is involved in the coordination of the viral translation and replication. Our data suggest the accuracy of translation termination as a sophisticated device determining viral adaptation to the host.

3' Untranslated Regions↗

Maternal mortality in Latin American urban areas: the case of São Paulo, Brazil.

This article describes maternal mortality trends in São Paulo, Brazil, from 1960 through 1990. In so doing, it compares mortality rates derived from death certificate data with rates suggested by three independent surveys conducted in the city of São Paulo in 1962-1963, 1974-1975, and 1986. In general, these data indicate that a substantial share of all maternal deaths in the city have been ascribed to other causes on death certificates, that prevailing maternal mortality levels are far higher than those found in the urban areas of most developed countries, and that in recent years levels of maternal mortality in the city have been rising. Various measures are suggested for improving the accuracy of available data and reducing the maternal mortality they describe.

Abortion, Spontaneous↗

Systematic review of the quality of surgical mortality monitoring.

BACKGROUND: Mortality is the most tightly defined and used adverse event for audit and performance monitoring in surgery. However, to identify cause and therefore scope for improvement, accurate and timely data are required. The aim of this study was to perform a systematic review of the quality of measurement, reporting and monitoring of mortality as an outcome after surgery. METHODS: A systematic review of published literature was undertaken for the 7-year interval 1993-1999. Grey and unpublished literature was obtained through the Royal College of Surgeons of England, from UK national audits and routine national hospital data collections. RESULTS: Eligible monitoring systems included six UK national surgical audits, and cardiac and vascular surgery monitoring systems from North America and the UK. The definitions of 'surgical death' varied in several respects and deaths after discharge from hospital were rarely ascertained unless there was routine linkage to national death registers. There were very few published studies on validation of the completeness and accuracy of the data collection. CONCLUSION: A comprehensive data collection system is needed for improving clinical performance, with ownership, but not necessarily data collection, resting with the surgeons concerned. Recording of risk factors and deaths after discharge from hospital is essential, whatever data collection system is used.

Health Care Surveys↗

Interspecies scaling: predicting volumes, mean residence time and elimination half-life. Some suggestions.

Extrapolation of animal data to assess pharmacokinetic parameters in man is an important tool in drug development. Clearance, volume of distribution and elimination half-life are the three most frequently extrapolated pharmacokinetic parameters. Extensive work has been done to improve the predictive performance of allometric scaling for clearance. In general there is good correlation between body weight and volume, hence volume in man can be predicted with reasonable accuracy from animal data. Besides the volume of distribution in the central compartment (Vc), two other volume terms, the volume of distribution by area (Vbeta) and the volume of distribution at steady state (VdSS), are also extrapolated from animals to man. This report compares the predictive performance of allometric scaling for Vc, Vbeta and VdSS in man from animal data. The relationship between elimination half-life (t(1/2)) and body weight across species results in poor correlation, most probably because of the hybrid nature of this parameter. To predict half-life in man from animal data, an indirect method (CL=VK, where CL=clearance, V is volume and K is elimination rate constant) has been proposed. This report proposes another indirect method which uses the mean residence time (MRT). After establishing that MRT can be predicted across species, it was used to predict half-life using the equation MRT=1.44 x t(1/2). The results of the study indicate that Vc is predicted more accurately than Vbeta and VdSS in man. It should be emphasized that for first-time dosing in man, Vc is a more important pharmacokinetic parameter than Vbeta or VdSS. Furthermore, MRT can be predicted reasonably well for man and can be used for prediction of half-life.

Animals↗

Graphical comparison of image analysis and laser diffraction particle size analysis data obtained from the measurements of nonspherical particle systems.

The purpose of this paper is to describe results from the use of a set of Excel macros written to facilitate the comparison of image analysis (IA) and laser diffraction (LD) particle size analysis (psa) data. Measurements were made on particle systems of differing morphological characteristics including differing average aspect ratios, particle size distribution widths and modalities. The IA and LD psa data were plotted on the same graph treating both the weighting and the size unit of the LD psa data as unknowns. Congruency of the IA and LD plots was considered to indicate successful experimental determination of the weighting and size unit .The weighting of the resulting LD psa data (so-called volume-weighted) is shown to be better correlated with IA area-weighted data. The size unit of LD psa data is shown to be a function of particle shape. In the case of high aspect ratio particles characterized by approximately rectangular faces the LD psa data is shown to be a function of multiple particle dimensions being related to IA size descriptors through a simple variation of the law of mixtures. The results demonstrate that successful correlations between IA and LD psa data can be realized in the case of non-spherical particle systems even in the case of high aspect ratio particles; however, the inappropriateness of the application of the Equivalent Spherical Volume Diameter and the Random Particle Orientation assumptions to the interpretation of the LD psa results must first be acknowledged. Correlation permits cross validation of IA and LD psa results increasing confidence in the accuracy of the data from each orthogonal technique.

Humans↗

Childhood cancer in Britain: the National Registry of Childhood Tumours and incidence rates 1978-1987.

The National Registry of Childhood Tumours contains population-based data on childhood cancers diagnosed throughout Great Britain from 1962 onwards. This paper describes the methodology of the Registry, presents incidence rates for 1978-1987 and describes other uses of the data. Total age-standardised annual incidence was 118.3 per million. The most frequent diagnostic groups were leukaemias (age-standardised rate 39.8), brain and spinal tumours (27.0), lymphomas (11.1), sympathetic nervous system tumours (8.3), kidney tumours (7.7) and soft-tissue sarcomas (7.5). Incidence rates were similar to those reported from other Western industrialised countries. The data are also used for a wide range of epidemiological and other studies. These include analyses of geographical variations in incidence, trends in survival, health of long-term survivors and their offspring and the genetics of childhood cancer. Information is frequently provided for clinicians and research workers, and series of specific types of cancer are compiled for further study. The Registry depends for the completeness and accuracy of its data on a wide range of organisations and individuals, and it is essential that this cooperation continues if the Registry is to be maintained.

Adolescent↗

Performances of Wang-Landau algorithms for continuous systems.

The relative performances of different implementations of the Wang-Landau method are assessed on two classes of systems with continuous degrees of freedom, namely, two polypeptides and two atomic Lennard-Jones clusters. Parallel tempering Monte Carlo simulations serve as a reference, and we pay particular attention to the variations of the multiplicative factor f during the course of the simulation. For the systems studied, the Wang-Landau method is found to be of comparable accuracy as parallel tempering, but has significant difficulties in reproducing low-temperature transitions exhibited by the Lennard-Jones clusters at low temperature. Using a complementary order parameter and calculating a two-dimensional joint density of states significantly improves the situation, especially for the notoriously difficult LJ(38) system. However, while parallel tempering easily converges for LJ(31), we have not been able to get data of comparable accuracy with Wang-Landau multicanonical sampling.

Journal Article↗