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PubMed1996

An empirical comparison of expert-derived and data-derived classification trees.

Classification trees provide an attractively transparent discrimination technique, and may be derived from both expert opinion and from data analysis. We consider a real and complex problem concerning the diagnosis of babies with suspected critical congenital heart disease into one of 27 classes. A full loss matrix for all possible misclassifications was obtained from clinical assessments. A tree derived from expert opinion was compared with those derived from analysis of 571 past cases, both for the full problem and for a subset of 6 diseases. Automatic methods for tree creation and pruning were found to have problems for rare diseases, and hand-pruning was carried out. Inclusion of costs led to much improved clinical performance, even for trees that had originally been constructed to minimize classification errors. The expert tree showed a specific building strategy that could not be reproduced automatically. The expert tree generally outperformed those derived from data, particularly in the ability to identify important composite features.

Algorithms↗

PubMed2000

Field mapping without reference scan using asymmetric echo-planar techniques.

Improvements in Bo mapping and shimming were achieved by measuring the static field information in multiple subsequent echoes generated by an asymmetric echo-planar readout gradient train. With careful compensation, eddy current effects were shown to affect the adjustment of the shim coils minimally. In addition to reducing the time required for field mapping by two-fold, the sensitivity was simultaneously optimized irrespective of the prevalent T2* present, thereby minimizing the error of the static field measurement to below 0.1 Hz. With adiabatic low flip-angle excitation, the time required for field mapping was below 1 second.

Echo-Planar Imaging↗

PubMed1978

Mosaicism in amniotic fluid cell cultures: classification and significance.

The last decade has witnessed increasing application of human cytogenetic technology to prenatal chromosome analysis. However, unlike the rather uniform peripheral blood T-lymphocyte system which has provided most of our experience in human cytogenetics, long-term amniotic-fluid cell cultures display extreme cellular heterogeneity and disproportionate growth of certain cell types as a consequence of clonal amplification. When they enter cell culture, many of these cells are approaching the terminal stages of their respective, life spans and may have accumulated chromosomal aberrations. Concern about the possibility of true fetal mosaicism seems warranted chiefly in situations were multiple colonies display potentially viable aberrations. Clonal analysis, preferably of multiple clonal types, and attention to details of clonal morphology are likely to minimize diagnostic errors and undue apprehension resulting from mosaicism in amniotic-fluid cell cultures.

Amniocentesis↗

PubMed1989

Meaning of biodistance statistics: a test case using adult monozygotic twins.

Anthropometry, historically one of the primary research techniques in physical anthropology, has been widely utilized in biodistance studies. The complex genetic and environmental interaction that governs the expression of anthropometric dimensions, together with concerns over measurement error, have sometimes clouded the interpretation of biodistances based upon anthropometry. In this study, 51 pairs of adult monozygotic twins were analysed using discriminant analysis and Mahalanobis' generalized distance. Both male and female twins, grouped by first- versus second-born, displayed very small, statistically insignificant distances between groups. When literature estimates of intra-observer measurement errors were used as a frame of reference, the average absolute differences between the twin pairs were approximately twice the size of the measurement error estimates. The results of this study suggest that, first, the environmental effect upon the genetically influenced traits measured by anthropometry is not large enough to bring about significant multivariate differences between identical twin pairs; and, second, biodistance studies based upon anthropometry can be reliable so long as measurement error is minimized.

Adult↗

PubMed1978

Determination and importance of the magnification factor in the calculation of ventricular volume: development of a simple, accurate method.

A study of single-plane right anterior oblique left ventricular angiography was undertaken to determine the importance of obtaining correct positioning of a magnification grid and to develop a simple but accurate technique to minimize magnification errors. Theoretical and experimental volume determinations demonstrated 3% to 28% volume errors for grid placement errors ranging from 1 centimeter to 5 centimeters. An experiment was designed whereby cross table lateral radiographs of the chest were taken during contrast injections of the left ventricle. The relative position of the left ventricular center was found at a point 66% of the distance from the anterior to the posterior margin of the heart. Finding this point on noncontrast lateral films of the chest for positioning of a square centimeter grid should yield a more accurate determination of the magnification factor than other current emperic methods.

Cardiac Volume↗

PubMed2004

Near-infrared time-resolved fluorescence lifetime determinations in poly(methylmethacrylate) microchip electrophoresis devices.

High aspect-ratio microstructures were hot-embossed in polymer substrates with a molding tool fabricated using lithography/electroplating/forming (LIGA). The resulting devices were used for the electrophoretic separation of oligonucleotides labeled with near-infrared (near-IR) dyes. Near-IR time-resolved fluorescence was used as an identification method for the labeling dyes. The detection apparatus consisted of a pulsed laser diode operating at 680 nm, a single-photon avalanche diode, an integrated microscope, and a PC-board incorporating time-correlated single photon counting electronics. Investigation of the optical quality and amount of autofluorescence generated from different polymer substrates was carried out in the near-IR region for determining compatibility with time-resolved fluorescence. Our results revealed that of several poly(methylmethacrylate)(PMMA) substrates, brand Plexiglas offered minimal replication errors in the embossed features using appropriate embossing conditions with low background fluorescence contributions to the observed decay. Near-IR dye-labeled oligonucleotides were separated to determine the applicability of fluorescence lifetime discrimination between Cy5.5 (tauf = 930 ps) and IRD700 (tauf = 851 ps) labeling dyes during the microchip separation. These dyes were used to label T-fragments (thymine) of an M13mp18 ssDNA template. The DNA ladders were electrophoresed at 130 V/cm in a 4% linear polyacrylamide gel (LPA) gel matrix in a 9.5 cm long serpentine channel heated to 50 degrees C. The electropherogram revealed that the lifetimes could be accurately read well beyond 450 bases, although single-base pair resolution in the electropherogram was difficult to achieve due to potential solute-wall interactions in the polymer microdevice or the electroosmotic flow (EOF) properties of the device. The relative standard deviations secured for individual bands in the electropherogram were similar to those obtained using capillary gel electrophoresis, in spite of the lower load volume.

Electrophoresis, Microchip↗

PubMed1994

Three-dimensional structure of the rotavirus haemagglutinin VP4 by cryo-electron microscopy and difference map analysis.

The three-dimensional structure of the rotavirus spike haemagglutinin viral protein 4 (VP4) has been determined to a resolution of 26 A by cryo-electron microscopy and difference analysis of intact virions and smooth (spikeless) particles. Native and spikeless virions were mixed prior to cryo-preservation so that both structures could be determined from the same micrograph, thereby minimizing systematic errors. This mixing strategy was crucial for difference map analysis since VP4 only accounts for approximately 1% of the virion mass. The VP4 spike is multi-domained and has a radial length of approximately 200 A with approximately 110 A projecting from the surface of the virus. Interactions between VP4 and cell surface receptors are facilitated by the bi-lobed head, which allows multi-site interactions, as well as the uniform distribution of the VP4 heads at maximum radius. The bi-lobed head is attached to a square-shaped body formed by two rods that have a slight left-handed helical twist. These rods merge with an angled, rod-like domain connected to a globular base approximately 85 A in diameter. The anchoring base displays pseudo 6-fold symmetry. This surprising finding may represent a novel folding motif in which a single polypeptide of VP4 contributes similar but non-equivalent domains to form the arms of the hexameric base. The VP4 spike penetrates the virion surface approximately 90 A and interacts with both outer (VP7) and inner (VP6) capsid proteins. The extensive VP4-VP7 and VP4-VP6 interactions imply a scaffolding function in which VP4 may participate in maintaining precise geometric register between the inner and outer capsids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Utility of a C-jun microsatellite marker in determining gene dosage for fatty (fa).

The Zucker fatty (fa) mutation provides a genetic model for obesity and non-insulin dependent diabetes mellitus. The molecular pathogenesis of the metabolic phenotype of these animals is not known. Detailed molecular maps of the region surrounding the fa locus on rat chromosome 5 can be used for positional cloning experiments as well as to permit genotyping of animals from appropriate crosses before the confounding metabolic effects of obesity have occurred. We describe the development of a polymerase chain reaction (PCR) assay for a polymorphic simple sequence repeat (SSR) in the promoter region of the protooncogene c-Jun. This assay was used to position c-Jun 4.5cM proximal to the fa locus in 111 F2 progeny of a 13MBN fa/+ F1 intercross. Concurrent use of the c-Jun SSR with a previously described assay for a microsatellite in the glucose transporter, Glut1, permits rapid and accurate assessment of genotypes at the fa locus in animals of any age using minimal amounts of DNA. A strategy is described which minimizes the error rate in assigning genotype at the fatty locus for backcross and intercross progeny.

Animals↗

PubMed1981

Friction and wear properties of polymer, metal, and ceramic prosthetic joint materials evaluated on a multichannel screening device.

A 12-channel wear screening device was used to compare the wear properties of a variety of prosthetic joint materials. Two types of tests were run: (1) Ultrahigh molecular weight (UHMW) polyethylene bearing against metal or ceramic counterfaces and (2) various polymers bearing against 316 stainless steel as a standard counterface. Wear was quantified by weighing the polymer specimens, with presoaking and control-soak specimens used to minimize the error due to fluid absorption. The specimens were lubricated with bovine blood serum. Friction and polyethylene wear was very low with each of the metals (316 stainless steel, cobalt-chrome alloy, multiphase alloy, and titanium 6-4 alloy) such that the differences in wear rate would not be significant in terms of choosing a material for clinical application. However, titanium 6-4 alloy was found to be especially susceptible to abrasive wear by particles of acrylic cement. Nitrided titanium 6-4 counterfaces were impervious to acrylic abrasion. Polyethylene wear against highly polished, fully dense ceramics (Sialon, Alumina, Macor, and pyrolytic graphite) was as low as that with the metal counterfaces. Wear increased slightly with increasing ceramic surface roughness. The coefficient of friction of polyethylene against pyrolytic graphite was two to three times higher than with the metals or other ceramics. All of the alternate polymers underwent more wear than UHMW polyethylene. Teflon and polyester, two polymers that have proven unsuccessful in prior clinical use, had wear rates 1,600 and 830 times greater than polyethylene, respectively, an indication that the laboratory wear test provided a quantitative prediction of the behavior of the materials in vivo. However, it was difficult to assess the clinical significance of the less extreme wear rates since the ability of the tissues encapsulating a prosthesis to accomodate wear debris is not known on a quantitative basis.

Animals↗

PubMed1990

In vivo toxicity and pulmonary effects of promazine and chlorpromazine in rats.

Cationic amphiphilic drugs induce a phospholipid storage disorder known as phospholipidosis. Halogenated analogs of the drugs are more potent inducers of phospholipidosis when compared to nonhalogenated analogs. Two such antipsychotic drugs, promazine and chlorpromazine, are effectively taken up by the lungs and induce lamellar inclusions in vitro. We compared the in vivo toxicity and efficacy of promazine and chlorpromazine to induce phospholipidosis in the lung and in pulmonary alveolar macrophages. Male Sprague-Dawley rats were given promazine or chlorpromazine (25 mg/kg/day, P.O., in water) for 5 weeks. Food intake was decreased in promazine- and chlorpromazine-treated rats, chlorpromazine rats being affected more than promazine rats. To minimize experimental error due to starvation, control rats were pair-fed. The body weight gain was decreased in chlorpromazine rats in comparison to pair-fed controls. Chlorpromazine-treated rats, but not promazine-treated rats, showed increased mortality over the 5-week treatment period. Histopathologic examination of lung revealed loss of alveolar macrophages with no other gross abnormalities in chlorpromazine-treated rats. Quantitative analysis of lung lavage also showed significant reduction in the number of macrophages. This finding is in contrast to other cationic amphiphilic drugs, which induce phospholipidosis as well as accumulation of alveolar macrophages. Phospholipid level increased in alveolar macrophages but not in lavaged lung following chlorpromazine treatment. Acid phosphatase activity in lavaged lung homogenate and macrophages of promazine- and chlorpromazine-treated rats, taken as an index of toxicity to cells, did not differ significantly from control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

PubMed1988

Mathematical modeling of fetal growth: V. Fetal weight changes at term.

Fetal growth after 37 weeks menstrual age was investigated by comparing ultrasound estimates of fetal weight with corresponding weights of newborns. Using a weight estimation equation with minimal systematic error, evidence was found that fetuses delivered at term do not increase in weight the last two weeks before delivery. This change in fetal growth is regarded as a biological process that is needed to prepare the fetus for its life after birth. Only one of three subsets, that of estimated weights below 3000 g, showed significant weight increase after 37 weeks. This subset had, however, on average the longest scan-delivery interval. We conclude that conventional birthweight standards are influenced both by a cessation of fetal growth approximately two weeks before delivery and by an association between fetal size and the duration of gestation.

Birth Weight↗

PubMed2006

Inter- and intraobserver variability in the evaluation of dynamic breast cancer MRI.

PURPOSE: To quantify variations within and between observers ascribable to manual region of interest (ROI) placement in patients with breast cancer undergoing dynamic MRI. MATERIALS AND METHODS: Expert and nonexpert observers independently outlined tumor ROIs on 30 dynamic T(1)-weighted (T(1)W) MRI scans on five occasions over two months. Lesion size (number of pixels) and kinetic parameter estimates, including the transfer constant (K(trans)), were calculated for each ROI placement. Inter- and intraobserver variability was assessed with respect to the interval between drawings, lesion morphology, and observer experience. RESULTS: For the nonexpert, the variability reduced with decreasing time intervals between ROI drawings (the coefficient of variance (wCV) values at two months, two weeks, one day, and same-day time intervals were respectively 11.6%, 10.7%, 4.8%, and 2.6% for lesion size, and 8.9%, 9.7%, 6.7%, and 3.2% for K(trans)). For the expert observer, the variability was smaller overall and more constant, but improved for same-day ROI placements (region size wCV: 7.5%, 6.2%, 7.1%, and 3.7%; K(trans) wCV: 5.4%, 5.3%, 5.6%, and 4.5%). CONCLUSION: Significant observer variability in manual ROI placement occurs in dynamic MRI of breast cancer. For serial patient studies, ROI placements should be outlined at the same sitting to minimize observer error.

Adult↗

PubMed1987

In-vitro ligament tension pattern in the flexed knee in passive loading.

Tensions generated in selected bands of the four major ligaments of the flexed knee (40-90 degrees) have been measured in vitro when the tibia is subjected to passive anterior translation and axial rotation with and without a compressive preload. The measurements were made in 30 fresh-frozen specimens using the buckle transducer attached to the anteromedial band of the anterior cruciate ligament [ACL (am)], the posterior fibres of the posterior cruciate ligament [PCL (pf)], the superficial fibres of the medial collateral ligament [MCL (sf)], and in the total lateral collateral ligament (LCL). Particular attention was placed on the evaluation of the performance of the transducer specific to such measurements in order to minimize the errors associated with the use of this transducer. The results indicate that, among the measured ligaments, substantial tension (greater than 20 N) is generated only in the ACL (am) in tibial anterior translation up to 5 mm. The tension pattern generated in response to tibial axial rotation, however, is complex and exhibits considerable variation between specimens. In general, both the MCL (sf) and LCL are tensed at all tested flexion angles, with the tension in external rotation being significantly greater than in internal rotation. At 40 degrees of flexion, the ACL (am) bears tension mainly in internal rotation, while at 90 degrees of flexion the PCL (pf) is tensed in both senses of rotation. The response of the LCL shows marked variation among specimens; very small tension (less than 15 N) is generated in internal rotation in 48% of the specimens, and in either sense of rotation in 20% of the specimens. The tension in the ACL (am) in internal rotation is invariably greater in those specimens in which LCL tension is negligible. This correlation between increased ACL (am) function and inadequate LCL restraint appears significant in terms of ACL injury and repair.

Humans↗

PubMed1984

Binding of sulfadimethoxine to isolated human blood protein fractions.

The binding of sulfadimethoxine to selected human blood protein fractions and to fresh serum has been examined by means of a new equilibrium dialysis technique which minimizes experimental error and permits the evaluation of low-level binding. Certain alpha-globulin fractions, containing mixtures of proteins, were found to bind the drug. Scatchard analysis of the binding of sulfadimethoxine to fresh serum, calculated as though all of the binding is due to albumin, gives a different result from that obtained with isolated albumin. This may be a reflection of the contribution of the alpha-globulins to the overall binding of sulfadimethoxine in fresh serum. Although sulfadimethoxine is amphoteric, it did not bind to the alpha 1-acid glycoprotein. The drug behaves as an acidic compound when binding to the blood proteins.

Alpha-Globulins↗

PubMed1989

The use of finite impulse response filters in pulse design.

We develop a new way of synthesizing pulse sequences with desirable frequency characteristics. By combining our previous results with techniques from the theory of finite impulse response filters, we can specify (1) the total duration of the pulse sequence, (2) the frequency ranges it is desired to perturb, (3) the desired perturbation, and (4) the frequency range it is desired not to perturb. We can then synthesize a hard pulse sequence which will yield that desired perturbation with the minimal possible error. The minimum error is global, in the sense that no pulse sequence can do better at achieving the specifications, and is not just a local minimum, around the pulse sequences close to the derived pulse.

Algorithms↗

PubMed1992

Experimental analysis of T1 imaging with a single-scan, multiple-point, inversion-recovery technique.

Look and Locker's single-scan, multiple-point, T1 determination technique modified for imaging applications was evaluated experimentally for its accuracy and reliability with respect to the pulse sequence parameters, in particular, to the interpulse delay, tD, and the tip angle, alpha. T1 imaging experiments were performed with a 0.5-T imaging system on a phantom which consisted of an array of vials containing 2% agarose gels doped with various amount of Mn2+ using different combinations of the parameter set (tD, alpha). T1 results obtained with this technique were compared with those measured by a conventional inversion-recovery procedure using the same spectrometer. Strategic choice of pulse sequence parameters to minimize experimental errors and the criteria for these choices will be discussed.

Humans↗

PubMed1995

High resolution renal diffusion imaging using a modified steady-state free precession sequence.

A modified steady-state free precession (SSFP) diffusion sequence is proposed for high resolution renal imaging. A pair of bipolar diffusion gradients was used to minimize the errors in measured apparent diffusion coefficient (ADC) caused by variations in T1, T2, and RF flip angle that have been observed with previously employed SSFP diffusion sequences. Motion sensitivity was reduced by the use of compensated gradients, frame-by-frame averaging, and a repetition time of 22 ms, which for a single-acquisition 128 x 128 image requires only 3 s. High resolution was achieved by signal averaging. The modified sequence was applied to in vivo diffusion measurements. In six normal rat kidneys the ADCs (mean +/- SD; x 10(-3) mm2/s) of the cortex, outer medulla, and inner medulla were 2.28 +/- 0.05, 2.38 +/- 0.10, and 2.95 +/- 0.05, respectively. The technique requires relatively large gradients to achieve adequate diffusion weighting.

1-Propanol↗

PubMed2006

Improved deconvolution of perfusion MRI data in the presence of bolus delay and dispersion.

Cerebral blood flow (CBF) is commonly estimated from the maximum of the residue function deconvolved from bolus-tracking data. The bolus may become delayed and/or dispersed in the vessels feeding the tissue, resulting in the calculation of an effective residue function, Reff(t), whose shape reflects the distortion of the bolus as well as the hemodynamic tissue status. Consequently the CBF is often underestimated. Since regularizing the deconvolution introduces additional distortions to Reff(t), it is impossible to distinguish a true decrease in the CBF from bias introduced by abnormal vasculature. This may result in misidentification of tissue regions at risk of infarction, which could have serious clinical consequences. We propose a modified maximum-likelihood expectation-maximization (mML-EM) method, which is shown by way of simulations to improve the characterization of Reff(t) across a wide range of shapes. A pointwise termination approach for the iteration minimizes the effects of noise, and appropriate integral approximations minimize discretization errors. mML-EM was applied to data from a patient with left internal carotid artery (ICA) occlusion. The shape of each calculated Reff(t) was used to create a map indicating voxels affected by bolus delay and/or dispersion, where CBF estimates are inherently unreliable. Such maps would be a useful adjunct for interpreting bolus-tracking data.

Computer Simulation↗