SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
For many years the analysis of plant proteomes has been restricted to the construction of descriptive catalogues or the search for markers. The analysis of plant proteomes is now gaining a functional dimension, however, because the focus has shifted onto well-defined plant-specific tissues and organelles, the simultaneous mining of proteomic and physiological data and specific methodological efforts.
RATIONALE AND OBJECTIVES: Statistical power, defined as the probability of detecting real differences between imaging modalities, determines the cost in terms of readers and cases of conducting receiver operating characteristic (ROC) studies. Neglect of location information in lesion-detection studies analyzed with the ROC method can compromise power. Use of the alternative free-response ROC (AFROC) method, which considers location information, has been discouraged, because it neglects intraimage correlations. The relative statistical powers of the two methods, however, have not been tested. The purpose of this study was to compare the statistical power of ROC and AFROC methods using simulations. MATERIALS AND METHODS: A new model including intraimage correlations was developed to describe the decision variable sampling and to simulate data for ROC and AFROC analyses. Five readers and 200 cases (half of which contained one signal) were simulated for each trial. Two hundred trials, equally split between the null hypothesis and alternative hypothesis, were run. Ratings were analyzed with the Dorfman-Berbaum-Metz method, and separation of the null hypothesis and alternative hypothesis distributions was calculated. RESULTS: The AFROC method yielded higher power than the ROC method. Separation of the null hypothesis and alternative hypothesis distributions was larger by a factor of 1.6 regardless of the presence or absence of intraimage correlations. The effect of the incorrect localizations during ROC analysis of localization data is believed to be the major reason for the enhanced power of the AFROC method. CONCLUSION: The AFROC method can yield higher power than the ROC method for studies involving lesion localization. Greater consideration of this methodology is warranted.
The current pace of functional genomic initiatives and genome sequencing projects has provided researchers with a bewildering array of sequence and biological data to analyze. The disease system-driven approach to identifying key genes frequently identifies nucleotide and protein sequences for which the gene and protein function are not known in sufficient detail to allow informed follow-up. Using a range of bioinformatic tools and sequence-based clues, most of unassigned sequences can now be annotated. This chapter takes as an example an unannotated expressed sequence tag, describing how to identify its related gene, and how to annotate the encoded protein using sequence, profile, and structure-based annotation methodologies.
Twentieth century medical science has embraced nineteenth century Boolean probability theory based upon two-valued Aristotelian logic. With the later addition of bit-based, von Neumann structured computational architectures, an epistemology based on randomness has led to a bivalent epidemiological methodology that dominates medical decision making. In contrast, fuzzy logic, based on twentieth century multi-valued logic, and computational structures that are content addressed and adaptively modified, has advanced a new scientific paradigm for the twenty-first century. Diseases such as stroke involve multiple concomitant causal factors that are difficult to represent using conventional statistical methods. We tested which paradigm best represented this complex multi-causal clinical phenomenon-stroke. We show that the fuzzy logic paradigm better represented clinical complexity in cerebrovascular disease than current probability theory based methodology. We believe this finding is generalizable to all of clinical science since multiple concomitant causal factors are involved in nearly all known pathological processes.
OBJECTIVE: To evaluate the prevalence of symptomatic bronchiectasis in patients with rheumatoid arthritis. METHODS: Cross-sectional retrospective study of 453 rheumatoid arthritis patients. All patients completed a questionnaire designed to detect manifestations of bronchiectasis and had a chest film taken. Computed tomography of the chest was performed in those patients whose chest film was normal. RESULTS: Thirteen patients (2.9%), all female, had symptoms that met Walker's criteria for definite (n = 7) or probable (n = 6) bronchiectasis. Symptom onset was during childhood or adolescence in 69% of cases and antedated the first symptoms of rheumatoid arthritis in all patients but one. Six of the 13 patients (46%) had chest film abnormalities suggestive of bronchiectasis, and three of the remaining seven patients had abnormal computed tomography findings, yielding a total of nine cases of bronchiectasis confirmed by imaging studies among the 13 patients with suggestive symptoms (69%). This proportion rose to 90% when the three patients who failed to come to their computed tomography appointment were excluded. CONCLUSION: Using a methodological approach similar to that previously used by pneumologists, we found a 2.9% prevalence of symptomatic bronchiectasis in a population of hospitalized rheumatoid arthritis patients, which is higher than the 0.03% prevalence previously reported in the population at large.
The determination of diffusion coefficients from fluorescence recovery data is often complicated by geometric constraints imposed by the complex shapes of intracellular compartments. To address this issue, diffusion of proteins in the lumen of the endoplasmic reticulum (ER) is studied using cell biological and computational methods. Fluorescence recovery after photobleaching (FRAP) experiments are performed in tissue culture cells expressing GFP-KDEL, a soluble, fluorescent protein, in the ER lumen. The three-dimensional (3D) shape of the ER is determined by confocal microscopy and computationally reconstructed. Within these ER geometries diffusion of solutes is simulated using the method of particle strength exchange. The simulations are compared to experimental FRAP curves of GFP-KDEL in the same ER region. Comparisons of simulations in the 3D ER shapes to simulations in open 3D space show that the constraints imposed by the spatial confinement result in two- to fourfold underestimation of the molecular diffusion constant in the ER if the geometry is not taken into account. Using the same molecular diffusion constant in different simulations, the observed speed of fluorescence recovery varies by a factor of 2.5, depending on the particular ER geometry and the location of the bleached area. Organelle shape considerably influences diffusive transport and must be taken into account when relating experimental photobleaching data to molecular diffusion coefficients. This novel methodology combines experimental FRAP curves with high accuracy computer simulations of diffusion in the same ER geometry to determine the molecular diffusion constant of the solute in the particular ER lumen.
A computerized image processing system for quantitative receptor autoradiography on tritium-sensitive film is described. The method implements an image analyzer (IBAS 1 + 2) for the acquisition of an image which is evaluated with respect to the regional distribution of binding site densities by a small computer which is connected to a digitizer. Several methodological problems must be considered when using tritium-labelled compounds and an image analyzer. The use of tissue standards and shading procedures, the improvement of signal-to-noise ratio, the calibration of the system which establishes the non-linear relation between grey values and concentration of radioactivity, the contrast enhancement and the quenching problem are discussed. This method permits a quick and precise quantitative analysis of binding site distribution in receptor autoradiography.
INTRODUCTION: Many of the complications in severe acute pancreatitis result from the amplifying effects of microcirculatory disruption. Contrast medium may cause significant additional reductions of capillary flow, which has been shown to aggravate acute pancreatitis in experimental studies. AIM: To investigate the role of serial contrast-enhanced computed tomography (CECT) in patients with acute pancreatitis. METHODOLOGY: A retrospective analysis evaluated 302 patients with moderate to severe acute pancreatitis. Among these patients, 264 underwent CECT within 96 hours of the onset of symptoms and again during the course, but in 38 patients no serial CECT was performed. Outcome measurement was analyzed by comparison of hospital stay and mortality rate between the two patient groups. Influences of contrast medium on severity of disease were detected by monitoring complications during the course of treatment, C-reactive protein, and APACHE II score. RESULTS: The 1-month mortality rate was less in patients with CECT (6.4% versus 15.8%, p <0.05). There were no significant differences considering the incidence of additional complications, and hospital stay was not significantly longer (29 +/- 36 versus 19 +/- 13 days). C-reactive protein and APACHE II score had similar time courses. CONCLUSION: Contrast-enhanced computed tomography remains crucial in identifying patients with acute pancreatitis at high risk to develop necrosis of the pancreas and systemic complications. Contrast medium has been found to aggravate acute pancreatitis in animal models. As compared with the patient group without being exposed to contrast medium, however, this study did not show a deterioration of acute pancreatitis by administration of contrast medium in men.
OBJECTIVE: To remotely test a stepwise framework of quality control measures, developed according to the 1997 European Society of Analytical Cellular Pathology consensus on diagnostic DNA image cytometry, in two series of measurements by means of the quantitation server EUROQUANT. STUDY DESIGN: In each of these series, 104 fine needle aspiration biopsies, imprints from breast cancer specimens and 28 rat liver imprints were measured twice at two different cytometry workstations. Further measurements on special rat liver specimens for evaluation of the stability of the machinery and of the preparation process were done at both workstations. Afterwards the measurement data from both machines were transferred to the quantitation server and analyzed automatically. Beside the classical DNA histograms, a set of further evaluations was performed to detect optical errors as well as inhomogeneities in the measurements. Running values for mean integrated optical density values, mean corrective factors and mean coefficients of variations of corrective factors were computed to control the stability of the entire methodology over time. RESULTS: The study demonstrated the preconditions and outcome of server-based quality control in DNA ploidy analysis. The results show that such a remote analysis is feasible and comparable to local DNA ploidy analysis. It is also demonstrated how quality control tests reflect the process performance of ploidy analysis at its different levels. CONCLUSION: Quality control must be an inherent part of the daily routine to allow a reliable diagnostic interpretation and ensure steadily high product quality.
Within health Operational Research, the use of 'computer package' methods such as simulation and system dynamics is becoming so prevalent that it feels somewhat old hat to use analytical methods to develop explicit mathematical formulae or even to explore the mathematical structure of problems. This paper will discuss the use of such 'back of the envelope' analysis illustrating its usefulness. It will be shown that not only does this approach yield considerable insight, but also that it can give rise to powerful and practical solution methods. Examples of this will be discussed in relation to issues such as bed needs estimation, admissions and facilities planning. The author is Director of the Clinical Operational Research Unit (CORU) which was established in 1983, receiving core funding from the UK Department of Health. The concept of a full time university-based research unit dedicated to applying expertise in Operational Research (OR) to problems in health care provides a relatively rare research resource. Yet, the scope for such research, applied to an increasing range of health care activity, is enormous. Issues such as treatment evaluation, performance measures, clinical governance, evidence based medicine and health service delivery are all amenable to OR. Further, OR often provides an immensely cost effective alternative to traditional methods of clinical research based on randomised controlled trials or large scale epidemiological studies. The nature of OR, and one of its main strengths, is that it encompasses a wide range of analytical and scientific methods. Mathematical modeling, statistics, computer-based methods, trial design and analysis all contribute to health OR and, under both of its Directors since 1983, a conscious effort has been made within CORU to foster a diversity of research methodologies. Particular emphasis is put on developing new mathematical methods and computer software. This is somewhat at odds with what seems to be a growing trend in health OR towards researchers specialising in just one or two areas of methodology; thus Tom does queueing theory, Dick does simulation and Harry does System Dynamics. Of course there are exceptions, but for whatever reason, the trend towards specialisation seems real. In this paper, benefits of a more diverse approach to health OR is advocated, particularly the use of 'back of envelope' mathematical methods as an alternative to the use of proprietary software packages. Three case studies are described to illustrate this approach.
First-principles molecular dynamics simulations have recently been found an effective tool to study a large variety of chemical problems. Finite temperature simulations reveal unique information, including explicit dynamical effects and the evaluation of proper free energy differences. Moreover, dynamics simulations reveal information on the flexibility of molecular systems, and elucidate, often otherwise inaccessible, mechanistic details of chemical reactions. In addition this methodology allows the study of larger, periodic, systems, revealing computationally unique information which may be directly compared to experiments on realistic chemical systems. A variety of examples will be given, although most focus on the important field of catalysis.
Delineation of target volumes is increasingly recognized as the most crucial step within the process of modern conformal radiotherapy. In the field of head and neck radiation oncology, the need for a standardized methodology in the delineation of nodal regions of the neck on computed tomography (CT) images has recently emerged. To address this issue, a consensus document has been prepared by the Head and Neck Working Party of the AIRO-Lombardia Cooperative Group, based on the proceedings of multidisciplinary meetings and on literature findings. The document contains detailed guidelines for the delineation on CT images of the nodal regions of the neck, including for each nodal region (1 to 7) the description of anatomical limits as seen on CT images.
The protein structure prediction (PSP) problem is concerned with the prediction of the folded, native, tertiary structure of a protein given its sequence of amino acids. It is a challenging and computationally open problem, as proven by the numerous methodological attempts and the research effort applied to it in the last few years. The potential energy functions used in the literature to evaluate the conformation of a protein are based on the calculations of two different interaction energies: local (bond atoms) and non-local (non-bond atoms). In this paper, we show experimentally that those types of interactions are in conflict, and do so by using the potential energy function Chemistry at HARvard Macromolecular Mechanics. A multi-objective formulation of the PSP problem is introduced and its applicability studied. We use a multi-objective evolutionary algorithm as a search procedure for exploring the conformational space of the PSP problem.
The application of the path-integral methodology of Chandler and Wolynes [D. Chandler and P. G. Wolynes, J. Chem. Phys. 74, 4078 (1981)] to the calculation of one-electron-tunneling probabilities is revisited. We show that the evaluation of the kink free energy that is related to the tunneling splitting is associated with "polymer bead" distributions over a continuous distribution of scaled barriers, which makes both the calculation and its physical interpretation relatively difficult. In particular, we find that relative to other available techniques the method converges slowly and suffers from inaccuracies associated with the finite-temperature aspect of the calculation, and that past tentative identification of the bead distribution over the barrier with a physical picture of a "tunneling path" should be reassessed.
MOTIVATION: A methodology to search for genes associated with multifactorial diseases by integrating the large amount of accumulated knowledge is seriously needed. A comprehensive understanding derived from a holistic view of gene relationship structures can be gained from our proposed analysis called the cross-subspace analysis (CSA). In this analysis, gene objects are generated by machine learning using their term occurrence patterns in MEDLINE abstracts and the degree of relationship between gene objects is quantified by matching these patterns. RESULTS: Structuralization of relationships of a set of genes was performed using CSA, which were retrieved using the terms, 'obesity', 'diabetes', 'hypertriglyceridemia' and 'hypertension' that refer to diseases comprising metabolic syndrome, on a 2D plane inferring important biomedical concepts from the gene distribution. Then, we prioritized the significance of 6131 well-annotated human genes in terms of the distance on the plane from the centroid of 'metabolic syndrome'-related genes distribution. The validity was confirmed by comparing the knowledge extracted by the ordering with existing medical knowledge.
Computer simulation has been used to study the behaviour of four estimators of the common rate ratio estimated from cohort data, in terms of bias and root mean square error. It is concluded that the maximum likelihood estimator is the preferable approach, though an excellent approximation to this is yielded by the analogue of the Mantel-Haenszel estimator. When the number of observed cases in the referent group is large, it may be preferable to present the results as the standardized mortality (morbidity) ratio, though under these circumstances all four estimators tend to the same value. The O/E estimator proposed for use with clinical trials data under some situations is noticeably biased and inefficient and therefore should be avoided.
Quantitative evaluation of radiographic changes by computer-assisted densitometric image analysis (CADIA) requires exact knowledge about method errors. In the present study, density change errors were determined from pairs of films with "no change". From this distribution of error values, a series of threshold values for correction of changes due to method errors was selected. The threshold values were then applied to results from analysis of densitometric changes in sites with "known loss" or "no change" of the alveolar bone among films from cynomolgus monkeys. The density errors formed non-normal distributions with no difference in magnitudes between the absolute values expressing density decreases and density increases in the same areas. Calculation of sensitivity, specificity, type 1 and type 2 errors showed that these variables were clearly influenced by selection of different threshold values for correction of the density change errors. It is therefore recommended that threshold values be determined for each analytical system initially as well as following any equipment or computer program modification. Before selecting the threshold value for a specific radiographic analysis, the desired level of sensitivity and specificity should be evaluated.
A computer method enabling metric measuring in radiographs has been presented. The measurements are time saving and precise and accurate measurements can be made. The statistical analysis can be performed based on a ratio scale, allowing more reliable and conclusive statistics. The most useful field for the presented method is offered in epidemiology where great materials are being handled. Since small changes can be studied, the method can be useful in studying marginal bone level changes in large populations. Or marginal bone levels around implants. In age estimation the digitizer method has no direct valuable application during adolescence, when the lower third molar is used. Here the present series of studies showed the traditional age estimation method and the digitizer method to be fairly unprecise with rather large systematic error. The skeletal age estimation method according to Greulich and Pyle was found to be more accurate and useful during the ages 14 up to 18 years. In younger children, where more parameters or teeth are available, there may be advantages to use a digital dental method instead of a traditional dental one.