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PubMed2006

Increased mortality in rural vehicular trauma: identifying contributing factors through data linkage.

BACKGROUND: Fatality rates from rural vehicular trauma are almost double those found in urban settings. Causes of this difference in rural and urban trauma fatality rates have yet to be fully explored. The purpose of this study is to identify prehospital causes of the higher rural fatality rates by linking, analyzing, and comparing prehospital data for rural and urban vehicular crashes. METHODS: A probabilistic algorithm was developed that permitted linkage of data from police motor vehicle crash reports, and from Emergency Medical Service (EMS), and hospital records. Motor vehicle crashes (MVCs) were defined as rural or urban by location of the crash using the United States Bureau of Census criteria. Areas that fell outside that urban definition were defined as rural. Linked data were analyzed to identify factors that were thought to be associated with the higher mortality rates observed in rural settings. RESULTS: During the 20-month period from November 2001 through May 2003, data were collected from police crash reports and EMS Patient Care Reports (PCRs) within seven counties in southwest Alabama. Using high probability match criteria and join specifications, 4,694 police crash reports were linked to EMS PCRs. Of these, 3,068 patients (65.4%) were injured in rural settings, and 1,626 (34.6%) were injured in urban settings. A total of 164 (3.5%) mortalities were identified. A total of 129 (4.2%) mortalities occurred in a rural setting and 35 (2.1%) were urban (p = 0.0001). Of the 129 rural deaths, 91 (70.5%) were dead on scene (DOS) and of 35 urban deaths, 20 (57.1%) were DOS (p < 0.0001). Mean EMS response time for rural MVCs with survivors was 11.2 minutes versus a mean of 13.9 minutes for rural MVC with survivors (p < 0.0002). When survivors were involved, mean EMS response time for an urban setting was 6.8 minutes versus 13.9 minutes for a rural setting (p < 0.0001). In a rural setting, mean EMS distance to the scene when patients were alive was 7.7 miles versus 10.5 miles when patients were DOS (p < 0.001). For patients who died after transfer from the scene, mean rural EMS time on scene was 16.1 minute versus 11.6 minutes in an urban setting (p < 0.04). CONCLUSION: In a setting of rural MVC, increased EMS response time, time on scene and distance to the scene are associated with higher rural trauma mortality rates.

Accidents, Traffic↗

PubMed2005

The place and the role of histological examination in diagnostic algorithm of urinary system tuberculosis.

The diagnosis of tuberculosis of renal and urinary tract is made by identifying Koch bacillus in special cultures and using histological examination of surgical removed pieces. Not in all cases the usual pathological techniques are very specific. Using special stain for acid-fast bacilli it can be certified the etiological diagnostic. Histological changes of renal parenchyma and/or upper urinary tract (renal pelvis and urether) structures in 57 patients clinical and paraclinical pyonephrosis diagnosed where studied. All the surgical removed pieces were studied using usual pathology methods. In order to find renal tuberculosis we performed on surgical pieces special staining (Ziehl-Nielsen), we noted the pathological finding in each case and we found 7 cases with certainly tuberculosis etiology.

Algorithms↗

PubMed2004

OS-EM and FBP reconstructions at low count rates: effect on 3D PET studies of [11C] WAY-100635.

11C-labeled neuroreceptor ligands frequently require long scan durations to quantify ligand-receptor binding. In this paper, we compare the accuracy of two three-dimensional (3D) positron emission tomography (PET) reconstructions: ordered-subset expectation-maximization (OS-EM) versus filtered backprojection (FBP) under low count rate conditions exhibited by 11C neuroreceptor studies. Data were obtained from a dynamic 11C phantom acquisition as well as six dynamic human [11C] WAY-100635 studies, all acquired in 3D mode using the EXACT HR+ PET scanner. Model-based scatter correction of the phantom datum was found to overcorrect in low count rate situations producing a negative bias in FBP reconstruction and a positive bias in OS-EM reconstruction, the OS-EM bias attributed to the non-negativity constraint of sinogram values. In the phantom OS-EM and FBP, reconstruction bias occurred at activities less than 25 Bq/cm3. In the human cerebellum, OS-EM deviated from FBP at activities less than 50 Bq/cm3. The total volume of distribution (VT), as determined from the metabolite corrected arterial input function and a two-tissue compartment kinetic model, was more sensitive to the positive bias of OS-EM than the negative bias of FBP at low count rates. To avoid reconstruction bias with 3D PET studies using the HR+, the scan duration should be limited so as to yield a final non-decay-corrected activity concentration of no less than 50 Bq/cm3. In neuroreceptor studies, if such a low count rate cannot be avoided, FBP reconstruction is preferable to OS-EM to estimate VT.

Algorithms↗

PubMed2004

Phan3D: design of biological phantoms in 3D electron microscopy.

Three-Dimensional Electron Microscopy (3DEM) has turned out to be a major player in structural proteomics. In 3DEM, tens of thousands of EM images from a macromolecule at different views are combined to derive its structure by means of a 3D reconstruction algorithm. However, for an optimal reconstruction, the most suitable algorithm has to be used and its parameters have to be tuned for the macromolecule under study and the experimental conditions found. The use of phantoms is central to objective comparison of reconstruction algorithms and optimization of their parameters. Phan3D is a tool intended to provide a fully visual and interactive environment that facilitates the design of phantoms resembling biological specimens in 3DEM. Phan3D has been developed as an alternative to the tedious, error-prone and old-fashioned phantom design that is based on hand-written text description files.

Computer Graphics↗

PubMed2005

Estimating the pen trajectories of static signatures using hidden Markov models.

Static signatures originate as handwritten images on documents and by definition do not contain any dynamic information. This lack of information makes static signature verification systems significantly less reliable than their dynamic counterparts. This study involves extracting dynamic information from static images, specifically the pen trajectory while the signature was created. We assume that a dynamic version of the static image is available (typically obtained during an earlier registration process). We then derive a hidden Markov model from the static image and match it to the dynamic version of the image. This match results in the estimated pen trajectory of the static image.

Algorithms↗

PubMedDate not supplied

Measuring the PSF from aperture images of arbitrary shape--an algorithm.

A new algorithm for determining the point spread function (PSF) of digital imaging systems is presented. The input is an image of an aperture whose shape need not be regular. The aperture shape is refined to an effective sub-pixel resolution and the PSF of the system is determined by de-convolution, assuming uniform illumination and a step function edge. The method has been tested on theoretical aperture images of varying shape and PSF, with and without noise. Depending on the degree of noise, a known PSF can be recovered to an accuracy of between 0.2 and 0.8%. Some typical results are given for a Gatan Image Filter with a 794 YAG multiscan camera on a Philips EM 430 transmission electron microscope at 200 and 300 kV. An example of a de-convoluted convergent beam electron diffraction pattern is included. The algorithm tolerates a small amount of de-focus.

Journal Article↗

PubMed1994

Testing the quality of electron microscope mapping data for DNA molecules with sequence-specific ligands.

A procedure for the testing of Electron Microscope (EM) mapping data for DNA molecules with site-specific bound ligands is suggested. The difficulty of distinguishing DNA molecule ends on electron micrographs indicates that their true orientations are not known. This in turn presents problems in obtaining correct maps relating to their alignment, and complicates checking the maps' validity. For these reasons a computer simulation of the EM study of double-stranded DNA molecules with site-specific bound ligands was carried out. The knowledge of the true orientations of the simulated DNA molecules allowed us to examine their final orientations after alignment. We used the number of improper-oriented molecules as the quantitative measure of the map quality. Detailed investigation based on this parameter permitted us to invent the criterion for the map validity, and to suggest the procedure for the testing of alignment of real DNA molecules. This procedure implies multiple randomization of initial orientations of the DNA molecules and minute analysis of the final maps. Most of the molecular, statistical and experimental parameters inherent to EM investigation of site-specific binding, such as the number of specific binding sites (N), the mean number of bound ligands (A), the length of the DNA molecules (L), the specific/non-specific ratio of binding (K), together with the standard deviation of DNA molecule lengths (HL) were tested for their influence upon the quality of EM mapping data. An empirical equation for the ultimate values of these parameters has been found, allowing us to predict the success of EM mapping.

Algorithms↗

PubMed2005

Folding of small helical proteins assisted by small-angle X-ray scattering profiles.

This paper reports a computational method for folding small helical proteins. The goal was to determine the overall topology of proteins given secondary structure assignment on sequence. In doing so, a Monte Carlo protocol, which combines coarse-grained normal modes and a Hamiltonian at a different scale, was developed to enhance sampling. In addition to the knowledge-based potential functions, a small-angle X-ray scattering (SAXS) profile was also used as a weak constraint for guiding the folding. The algorithm can deliver structural models with overall correct topology, which makes them similar to those of 5 approximately 6 A cryo-EM density maps. The success could contribute to make the SAXS technique a fast and inexpensive solution-phase experimental method for determining the overall topology of small, soluble, but noncrystallizable, helical proteins.

Animals↗

PubMed2002

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor alpha.

The purpose of this study was to classify selective oestrogen receptor modulators based on gene expression profiles produced in breast cancer cells expressing either wtERalpha or mutant(351)ERalpha. In total, 54 microarray experiments were carried out by using a commercially available Atlas cDNA Expression Arrays (Clontech), containing 588 cancer-related genes. Nine sets of data were generated for each cell line following 24 h of treatment: expression data were obtained for cells treated with vehicle EtOH (Control); with 10(-9) or 10(-8) M oestradiol; with 10(-6) M 4-hydroxytamoxifen; with 10(-6) M raloxifene; with 10(-6) M idoxifene, with 10(-6) M EM 652, with 10(-6) M GW 7604; with 5 x 10(-5) M resveratrol and with 10(-6) M ICI 182,780. We developed a new algorithm 'Expression Signatures' to classify compounds on the basis of differential gene expression profiles. We created dendrograms for each cell line, in which branches represent relationships between compounds. Additionally, clustering analysis was performed using different subsets of genes to assess the robustness of the analysis. In general, only small differences between gene expression profiles treated with compounds were observed with correlation coefficients ranged from 0.83 to 0.98. This observation may be explained by the use of the same cell context for treatments with compounds that essentially belong to the same class of drugs with oestrogen receptors related mechanisms. The most surprising observation was that ICI 182,780 clustered together with oestrodiol and raloxifene for cells expressing wtERalpha and clustered together with EM 652 for cells expressing mutant(351)ERalpha. These data provide a rationale for a more precise and elaborate study in which custom made oligonucleotide arrays can be used with comprehensive sets of genes known to have consensus and putative oestrogen response elements in their promoter regions.

Breast Neoplasms↗

PubMed2005

Assessment of vulnerable plaque composition by matching the deformation of a parametric plaque model to measured plaque deformation.

Intravascular ultrasound (IVUS) elastography visualizes local radial strain of arteries in so-called elastograms to detect rupture-prone plaques. However, due to the unknown arterial stress distribution these elastograms cannot be directly interpreted as a morphology and material composition image. To overcome this limitation we have developed a method that reconstructs a Young's modulus image from an elastogram. This method is especially suited for thin-cap fibroatheromas (TCFAs), i.e., plaques with a media region containing a lipid pool covered by a cap. Reconstruction is done by a minimization algorithm that matches the strain image output, calculated with a parametric finite element model (PFEM) representation of a TCFA, to an elastogram by iteratively updating the PFEM geometry and material parameters. These geometry parameters delineate the TCFA media, lipid pool and cap regions by circles. The material parameter for each region is a Young's modulus, EM, EL, and EC, respectively. The method was successfully tested on computer-simulated TCFAs (n = 2), one defined by circles, the other by tracing TCFA histology, and additionally on a physical phantom (n = 1) having a stiff wall (measured EM = 16.8 kPa) with an eccentric soft region (measured EL = 4.2 kPa). Finally, it was applied on human coronary plaques in vitro (n = 1) and in vivo (n = 1). The corresponding simulated and measured elastograms of these plaques showed radial strain values from 0% up to 2% at a pressure differential of 20, 20, 1, 20, and 1 mmHg respectively. The used/reconstructed Young's moduli [kPa] were for the circular plaque EL = 50/66, EM = 1500/1484, EC = 2000/2047, for the traced plaque EL = 25/1, EM = 1000/1148, EC = 1500/1491, for the phantom EL = 4.2/4 kPa, EM = 16.8/16, for the in vitro plaque EL = n.a./29, EM = n.a./647, EC = n.a./1784 kPa and for the in vivo plaque EL = n.a./2, EM = n.a./188, Ec = n.a./188 kPa.

Algorithms↗

PubMed2004

An automatic method for predicting transmembrane protein structures using cryo-EM and evolutionary data.

The transmembrane (TM) domains of many integral membrane proteins are composed of alpha-helix bundles. Structure determination at high resolution (<4 A) of TM domains is still exceedingly difficult experimentally. Hence, some TM-protein structures have only been solved at intermediate (5-10 A) or low (>10 A) resolutions using, for example, cryo-electron microscopy (cryo-EM). These structures reveal the packing arrangement of the TM domain, but cannot be used to determine the positions of individual amino acids. The observation that typically, the lipid-exposed faces of TM proteins are evolutionarily more variable and less charged than their core provides a simple rule for orienting their constituent helices. Based on this rule, we developed score functions and automated methods for orienting TM helices, for which locations and tilt angles have been determined using, e.g., cryo-EM data. The method was parameterized with the aim of retrieving the native structure of bacteriorhodopsin among near- and far-from-native templates. It was then tested on proteins that differ from bacteriorhodopsin in their sequences, architectures, and functions, such as the acetylcholine receptor and rhodopsin. The predicted structures were within 1.5-3.5 A from the native state in all cases. We conclude that the computational method can be used in conjunction with cryo-EM data to obtain approximate model structures of TM domains of proteins for which a sufficiently heterogeneous set of homologs is available. We also show that in those proteins in which relatively short loops connect neighboring helices, the scoring functions can discriminate between near- and far-from-native conformations even without the constraints imposed on helix locations and tilt angles that are derived from cryo-EM.

Algorithms↗

PubMed2001

A simple method for computer quantification of stage REM eye movement potentials.

We describe a simple method for computer quantification of eye movement (EM) potentials during REM sleep. This method can be applied by investigators using either period-amplitude (PA) or Fast Fourier Transform (FFT) spectral EEG analysis without special hardware or computer programming. It provides good correlations with visual ratings of EM in baseline sleep and after administration of GABAergic hypnotics. We present baseline data for both PA and FFT measures for 16 normal subjects, studied for 5 consecutive nights. Both visually rated and computer-measured EM density (EMD) showed high night-to-night correlations across baseline and drug nights and the computer measures detected the EMD suppression that is produced by GABAergic drugs. Measurement of EM in addition to stage REM provides biologically significant information and application of this simple computer method, which does not require pattern recognition algorithms or special hardware, could provide reliable data that can be compared across laboratories.

Computers↗

PubMed2004

Auto-accumulation method using simulated annealing enables fully automatic particle pickup completely free from a matching template or learning data.

Single-particle analysis is a 3-D structure determining method using electron microscopy (EM). In this method, a large number of projections is required to create 3-D reconstruction. In order to enable completely automatic pickup without a matching template or a training data set, we established a brand-new method in which the frames to pickup particles are randomly shifted and rotated over the electron micrograph and, using the total average image of the framed images as an index, each frame reaches a particle. In this process, shifts are selected to increase the contrast of the average. By iterated shifts and further selection of the shifts, the frames are induced to shift so as to surround particles. In this algorithm, hundreds of frames are initially distributed randomly over the electron micrograph in which multi-particle images are dispersed. Starting with these frames, one of them is selected and shifted randomly, and acceptance or non-acceptance of its new position is judged using the simulated annealing (SA) method in which the contrast score of the total average image is adopted as an index. After iteration of this process, the position of each frame converges so as to surround a particle and the framed images are picked up. This method is the first unsupervised fully automatic particle picking method which is applicable to EM of various kinds of proteins, especially to low-contrasted cryo-EM protein images.

Algorithms↗

PubMed1986

Inverse Monte Carlo as a unified reconstruction algorithm for ECT.

Tomographic reconstruction for single photon emission computed tomography (SPECT) with simultaneous compensation for attenuation, scatter, and distance dependent collimator resolution is provided by an Inverse Monte Carlo (IMOC) reconstruction algorithm. A detection probability matrix is formed by Monte Carlo solution to the photon transport equation for SPECT acquisition from a unit source activity in each reconstruction source voxel. The measured projection vector will equal the product of this detection probability matrix with the unknown source distribution vector. The resulting large, nonsparse system of equations is solved for the source distribution using an iterative Maximum Likelihood EM estimator. Reconstruction of experimentally acquired projections from phantoms shows quantitative compensation for scatter and attenuation. Comparison with filtered backprojection (FBP) reconstruction shows an improvement in resolution recovery, contrast, and signal-to-noise for the IMOC algorithm. Reconstruction of clinical studies shows improved contrast, structural resolution, and noise characteristics.

Humans↗

PubMed2006

SIGNATURE: a single-particle selection system for molecular electron microscopy.

SIGNATURE is a particle selection system for molecular electron microscopy. It applies a hierarchical screening procedure to identify molecular particles in EM micrographs. The user interface of the program provides versatile functions to facilitate image data visualization, particle annotation and particle quality inspection. The system design emphasizes both functionality and usability. This software has been released to the EM community and has been successfully applied to macromolecular structural analyses.

Algorithms↗

PubMed2006

EMatch: an efficient method for aligning atomic resolution subunits into intermediate-resolution cryo-EM maps of large macromolecular assemblies.

Structural analysis of biological machines is essential for inferring their function and mechanism. Nevertheless, owing to their large size and instability, deciphering the atomic structure of macromolecular assemblies is still considered as a challenging task that cannot keep up with the rapid advances in the protein-identification process. In contrast, structural data at lower resolution is becoming more and more available owing to recent advances in cryo-electron microscopy (cryo-EM) techniques. Once a cryo-EM map is acquired, one of the basic questions asked is what are the folds of the components in the assembly and what is their configuration. Here, a novel knowledge-based computational method, named EMatch, towards tackling this task for cryo-EM maps at 6-10 A resolution is presented. The method recognizes and locates possible atomic resolution structural homologues of protein domains in the assembly. The strengths of EMatch are demonstrated on a cryo-EM map of native GroEL at 6 A resolution.

Algorithms↗

PubMed2006

Medically unnecessary emergency medical services (EMS) transports among children ages 0 to 17 years.

OBJECTIVES: Estimate the prevalence of medically unnecessary Emergency Medical Services (EMS) transports among children. METHODS: We linked EMS and emergency department (ED) billing records for all EMS-to-hospital transports of children originating in three counties in South Carolina between January 1, 2001 and March 31, 2003. EMS responses resulting in no transport, transports to destinations other than the ED, or multiple trips for the same child in a single day could not be linked to ED data and were excluded. Medically unnecessary transports were identified with an algorithm using pre-hospital impressions, ED diagnoses and ED procedures. After exclusions, 5,693 transports of children between 0 and 17 years were available for study. RESULTS: Sixteen percent (16.4%) of all transports were medically unnecessary. Among children through age 12, upper respiratory and viral problems were the most common diagnoses associated with medically unnecessary transports; among older children, behavioral problems such as conduct disturbance or drug abuse were common. In multivariable analysis, the odds of an unnecessary transport were higher among younger children, non-white children, rural children, and children insured by Medicaid. CONCLUSIONS: The proportion of EMS transports which may be medically unnecessary is relatively modest compared to previous studies. However, many questions remain for future research. Further investigation should include examination of primary care availability and occurrence of unnecessary EMS use, existence of race-based disparities, and transports involving conduct disturbance and other behavioral conditions among children.

Adolescent↗

PubMed1999

Automated model-based bias field correction of MR images of the brain.

We propose a model-based method for fully automated bias field correction of MR brain images. The MR signal is modeled as a realization of a random process with a parametric probability distribution that is corrupted by a smooth polynomial inhomogeneity or bias field. The method we propose applies an iterative expectation-maximization (EM) strategy that interleaves pixel classification with estimation of class distribution and bias field parameters, improving the likelihood of the model parameters at each iteration. The algorithm, which can handle multichannel data and slice-by-slice constant intensity offsets, is initialized with information from a digital brain atlas about the a priori expected location of tissue classes. This allows full automation of the method without need for user interaction, yielding more objective and reproducible results. We have validated the bias correction algorithm on simulated data and we illustrate its performance on various MR images with important field inhomogeneities. We also relate the proposed algorithm to other bias correction algorithms.

Algorithms↗