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Modelling the effect of incorporated halogenated pyrimidine on radiation-induced DNA strand breaks.

PURPOSE: To estimate the enhancement of DNA strand breaks induced by low linear energy transfer (LET) radiation in the presence of halogenated pyrimidines and to examine complexity and clustering properties of damage that could provide a correlation between DNA damage and lethality. MATERIALS AND METHODS: Monte Carlo track structure methods were used to model and estimate the induction of strand breakage by X-ray photons with and without the incorporated Br/I deoxyuridine in cell-mimetic conditions. The increase of DNA strand break induction was modelled by taking into account the direct energy deposition and the reactions of radicals. The yield and spectrum of strand breaks were calculated at various degrees of Br/IdU incorporation. The excess strand breaks due to Br/IdU incorporation was assumed to be induced by highly reactive uracilyl radicals. Four mechanisms were considered for the production of uracilyl radicals classified into three groups, by hydrated electrons, by direct energy deposition, and by both hydrated electrons and direct energy depositions. In total, nine different models were considered to test the excess strand breaks by incorporated Br/IdU assuming different pathways. RESULTS: Model calculations show the following: the yield of strand breaks is enhanced by both the e(aq)(-) reaction and the direct energy deposition on base moiety; there is a significant contribution to the enhancement of yield of strand breaks due to energy transfer about four bases along the DNA to Br/IdU and DNA strand break complexity increases with degree of Br/IdU incorporation. Enhancement ratios of 1.8 and 2.5 for 40% Br/IdU substitution were obtained for single- and double-strand breaks, respectively. CONCLUSIONS: The increase in the yield of strand breaks due to Br/IdU incorporation could be explained by the mechanism of uracilyl radical production by e(aq)(-) and direct energy deposition. The importance of energy transfer along the DNA is demonstrated. It is shown that the incorporation of Br/IdU causes a spectral shift towards a greater complexity of clustered DNA damage.

Base Sequence↗

Emergency department visits in Wisconsin 1998-2002: trends in usage and accuracy of reported data.

INTRODUCTION: There is a paucity of data regarding the utilization of emergency departments (EDs) across Wisconsin. It is unknown if national trends in increased utilization are consistent within our state. Several years ago, mandatory reporting of ED visits to the Department of Health and Family Services was instituted and, if accurate, may provide a method for tracking ED usage. METHODS: We conducted a survey of existing EDs to study the trend in patient visits for the 5-year time period 1998-2003. Data reported in the surveyed departments were compared to those reported to the state database. RESULTS: On average, all EDs reported a consistent yearly increase in patient visits over the time period (an average overall increase of 10%). On average, this increase was larger for smaller hospitals. Growth was consistent over the time period, but the yearly rate steadily slowed down. Data reported to the state consistently underreported the actual census. CONCLUSION: All sizes of EDs across Wisconsin continue to show increases in ED utilization. The growth rate is consistent but may be slowing. This has implications for planning for ED resources. Reported data have many discrepancies and need to be independently checked before they can be utilized in any research or planning.

Catchment Area, Health↗

Cardiac output--pulse contour analysis vs. pulmonary artery thermodilution.

BACKGROUND: The aims of this study were to determine the agreement between pulmonary artery thermodilution (PA-TD), transpulmonary thermodilution (TP-TD) and the pulse contour method, and to test the ability of the pulse contour method to track changes in cardiac output. METHODS: Cardiac output was determined twice before cardiac surgery with both PA-TD and TP-TD. The precision (two standard deviations of the difference between repeated measurements) and agreement of the two methods were calculated. Post-operatively, cardiac output was determined with the PA-TD and pulse contour methods, and the bias and limits of agreement were again calculated. Finally, in patients with heart rates below 60 beats/min or a cardiac index of less than 2.5 l/min/m2, atrial pacing was started and the haemodynamic consequences were monitored with the PA-TD and pulse contour methods. RESULTS: Twenty-five patients were included. The precisions of PA-TD and TP-TD were 0.41 l/min [95% confidence interval (CI), +/- 0.07] and 0.48 l/min (95% CI, +/- 0.08), respectively. The bias and limits of agreement between PA-TD and TP-TD were - 0.46 l/min (95% CI, +/- 0.11) and +/- 1.10 l/min (95% CI, +/- 0.19), respectively. Post-operatively, the bias and limits of agreement between the PA-TD and pulse contour methods were 0.07 l/min and +/- 2.20 l/min, respectively. The changes in cardiac output with atrial pacing were in the same direction and of the same magnitude in 15 of the 16 patients. CONCLUSION: The precision of cardiac output measurements with PA-TD and TP-TD was very similar. The transpulmonary method, however, overestimated the cardiac output by 0.46 l/min. Post-operatively, cardiac output measurements with the PA-TD and pulse contour methods did not agree, but the pulse contour method reliably tracked pacing-induced changes in cardiac output.

Adult↗

A mathematical algorithm that computes breast cancer sizes and doubling times detected by screening.

This paper presents a mathematical algorithm that computes the sizes and growth rates of breast cancer detected in a hypothetical population that is screened for the disease. The algorithm works by simulating the outcomes of the hypothetical population twice, first without screening and then with screening. The simulation without screening relies on an underlying model of the natural history of the disease. The simulation with screening uses this natural history model to track the growth of breast tumors backwards in the time starting from the time they would have been detected without screening. The method of tracking tumor growth backward in time is different from methods that track tumor growth forward in time by starting from an estimated time of tumor onset. The screening algorithm combines the natural history model, the method tracking of tumor growth backward in time, the age group, the interval between screening exams, and the detection threshold of the screening exam to compute the joint distribution of tumor size and growth rate among screen-detected and interval patients. The algorithm also computes the sensitivity and leadtime distribution. It allows for arbitrary age groups, detection thresholds and screening intervals and may contribute to the design of future screening trials.

Age Factors↗

The catheter-driven MRI scanner: a new approach to intravascular catheter tracking and imaging-parameter adjustment for interventional MRI.

OBJECTIVE: Our aim was to test the feasibility of a hands-free approach to MRI that allows the interventionalist to track an angiographic catheter in real time throughout the procedure and to automatically change imaging parameters by catheter manipulation. MATERIALS AND METHODS: A tracking method that is based on an active device localization was implemented on a 1.5-T MRI scanner. The system determines the current position and orientation of a catheter in 3D space in an endless feedback loop. Automatic scanning plane-adjustment procedures written in the software of the MRI system ensure image acquisition at the location of the catheter tip. The system calculates the device velocity to automatically adjust parameters such as field of view (FOV) and resolution. To evaluate the feasibility and performance in vivo and ex vivo, we performed experiments in two vessel phantoms and on six pigs. RESULTS: The system collected the tracking data within 40 msec; an additional 10-20 msec was then required to perform the localization and velocity calculations and to update the image parameters. The system could localize a motionless catheter in the aorta in 100% and a moving catheter in 98% of measured attempts. The system responded in real time to changes in device velocity by dynamically adjusting spatial resolution and FOV in both phantom and porcine trials. Using this technique, we successfully catheterized the renal artery in two pigs. CONCLUSION: Active tracking, combined with automatic scanning plane and imaging parameter adjustment, provides an intuitive MRI scanner interface for the guidance of the vascular procedure.

Algorithms↗

A new method for eye location tracking.

A standard scleral search coil (SSC) system is supplied with a single three-axial transmitter (or with a triad of transmitters) and the direct magnetic coupling between the transmitting coils and the SSC is used for computing the eye location. The SSC's orientation components measured by the SSC system are involved in the location-tracking algorithm as well. The suggested method differs from traditional ones where the eye location is computed indirectly, relative to the measured location and orientation of a transitional three-axial magnetic sensor attached to the subject's head. The new method eliminates systematic errors caused by inaccurate situating the transitional sensor relative to the eye. It also eliminates systematic errors caused by imperfect orthogonality of the transitional sensor. It is found that an accurate location tracking with a single transmitter is possible only if orientation freedom of the eye is limited. To track the eye location with no orientation limitations, a triad of transmitters is employed. The resulting accuracy can be as good as +/- 1 mm (in a 200-Hz bandwidth) over a relatively large (0.5 x 0.5 x 0.5 m) operating region in the center of a 1 x 1 x 1 m SSC system. The analytical results obtained are confirmed with the help of computer simulations.

Computer Simulation↗

An immunocytochemical method for marking microelectrode tracks following single-unit recordings in long surviving, awake monkeys.

We describe an immunocytochemical method for marking microelectrode tracks made during single-unit recordings in long surviving, awake monkeys. This procedure detects the increase in glial fibrillary acidic protein in the glial cells along a microelectrode track using commercially available antibodies. We have successfully marked electrode tracks in tissue from preparations having postrecording survival times ranging into months even though the gliosis can no longer be detected with conventional stains for cell bodies. When this method is combined with data from electrophysiological recordings in chronic preparations it will be possible to reconstruct functional architecture using chronic preparations, as has been done previously with acute preparations.

Animals↗

Simplified Parsonnet risk scale identifies limits to early patient discharge.

BACKGROUND: Fast-track recovery after coronary artery bypass surgery has influenced patient care positively. Predicting patients who fall off track and require prolonged (> or =7 days) hospitalization remains uncertain. The Parsonnet risk assessment score is effective in predicting length of stay, but is limited by inaccurate subdivision of risk categories. We simplified the Parsonnet risk scale to better identify patients eligible for fast-track recovery. METHOD: The cases of 604 consecutive patients who underwent isolated coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) were reviewed retrospectively. A rapid recovery protocol emphasizing reduced CPB time, preoperative intra-aortic balloon pump (IABP) criteria, and atrial fibrillation prophylaxis was applied to all patients. The five original divisions of the Parsonnet risk scale were reduced to three risk categories: Low (0-10; Group A), Intermediate (11-20; Group B), High (> 20; Group C). Comparisons of progressive risk categories were analyzed to identify predictive factors associated with fast-track outcomes. RESULTS: The thirty-day operative mortality for the entire group was 3.6%. Three clinical features were identified that distinguished risk progression-female gender, reoperative CABG, and increased age. Additionally, the presence of diabetes (p < 0.05), congestive heart failure (p < 0.01), and peripheral vascular disease (p < 0.001) distinguished Groups A and B, while acute myocardial infarction (p < 0.05) influenced outcomes in Group C. Group A (48%) mean risk score 5.9+/-3.2 was compared to Group B (34%) 14.8+/-2.6, which was further compared to Group C (18%) 26.4+/-2.8. The mean length of stay for Group A (5.3+/-4.1 days) was notably less than Group B (6.1+/-4.7 days; p < 0.05); however, both groups responded favorably to fast-track techniques. Group C did not respond comparably (9.2+/-9.2 vs 6.1+/-4.7 days; p < 0.001) and experienced prolonged recovery. The simplified Parsonnet risk scale did not identify differences in operative mortality and revealed only pneumonia (p < 0.05) and atrial fibrillation (p < 0.01) to be greater in Group C. As risk increased, significantly less revascularization was performed (Group A 3.6+/-1.2 grafts/patient vs Group B 3.3+/-1.2 [p < 0.01]; Group B 3.3+/-1.2 vs Group C 2.5+/-1.0 [p < 0.001]). CONCLUSION: A simplified Parsonnet risk scale (three categories) is an effective tool in identifying factors limiting fast-track recovery. Low- and intermediate-risk patients represent the majority (82%) and respond well to fast-track methods. High-risk patients (18%) are limited by a greater percentage of female patients, reoperative CABG, and the very elderly, resulting in fast-track failure. Strategies to improve recovery in high-risk patients may include evolving off-pump techniques.

Aged↗

Tracking of a bronchoscope using epipolar geometry analysis and intensity-based image registration of real and virtual endoscopic images.

This paper describes a method for tracking the camera motion of a flexible endoscope, in particular a bronchoscope, using epipolar geometry analysis and intensity-based image registration. The method proposed here does not use a positional sensor attached to the endoscope. Instead, it tracks camera motion using real endoscopic (RE) video images obtained at the time of the procedure and X-ray CT images acquired before the endoscopic examination. A virtual endoscope system (VES) is used for generating virtual endoscopic (VE) images. The basic idea of this tracking method is to find the viewpoint and view direction of the VES that maximizes a similarity measure between the VE and RE images. To assist the parameter search process, camera motion is also computed directly from epipolar geometry analysis of the RE video images. The complete method consists of two steps: (a) rough estimation using epipolar geometry analysis and (b) precise estimation using intensity-based image registration. In the rough registration process, the method computes camera motion from optical flow patterns between two consecutive RE video image frames using epipolar geometry analysis. In the image registration stage, we search for the VES viewing parameters that generate the VE image that is most similar to the current RE image. The correlation coefficient and the mean square intensity difference are used for measuring image similarity. The result obtained in the rough estimation process is used for restricting the parameter search area. We applied the method to bronchoscopic video image data from three patients who had chest CT images. The method successfully tracked camera motion for about 600 consecutive frames in the best case. Visual inspection suggests that the tracking is sufficiently accurate for clinical use. Tracking results obtained by performing the method without the epipolar geometry analysis step were substantially worse. Although the method required about 20 s to process one frame, the results demonstrate the potential of image-based tracking for use in an endoscope navigation system.

Algorithms↗

A method for radioprobing DNA structures using Auger electrons.

PURPOSE: To present a new method for radioprobing a DNA triple helix structure by Auger electrons emitted in the decay of 125I using theoretical/computational approaches. MATERIALS AND METHODS: A Monte Carlo track structure method was used to simulate the damage to a triplex resulting from Auger electrons emitted in the decay of an incorporated 125I atom in plasmid DNA. Comparison of the theoretical frequency distributions of single-strand breaks induced on the Pu and Py strands with the experimental data and a knowledge of the distances from the strand breaks to the iodine provide information on the structures otherwise difficult to obtain with X-ray crystallography. RESULTS: In comparing theoretical frequency distributions of single-strand breaks with the experimental data it is found that the results are very sensitive to the conformation of the triplex model used. It is found that the best fit to the experimental data results from using a hybrid triplex model, in which the base-step geometry is A-like, while the sugar puckers adopt the B-like C2'-endo conformation. CONCLUSIONS: The approach and technique presented here represent a valuable new addition to the methods available for DNA structure determination since they provide information on medium-range structure otherwize difficult to obtain in the absence of X-ray crystallography. It is concluded that currently accepted models for triplex structure are not optimal, and a modified structure is proposed that fits the radioprobing results better, while maintaining agreement with the fibre diffraction and NMR data. Although the method has proved to be very useful for scoring alternative trial solutions, further studies combining experimental data from multiple iodine positions with track structure modelling are required for directing structural optimization.

Base Sequence↗

A novel computerized system for analyzing motor and social behavior in groups of animals.

We present here the VMB Tracking System, a novel method for tracking locomotor activity, posture, thigmotactic scanning behavior and social interactions of up to eight animals at a time, at a high resolution (up to+/-0.1 mm). We used a commercially available computerized system that is considerably cheaper than other available methods. This system utilizes a basic personal computer controlling three transponders ('towers') fixed in space above the tested area, where animals as small as rats stroll freely in their normal habitat or in an experimental arena. Each tower emits infra-red (IR) pulses to a transponder ('button') adhered to a plastic mount glued to a shaved area of skin on the animal's back. When the button detects the IR pulses it responds with a button-specific ultrasonic signal that is fed back to the towers. The 3D location of the buttons is calculated by triangulation. Movement parameters of each button, such as displacement trajectory, time, speed and acceleration, can be displayed on-line and stored for off-line analysis. This system can be used to track animals in any lighting conditions, and to assess drug effects on the CNS, neuromuscular junction or muscle. As an example we demonstrate the ataxic effects of pentobarbital in rats.

Animals↗

Tracking clinical competencies on the web.

CONTEXT: The American Registry of Radiologic Technologists (ARRT) has defined several core examinations that student radiographers must perform to demonstrate competency. Furthermore, the ARRT has left the method of tracking competency exams to educators. OBJECTIVE: This article describes a Web-based system that can be used to track clinical competencies. METHOD: The pedagogy employed in designing a meaningful and successful Web site to track competencies can be overwhelming. Considerations include selecting software, the design and implementation process, and providing security to protect confidential information. CONCLUSION: The Web-based system described in this article is innovative, sensible and relatively easy to adopt. This tracking method provides faculty members with instantaneous access and a quick review of the student's competency examinations. Students' competency information for the entire program is contained in 1 electronic file. With minor modification, the system can be used in a variety of educational and administrative settings.

Certification↗

System identification of the human vestibulo-ocular reflex during head-free tracking.

A method was developed to identify the linear, system level dynamics of the horizontal, angular vestibulo-ocular reflex (VOR) as it stabilized vision during head-free tracking of a visual target. Small amplitude, broad spectrum, stochastic torque perturbations were applied to the head while the subject tracked an unpredictable, moving target with active head and eye motions. Stochastic system identification techniques were used to design the torque and target inputs and to conduct the analysis such that the linear dynamics of the VOR, independently of the visual system's influence on eye motions, were determined. The linear analysis was limited to evaluating VOR dynamics from approximately 0.5 to 4.5 Hz. Nonlinearities in the head-neck system affected the low frequency response of the head to the torque perturbations, and the eye velocity sequence was affected by nonlinearities and degraded by noise at high frequencies. The VOR's gain was near 1.0 between about 0.5 and 2.5 Hz, and then decreased steadily to 0.85 as the frequency increased towards 4.0 Hz. The VOR phase angle was also frequency dependent and corresponded to VOR eye motions lagging the head's disturbance motion by less than 10 ms at frequencies greater than 1.0 Hz.

Adult↗

Harmonic phase MR tagging for direct quantification of Lagrangian strain in rat hearts after myocardial infarction.

The utility of harmonic phase (HARP) analysis was recently demonstrated in humans and large animals as a technique for rapid and automatic analysis of tagged magnetic resonance images. In the current study, the applicability and accuracy of HARP analysis for automatic strain quantification in small animals were investigated. A validation study was performed on seven postinfarct rats and seven age-matched controls. A method for direct computation of 2D Lagrangian strain fields from spatial derivatives of HARP images was also developed in this paper. The results of HARP analysis were evaluated by comparison with those of homogeneous strain analysis employing finite element method and manual tag tracking. Both methods were validated with simulated digital images. Compared to conventional homogeneous strain analysis, HARP analysis yielded similar results in the assessment of regional strain patterns in both control and infarct rats. Both methods detected a reduction in maximal stretch and shortening in infarct rats. Our results suggest that HARP analysis can also be applied to quantify alterations in regional myocardial wall motion in small animals.

Animals↗

Hybrid bronchoscope tracking using a magnetic tracking sensor and image registration.

In this paper, we propose a hybrid method for tracking a bronchoscope that uses a combination of magnetic sensor tracking and image registration. The position of a magnetic sensor placed in the working channel of the bronchoscope is provided by a magnetic tracking system. Because of respiratory motion, the magnetic sensor provides only the approximate position and orientation of the bronchoscope in the coordinate system of a CT image acquired before the examination. The sensor position and orientation is used as the starting point for an intensity-based registration between real bronchoscopic video images and virtual bronchoscopic images generated from the CT image. The output transformation of the image registration process is the position and orientation of the bronchoscope in the CT image. We tested the proposed method using a bronchial phantom model. Virtual breathing motion was generated to simulate respiratory motion. The proposed hybrid method successfully tracked the bronchoscope at a rate of approximately 1 Hz.

Algorithms↗

Measurement of CD2 expression levels of IFN-alpha-treated fibrosarcomas using cell tracking velocimetry.

METHODS: A methodology and a mathematical relationship have been developed that allow quantitation of the expression levels of cellular surface antigens, in terms of antibody binding capacities (ABC). This methodology uses immunomagnetically labeled cells and calibration microbeads combined with cell tracking velocimetry (CTV) technology to measure magnetophoretic mobilities corresponding to cellular ABC. The mobility measurements were accomplished by microscopically recording and calculating the velocity of immunomagnetically labeled QSC microbeads and cells in a nearly constant magnetic energy gradient. RESULTS: Transformed fibrosarcoma cells were given controlled treatments of interferon-alpha in order to manipulate CD2 antigen expression levels. These cells were then immunomagnetically labeled with anti-CD2 FITC antibodies and anti-FITC MACS paramagnetic nanoparticles. Measured magnetophoretic mobilities were used to calculate ABC for these cells, corresponding to CD2 expression levels. CONCLUSION: The results from CTV and flow cytometry (FCM) qualitatively verify that these fibrosarcoma cells express elevated levels of CD2 molecules with increasing interferon-alpha treatment from 0 to 24 h. The mean basal CD2 expression level, in terms of ABC, was calculated to be 27,000 from CTV analysis, whereas FCM indicates a comparable ABC value of 33,000.

CD2 Antigens↗