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PubMed2003

Assessment criteria for MEG/EEG cortical patch tests.

To validate newly developed methods or implemented software for magnetoencephalography/electroencephalography (MEG/EEG) source localization problems, many researchers have used human skull phantom experiments or artificially constructed forward data sets. Between the two methods, the use of an artificial data set constructed with forward calculation attains superiority over the use of a human skull phantom in that it is simple to implement, adjust and control various conditions. Nowadays, for the forward calculation, especially for the cortically distributed source models, generating artificial activation patches on a brain cortical surface has been popularized instead of activating some point dipole sources. However, no well-established assessment criterion to validate the reconstructed results quantitatively has yet been introduced. In this paper, we suggest some assessment criteria to compare and validate the various MEG/EEG source localization techniques or implemented software applied to the cortically distributed source model. Four different criteria can be used to measure accuracy, degrees of focalization, noise-robustness, existence of spurious sources and so on. To verify the usefulness of the proposed criteria, four different results from two different noise conditions and two different reconstruction techniques were compared for several patches. The simulated results show that the new criteria can provide us with a reliable index to validate the MEG/EEG source localization techniques.

Algorithms↗
PubMed2001

Template images for nonhuman primate neuroimaging: 1. Baboon.

Coregistration of functional brain images across many subjects offers several experimental advantages and is widely used for studies in humans. Voxel-based coregistration methods require a high-quality 3-D template image, preferably one that corresponds to a published atlas. Template images are available for human, but we could not find an appropriate template for neuroimaging studies in baboon. Here we describe the formation of a T1-weighted structural MR template image and a PET blood flow template, derived from 9 and 7 baboons, respectively. Custom software aligns individual MR images to the MRI template; human supervision is needed only to initially estimate any gross rotational misalignment. In these aligned individual images, internal subcortical fiducial points correspond closely to a photomicrographic baboon atlas with an average error of 1.53 mm. Cortical test points showed a mean error of 1.99 mm compared to the mean location for each point. Alignment of individual PET blood flow images directly to the PET template was compared to a two-step alignment process via each subject's MR image. The two transformations were identical within 0.41 mm, 0.54 degrees, and 1.0% (translation, rotation, and linear stretch; mean). These quantities provide a check on the validity of the alignment software as well as of the template images. The baboon structural MR and blood flow PET templates are available on the Internet (purl.org/net/kbmd/b2k) and can be used as targets for any image registration software.

Animals↗
PubMed2006

Transient temperature rise in a mouse due to low-frequency regional hyperthermia.

A refined nonlinear heat transfer model of a mouse has been developed to simulate the transient temperature rise in a neoplastic tumour and neighbouring tissue during regional hyperthermia using a 150 kHz inductive coil. In this study, we incorporate various bio-energetic enhancements to the heat transfer equation and numerical validations based on experimental findings for the mouse, in terms of nonlinear metabolic heat production, homeothermy, blood perfusion parameters, thermoregulation, psychological and physiological effects. The discretized bio-heat transfer equation has been validated with the commercial software FEMLAB on a canonical multi-sphere object before applying the scheme to the inhomogeneous mouse voxel phantom. The time-dependent numerical results of regional hyperthermia of mouse thigh have been compared with the available experimental temperature results with only a few small disparities. During the first 20 min of local unfocused heating, the temperature in the tumour and the surrounding tissue increased by around 7.5 degrees C. The objective of this preliminary study was to develop a validated electrothermal numerical scheme for inductive hyperthermia of a small mammal with the intention of expanding the model into a complete numerical solution involving ferromagnetic nanoparticles for targeted heating of tumours at low frequencies. In addition, the numerical scheme herein could assist in optimizing and tailoring of focused electromagnetic fields for hyperthermia.

Animals↗
PubMed2007

Spot the match - wildlife photo-identification using information theory.

BACKGROUND: Effective approaches for the management and conservation of wildlife populations require a sound knowledge of population demographics, and this is often only possible through mark-recapture studies. We applied an automated spot-recognition program (I3S) for matching natural markings of wildlife that is based on a novel information-theoretic approach to incorporate matching uncertainty. Using a photo-identification database of whale sharks (Rhincodon typus) as an example case, the information criterion (IC) algorithm we developed resulted in a parsimonious ranking of potential matches of individuals in an image library. Automated matches were compared to manual-matching results to test the performance of the software and algorithm. RESULTS: Validation of matched and non-matched images provided a threshold IC weight (approximately 0.2) below which match certainty was not assured. Most images tested were assigned correctly; however, scores for the by-eye comparison were lower than expected, possibly due to the low sample size. The effect of increasing horizontal angle of sharks in images reduced matching likelihood considerably. There was a negative linear relationship between the number of matching spot pairs and matching score, but this relationship disappeared when using the IC algorithm. CONCLUSION: The software and use of easily applied information-theoretic scores of match parsimony provide a reliable and freely available method for individual identification of wildlife, with wide applications and the potential to improve mark-recapture studies without resorting to invasive marking techniques.

Journal Article↗
PubMed1995

A consensus view on the technique of ambulatory blood pressure monitoring. The Fourth International Consensus Conference on 24-Hour Ambulatory Blood Pressure Monitoring.

This review, based on the Fourth International Consensus Conference on Ambulatory Blood Pressure Monitoring (Leuven, Belgium, 1994), deals with the technical aspects of ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring by noninvasive intermittent techniques is widely used despite artifacts due to cuff size, movement, body position, short-term blood pressure variability, and interference with sleep. The performance of the currently available monitors under truly ambulatory conditions and during exercise remains a matter of debate, as are the procedures required to validate portable monitors under these circumstances. There is general agreement that whenever a monitor is to be used in special populations, such as older subjects or pregnant women, or in special conditions, such as exercise, a specific demonstration of its accuracy in these defined subgroups or conditions is warranted. Whether the auscultatory or oscillometric method is preferred remains controversial because each technique has specific advantages and disadvantages and because both can provide accurate results. Most experts in the field strongly believe that manufacturers should disclose the algorithms of their devices and that they should specify all changes made to the hardware and software of a previously validated monitor. Finally, the development of the volume-clamp method, which makes continuous noninvasive registration of blood pressure at the finger possible in both stationary and ambulatory conditions, opens new perspectives in research, in particular in relation to short-term blood pressure variability.

Adult↗
PubMed2000

STAR/mmCIF: an ontology for macromolecular structure.

MOTIVATION: Crystallographers were motivated 10 years ago to develop a simple and consistent data representation for the exchange and archiving of data associated with the crystallographic experiment and the final structure. As this process evolved (and the data grew at near exponential rates) came the recognition that this representation should also facilitate the automated management of the data and, with the aid of additional software for verification and validation, provide improved consistency and accuracy and hence improved scientific inquiry. This realization led to a new Dictionary Definition Language (DDL) and an extensive dictionary based on this DDL for describing macromolecular structure. In broad terms this could be considered an ontology. An important feature in the development of the ontology was the endorsement and ongoing maintenance and support of the International Union of Crystallography (IUCr). While the description of macromolecular structure and the x-ray crystallographic experiment used to derive it represent explicit data, the ontology is extensible and applicable to other less well-characterized data domains. RESULTS: Details of the DDL, the dictionaries that have been developed, and software for reading and using this ontology are presented. AVAILABILITY: Extensive documentation, software tools and the DDL and dictionaries are available from http://ndbserver.rutgers.edu/mmcif and associated mirror sites. CONTACT: Bourne: bourne@sdsc.edu and Westbrook:jwest@rcsp.rutgers.edu

Crystallography, X-Ray↗
PubMed1996

An automated system for bedside verification of the match between patient identification and blood unit identification.

BACKGROUND: The administration of blood to the wrong patient remains the leading cause of acute hemolytic transfusion reactions and subsequent death. A process control system for blood administration was developed that verifies, at the bedside, the match between barcoded patient identification and blood unit identification. STUDY DESIGN AND METHODS: The system is composed of 1) a portable bedside scanner that reads barcoded patient identification and blood unit identification, 2) a host computer system capable of accepting transfusion data from the bedside scanner, 3) printed documentation of the transfusion episode, and 4) audit trail monitoring of whether all steps in the automated patient and blood unit identification process have been performed. Software design, development, and validation protocols followed industry standards. RESULTS: A pilot study was performed over a 2-month period evaluating the blood administration process using the computerized bedside transfusion identification system prototype for transfusions in 39 oncology patients. CONCLUSION: This system controls the blood administration process and includes bedside verification of the match between patient identification and blood unit identification.

Blood Transfusion↗
PubMed2004

Development and validation of computational models of cellular interaction.

In this paper we take the view that computational models of biological systems should satisfy two conditions - they should be able to predict function at a systems biology level, and robust techniques of validation against biological models must be available. A modelling paradigm for developing a predictive computational model of cellular interaction is described, and methods of providing robust validation against biological models are explored, followed by a consideration of software issues.

Animals↗
PubMed2005

MedFlow - Improving Modelling and Assessment of Clinical Processes.

INTRODUCTION: Clinical processes are meant to restore the patient's health but often show weaknesses regarding their efficiency (e.g. ineffective task distribution for clinicians, long waiting times for patients). In order to improve these processes an assessment of their quality is needed. This assessment is based on adequate process models and proper systematic assessment procedures. Both seem not sufficiently present in the Activity Diagrams of the Unified Modeling Language (UML) or ARIS Event-driven Process Chains (EPC). OBJECTIVES: The aim of this paper is to develop and test a process modelling method which explicitly includes all details of clinical processes necessary for a systematic and even semiautomatic quality assessment. METHODS: We propose a model which is separated into process model, tool model, organisation model and information model. Its visualisation is based on the extended UML Activity Diagrams. RESULTS: After being defined formally the graphical elements of the proposed model were implemented into a commonly used modelling software. As a first validation step, various versions of the process of ordering a radiological examination were modelled. DISCUSSION: The advantage of our modelling approach is the combination of different aspects (i.e. description of processes, used tools, information objects and actor roles) into an integrated model so that details important for a systematic process assessment are now more explicitly included than in Activity Diagrams or EPC. Further evaluations will help to improve the model and to develop strategies for the semi-automatic analysis.

Humans↗
PubMed2002

Quantification of wall shear stress in large blood vessels using Lagrangian interpolation functions with cine phase-contrast magnetic resonance imaging.

Arterial wall shear stress is hypothesized to be an important factor in the localization of atherosclerosis. Current methods to compute wall shear stress from magnetic resonance imaging (MRI) data do not account for flow profiles characteristic of pulsatile flow in noncircular vessel lumens. We describe a method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall. Validation was performed with software phantoms and an in vitro flow phantom. At an image resolution corresponding to in vivo imaging data of the human abdominal aorta, time-averaged, spatially averaged wall shear stress for steady and pulsatile flow were determined to be within 16% and 23% of the analytic solution, respectively. These errors were reduced to 5% and 8% with doubling in image resolution. For the pulsatile software phantom, the oscillation in shear stress was predicted to within 5%. The mean absolute error of circumferentially resolved shear stress for the nonaxisymmetric phantom decreased from 28% to 15% with a doubling in image resolution. The irregularly shaped phantom and in vitro investigation demonstrated convergence of the calculated values with increased image resolution. We quantified the shear stress at the supraceliac and infrarenal regions of a human abdominal aorta to be 3.4 and 2.3 dyn/cm2, respectively.

Adult↗
PubMed1992

Evaluation of a photodiode array/HPLC-based system for the detection and quantitation of basic drugs in postmortem blood.

A systematic analytical approach has been developed for liquid chromatography determination of a number of basic drugs in postmortem blood. Using selective extraction, that is, back extraction into 0.2N sulfuric acid and 6N hydrochloric acid after the initial extraction with toluene under basic conditions (from 2 mL of blood), basic and weakly basic drugs, such as propranolol and diazepam, can be simultaneously quantitated and identified with a high degree of confidence. A microcomputer-based photodiode array detector was used to evaluate peak purity and facilitate peak identification. An automatic library search was performed at the end of each analysis using the system software. The method was validated for within-day and between-day precision for ten basic drugs at two concentrations. The coefficient of variation for the between-day precision was less than 8.7%. Accuracy of the assay was tested at four concentrations using linear regression analysis. The coefficients of determination (r2) for all ten drugs were greater than 0.99, and their slopes were close to unity. The chromatographic conditions developed are suitable for the screening of several basic, acidic, amphoteric, and neutral drugs. Retention data and ultraviolet spectral data for 119 drugs on two reversed-phase columns, using acidic mobile phases, are also presented.

Blood Chemical Analysis↗
PubMed2003

Measuring dietary fatty acid intake:validation of a food-frequency questionnaire against 7 d weighed records.

There are few validated methods of measuring dietary fatty acid intake that are suitable for epidemiological research. The purpose of the present study was to develop and validate a food-frequency questionnaire (FFQ) developed to measure individual dietary fatty acid intakes against 7 d weighed dietary records, in a sample of thirty-one healthy adult volunteers. The FFQ was based on a previously validated questionnaire (DIETQ; Tinuviel Software, Warrington, Ches., UK), adapted to include greater detail on those foods from which the majority of dietary fatty acids are obtained. The FFQ and weighed records were analysed using food nutrient data from McCance and Widdowson's Food Composition Tables, supplemented with a food fatty acid content database (Foodbase, London, UK). Results from the two dietary assessment methods were compared by correlation coefficients and limits of agreement. The mean intake of individual fatty acids tended to be lower when assessed by FFQ. Correlation coefficients comparing unadjusted individual fatty acid intakes assessed by FFQ and weighed records ranged from 0.29 for 18 : 1n-9 to 0.71 for 20 : 4n-6. Adjusting for energy intake tended to increase the correlation coefficients between saturated fatty acids and decrease those between unsaturated fatty acids. In conclusion, this food-frequency method provides reliable estimates of dietary intake of many individual fatty acids for use in epidemiological studies.

Adult↗
PubMed2003

Fan beam dual energy X-ray absorptiometry body composition measurements in piglets.

OBJECTIVES: A piglet model was used to validate and cross validate the fan-beam (FB) dual energy X-ray absorptiometry (DXA) software vKH6 and to determine the predictive values of physiologic parameters (weight, length, age and gender) on body composition. METHODS: Nineteen piglets (Group A: 600 to 21100 g) were used to validate the FB-DXA measurements of body composition based on chemical analysis of the carcass. An additional 22 piglets (Group B: 640 g to 17660 g) had FB-DXA measurements, and these values were compared to the predicted values generated from regression equations computed from group A piglets. Body composition for bone mass, lean mass and fat mass was based on ash weight, nitrogen and fat measured from three aliquots of homogenate from each carcass. Data from all piglets (n = 41) were used to determine the variations in body composition. Data analysis used regression, t test and analysis of variance. RESULTS: Duplicate DXA (total weight TW, bone mineral content BMC, bone area BA, bone mineral density BMD, lean mass LM and fat mass FM) measurements were highly correlated (r = 0.98 to 1.00, p < 0.001 for all comparisons) and were not significantly different. No significant differences were found in the residuals from predicted versus measured DXA values between the larger and the smaller (<1.6 kg) piglets from Group A. For Group B piglets, the DXA measured TW of 5666 +/- 5692 g (mean +/- SD), LM (5063 +/- 5048 g), FM (465 +/- 510 g), BMC (138 +/- 139 g), BA (486 +/- 365 cm(2)) and BMD (0.235 +/- 0.071 g/cm(2)) were highly significantly correlated with (r = 0.94 to 1.00, p < 0.001 for all comparisons) and were not significantly different from the predicted values. Data from all piglets (n = 41) showed that weight is the dominant predictor of whole body and regional body composition. Length, age or gender contributed to <2% of the variability of body composition. CONCLUSION: Body composition measurements using the FB DXA software vKH6 is highly reproducible. The software vKH6 is validated for use in a wide range of body weights and body composition, and cross-validated using a separate group of animals. Body weight is the dominant predictor of body composition in immature piglets.

Absorptiometry, Photon↗
PubMed2001

Deformation-based morphometry and its relation to conventional volumetry of brain lateral ventricles in MRI.

Deformation-based morphometry (DBM) is a useful technique to detect morphological differences over the entire brain since it analyses positional differences between every voxel and a standard brain. In this report we compare DBM to semimanual tracing of brain ventricles in a population of 39 patients with schizophrenia. High-resolution T(1)-weighted magnetic resonance images were obtained and processed with DBM and interactive tracing software. We evaluate the validity of the DBM in two different approaches. First, we divide subjects into two groups based on the mean ventricular/brain ratios and compute statistical maps of displacement vectors and their spatial derivatives. This analysis demonstrates a striking consistency of the DBM and visual tracing results. We show that restricting the information about the deformation fields by computing the local Jacobian determinant (as a measure of volume change) provides evidence of the shape of ventricular deformation which is unavailable from ventricular volume measures alone. Second, we compute a mean measure of the Jacobian values over the entire ventricles and observe a correlation of r = 0.962 with visual tracing based ventricular/brain ratios. The results support the usefulness and validity of DBM for the local and global examination of brain morphology.

Adolescent↗
PubMed1999

Usefulness of a state-legislated, comparative database to evaluate quality in colorectal surgery.

PURPOSE: Colorectal surgery, a high-volume procedure, has been targeted for performance improvement to reduce length of stay. Specific postoperative quality indicators and readmission rates should be analyzed concomitantly to assure that adverse events are not associated with earlier discharge. METHODS: From July 1, 1990, to June 30, 1997, 1,218 consecutive patients who underwent transabdominal colorectal surgery were analyzed for length of stay, mortality, morbidity, and discharge disposition. Each patient was assigned an Admission Severity Group rating 0 to 4 using a hospital-based state-legislated software system (Atlas) to validate comparative performance internally and externally. Readmission data within 120 days of discharge were available for the last 678 consecutive patients from July 1, 1993, to June 30, 1997, using Lastword (computerized medical records). RESULTS: The annual frequencies of the 1,218 procedures were 173, 183, 175, 146, 167, 189, and 185, respectively, from July 1990 through June 1997. Severity distribution was 32 for Admission Severity Group 0, 517 for Admission Severity Group 1, 540 for Admission Severity Group 2, 128 for Admission Severity Group 3, and 1 for Admission Severity Group 4, with no annual difference (P = 0.012). There was a significant reduction in total length of stay of 3.1 (12.9-9.8) days during the seven years (P = 0.001). The overall operative mortality rate was 1.4 percent, and the morbidity was 2.6 percent, with no annual differences (P = 0.655 and P = 0.033, respectively). The disposition to home did not change (P = 0.21). Of the 678 patients followed up for readmission, 100 (14.7 percent) were readmitted within 120 days, with no annual difference (P = ().302). CONCLUSION: Mortality, morbidity, disposition, and readmission rates were not affected by a decreased length of stay after colorectal surgery.

Colonic Diseases↗
PubMed2002

Subcellular mass determination by 4He+ energy-loss micro-spectrometry.

The scanning transmission ion microscope (STIM) has been used to determine the intracellular mass of human cultured cells. A 4He+ microbeam of 2.0 MeV energy was chosen to obtain enhanced ion-energy-loss sensitivity through the micron-thick freeze-dried cells. Local sample mass calculation, based on energy-loss conversion by use of appropriate matrix stopping powers, was performed by use of dedicated software. The method was validated with epoxy resin sections and polymer foil as analogues of biological samples in the range of (intra)cellular thickness, 150 to 3000 nm. STIM analysis resulted in less than 5% error in mass determination. 4He+ energy-loss micro-spectrometry was performed on freeze-dried human ovarian cancer cells, the mean areal mass obtained was 120 microg cm(-2) (200 microg cm(-2) in the nucleus and 250 microg cm(-2) in nucleoli). This method is particularly useful for mass normalization of X-ray fluorescence yields resulting from particle-induced X-ray emission microanalysis (micro-PIXE). When performed successively these two ion-beam micro-analytical methods enable the mapping of true element concentrations within single cells.

Adenocarcinoma↗
PubMed2004

In silico physical mapping software for the Triticum aestivum genome.

The large size of the Triticum aestivum genome makes it unlikely that a complete genome sequence for wheat will be available in the near future. Exploiting the conserved genome organization between wheat and rice and existing genomic resources, we have constructed in silico physical mapping software for wheat, assigning a gross physical location(s) into chromosome bins to 22,626 representative wheat gene sequences. To validate the predictions from the software we compared the predicted locations of ten ESTs to their positions experimentally determined by SNP marker analysis. Six of the sequences were correctly positioned on the map including four that demonstrated a high level of colinearity with their orthologous rice genomic region. This tool will facilitate the development of molecular markers for regions of interest and the creation of map-based cloning strategies in areas demonstrating high levels of sequence conservation and organization between wheat and rice.

Computational Biology↗
PubMed2006

Pharmacogenomics of phenolic antioxidant butylated hydroxyanisole (BHA) in the small intestine and liver of Nrf2 knockout and C57BL/6J mice.

PURPOSE: The objective of this study was to investigate the pharmacogenomics and the spatial regulation of global gene expression profiles elicited by cancer chemopreventive agent butylated hydroxyanisole (BHA) in mouse small intestine and liver as well as to identify BHA-modulated nuclear factor-E2-related factor 2 (Nrf2)-dependent genes. METHODS: C57BL/6J (+/+; wildtype) and C57BL/6J/Nrf2(-/-; knockout) mice were administered a single 200 mg/kg oral dose of BHA or only vehicle. Both small intestine and liver were collected at 3 h after treatment and total RNA was extracted. Gene expression profiles were analyzed using 45,000 Affymetrix mouse genome 430 2.0 array and GeneSpring 7.2 software. Microarray results were validated by quantitative real-time reverse transcription-PCR analyses. RESULTS: Clusters of genes that were either induced or suppressed more than two fold by BHA treatment compared with vehicle in C57BL/6J/Nrf2(-/-; knockout) and C57BL/6J Nrf2 (+/+; wildtype) mice genotypes were identified. Amongst these, in small intestine and liver, 1,490 and 493 genes respectively were identified as Nrf2-dependent and upregulated, and 1,090 and 824 genes respectively as Nrf2-dependent and downregulated. Based on their biological functions, these genes can be categorized into ubiquitination/proteolysis, apoptosis/cell cycle, electron transport, detoxification, cell growth/differentiation, transcription factors/interacting partners, kinases and phosphatases, transport, biosynthesis/metabolism, RNA/protein processing and nuclear assembly, and DNA replication genes. Phase II detoxification/antioxidant genes as well as novel molecular target genes, including putative interacting partners of Nrf2 such as nuclear corepressors and coactivators, were also identified as Nrf2-dependent genes. CONCLUSIONS: The identification of BHA-regulated and Nrf2-dependent genes not only provides potential novel insights into the gestalt biological effects of BHA on the pharmacogenomics and spatial regulation of global gene expression profiles in cancer chemoprevention, but also points to the pivotal role of Nrf2 in these biological processes.

Animals↗