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Large efficiency improvements in BEAMnrc using directional bremsstrahlung splitting.

The introduction into the BEAMnrc code of a new variance reduction technique, called directional bremsstrahlung splitting (DBS), is described. DBS uses a combination of interaction splitting for bremsstrahlung, annihilation, Compton scattering, pair production and photoabsorption, and Russian Roulette to achieve a much better efficiency of photon beam treatment head simulations compared to the splitting techniques already available in BEAMnrc (selective bremsstrahlung splitting, SBS, and uniform bremsstrahlung splitting, UBS). In a simulated 6 MV photon beam (10 x 10 cm2 field) photon fluence efficiency in the beam using DBS is over 8 times higher than with optimized SBS and over 20 times higher than with UBS, with a similar improvement in electron fluence efficiency in the beam. Total dose efficiency in a central-axis depth-dose curve improves by a factor of 6.4 over SBS at all depths in the phantom. The performance of DBS depends on the details of the accelerator being simulated. At higher energies, the relative improvement in efficiency due to DBS decreases somewhat, but is still a factor of 3.5 improvement over SBS for total dose efficiency using DBS in a simulated 18 MV photon beam. Increasing the field size of the simulated 6 MV beam to 40 x 40 cm2 (broad beam) causes the relative efficiency improvement of DBS to decrease by a factor of approximately 1.7 but is still up to 7 times more efficient than with SBS.

Algorithms↗

Feature selection using Haar wavelet power spectrum.

BACKGROUND: Feature selection is an approach to overcome the 'curse of dimensionality' in complex researches like disease classification using microarrays. Statistical methods are utilized more in this domain. Most of them do not fit for a wide range of datasets. The transform oriented signal processing domains are not probed much when other fields like image and video processing utilize them well. Wavelets, one of such techniques, have the potential to be utilized in feature selection method. The aim of this paper is to assess the capability of Haar wavelet power spectrum in the problem of clustering and gene selection based on expression data in the context of disease classification and to propose a method based on Haar wavelet power spectrum. RESULTS: Haar wavelet power spectra of genes were analysed and it was observed to be different in different diagnostic categories. This difference in trend and magnitude of the spectrum may be utilized in gene selection. Most of the genes selected by earlier complex methods were selected by the very simple present method. Each earlier works proved only few genes are quite enough to approach the classification problem 1. Hence the present method may be tried in conjunction with other classification methods. The technique was applied without removing the noise in data to validate the robustness of the method against the noise or outliers in the data. No special software or complex implementation is needed. The qualities of the genes selected by the present method were analysed through their gene expression data. Most of them were observed to be related to solve the classification issue since they were dominant in the diagnostic category of the dataset for which they were selected as features. CONCLUSION: In the present paper, the problem of feature selection of microarray gene expression data was considered. We analyzed the wavelet power spectrum of genes and proposed a clustering and feature selection method useful for classification based on Haar wavelet power spectrum. Application of this technique in this area is novel, simple, and faster than other methods, fit for a wide range of data types. The results are encouraging and throw light into the possibility of using this technique for problem domains like disease classification, gene network identification and personalized drug design.

Artificial Intelligence↗

A novel approach toward development of a rapid blood test for breast cancer.

Mammography remains the diagnostic test of choice for breast cancer, but 20% of cancers still go undetected. Many serum biomarkers have been reported for breast cancer but none have proven to represent effective diagnostic strategies. ProteinChip mass spectrometry is an innovative technology that searches the proteome for differentially expressed proteins, allowing for the creation of a panel or profile of biomarkers. The objective of this study was to construct unique cancer-associated serum profiles that, combined with a classification algorithm, would enhance the detection of breast cancer Pretreatment serum samples from 134 female patients (45 with cancer, 42 with benign disease, 47 normal) were procured prospectively following institutional review board-approved protocols. Proteins were denatured, applied onto ProteinChip affinity surfaces, and subjected to surface enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry. The SELDI output was analyzed using Biomarker Pattern Software to develop a classification tree based on group-specific protein profiles. The cross-validation analysis of cancer versus normal revealed sensitivity and specificity rates of 80% and 79%, and for cancer versus benign disease, 78% and 83%, respectively. When 2 different chip surfaces were combined the sensitivity and specificity increased to 90% and 93%, respectively. The sensitivity and specificity of this technique are comparable to those of mammography and, if confirmed in a larger study, this technique could provide the means toward development of a simple blood test to aid in the early detection of breast cancer. The combination of SELDI ProteinChip mass spectrometry and a classification- and regression-tree algorithm has the potential to use serum protein expression profiles for detection and diagnosis of breast cancer.

Adult↗

Improvement of algorithm for quantification of regional myocardial blood flow using 15O-water with PET.

UNLABELLED: (15)O-Water and dynamic PET allow noninvasive quantification of myocardial blood flow (MBF). However, complicated image analyzing procedures are required, which may limit the practicality of this approach. We have designed a new practical algorithm, which allows stable, rapid, and automated quantification of regional MBF (rMBF) using (15)O-water PET. We designed an algorithm for setting the 3-dimensional (3D) region of interest (ROI) of the whole myocardium semiautomatically. Subsequently, a uniform input function was calculated for each subject using a time-activity curve in the 3D whole myocardial ROI. The uniform input function allows the mathematically simple and robust algorithm to estimate rMBF. METHODS: Thirty-six volunteers were used in the static (15)O-CO and dynamic (15)O-water PET studies. To evaluate the reproducibility of the estimates, a repeated (15)O-water scan was obtained under resting condition. In addition, to evaluate the stability of the new algorithm in the hyperemic state, a (15)O-water scan was obtained with adenosine triphosphate. This algorithm includes a procedure for positioning a 3D ROI of the whole myocardium from 3D images and dividing it into 16 segments. Subsequently, the uniform input function was calculated using time-activity curves in the whole myocardial ROI and in the LV ROI. The uniform input function allowed this simple and robust algorithm to estimate the rMBF, perfusable tissue fraction (PTF), and spillover fraction (Va) according to a single tissue compartment model. These estimates were compared with those calculated using the original method. A simulation study was performed to compare the effects of errors in PTF or Va on the MBF using the 2 methods. RESULTS: The average operating time for positioning a whole myocardial ROI and 16 regional myocardial ROIs was <5 min. The new method yielded less deviation in rMBF (0.876 +/- 0.177 mL/min/g, coefficient of variation [CV] = 20.2%, n = 576) than those with the traditional method (0.898 +/- 0.271 mL/min/g, CV = 30.1%, n = 576) (P < 0.01). In the hyperemic state, the new method yielded less deviation in rMBF (3.890 +/- 1.250 mL/min/g, CV = 32.1%) than those with the traditional method (3.962 +/- 1.762 mL/min/g, CV = 44.4%) (P < 0.05). This method yielded significantly higher reproducibility of rMBF (r = 0.806, n = 576) than the original method (r = 0.756, n = 576) (P < 0.05). Our new method yielded a better correlation in the repeated measurement values of rMBF and less variability among the regions in the myocardium than with the original theory of the (15)O-water technique. The simulation study demonstrated fewer effects of error in the PTF or Va on the MBF value with the new method. CONCLUSION: We have developed a technique for an automated, simplified, and stable algorithm to quantify rMBF. This software is considered to be practical for clinical use in myocardial PET studies using (15)O-water with a high reproducibility and a short processing time.

Algorithms↗

Nutrient analysis methodology: a review of the DINE developmental literature.

In 1986, a collaborative effort among professional associations resulted in the publication of Worksite Nutrition: A Decision Maker's Guide (The American Diabetic Association, 1986). The booklet describes nutrient analysis methodology as a good "promotional gimmick". The development of DINE was an effort to move nutrient analysis from the gimmick level to a viable educational component level. A few examples of the innovative effects of this methodology are (1) individuals' using their own data can learn energy balance by monitoring their food intake and physical activity, (2) individuals can learn the Dietary Goals for the United States (U. S. Senate Select Subcommittee on Nutrition and Human Needs, 1977) and are able graphically to compare how their diet approximates or is different from these goals, and (3) individuals can also learn, from verifications of their own food records, which of their food selections were high in calories, total fat, saturated fat, and cholesterol, and low in complex carbohydrates and dietary fiber. Alternative healthful food choices are identified and the effects of reducing or increasing portion sizes is described. The DINE development team has been working for the past eight years to decrease nutrient analysis variability so that the procedure can be used as an effective independent measure to improve nutritional behavior. Research has been conducted related to database validity and reliability. Formative and process evaluations have been conducted to improve interactive aspects of the software and related manuals and books. DINE procedures have been modified for ease of use, in general, and specifically for elementary students and university students.

Computer-Assisted Instruction↗

Validity of the Pedar Mobile system for vertical force measurement during a seven-hour period.

Objective measurement of weight bearing during a long-term period can give insight into the postoperative loading of the lower extremity of orthopedic patients to avoid complications. This study investigated the validity of vertical ground reaction force measurements during a long-term period using the Pedar Mobile insole pressure system, by comparing it with a Kistler force platform. In addition, the validity of a new sensor drift correction algorithm to correct for offset drift in the Pedar signal was evaluated. Ground reaction force data were collected during dynamic and static conditions from five healthy subjects every hour for 7 h. A mean offset drift of 14.6% was found after 7 h. After applying the drift correction algorithm the Pedar system showed a high accuracy for the second peak in the ground reaction force-time curve (1.1 to 3.4% difference, p>0.05) and step duration (-2.0 to 4.4% difference, p>0.05). Less accuracy was found for the first peak in the ground reaction force-time curve (5.2 to 12.0% difference; p<0.05 for the first 3 h, p>0.05 for the last 4 h) and, consequently, in the vertical force impulse (5.5 to 11.0% difference, p>0.05). The Pedar Mobile system appeared to be a valid instrument to measure the vertical force during a long-term period when using the drift correction program described in this study.

Adult↗

[The use of a Russian software-hardware package for the quantitative analysis of coronary angiograms].

The software and hardware complex developed by the Cardiology Research Center, Russian Academy of Medical Sciences, jointly with the Technomash Research Production Association on the basis of a IBM 386DX personal computer equipped with a VS-100 video controller and a DS P31 VS signal processor board. Testing has indicated that it provides a qualitative image and a quantitative analysis both of phantoms and real images of coronarograms, but more accurately in the analysis of the image obtained from a film projector. Valid results are yielded when lenses more than 1 mm in diameter are used. Clinical tests have shown that the software and hardware complex may yield a rather qualitative image and calculate the required diameter of a vessel, virtually without prolonging the time of intervention, which is particularly important while making intervention procedures and implementing research programmes.

Analog-Digital Conversion↗

Combined use of oligonucleotide and tissue microarrays identifies cancer/testis antigens as biomarkers in lung carcinoma.

High density oligonucleotide microarrays (OMAs) have been used recently to profile gene expression in lung carcinoma tissue homogenates. The length of the lists of potentially interesting genes generated by these studies is daunting, and biological and clinical relevance of these lists remains to be validated. Moreover, specific identification of individual biomarkers that might be used for early detection and surveillance has not been the objective of these early studies. We have developed a schema for combining the data derived from the OMA analysis of a few lung cancer cell lines with immunohistochemical testing of tissue microarrays to rapidly identify biomarkers of potential clinical relevance. Initially, we profiled gene expression in lung tumor cell lines using the Affymetrix HG-U95Av2 OMA. RNA from 2 non-small cell lung cancer (NSCLC) cell lines (A549 and H647) and 2 small cell lung cancer (SCLC) cell lines (SHP-77 and UMC-19) were tested. Cells from 1 histologically and cytogenetically normal bronchial epithelial primary culture from a volunteer who had never smoked and 10 samples of histologically unremarkable lung tissue from resection specimens served as normalization controls. Array results were analyzed with Gene Spring software. Results were confirmed by reverse transcription-PCR in an expanded number of cell lines. We then validated the cell line data by immunohistochemical testing for protein using a tissue microarray containing 187 NSCLC clinical samples. Of the 20 most highly expressed genes in the tumor lines, 6 were members of the cancer/testis antigen (CTAG) gene group including 5 MAGE-A subfamily members and NY-ESO-1. SCLC lines strongly expressed all of the MAGE-A genes as well as NY-ESO-1, whereas NSCLC lines expressed a subset of MAGE-A genes at a lower level of intensity and failed to express NY-ESO-1. Reverse transcription-PCR of an extended series of 25 lung cancer cell lines including 13 SCLC, 9 NSCLC, and 3 mesothelioma lines indicated that MAGE-A10 and NY-ESO-1 were expressed only by SCLC, and that MAGE-A1, 3, 6, 12, and 4b were expressed by both SCLC and NSCLC. By immunohistochemistry using the monoclonal antibody 6C1 that recognizes several MAGE-A gene subfamily members, 44% of NSCLC clearly expressed MAGE-A proteins in cytoplasm and/or nucleus. Expression of MAGE-A genes did not correlate with survival but did correlate with histological classification with squamous carcinomas more frequently MAGE-A positive than other NSCLC types (P < 0.00002). We conclude that expression of CTAG gene products, whereas apparently not of prognostic importance, may be useful for early detection and surveillance because of a high level of specificity for central airway squamous and small cell carcinomas.

Antigens, Neoplasm↗

Reliability of linear measurements on a virtual bilateral cleft lip and palate model.

OBJECTIVE: To assess the reliability and validity of measurements performed on three-dimensional virtual models of neonatal bilateral cleft lip and palate patients, compared with measurements performed on plaster cast models. MATERIALS AND METHODS: Ten high-quality plaster cast models of bilateral cleft lip and palate patients were scanned with an LDI-scanner to obtain a three-dimensional virtual model. Linear measurements were performed on the plaster cast models using a digital caliper and also on the three-dimensional virtual model using Viscam RP version 2.1 software. The measurements were performed by two observers on two occasions. RESULTS: Intraclass correlations ranging from .81 to .96 were found for all measurements except the measurement between the constructed reference point pr and reference point i (intraclass correlation = .40). A post hoc procedure in which top-view screen prints of the three-dimensional virtual model were used to perform the measurement between reference points pr and i demonstrated an intraclass coefficient of .90. CONCLUSIONS: Three-dimensional virtual models obtained by laser scanning neonatal cast models of bilateral cleft lip and palate patients can be used reliably and validly to perform linear measurements between existing reference points on the surface of the model using Viscam RP version 2.1 software. Measurements between reference points constructed outside the surface of the model cannot be validly performed on the three-dimensional virtual model with the software used in this study. For these measurements, top-view screen prints of the three-dimensional virtual model can be used.

Cephalometry↗

Automated storage and retrieval of thin-section CT images to assist diagnosis: system description and preliminary assessment.

A software system and database for computer-aided diagnosis with thin-section computed tomographic (CT) images of the chest was designed and implemented. When presented with an unknown query image, the system uses pattern recognition to retrieve visually similar images with known diagnoses from the database. A preliminary validation trial was conducted with 11 volunteers who were asked to select the best diagnosis for a series of test images, with and without software assistance. The percentage of correct answers increased from 29% to 62% with computer assistance. This finding suggests that this system may be useful for computer-assisted diagnosis.

Databases, Factual↗

Evaluation of peristalsis in multiple segments of the guinea-pig isolated small intestine: optimisation of tissue use by refined in vitro methodology.

Peristalsis is the aboral movement by which the intestine propels its contents. Since pharmacological research requires an experimental model with which drug-induced modifications of peristalsis can be reliably quantified, we set out to develop and validate an in vitro method for studying peristalsis in multiple gut segments. In our arrangement, up to four 10cm segments isolated from the guinea-pig jejunum and ileum can be set up in parallel and their lumens perfused. Peristalsis was elicited by pressure-evoked wall distension, and the peristalsis-induced changes in the intraluminal pressure were evaluated with software that determined the peristaltic pressure threshold, the frequency, maximal acceleration and amplitude of the peristaltic waves, and the residual baseline pressure. Validation experiments showed that the peristalsis parameters at baseline and after modification by morphine (0.01-10microM) did not differ between segments from the jejunum and ileum, or between segments examined in a consecutive manner. In conclusion, our work succeeded in optimising the use of the guinea-pig jejunum and ileum for multiple recordings of peristalsis in vitro, and in refining the recording and evaluation of peristaltic motility. This system promises to be particularly useful in the pharmacological screening and testing of drugs which modify peristalsis.

Animal Use Alternatives↗

Development, characterization, and validation of a sensitive primate-specific quantification assay for forensic analysis.

Accurate human-specific DNA quantification is essential for forensic casework analysis. In this work, we describe a microplate-based quantification assay that utilizes the PCR amplification of human-specific TH01 primers. This method enables the reliable quantification of human DNA samples from 0.2 to 40 ng, even in mixtures with nonhuman DNA. Analysis of samples can be semi-automated using 96-well microplates and a spreadsheet-based concentration calculator for high-throughput demands. We have used this quantification method with more than 15,000 forensic samples.

Animals↗

Suregene, a scalable system for automated term disambiguation of gene and protein names.

Researchers, hindered by a lack of standard gene and protein-naming conventions, endure long, sometimes fruitless, literature searches. A system that is able to automatically assign gene names to their LocusLink ID (LLID) in previously unseen MEDLINE abstracts is described. The system is based on supervised learning and builds a model for each LLID. The training sets for all LLIDs are extracted automatically from MEDLINE references in the LocusLink and SwissProt databases. A validation was done of the performance for all 20,546 human genes with LLIDs. Of these, 7344 produced good quality models (F-measure >0.7, nearly 60% of which were >0.9) and 13,202 did not, mainly due to insufficient numbers of known document references. A hand validation of MEDLINE documents for a set of 66 genes agreed well with the system's internal accuracy assessment. It is concluded that it is possible to achieve high quality gene disambiguation using scaleable automated techniques.

Algorithms↗

Assessing construct reliability through open-ended survey response analysis.

Online surveys often include quantitative attention checks, but inattentive participants might also be identified using their qualitative responses. We used the software Turnitin&#x2122; to assess the originality of open-ended responses in four mixed-method surveys that included validated multi-item rating scales (i.e., constructs). Across surveys, 18-35% of participants (n =&#x2009; 3,771) were identified as having copied responses from online sources. We assessed indicator reliability and internal consistency reliability and found that both were lower for participants identified as using copied text versus those who wrote more original responses. Those who provided more original responses also provided more consistent responses to the validated scales, suggesting that these participants were more attentive. We conclude that this process can be used to screen open-ended responses from online surveys. We encourage future research to replicate this screening process using similar tools, investigate strategies to reduce copying behaviour, and explore the motivation of participants to search for information online, including what sources they find compelling.

Adult↗

Radiographic measurements in developmental dysplasia of the hip: reliability and validity of a digitizing program.

A fundamental goal of research in developmental dysplasia of the hip (DDH) has been the identification of radiographic quantitative factors predictive of long-term outcome. The rapid development of digital imaging modalities opens the possibility for more systematic, automated measurement of radiographs. The authors have developed a software program for the study of DDH that integrates a user interface to select, store, and edit prescribed landmarks on digital radiographs. These points are used to construct and display reference lines analogous to those commonly drawn on physical films. Measurements are stored as a printable text file and as a data record. The results of this study demonstrated very good intrarater and interrater reliability coefficients and intermethod validity coefficients for the digitizing program. If this program is added to a software reporting system, measurements can be done on a real-time basis and can be included in the patient's medical record.

Body Weights and Measures↗

Use of a virtual reality, real-time, simulation model for the training of urologists in transurethral resection of the prostate.

OBJECTIVE: There is a growing need to develop surgical skills outside the operating theatre. In this study we describe the development of a virtual reality training system for practising transurethral resection of the prostate (TURP). MATERIAL AND METHODS: A face validity study was performed using a questionnaire sent to 28 experienced urologists to find out the ideal characteristics of a simulated TURP. Based on the comments a simulator was constructed and a content validity study was then performed in which nine experienced urologists tested the simulator and answered a second questionnaire. After corrections to the simulator, a basic construct validity test was performed. RESULTS: We have developed a computer-based simulator based on the requirements listed by 17 urologists. It consists of a modified resectoscope connected to a haptic device and supported by a frame. The software provides a virtual view of the prostatic lumen and resectoscope tip, a haptic rendering that generates force feedback and a simulation module that computes the information from the haptic device, resectoscope fluid tap and handle and the foot pedals. The software also simulates bleeding, absorption of irrigation fluid and pressure gradients. Variables are measured and presented in a result file after each "operation". Nine experienced urologists performed a content validity study and changes were made accordingly. A basic construct validity test performed by seven inexperienced students showed a significant improvement in performance after they each performed six simulated procedures. CONCLUSION: We have developed a simulator that may be used to practise TURP and which meets most of the demands raised in a face validity study. A basic construct validity test showed improved performance after repeated practice in the simulated environment.

Computer Simulation↗

BrainSuite: an automated cortical surface identification tool.

We describe a new magnetic resonance (MR) image analysis tool that produces cortical surface representations with spherical topology from MR images of the human brain. The tool provides a sequence of low-level operations in a single package that can produce accurate brain segmentations in clinical time. The tools include skull and scalp removal, image nonuniformity compensation, voxel-based tissue classification, topological correction, rendering, and editing functions. The collection of tools is designed to require minimal user interaction to produce cortical representations. In this paper we describe the theory of each stage of the cortical surface identification process. We then present classification validation results using real and phantom data. We also present a study of interoperator variability.

Algorithms↗

Validity and reliability of dual-energy X-ray absorptiometry for the assessment of abdominal adiposity.

A number of methods exist for the estimation of abdominal obesity, ranging from waist-to-hip ratio to computed tomography (CT). Although dual-energy X-ray absorptiometry (DXA) was originally used to measure bone density and total body composition, recent improvements in software allow it to determine abdominal fat mass. Sixty-five men and women aged 18-72 yr participated in a series of studies to examine the validity and reliability of the DXA to accurately measure abdominal fat. Total body fat and abdominal regional fat were measured by DXA using a Lunar DPX-IQ. Multislice CT scans were performed between L1 and L4 vertebral bodies (region of interest) using a Picker PQ5000 CT scanner, and volumetric analyses were carried out on a Voxel Q workstation. Both abdominal total tissue mass (P = 0.02) and abdominal fat mass (P < 0.0001) in the L1-L4 region of interest were significantly lower as measured by DXA compared with multislice CT. However, Bland-Altman analysis demonstrated good concordance between DXA and CT for abdominal total tissue mass (i.e., limits of agreement = -1.56-2.54 kg) and fat mass (i.e., limits of agreement = -0.40-1.94 kg). DXA also showed excellent reliability among three different operators to determine total, fat, and lean body mass in the L1-L4 region of interest (intraclass correlations, R = 0.94, 0.97, and 0.89, respectively). In conclusion, the DXA L1-L4 region of interest compared with CT proved to be both reliable and accurate method to determine abdominal obesity.

Abdomen↗