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Fast algorithms for computing and displaying dose-distributions in tomogram-oriented brachy-radiotherapy.

This paper describes in detail a dose calculation algorithm tailored to the needs of tomogram-oriented brachy-radiotherapy and a general-purpose dose visualization for displaying the dose distribution as isolines (or rather interval planes). The verbal description of the algorithms is accompanied by structograms. However, the intention of the authors is to present very fast algorithms that are easy to implement and to give a ready-to-use example formulated in 68020 assembler code. Execution times are estimated theoretically by counting clock cycles and practically by measuring the execution time of sample calculations. It turns out that both the dose calculation as well as the visualization algorithm need less than 1 s when applied to a radioactive point source lying on an arbitrary 320 x 256 grid of three-dimensional space.

Algorithms

Two novel T cell epitope prediction algorithms based on MHC-binding motifs; comparison of predicted and published epitopes from Mycobacterium tuberculosis and HIV protein sequences.

We have designed two computer-based algorithms for T cell epitope prediction, OptiMer and EpiMer, which incorporate current knowledge of MHC-binding motifs. OptiMer locates amphipathic segments of protein antigens with a high density of MHC-binding motifs. EpiMer identifies peptides with a high density of MHC-binding motifs alone. These algorithms exploit the striking tendency for MHC-binding motifs to cluster within short segments of each protein. Putative epitopes predicted by these algorithms contain motifs corresponding to many different MHC alleles, and may contain both class I and class II motifs, features thought to be ideal for the peptide components of synthetic subunit vaccines. In this study, we describe the use of OptiMer and EpiMer for the prediction of putative T cell epitopes from Mycobacterium tuberculosis and human immunodeficiency virus protein antigens, and demonstrate that these two algorithms may provide sensitive and efficient means for the prediction of promiscuous T cell epitopes that may be critical to the development of vaccines against these and other pathogens.

Algorithms

A genetic algorithm to search for optimal and suboptimal RNA secondary structures.

Genetic algorithms are a search method used in solving problems by selection, recombination and mutation of tentative solutions, until the better ones are achieved. They are very efficient when the 'building block' hypothesis is effective for the solutions, which means that a better solution can be obtained by assembling short 'motifs' or 'schemata' that can be retrieved in some other worse solutions. The additive nature of the secondary structure free energy rules suggests the validity of this hypothesis, and therefore the likely power of a genetic algorithm approach to search for RNA secondary structures. We describe in detail an original genetic algorithm specific for this problem. The sharing function used to obtain differentiated solutions is also described. It results in a greater effectiveness of the algorithm in retrieving a large number of suboptimal RNA foldings besides the optimal one. RNA sequences of different length are used to test the method. The PSTV viroid sequence has been studied.

Algorithms

A comparison of methods for self-adaptation in evolutionary algorithms.

Evolutionary algorithms, including evolutionary programming and evolution strategies, have often been applied to real-valued function optimization problems. These algorithms generally operate directly on the real values to be optimized, in contrast with genetic algorithms which usually operate on a separately coded transformation of the objective variables. Evolutionary algorithms often rely on a second-level optimization of strategy parameters, tunable variables that in part determine how each parent will generate offspring. Two alternative methods for performing this second-level optimization have been proposed and are compared across a series of function optimization tasks. The results appear to favor the approach offered originally in evolution strategies, although the applicability of the findings may be limited to the case where each parameter of a parent solution is perturbed independently of all others.

Algorithms

A computer algorithm to determine the nadir and rise time in nocturnal cortisol secretion.

The nadir concentration value and the time of the circadian rise are two important characteristics of the nocturnal cortisol secretory pattern. A computer algorithm has been developed which objectively determines these parameters, supplementing the subjective evaluating methods previously used. The algorithm smooths the cortisol values and incorporates the intra-assay variability when calculating the nadir and rise. It was tested on 156 nights of cortisol data for healthy control and depressed subjects. The algorithm results closely matched the nadir and rise time subjectively determined by the investigators. With careful screening of the computer generated results, the algorithm decreases the reliance on subjective methods to determine the actual nocturnal cortisol nadir and rise time.

Adolescent

Random search algorithm (RONSC) for optimization of radiation therapy with both physical and biological end points and constraints.

A new algorithm for the optimization of 3-dimensional radiotherapy plans is presented. The RONSC algorithm (Random Optimization with Non-linear Score functions and Constraints) is based on the idea of random search in the space of feasible solutions. RONSC takes advantage of some specific properties of the dose distribution and derivable information such as dose-volume histograms and calculated estimates of tumor control and normal tissue complication probabilities. The performance of the algorithm for clinical and test cases is discussed and compared with the performance of the simulated annealing algorithm, which is also based on the idea of random search.

Algorithms

Clinical experience with antitachycardia pacing and improved detection algorithms in a new implantable cardioverter-defibrillator.

OBJECTIVES: This study was conducted to assess the effectiveness of antitachycardia pacing modes and detection algorithms in patients with a new third-generation implantable cardioverter-defibrillator. METHODS: Twenty-three of 42 consecutive patients had coronary artery disease, 14 had dilated cardiomyopathy, 2 had prior valve replacement and 3 had arrhythmogenic right ventricular dysplasia. The mean ejection fraction was 41 +/- 14%; there were 31 men (74%) and 11 women, with a mean age of 53 years. On the basis of preoperative and postoperative electrophysiologic studies, in 28 patients antitachycardia pacing was postoperatively programmed randomly as "burst" (66%) or autodecremental "ramp" (34%) stimulation with a first coupling interval of 81% of tachycardia cycle length and up to 8 sequences with 3 to 10 stimuli. RESULTS: During a follow-up interval of 6.3 +/- 2.2 months, 15 patients were treated by antitachycardia pacing for a median of 6 (range 1 to 59) hemodynamically stable ventricular tachycardias (175 +/- 12 beats/min). In 5 patients, 22 ventricular tachycardias (9%) were not terminated by antitachycardia pacing but by cardioversion. Seven (3%) of these episodes accelerated (> 50 ms) during antitachycardia pacing. Syncope did not occur during these episodes. In seven patients initial antitachycardia pacing in cases of supraventricular tachycardias delayed charging and redetection prevented inappropriate discharges. Additional detection algorithms were programmed only after inappropriate therapy. The sudden "onset" and "sustained rate duration" criteria were programmed in three patients and the cycle length "stability" criteria in six patients, respectively. After activation of these detection algorithms only two of the seven patients had further inappropriate device discharges. CONCLUSIONS: Thus, antitachycardia pacing by this implantable cardioverter-defibrillator effectively and appropriately terminated 91% of hemodynamically stable ventricular tachycardias. Inappropriate device discharges were prevented in some patients by antitachycardia pacing and additional detection algorithms.

Adult

Underdetection of ventricular tachycardia by algorithms to enhance specificity in a tiered-therapy cardioverter-defibrillator.

OBJECTIVES: The goal of this study was to determine the incidence and clinical significance of underdetection in 125 patients treated with a tiered-therapy cardioverter-defibrillator, the Medtronic PCD. BACKGROUND: Underdetection, distinct from undersensing, is a unique, potential complication of new algorithms that enhance specificity in tiered-therapy cardioverter-defibrillators. These algorithms may delay or prevent recognition of ventricular tachycardia even though electrograms are sensed accurately and RR intervals meet the programmed interval criterion. METHODS: Underdetection was defined as delay in detection > 5 s at electrophysiologic study or symptomatic delay or detection failure at follow-up of 15 +/- 8 months. RESULTS: We identified six specific mechanisms of underdetection caused by algorithms to discriminate sustained ventricular tachycardia from sinus tachycardia, atrial fibrillation, ventricular fibrillation and nonsustained ventricular tachycardia. Underdetection caused detection delays in 13 (1.9%) of 677 induced ventricular tachyarrhythmia episodes in 12 patients (9.6%). During follow-up, underdetection occurred in 7 (9.9%) of 71 patients in whom ventricular tachycardia therapies were programmed. Failure to detect ventricular tachycardia occurred in 6 (0.6%) of 988 spontaneous ventricular tachycardia episodes in four patients (5.6%); 2 episodes required external cardioversion. After defibrillator reprogramming, underdetection did not occur. CONCLUSIONS: Algorithms to enhance specificity cause underdetection of ventricular tachycardia in a significant minority of patients with tiered-therapy cardioverter-defibrillators. Optimal programming can minimize underdetection.

Algorithms

Searching protein sequence libraries: comparison of the sensitivity and selectivity of the Smith-Waterman and FASTA algorithms.

The sensitivity and selectivity of the FASTA and the Smith-Waterman protein sequence comparison algorithms were evaluated using the superfamily classification provided in the National Biomedical Research Foundation/Protein Identification Resource (PIR) protein sequence database. Sequences from each of the 34 superfamilies in the PIR database with 20 or more members were compared against the protein sequence database. The similarity scores of the related and unrelated sequences were determined using either the FASTA program or the Smith-Waterman local similarity algorithm. These two sets of similarity scores were used to evaluate the ability of the two comparison algorithms to identify distantly related protein sequences. The FASTA program using the ktup = 2 sensitivity setting performed as well as the Smith-Waterman algorithm for 19 of the 34 superfamilies. Increasing the sensitivity by setting ktup = 1 allowed FASTA to perform as well as Smith-Waterman on an additional 7 superfamilies. The rigorous Smith-Waterman method performed better than FASTA with ktup = 1 on 8 superfamilies, including the globins, immunoglobulin variable regions, calmodulins, and plastocyanins. Several strategies for improving the sensitivity of FASTA were examined. The greatest improvement in sensitivity was achieved by optimizing a band around the best initial region found for every library sequence. For every superfamily except the globins and immunoglobulin variable regions, this strategy was as sensitive as a full Smith-Waterman. For some sequences, additional sensitivity was achieved by including conserved but nonidentical residues in the lookup table used to identify the initial region.

Algorithms

Separation of fetal and maternal ECG complexes from a mixed signal using an algorithm based on linear regression.

Fetal scalp ECG and Doppler ultrasound are the two methods universally used to derive the fetal heart rate (FHR) for cardiotocography. Other fetal signal sources have not been used successfully because of the complexity of the signal and the need for an additional maternal ECG input. In this paper, we present an algorithm for separating the fetal and maternal ECG signals obtained from intrauterine electrodes during labour. The algorithm detects all occurrences of ECG complexes and uses linear regression functions to compare each complex with a set templates. Sets of templates are identified as either maternal or fetal in origin and two signals are output for heart rate measurement. The outputs are also processed to eliminate artefacts that may occur when the maternal and fetal complexes are coincident. The algorithm processes 10 seconds of data at a time (in about 200 ms on a standard PC) while a further 10 s of data is being acquired. It has the advantage that no extra input is required, such as maternal ECG obtained from chest leads, and only assumes that two different populations of complexes of two different shapes are present in the input signal. The algorithm could also be used for the separation of fetal and maternal signals obtained from abdominal electrodes.

Algorithms

Phosphorescence lifetime analysis with a quadratic programming algorithm for determining quencher distributions in heterogeneous systems.

A new method for analysis of phosphorescence lifetime distributions in heterogeneous systems has been developed. This method is based on decomposition of the data vector to a linearly independent set of exponentials and uses quadratic programming principles for x2 minimization. Solution of the resulting algorithm requires a finite number of calculations (it is not iterative) and is computationally fast and robust. The algorithm has been tested on various simulated decays and for analysis of phosphorescence measurements of experimental systems with descrete distributions of lifetimes. Critical analysis of the effect of signal-to-noise on the resolving capability of the algorithm is presented. This technique is recommended for resolution of the distributions of quencher concentration in heterogeneous samples, of which oxygen distributions in tissue is an important example. Phosphors of practical importance for biological oxygen measurements: Pd-meso-tetra (4-carboxyphenyl) porphyrin (PdTCPP) and Pd-meso-porphyrin (PdMP) have been used to provide experimental test of the algorithm.

Algorithms

Nonparametric comparison of entire ROC curves for computerized ECG left ventricular hypertrophy algorithms using data from the Framingham Heart Study.

A computer program may be capable of several different statements for left ventricular hypertrophy (eg, possible LVH, probable LVH, consistent with LVH), but such statements resulting from discretized levels of sensitivity/specificity would represent only isolated points on a receiver-operating characteristic (ROC) curve, which is a plot of all levels of sensitivity versus specificity. Even if two algorithms use the same discrete scales, their performances may not readily be compared. The authors present a comparison methodology for ROC curves using ROC area as a nonparametric measure of the ability of the algorithm to separate the two populations; the ROC area ranges from 0.5 (no ability) to 1.0 (perfect separation) and is unbiased if the normal versus abnormal populations have no common values for the measurement. The methodology compares the performance of ECG algorithms on the same population of cases by testing for significant differences of ROC areas and incorporating correlation of the algorithms in a nonparametric way. To illustrate this methodology, they use ECG and echocardiographic data from the Framingham Heart Study.

Algorithms

An algorithmic approach to diagnosis of hypoglycemia.

An algorithm has been devised to facilitate the diagnostic approach to the causes of hypoglycemia. This systematic approach enables the physician to reach the final diagnosis in a logical way without subjecting the child to unnecessary and possibly hazardous investigations. The algorithm is based on the following measurements as required by each patient: concentrations of blood glucose, lactate, ketone bodies, and glucose-regulating hormones. These measurements are performed with the patient in the fasting state and after loading tests (glycerol and galactose) as needed. If indicated, an enzymatic test is performed to establish the final diagnosis. Eighteen children aged 1 month to 7 years who had persistent or recurrent hypoglycemia have been examined according to this algorithm. The correct diagnosis was arrived at in 17 patients. The diagnosis was not reached in one neonate who had glucose-6-phosphatase deficiency and initially did not have lactic acidosis; once lactic acidosis developed, his illness fitted perfectly into the algorithm.

Algorithms

Screening and managing abdominal aortic aneurysms at the Ochsner Clinic: suggested algorithm and method of derivation. Department of Surgery and Ochsner Clinic Quality Assurance Committee.

An algorithm for screening and management of abdominal aortic aneurysms was developed at the Ochsner Medical Institutions to address the considerable variation identified in clinical practice. A consensus panel of physicians whose opinions differed regarding the management of abdominal aortic aneurysms was convened to develop the algorithm. Based on a literature review and clinical experience, the panel established criteria to determine how frequently and by which methodologies patients with abdominal aortic aneurysms should be followed and when a referral to a vascular surgeon is appropriate. The algorithm developed by the consensus panel method was used to establish practice guidelines that are flexible enough to address individual patient needs yet structured enough to eliminate inappropriate care. Data are being collected and analyzed in real time to determine whether elements of the algorithm should be revised.

Aftercare

Developing a clinical algorithm for early management of cervical spine injury in child trauma victims.

To define a subset of injured children for whom emergency cervical spine radiography may be unnecessary, we performed a retrospective chart and radiologic review. Two entry methods were used: All injured children, from birth through 16 years, who had received cervical spine radiographs at The Children's Memorial Hospital from September 1983, to September 1984, were included. All patients from birth to 16 years with proven or suspected cases of cervical spine injury who had received cervical spine radiographs and who had been treated at either the Children's Memorial Hospital or the Northwestern University Spine Trauma Unit during period 1974 to 1984 also were included. Each child's chart was reviewed, and 84 clinical variables were recorded. All radiographs were reviewed by a pediatric neuroradiologist. Of 206 children studied, 59 had cervical spine injuries. A clinical algorithm was derived using the following eight variables: neck pain; neck tenderness; limitation of neck mobility; history of trauma to the neck; and abnormalities of reflexes, strength, sensation, or mental status. The following decision rule was selected: Positive findings in any of these eight variables mandates cervical spine radiography. This algorithm correctly identified 58 of 59 children with cervical spine injury, yielding a sensitivity of 98% and specificity of 54%. Cervical spine radiographs could have been avoided in 79 children (38% of the entire sample). This algorithm performed better than did models derived from logistic regression analysis of the same data. Validation trials are required prior to the implementation of this or other clinical decision algorithms in practice.

Accidents

Development of a decision algorithm for a semiautomatic defibrillator.

A decision algorithm was developed for a semiautomatic defibrillator. The function of the algorithm is to evaluate the ECG of a patient and determine whether a defibrillation shock should be delivered. The development process included establishment of defibrillation criteria, creation of ECG databases, algorithm design, development of test protocols, and clinical testing. The result was an algorithm with sensitivity and specificity sufficiently accurate to allow a defibrillation shock to be delivered safely outside the hospital.

Algorithms

Resuscitation algorithm for management of acute emergencies.

Assuming that unrecognized or inadequately corrected hypovolemia results in higher mortality and morbidity rates, we developed a systematic approach to resuscitation that would: 1) identify criteria to aid in the recognition of hypovolemia and ensure the expeditious correction of this defect without interfering with diagnostic workup and management; 2) define criteria to prevent fluid overload which may jeopardize the patient's course, and 3) express these criteria in an explicit, systematic, patient care algorithm, ie, protocol, useful to both the resident and the practicing physician. We are now conducting prospective clinical trials with one service using the algorithm and the others acting as the control group. Preliminary results comparing patient outcomes suggest that the algorithm improves patient care by shortening resuscitation time and results in fewer hospital days, intensive care unit days, febrile days, and days on mechanical ventilation as well as reduced mortality. The algorithm provides a systematic plan to organize patient care so that the most urgently needed procedures are not delayed or overlooked.

Algorithms

New joint prediction algorithm (Q7-JASEP) improves the prediction of protein secondary structure.

The classical problem of secondary structure prediction is approached by a new joint algorithm (Q7-JASEP) that combines the best aspects of six different methods. The algorithm includes the statistical methods of Chou-Fasman, Nagano, and Burgess-Ponnuswamy-Scheraga, the homology method of Nishikawa, the information theory method of Garnier-Osgurthope-Robson, and the artificial neural network approach of Qian-Sejnowski. Steps in the algorithm are (i) optimizing each individual method with respect to its correlation coefficient (Q7) for assigning a structural type from the predictive score of the method, (ii) weighting each method, (iii) combining the scores from different methods, and (iv) comparing the scores for alpha-helix, beta-strand, and coil conformational states to assign the secondary structure at each residue position. The present application to 45 globular proteins demonstrates good predictive power in cross-validation testing (with average correlation coefficients per test protein of Q7, alpha = 0.41, Q7, beta = 0.47, Q7,c = 0.41 for alpha-helix, beta-strand, and coil conformations). By the criterion of correlation coefficient (Q7) for each type of secondary structure, Q7-JASEP performs better than any of the component methods. When all protein classes are included for training and testing (by cross-validation), the results here equal the best in the literature, by the Q7 criterion. More generally, the basic algorithm can be applied to any protein class and to any type of structure/sequence or function/sequence correlation for which multiple predictive methods exist.

Algorithms