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Adverse drug reactions causing hospital admission in an elderly population: experience with a decision algorithm.

An adverse drug reaction (ADR) decision algorithm was used in the review of 100 consecutive hospital admissions of elderly patients cared for by family physicians. The algorithm is a valid methodologic alternative to using pharmacological experts for verification of an ADR. In this study, the algorithm was easily applied by family physicians, and the results were similar to those reported by expert clinical pharmacologists. Nine percent of our elderly patients' hospital admissions were caused by ADRs that were due to usual doses of medications commonly prescribed for elderly patients. Average age of patients and number of medications were similar for persons with and without ADRs. The algorithm can be useful to physicians investigating ADRs for clinical research, physician education, quality assurance, and improved patient care.

Aged

Quantitative structure-activity relationships. V. A simple simple algorithm for Fujita-Ban and Free-Wilson analyses.

For quantitative structure-activity analyses a simple algorithm for the calculation of de novo group contributions by Fujita-Ban analysis is given. This algorithm corresponds in all details to a computer program for linear multiple regression analysis. However, the transformation of the original matrix to the normal equations matrix is easily achieved without a computer. The normal equations matrix can be solved with a modern desk calculator being equipped with a matrix ROM. Two examples are given to explain the algorithm; the calculation of all important statistical parameters is illustrated. As for quantitative structure-activity analyses this algorithm can be applied as well for the calculation of other additive parameters, such as pi from log P-values or omega from equilibrium constants.

Electronic Data Processing

Streamlining Diagnosis of Bardet-Biedl Syndrome: New Diagnostic Algorithm With Updated Criteria.

Considerable advances have been made in our understanding of Bardet-Biedl syndrome (BBS), particularly in its core clinical features and molecular genetics, warranting an update to the existing diagnostic criteria framework. Using a rigorous, evidence-based, and consensus-driven process, a multidisciplinary group of international experts and patient-led organizations developed an updated diagnostic algorithm. This algorithm provides practical, updated guidance for clinicians, including a pathway for accurately incorporating genetic findings into the diagnostic process. We recommend that a clinical diagnosis requires either 4 major criteria or 3 major and 2 minor criteria. Revised major criteria are retinal dystrophy, obesity (or overweight in individuals <&#x2009;2&#x2009;years old), congenital anomalies of the kidney and urinary tract or chronic kidney disease, hypogonadism/genital anomalies, neurodevelopmental/neurocognitive manifestations, and postaxial polydactyly. The diagnosis can also be established with a positive genetic testing result in patients exhibiting &#x2265;&#x2009;1 major criterion, provided that genetic findings should be interpreted in the context of the patient's clinical presentation, age, family history, and overlap with related ciliopathies. These consensus criteria offer a simple algorithm incorporating updated definitions for major and minor criteria and genetic testing to support a timely and accurate diagnosis of patients with BBS, inform genetic counseling, and potentially facilitate earlier access to treatment. Trial Registration: CRIBBS Registry; ClinicalTrials.gov: NCT02329210.

Humans

Generating three-dimensional genome structures with a variational quantum algorithm.

Chromosome conformation capture experiments have revealed the underlying spatial interactions that govern three-dimensional (3D) genome organization and topology. Detecting 3D contacts between genomic loci considerably enhances our understanding of fundamental regulatory processes. Modeling 3D structures from experimental contact matrices can further contextualize the relationship between 3D genome organization and regulation. While classical algorithms have been successful in reconstructing genomic conformations, we investigate the prospect of quantum computation to aid in modeling the conformational space. In this context, we propose a novel variational quantum algorithm (VQA) to model the distribution of 3D genomic structures from experimental contact data. Through rigorous evaluations, we demonstrate the capability of our algorithm to sample ensembles of viable 3D conformations that agree well with experimental and simulated contact data. Furthermore, we extend our methodology to model the conformational space of a single cell or a population of cells. In the advent of sufficient quantum utility, the insights gained from this study can serve as a foundation for investigating high-resolution, large-scale ensembles of genomic conformations through generative VQAs.

Algorithms

Effects of limited input distance constraints upon the distance geometry algorithm.

In this paper we examine the distance geometry (DG) algorithm in the form used to determine the structure of proteins. We focus on three aspects of the algorithm: bound smoothing with the triangle inequality, the random selection of distances within the bounds, and the number of distances needed to specify a structure. Computational experiments are performed using simulated and real data for basic pancreatic trypsin inhibitor (BPTI) from nmr and crystallographic measurements. We find that the upper bounds determined by bound smoothing to be a linear function of the true crystal distance. A simple model that describes the results obtained with randomly selected trial distances is proposed. Using this representation of the trial distances, we show that BPTI DG structures are more compact than the true crystal structure. We also show that the DG-generated structures no longer resemble test structures when the number of these interresidue distance constraints is less than the number of degrees of freedom of the protein backbone. While the actual model will be sensitive the way distances are chosen, our conclusions are likely to apply to other versions of the DG algorithm.

Algorithms

Statistical evaluation of cell kinetic data from DNA flow cytometry (FCM) by the EM algorithm.

Flow cytometric DNA measurements yield the amount of DNA for each of a large number of cells. A DNA histogram normally consists of a mixture of one or more constellations of G0/G1-, S-, G2/M-phase cells, together with internal standards, debris, background noise, and one or more populations of clumped cells. We have modelled typical DNA histograms as a mixed distribution with Gaussian densities for the G0/G1 and G2/M phases, an S-phase density, assumed to be uniform between the G0/G1 and G2/M peaks, observed with a Gaussian error, and with Gaussian densities for standards of chicken and trout red blood cells. The debris is modelled as a truncated exponential distribution, and we also have included a uniform background noise distribution over the whole observation interval. We have explored a new approach for maximum-likelihood analyses of complex DNA histograms by the application of the EM algorithm. This algorithm was used for four observed DNA histograms of varying complexity. Our results show that the algorithm works very well, and it converges to reasonable values for all parameters. In simulations from the estimated models, we have investigated bias, variance, and correlations of the estimates.

Algorithms

Clinical performance of a polymerase chain reaction testing algorithm for diagnosis of HIV-1 infection in peripheral blood mononuclear cells.

The clinical performance of a modified polymerase chain reaction (PCR) testing algorithm was evaluated for confirming the presence of HIV-1 proviral DNA in peripheral blood mononuclear cells. A whole cell lysate, rather than phenol-purified DNA, was used for PCR amplification, under systematically optimized conditions designed and verified within each PCR run to detect as few as 10 copies of proviral DNA. A sequential testing algorithm was designed requiring reactivity in duplicate (with corresponding non-reactivity in negative controls) with at least two sets of primers, before reporting a specimen as HIV-1-positive. In 196 specimens from patients staged according to the Walter Reed staging system, the PCR test sensitivity and the coculture isolation rate (in parentheses) were found to be: 97% (71%), 100% (85%), and 100% (76%) in stage 1, stage 2, and stage 3 specimens, respectively; and 100% (100%) in stage 4, 5, and 6 specimens. Results were uniformly negative for PCR and coculture isolation from 21 blind negative specimens and 105 (negative) donor leukopacks. These data indicate that this PCR testing algorithm is more accurate than tissue culture isolation methods, especially with early stage patients, and results in detection of HIV-1 in virtually 100% of seropositive individuals, with no false positives.

Acquired Immunodeficiency Syndrome

Volume rendering and connectivity algorithms for MR angiography.

Several display algorithms for three-dimensional angiographic data are evaluated. The mathematical analysis assumes additive Gaussian noise to predict the background distribution function for maximum intensity projection, sum projection, and connectivity display methods. In the maximum intensity projection method the mean noise level increases with the number of voxels in the ray, while in the sum projection the noise distribution width increases with the projection thickness, but the mean level remains constant. Comparisons of maximum intensity projection, sum projection, and connectivity algorithms applied to an MR angiogram of the circle of Willis are made. Measurements of the noise distribution are in agreement with the analysis. Algorithms combining connectivity with maximum intensity and sum projection are also evaluated. In these methods, a projection image is created using only the voxels marked by connectivity, typically with a 6% threshold of the data. Fine vessels are resolved and background noise is reduced in agreement with the analysis.

Algorithms

Describing protein structure: a general algorithm yielding complete helicoidal parameters and a unique overall axis.

We present a general and mathematically rigorous algorithm which allows the helicoidal structure of a protein to be calculated starting from the atomic coordinates of its peptide backbone. This algorithm yields a unique curved axis which quantifies the folding of the backbone and a full set of helicoidal parameters describing the location of each peptide unit. The parameters obtained form a complete and independent set and can therefore be used for analyzing, comparing, or reconstructing protein backbone geometry. This algorithm has been implemented in a computer program named P-Curve. Several examples of its possible applications are discussed.

Algorithms

CLIX: a search algorithm for finding novel ligands capable of binding proteins of known three-dimensional structure.

A computer algorithm, CLIX, capable of searching a crystallographic data-base of small molecules for candidates which have both steric and chemical likelihood of binding a protein of known three-dimensional structure is presented. The algorithm is a significant advance over previous strategies which consider solely steric or chemical requirements for binding. The algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenza-virus hemagglutinin and of proposing a number of potential new ligands to this protein.

Algorithms

A new algorithm for the identification of multiple input Wiener systems.

Multiple-input Wiener systems consist of two or more linear dynamic elements, whose outputs are transformed by a multiple-input static non-linearity. Korenberg (1985) demonstrated that the linear elements of these systems can be estimated using either a first order input-output cross-covariance or a slice of the second, or higher, order input-output cross-covariance function. Korenberg's work used a multiple input LNL structure, in which the output of the static nonlinearity was then filtered by a linear dynamic system. In this paper we show that by restricting our study to the slightly simpler Wiener structure, it is possible to improve the linear subsystem estimates obtained from the measured cross-covariance functions. Three algorithms, which taken together can identify any multiple-input Wiener system, have been developed. We present the theory underlying these algorithms and detail their implementation. Simulation results are then presented which demonstrate that the algorithms are robust in the presence of output noise, and provide good estimates of the system dynamics under a wide set of conditions.

Algorithms

[Algorithms, brains, computer. What they know and what not. II].

In order to say something substantial about the fundamental limits of machines (especially of computers) and of human calculations, we must explicate the concept of algorithm. Such an explication is provided by the Turing machine. Thus, problems have been discovered which cannot be solved algorithmically. For other problems there are problem-solving procedures, but no elegant algorithms. That men are fundamentally superior to machines has not been shown as yet.

Algorithms

Methods of decision analysis: protocols, decision trees, and algorithms in medicine.

Algorithms, decision trees, and protocols are defined and explained since they constitute an accepted part of clinical decision analysis and application to clinical care. Algorithms are particularly useful for common clinical problems where uncertainties are unlikely. Decision trees are helpful when--as usually occurs in difficult clinical decisions--there are problems in probability. Clinical protocols, which, at best, are based on algorithms and decision trees, provide instruction of how to best treat a patient given the strict definitions of the clinical problem. These techniques are, in essence, merely graphic representations of a logical scientific approach to clinical problems. Criticisms of these techniques center on their rigidity and the automatic unthinking cookbook medicine they might sponsor. It is concluded that if these techniques are wisely designed and, even more importantly, wisely administered with an understanding flexibility, they can lead to both economy and patient benefit.

Algorithms

Algorithms for the optimal identification of segment neighborhoods.

Two algorithms for the efficient identification of segment neighborhoods are presented. A segment neighborhood is a set of contiguous residues that share common features. Two procedures are developed to efficiently find estimates for the parameters of the model that describe these features and for the residues that define the boundaries of each segment neighborhood. The algorithms can accept nearly any model of segment neighborhood, and can be applied with a broad class of best fit functions including least squares and maximum likelihood. The algorithms successively identify the most important features of the sequence. The application of one of these methods to the haemagglutinin protein of influenza virus reveals a possible mechanism for conformational change through the finding of a break in a strong heptad repeat structure.

Algorithms

An O (N2 log N) restriction map comparison and search algorithm.

We present an O (R log P) time, O (M+P2) space algorithm for searching a restriction map with M sites for the best matches to a shorter map with P sites, where R, the number of matching site pairs, is bounded by MP. As first proposed by Waterman et al. (1984, Nucl. Acids Res. 12, 237-242) the objective function used to score matches is additive in the number of unaligned sites and the discrepancies in the distances between adjacent aligned sites. Our algorithm is basically a sparse dynamic programming computation in which "candidate lists" are used to model the future contribution of all previously computed entries to those yet to be computed. A simple modification to the algorithm computes the distance between two restriction maps with M and N sites, respectively, in O (MN (log M+log N)) time.

Algorithms

Breath detection algorithm in digital computers.

An algorithm for the detection and delineation of breaths is described. The proposed algorithm takes into account the different, common modes of ventilation like the pressure controlled, volume controlled and patient triggered modes of ventilation. Airway flow curve is used as the basic delineator and the airway pressure and the Co2 concentration curves are used to confirm the delineation. A flow chart is also included to explain the algorithm. The detailed explanation and modifications, for additional confirmation and for the selections of constants, to check for the rise or fall of the pressure and Co2 curves, are also included.

Algorithms

Optimising parent selection in plant breeding: comparing metaheuristic algorithms for genotype building.

Stacking desirable haplotypes across the genome to develop superior genotypes has been implemented in several crop species. A major challenge in Optimal Haplotype Selection is identifying a set of parents that collectively contain all desirable haplotypes, a complex combinatorial problem with countless possibilities. In this study, we evaluated the performance of metaheuristic search algorithms (MSAs)-genetic algorithm (GA), differential evolution (DE), particle swarm optimisation (PSO), and simulated annealing (SA) for optimising parent selection under two genotype building (GB) objectives: Optimal Haplotype Selection (OHS) and Optimal Population Value (OPV). Using a diverse wheat population of 583 lines genotyped for 29,972 SNPs, forming 7645 haplotype blocks and phenotyped for stripe rust scores, we assessed each algorithm's performance across fitness optimisation, convergence speed, and computational efficiency. GA consistently achieved high fitness and rapid convergence, while DE showed robustness but required longer runtime and careful tuning. PSO performed well under the OHS criterion but was less effective for OPV. SA, although computationally lighter, was less consistent in finding optimal solutions. Simulation over 100 breeding cycles showed that OHS outperformed both OPV and GEBV-based selection in long-term genetic gain and diversity retention. OHS maintained heterozygosity and additive variance, which are key for sustainable improvement, while GEBV selection led to early allele fixation. Our findings underscore the potential of GB strategies that prioritise the collective performance of parent sets rather than individual ranking to enhance selection outcomes in genomic-assisted breeding programmes.

Plant Breeding

Determination of pulse wave velocities with computerized algorithms.

Careful determination of pulse wave velocity is important in the study of arterial viscoelastic properties, wave reflections, and ventricular-arterial interactions. In spite of its increasingly widespread use, there is as yet no standardized method for its determination. Most studies have manually identified the transit time of the pressure wave front as it travels over a known distance in the arterial system, but the issues of accuracy and reproducibility have not been addressed. This study was designed to investigate the efficacy of four computerized algorithms in the determination of pulse wave velocities in invasive as well as in noninvasive pressure determinations. The four methods were the identification of: (1) the point of minimum diastolic pressure, (2) the point at which the first derivative of pressure is maximum, (3) the point at which the second derivative of pressure is maximum, and (4) the point yielded by the intersection of a line tangent to the initial systolic upstroke of the pressure tracing and a horizontal line through the minimum point. High-fidelity aortic pressure recordings were obtained in 26 patients with a multi-sensor micromanometer catheter. Noninvasive brachial and radial pressure waveforms were recorded in 11 volunteers with external piezoelectric transducers. The results show that the first derivative method consistently provided results that were different from the other methods for both the invasive and noninvasive methods because of changes in the structure of the upstroke as the arterial pulse propagates distally. Although the minimum method worked well for the invasive determinations, it was erratic with the noninvasive determinations, probably because of the higher amount of noise and reflection in the latter. Among the four algorithms, the second derivative and the intersecting tangents methods worked well with both invasive and noninvasive determinations with mean variation coefficients of less than 7% and correlation coefficients between the methods of greater than 0.90 for all data. In conclusion, computerized algorithms allow accurate determination of pulse wave velocity in invasively and noninvasively measured arterial pressure waveforms.

Adult