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PubMed2005

Implementation of automated signal generation in pharmacovigilance using a knowledge-based approach.

Automated signal generation is a growing field in pharmacovigilance that relies on data mining of huge spontaneous reporting systems for detecting unknown adverse drug reactions (ADR). Previous implementations of quantitative techniques did not take into account issues related to the medical dictionary for regulatory activities (MedDRA) terminology used for coding ADRs. MedDRA is a first generation terminology lacking formal definitions; grouping of similar medical conditions is not accurate due to taxonomic limitations. Our objective was to build a data-mining tool that improves signal detection algorithms by performing terminological reasoning on MedDRA codes described with the DAML+OIL description logic. We propose the PharmaMiner tool that implements quantitative techniques based on underlying statistical and bayesian models. It is a JAVA application displaying results in tabular format and performing terminological reasoning with the Racer inference engine. The mean frequency of drug-adverse effect associations in the French database was 2.66. Subsumption reasoning based on MedDRA taxonomical hierarchy produced a mean number of occurrence of 2.92 versus 3.63 (p < 0.001) obtained with a combined technique using subsumption and approximate matching reasoning based on the ontological structure. Semantic integration of terminological systems with data mining methods is a promising technique for improving machine learning in medical databases.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

Medical activities and statistics.

The evaluation of the medical activity is a major concern for hospitals and public health services. With the introduction of coding (IDC-10 and CHOP classifications) hospitals are now able to analyze their medical activity. A way to improve physicians' acceptance in analyzing their work is to give them valuable feedback information. Building statistics tools is costly and time consuming. Therefore introducing data warehouse tools is helpful. Nice Code is an easy-to-use software that helps medical encoding while immediately offering understandable statistics. In Switzerland, physicians demand real feedback based on the data transmitted at the "cantonal" or federal levels and more transparency in third payer's decisions. In this respect, several cantons decided to equip public health services and hospitals with this tool. The goal is to give, physicians and economists, powerful tools for analyzing the medical activity.

Hospital Information Systems↗

PubMed2005

Physician-patient communication following invasive procedures: an analysis of post-angiogram consultations.

Although rarely studied, physician-patient interactions immediately following diagnostic tests are significant medical events because during these encounters the physician and patient often make decisions about major and sometimes invasive treatment. This investigation analyzed patterns of physician-patient communication following coronary angiography with particular attention to behaviors important to decision-making: physician information-giving, physician use of partnership-building, and active forms of patient participation (e.g., asking questions, being assertive, expressing concerns). We were particularly interested in effects related to the patient's race in light of documented evidence of racial disparities in cardiac care and outcomes. From audiotape recordings, 93 physician-patient interactions after coronary angiogram in a catheterization laboratory in a large US Veterans Affairs Medical Center were coded to measure the frequency of physicians' information-giving and partnership-building and the frequency of active patient participation. We also stratified these behaviors according to whether the behavior was prompted (e.g., physician information in response to a patient's question; a patient's opinion solicited by the doctor) or self-initiated. Several findings were noteworthy. First, these interactions were very brief and dominated by the physician. Second, although physician information-giving increased with more active patient participation, which in turn was correlated with physicians' use of partnership-building, proportionally little of the physicians' information (8%) and active patient participation (9%) was directly prompted by the other interactant. Finally, there was a tendency for physicians to self-initiate less information giving to black patients and for black patients to self-initiate less active participation than white patients. Although these differences were attenuated when other variables (e.g., the physician's training, disease severity) were included in the analysis, the pattern suggests a potential cycle of passivity where certain patients tend to receive fewer informational resources and these patients in turn do less to prompt the doctor for more.

Assertiveness↗

PubMed1993

Modelling photon transport in non-uniform media for SPECT with a vectorized Monte Carlo code.

A vectorized Monte Carlo code has been developed for modelling photon transport in non-uniform media for single-photon-emission computed tomography (SPECT). The code is designed to compute photon detection kernels, which are used to build system matrices for simulating SPECT projection data acquisition and for use in matrix-based image reconstruction. Non-uniform attenuating and scattering regions are constructed from simple three-dimensional geometric shapes, in which the density and mass attenuation coefficients are individually specified. On a Stellar GS1000 computer, Monte Carlo simulations are performed between 1.6 and 2.0 times faster when the vector processor is utilized than when computations are performed in scalar mode. Projection data acquired with a clinical SPECT gamma camera for a line source in a non-uniform thorax phantom are well modelled by Monte Carlo simulations. The vectorized Monte Carlo code was used to stimulate a 99Tcm SPECT myocardial perfusion study, and compensations for non-uniform attenuation and the detection of scattered photons improve activity estimation. The speed increase due to vectorization makes Monte Carlo simulation more attractive as a tool for modelling photon transport in non-uniform media for SPECT.

Humans↗

PubMed2006

[Chromatin diminution at the border of the XX and XXI centuries].

The size of genomes in eukaryotic organisms is one of the greatest mysteries of biology. As known from the middle of the XX century, the level of organization of a particular organism, does not depend on its genome size, i. e. on DNA amount in the nucleus. We believe that an actual function of non-coding DNA stands behind the phenomenon of chromatin diminution, known already for 100 years. Diminution of chromatin normally takes place in cells involved in body building and never occurs in developmental precursors of germ cells. Apparently, the former are cells, in which non-coding DNA is functionally significant. We cloned a fraction of DNA eliminated during chromatin diminution of Cyclops kolensis (Cyclopoida, Crustascea) and sequenced 90 clones totally making 32 kb. Taken together, the provided evidence has demonstrated a high organization ordering of DNA sequences restricted to the germ line. Chromatin diminution never takes place in human cells and in cells of the majority of animals. These cells may isolate non-coding DNA in other ways, making it unreactable for most enzymes and thus functionally cut off. Thus, a certain part of genome with a particular size and structure may serve for genetic isolation of species as shellfish or junk DNA are vital components rather than pieces of garbage.

Animals↗

PubMed2003

On the evolution of primitive genetic codes.

The primordial genetic code probably has been a drastically simplified ancestor of the canonical code that is used by contemporary cells. In order to understand how the present-day code came about we first need to explain how the language of the building plan can change without destroying the encoded information. In this work we introduce a minimal organism model that is based on biophysically reasonable descriptions of RNA and protein, namely secondary structure folding and knowledge based potentials. The evolution of a population of such organism under competition for a common resource is simulated explicitly at the level of individual replication events. Starting with very simple codes, and hence greatly reduced amino acid alphabets, we observe a diversification of the codes in most simulation runs. The driving force behind this effect is the possibility to produce fitter proteins when the repertoire of amino acids is enlarged.

Amino Acid Sequence↗

PubMed2003

Natural selection and algorithmic design of mRNA.

Messenger RNA (mRNA) sequences serve as templates for proteins according to the triplet code, in which each of the 4(3) = 64 different codons (sequences of three consecutive nucleotide bases) in RNA either terminate transcription or map to one of the 20 different amino acids (or residues) which build up proteins. Because there are more codons than residues, there is inherent redundancy in the coding. Certain residues (e.g., tryptophan) have only a single corresponding codon, while other residues (e.g., arginine) have as many as six corresponding codons. This freedom implies that the number of possible RNA sequences coding for a given protein grows exponentially in the length of the protein. Thus nature has wide latitude to select among mRNA sequences which are informationally equivalent, but structurally and energetically divergent. In this paper, we explore how nature takes advantage of this freedom and how to algorithmically design structures more energetically favorable than have been built through natural selection. In particular: (1) Natural Selection--we perform the first large-scale computational experiment comparing the stability of mRNA sequences from a variety of organisms to random synonymous sequences which respect the codon preferences of the organism. This experiment was conducted on over 27,000 sequences from 34 microbial species with 36 genomic structures. We provide evidence that in all genomic structures highly stable sequences are disproportionately abundant, and in 19 of 36 cases highly unstable sequences are disproportionately abundant. This suggests that the stability of mRNA sequences is subject to natural selection. (2) Artificial Selection--motivated by these biological results, we examine the algorithmic problem of designing the most stable and unstable mRNA sequences which code for a target protein. We give a polynomial-time dynamic programming solution to the most stable sequence problem (MSSP), which is asymptotically no more complex than secondary structure prediction. We show that the corresponding least stable sequence problem (LSSP) is NP-complete, and develop two heuristics for the construction of such sequences. We have implemented these algorithms, and present experimental results placing the high/low stability sequences in context with both wildtype and random encodings. Our implementation has already been applied to the design of RNA "code-words" creating little or no secondary structure in RNA computing (Brenneman and Condon, 2001; Marathe et al., 2001), and we anticipate a variety of other applications of this work to sequence design problems (Skiena, 2001).

Algorithms↗

PubMed2004

Incorporation of nonnatural amino acids into proteins.

The genetic code is established by the aminoacylation of transfer RNA, reactions in which each amino acid is linked to its cognate tRNA that, in turn, harbors the nucleotide triplet (anticodon) specific to the amino acid. The accuracy of aminoacylation is essential for building and maintaining the universal tree of life. The ability to manipulate and expand the code holds promise for the development of new methods to create novel proteins and to understand the origins of life. Recent efforts to manipulate the genetic code have fulfilled much of this potential. These efforts have led to incorporation of nonnatural amino acids into proteins for a variety of applications and have demonstrated the plausibility of specific proposals for early evolution of the code.

Amino Acids↗

PubMed2000

Intracranial pressure processing with artificial neural networks: classification of signal properties.

Intracranial pressure (ICP) is commonly used by neurosurgeons as a source of valuable information about the current condition of the neurosurgical patient. Nevertheless, despite years of effort, extracting clinically valuable information from the ICP signal is still problematical. Approaches, using current values of ICP, may fail to disclose imminent risk, because unpredictable factors can rapidly change the properties of the signal. An alternative approach is to determine some global characteristics of the signal within a longer time interval and such statistical analyses have been proposed by several authors. A further, rarely considered, problem is assessment of the results obtained from the point of view of their practical utility and/or such classification of the obtained properties of the signal that they correspond to certain clinical states of the patient. While this might be a typical task for discriminant analysis, we approached the analysis using an alternative methodology, that of computational intelligence, implemented in artificial neural networks (ANN). We tested two variants of the ANN algorithms for classification and discrimination of global properties of the ICP signal. In a "dynamic pattern classification" the network was presented with several sections of ICP records together with information from the expert-neurosurgeon, classifying 4 risk groups. In this mode no data pre-processing was carried out, in contrast to our second approach, in which the signal had been pre-processed using published statistical analyses and only these intermediate coefficients were fed into the ANN classifier. The results obtained with both classification methods at their current stage of training were similar and approximated to a 70% rate of judgements consistent with the expert scoring. Nevertheless, the method based on the assessment of global parameters from the ICP record looks more promising, because it leaves the possibility for modification of the set of parameters analysed. The new parameters may include information extracted not only from the ICP signal, but also from other diagnostic modalities, like colour coded Doppler ultrasonography. The ultimate goal of this work is to build up a pseudo-intelligent computer expert system, which would be able to reason from a reduced set of input information, available from a standard monitoring modality, because it had been taught salient links between these data and higher-order data, upon which expert scoring was based.

Cerebral Hemorrhage↗

PubMed2004

Vented gaseous deflagrations modelling of hinged inertial vent covers.

The model of explosion pressure build up in enclosures with inertial vent covers and the CINDY code implementing the model are validated against experiments by Hochst and Leuckel (1998) in a 50 m3 vessel with a pair of ceiling-mounted upwards-opening hinged doors in a 'butterfly' configuration with surface densities of 73 and 124 kg/m2 under conditions of initially quiescent and turbulent mixtures. The model and the code are further validated against an experiment by Zalosh (1978) in a 33.5 m3 room-like enclosure with a pair of wall-mounted rectangular doors, in a parallel configuration, each hinged at its bottom edge with a surface density of 23.1 kg/m2 and initially quiescent mixture. A formula for the torque acting upon a rotating venting door is derived under conditions of vent cover jet formation. The vent cover jet effect decreases the torque three times compared to an elementary approach valid at the start of vent cover movement. It is demonstrated that, similar to translating vent covers, the vent cover jet effect is crucial for prediction of interdependent vent cover displacement in time and pressure transients.

Explosions↗

PubMed2000

ANN modeling of DNA sequences: new strategies using DNA shape code.

Two new encoding strategies, namely, wedge and twist codes, which are based on the DNA helical parameters, are introduced to represent DNA sequences in artificial neural network (ANN)-based modeling of biological systems. The performance of the new coding strategies has been evaluated by conducting three case studies involving mapping (modeling) and classification applications of ANNs. The proposed coding schemes have been compared rigorously and shown to outperform the existing coding strategies especially in situations wherein limited data are available for building the ANN models.

Algorithms↗

PubMed1997

Vascular surgery and the Resource-based Relative Value Scale five-year review.

PURPOSE: The first 5-year review of the Medicare Resource-based Relative Value Scale (RBRVS) work values (RVUs) began in 1995, and adjustments became effective January 1, 1997. This report summarizes the methods used by The Society for Vascular Surgery (SVS) and the International Society for Cardiovascular Surgery, North American Chapter, (ISCVS-NA) Joint Council Government Relations Committee (GRC) to evaluate vascular surgery work RVUs and the results that were achieved. METHODS: The GRC performed a work study to determine accurate skin-to-skin operative times for typical vascular and nonvascular operations. These were compared with the original Harvard/Hsiao time estimates and intraservice work per unit time (IWPUT) values that had been used to determine work RVUs. For most vascular procedures the current operative times were longer than the original Harvard estimates, resulting in calculated IWPUTs substantially less than the Harvard values. This lack of correspondence was not identified in the nonvascular procedures, where operating room times and IWPUT values were more consistent with Harvard data. These study results were then used to support compelling evidence arguments in a petition to the Health Care Financing Administration (HCFA) that identified vascular surgery as being undervalued in the RBRVS. Nine commonly performed vascular procedures were cited for review in the 5-year update, and five distinct work analysis methods were used to justify each recommended RVU increase. These techniques included a standardized survey from the American Medical Association (AMA)/Specialty Society Relative Value Update Committee (RUC), a work calculation using accurate intraservice times and appropriate IWPUT values, and an evaluation and management (E&M) building-block approach. RESULTS: The RUC met throughout 1995 to assess codes submitted for review, and recommendations were forwarded to HCFA. The Notice of Proposed Rule Making (NPRM), which contained HCFA's preliminary RVU determinations, was released in May 1996. RVU increases from 11.5% to 44.6% were proposed for the nine vascular services cited by the SVS/ISCVS-NA. Also included were two increases and two reductions in less-common vascular operations. Of far greater overall fiscal import, HCFA proposed substantial increases in the work RVU for all E&M except that performed within global surgical packages. The SVS/ISCVS and most other surgical societies appealed HCFA's proposal regarding E&M. The Final Rule for the 1997 Medicare Fee Schedule was published late in 1996. CONCLUSIONS: The Final Rule upheld the 11 vascular work value improvements and the E&M increases that excluded global service packages. Because most surgical E&M is performed within 10- or 90-day global periods, the E&M ruling will produce an estimated annual $2.5 billion shift from surgical to nonsurgical specialties. Because the overall fiscal impact of the 5-year review was mandated to be budget-neutral, HCFA imposed an 8.3% reduction in the work payment of every service in Part B of the Medicare program, primarily to compensate for the increased nonsurgical E&M payments. The net fiscal impact of the 5-year review for vascular surgery has been estimated at +0.5%.

Centers for Medicare and Medicaid Services, U.S.↗

PubMed2025

The development and usability of 'The Genetics Navigator': a digital solution for adult and paediatric clinical genetics services.

Clinical genetic services address diverse genetic testing needs, but there is no comprehensive digital solution to meet this variety. We aimed to develop and test the usability of the Genetics Navigator (GN), a platform designed to enhance genetic services for paediatric and adult patients. The GN prototype was created with input from a patient and clinician advisory board, informed by prior research. Usability testing involved genetics patients (N = 14), parents of paediatric patients (N = 4), and the general public (N = 10). Participants provided feedback using the 'think aloud' method when using the platform. We used the System Usability Scale (SUS) for quantitative evaluation. Qualitative data were coded by platform section, item, and identified key areas for improvement. Building on the Genetics Adviser platform, we added video and written content for various genetic conditions and patient groups, including pre-test education, counselling, decision support, history collection, post-test result disclosure, and management. Key feedback during rounds of usability testing emphasized the need for a supportive design, seamless workflow, and engaging experience of the tool. The tool was modified to reflect the feedback, and the GN achieved an average SUS score of 87.7 ± 10.9 (N = 28), indicating above-average usability. Future research will evaluate its clinical and cost-effectiveness in a randomized trial.

Humans↗

PubMed1995

A comparison of results for the University of Missouri Research Reactor radiological airborne release assessments obtained from PC-based computer programs.

The United States Environmental Protection Agency has published three computer programs, COMPLY, AIRDOS-PC, and CAP88-PC, to assist the regulated community in determining compliance with the Environmental Protection Agency radionuclide air emission standards. The programs calculate radiation doses from routine airborne release to the general public residing outside a nuclear facility site. They consider doses from inhalation, ingestion of contaminated food, air immersion, and ground deposition. A PC-based computer code, XOQDOQ-82, developed for the Nuclear Regulatory Commission, was also chosen to compare and evaluate dispersion results from the Environmental Protection Agency codes for the University of Missouri Research Reactor Center. Effects of building parameters, terrain conditions, and downwind distances on dispersion factors were calculated. The results of this study indicated that dispersion factors calculated using AIRDOS-PC and CAP88-PC were several times lower than those calculated using XOQDOQ-82 at all distances, and those dispersion factors calculated using COMPLY were several times lower than the XOQDOQ-82 values at distances greater than 600 m.

Air Pollutants, Radioactive↗

PubMedDate not supplied

Legacy leadership: stewardship and courage. Five attributes characterize genuine healthcare leaders.

In organizations with the power to persist through turbulent eras, one finds leaders who live as if they were stewards of a legacy-the culture, mission, and founding spirit of the organization. These legacy leaders may be physicians, administrators, chief executives, or board members, but they all have the ability to weave a thread of constancy through times of peril. Five attributes characterize legacy leaders: Their work is a vocation, they possess a moral code, they are committed to stewardship, they have a bias for building, and they instill hope. Legacy leaders stay with one organization a very long time, patiently removing obstacles to worthy accomplishments. Because the profession of healthcare is at heart a vocation, not a business, we must pay attention to the kinds of leaders we place in our healthcare institutions. To carry out their responsibility of transforming healthcare delivery, boards of directors must hire legacy leaders, manage their business focus, carefully evaluate executives, enhance mechanisms for board evaluation, and raise the bar for decision making.

Catholicism↗

PubMed2001

Integrated patient data for optimal patient management: the value of laboratory data in quality improvement.

Managed care organizations are shifting from traditional utilization management programs to focus on initiatives that improve the health of an insured population. This strategy requires sophisticated data integration to identify at-risk individuals and track outcomes. Laboratory data are becoming increasingly valuable tools for managed care organizations and healthcare providers. The HEDIS Effectiveness of Care measures have incorporated laboratory data into several key performance indicators. By building a comprehensive repository of laboratory data that includes both procedure codes and laboratory values, managed care organizations can realize substantial savings by avoiding the costly medical record reviews required when administrative data are incomplete. In addition to tracking clinical outcomes, laboratory data provide the ability to risk-stratify a population to target high-risk individuals for case management and disease management interventions. Healthcare organizations face several challenges in the integration of laboratory data into medical databases and practice management software. Confidentiality is a key consideration in view of recent healthcare regulations. Providers of laboratory services should work collaboratively with organizations setting standards for healthcare informatics to facilitate the pooling of data for quality improvement and outcomes research. Health Level Seven, Inc. (HL7), Logical Observation Identifier Names and Codes (LOINC), and Systematized Nomenclature of Medicine (SNOMED) will likely play a key role in this process.

Clinical Laboratory Techniques↗

PubMed2000

The robust statistical bases of the coevolution theory of genetic code origin.

A paper (Amirnovin R, J Mol Evol 44:473-476, 1997) seems to undermine the validity of the coevolution theory of genetic code origin by shedding doubt on the connection between the biosynthetic relationships between amino acids and the organization of the genetic code, at a time when the literature on the topic takes this for granted. However, as a few papers cite this paper as evidence against the coevolution theory, and to cast aside all doubt on the subject, we have decided to reanalyze the statistical bases on which this theory is founded. We come to the following conclusions: (1) the methods used in the above referred paper contain certain mistakes, and (2) the statistical foundations on which the coevolution theory is based are extremely robust. We have done this by critically appraising Amirnovin's paper and suggesting an alternative method based on the generation of random codes which, along with the method reported in the literature, allows us to evaluate the significance, in the genetic code, of different sets of amino acid pairs in biosynthetic relationships. In particular, by using this method and after building up a certain set of amino acid pairs reflecting the expectations of the coevolution theory, we show that the presence of this set in the genetic code would be obtained, purely by chance, with a probability of 6x10(-5). This observation seems to provide particularly strong support to the coevolution theory.

Amino Acids↗

PubMedDate not supplied

Coding exon detection using comparative sequences.

We introduce a new system, called shortHMM, for predicting exons, which predicts individual exons using two related genomes. In this system, we build a hidden semi-Markov model to identify exons. In the hidden Markov model, we propose joint probability models of nucleotides in introns, splice sites, 5'UTR, 3'UTR, and intergenic regions by exploiting the homology between related genomes. In order to reduce the false positive rate of the hidden Markov model, we develop a screening process which is able to identify intergenic regions. We then build a classifier by combining the statistics from the hidden Markov model and the screening process. We implement shortHMM on human-mouse sequence alignments. The source codes are available at < www.stat.purdue.edu/ jingwu/hmm >. Compared to TWINSCAN and SLAM, shortHMM is substantially more powerful in identifying AT-rich RefSeq exons (8% more AT-rich RefSeq exons were predicted), as well as slightly more powerful in identifying RefSeq exons (3-10% more RefSeq exons were predicted), at a similar or lower false positive rate, with less computing time and with less memory usage. Last, shortHMM is also capable of finding new potential exons.

Algorithms↗