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PubMed2003

2003 update on the Hypertension Initiative of South Carolina. Bringing South Carolina from "worst to first" in cardiovascular health.

Hypertension and its related comorbidities continue to drain South Carolina of approximately $9 billion dollars a year in direct medical costs and indirectly through lost productivity. Improving control rates of blood pressure and associated cardiovascular risk factors in the primary care physician's office is a fundamental and crucial step to decrease the very high incidence of stroke and cardiorenal diseases. By monitoring prescribing patterns through the Initiatives' data feedback program, providing evidence-based management approaches through educational seminars, and by applying improved treatment protocols, physicians can have a profound impact on outcomes. The growing collaborative partnership spawned by the Hypertension Initiative now includes primary care providers, Hypertension Specialists in the local community, and the ASH Carolinas-Georgia Chapter. The growth and impact of the partnership is facilitated by a dynamic data auditing and feedback program that provides the basis for constructive change focused on optimizing cardiovascular risk factor control in patients across the State. By continuing to make progress in addressing the control of blood pressure and associated cardiovascular risk factors through a growing collaborative partnership with primary care providers statewide, South Carolina can move from worst to first in cardiovascular health. In the future, we hope to add a dynamic health promotion program to active disease management efforts. In the process, South Carolina can move from a leader in cardiovascular disease to a model of cardiovascular health.

Education, Medical, Continuing↗
PubMed2005

What sex abusers say about their treatment: results from a qualitative study on pedophiles in treatment at a Canadian penitentiary clinic.

This exploratory study used qualitative methodology to examine what pedophiles think about treatment, as well as their daily experience of a treatment program. To this end, twenty-three offenders receiving treatment from the La Macaza federal penitentiary clinic were interviewed using non-directive semi-structured interviews. Comparative analysis was used to analyze the resulting material. The following themes are discussed based on the results of this analysis: (a) the participants' past experience of therapy; (b) motivations for choosing the La Macaza clinic for treatment; (c) the structure of the program; (d) the group dynamics; (e) the therapists; and (f) the hardships and difficulties of treatment. Results suggest that the therapists and the program may have a function of containment or holding. Although part of the therapeutic process involves a focus on identifying and reducing cognitive distortions, results also warn therapists against misusing this concept by applying it to legitimately different opinions. Findings are discussed in terms of possible program improvements. The authors conclude that greater attention must be given to process research.

Adolescent↗
PubMed2003

[Brazil's national immunization program: origins and development].

The article discusses the central aspects of the trajectory of the National Immunization Program as regards the dynamics of sectoral policy. Heir to successful experiences of the past yet conceived at an entirely different moment, the Program followed the triumphant Campaign to Eradicate Smallpox and inaugurated a new phase in the history of public policy in the field of prevention. Under one sole command, the Program came to articulate a set of practices that had previously been spread across a number of government agencies and jurisdictions. The article examines the process by which the Program was conceived, structured, and developed within government health policy, and also underscores the main determinants of this policy, its institutional actors, and the political and ideological conflicts born of its implementation, whose success was an important component in the structuring of a vaccine market in Brazil.

Brazil↗
PubMed1991

Structure determination of [d(ATATATAUAT)]2 via two-dimensional NOE spectroscopy and molecular dynamics calculations.

Proton homonuclear two-dimensional (2D) NOE spectra were obtained for the decamer [d(ATATATAUAT)]2 as a function of mixing time, and proton resonance assignments were made. Quantitative assessment of the 2D NOE cross-peak intensities was used in conjunction with the program MARDIGRAS, which entails a complete relaxation matrix analysis of the 2D NOE peak intensities, to obtain a set of upper and lower bound interproton distance constraints. The analysis with MARDIGRAS was carried out using three initial models: A-DNA, B-DNA and Z-DNA. The distance constraints determined were essentially the same regardless of initial structure. These experimental structural constraints were used with restrained molecular dynamics calculations to determine the solution structure of the decamer. The molecular dynamics program AMBER was run using A-DNA or B-DNA as starting model. The root-mean-square (rms) difference between these two starting models is 0.504 nm. The two starting models were subjected to 22.5 ps of restrained molecular dynamics calculations. The coordinates of the last 10.5 ps of the molecular dynamics runs were averaged to give two final structures. MDA and MDB. The rms difference between these two structures is 0.09 nm, implying convergence of the two molecular dynamics runs. The 2D NOE spectral intensities calculated for the derived structures are in good agreement with experimental spectra, based on sixth-root residual index analysis of intensities. A detailed examination of the structural features suggests that while the decamer is in the B-family of DNA structures, many torsion angle and helical parameters alternate from purine to pyrimidine, with kinks occurring at the U-A steps.

Base Sequence↗
PubMed1993

A refined three-dimensional solution structure of a carboxy terminal fragment of apolipoprotein CII.

The three-dimensional structure of a synthetic fragment of human apolipoprotein CII (apo-CII) in 35%, 1,1,1,3,3,3-hexafluoro-2-propanol (HFP) has been determined on the basis of distance and intensity constraints derived from two-dimensional proton nuclear magnetic resonance measurements. The NOE crosspeak build-up rates were converted to distance constraints which were used in the distance geometry program DI-ANA. A set of one hundred structures were generated and of these ten structures were used in molecular dynamics simulations using the program XPLOR. This program enabled a direct minimization between the difference of the two-dimensional NOE intensities and those calculated from the full relaxation matrix. In this way spin diffusion is fully taken into account, which can be seen from the considerable improvement of the R-factor after the relaxation matrix refinement. These calculations show that this fragment, which corresponds to the carboxy terminal 30 amino acids of intact apo-CII and which retains its ability to activate lipoprotein lipase, is essentially flexible, but has three defined secondary structural elements. The most significant one is an alpha-helix between residues 67 and 74. The following three residues adopt a turn-like structure. Another turn of alpha-helix is seen between residues 56 and 59. The effect of the solvent system on the secondary structure was studied by circular dichroism spectroscopy. The results show that the mixed aqueous 35% HFP solvent induces secondary structure of a very similar nature to the one induced by sodium dodecyl sulphate.

Apolipoprotein C-II↗
PubMed2006

Payoff-monotonic game dynamics and the maximum clique problem.

Evolutionary game-theoretic models and, in particular, the so-called replicator equations have recently proven to be remarkably effective at approximately solving the maximum clique and related problems. The approach is centered around a classic result from graph theory that formulates the maximum clique problem as a standard (continuous) quadratic program and exploits the dynamical properties of these models, which, under a certain symmetry assumption, possess a Lyapunov function. In this letter, we generalize previous work along these lines in several respects. We introduce a wide family of game-dynamic equations known as payoff-monotonic dynamics, of which replicator dynamics are a special instance, and show that they enjoy precisely the same dynamical properties as standard replicator equations. These properties make any member of this family a potential heuristic for solving standard quadratic programs and, in particular, the maximum clique problem. Extensive simulations, performed on random as well as DIMACS benchmark graphs, show that this class contains dynamics that are considerably faster than and at least as accurate as replicator equations. One problem associated with these models, however, relates to their inability to escape from poor local solutions. To overcome this drawback, we focus on a particular subclass of payoff-monotonic dynamics used to model the evolution of behavior via imitation processes and study the stability of their equilibria when a regularization parameter is allowed to take on negative values. A detailed analysis of these properties suggests a whole class of annealed imitation heuristics for the maximum clique problem, which are based on the idea of varying the parameter during the imitation optimization process in a principled way, so as to avoid unwanted inefficient solutions. Experiments show that the proposed annealing procedure does help to avoid poor local optima by initially driving the dynamics toward promising regions in state space. Furthermore, the models outperform state-of-the-art neural network algorithms for maximum clique, such as mean field annealing, and compare well with powerful continuous-based heuristics.

Journal Article↗
PubMed2006

Permanent prostate brachytherapy: Dosimetric results and analysis of a learning curve with a dynamic dose-feedback technique.

PURPOSE: A permanent prostate brachytherapy (PPB) program utilizing intraoperative inverse-planned dynamic dose-feedback was initiated without prior firsthand experience of alternative techniques. The purpose of this study is to assess the dosimetric learning curve associated with this approach. METHODS AND MATERIALS: A total of 77 patients underwent PPB implants as monotherapy for localized prostate cancer to a prescription dose of 145 Gy with loose 125I seeds between December 2003 and June 2004. Intraoperative and postoperative dosimetric values, total implanted radioactivity, and operating room (OR) times were compared by sequential case number for all cases. RESULTS: The median intraoperative dosimetric values were: D90 (the minimum dose to 90% of the prostate) = 170 Gy (range, 135-203 Gy), V100 (the volume of the prostate that receives 100% of the prescription dose) = 96% (range, 86-100), V150 = 66% (range, 34-86). Median postoperative dosimetric values were as follows: D90 = 168 Gy (range, 132-197 Gy), V100 = 95% (range, 86-99), V150 = 74% (range, 51-84). Median implanted activity was 0.79 mCi per cubic centimeter of prostate (range, 0.541-1.13). There was no significant correlation by case number on any postoperative dosimetric parameter studied. Door-to-door OR time was reduced from median 138 to 97.5 min per case at the end of the series with a correlation coefficient of -0.76 for the initial 28 cases. CONCLUSION: Satisfactory dosimetric parameters can be achieved from the outset without a learning curve effect in an appropriately trained environment. The learning curve for dynamic dose-feedback PPB in a clinic naïve to other techniques is apparent in terms of OR time.

Aged↗
PubMed2005

Ribosome builder: a software project to simulate the ribosome.

The Ribosome Builder is a software project that provides tools and techniques to create dynamic models of macromolecular systems from the rapidly growing numbers of atomic structural models. It includes a computer program that allows the user to assemble the multiple molecular components within a 3D space and to define the hypothetical interactions of these components with the initial goal of understanding protein translation at an atomic level of detail. The program employs a simplified molecular dynamics forcefield that can simulate the long time-scale events, such as docking of translation factors and mRNA translocation. An embedded scripting language and Application Programming Interface (API) enable the creation of Steered Molecular Dynamics (SMD) simulations through the programmable application of external forces and torques on atoms and bonds. A graphical interface is provided for displaying and interacting with models, recording movies of molecular dynamics movements, and creating annotated 3D simulations of complex macromolecular events. Initial applications of the project include simulation of tetraloop folding, docking of an mRNA on the 30S subunit and a schematic simulation of the translation elongation cycle. The program is an open source project released under the GNU public license.

Computer Simulation↗
PubMed1998

Organizational responses to managed care: issues for academic health centers and implications for pediatric programs.

The health care market dynamics that supported and directed the growth and development of Academic Health Centers (AHCs) have changed dramatically in the last 10 years. AHCs are struggling to adapt to new reimbursement mechanisms and to compete effectively for limited dollars, but are constrained by administrative and governance structures that are slow to evolve. Their multiple missions, including education, research, and care for complex patients and underserved populations, are at risk. Although most recognize the need for substantive reorganization, available resources and market specifics vary dramatically from one AHC to another. The current approaches to adaptation by four AHCs are described, along with some of the unique challenges confronted by academic pediatric programs.

Academic Medical Centers↗
PubMed1996

Object-oriented sequence analysis: SCL--a C++ class library.

SCL (Sequence Class Library) is a class library written in the C++ programming language. Designed using object-oriented programming principles, SCL consists of classes of objects performing tasks typically needed for analyzing DNA or protein sequences. Among them are very flexible sequence classes, classes accessing databases in various formats, classes managing collections of sequences, as well as classes performing higher-level tasks like calculating a pairwise sequence alignment. SCL also includes classes that provide general programming support, like a dynamically growing array, sets, matrices, strings, classes performing file input/output, and utilities for error handling. By providing these components, SCL fosters an explorative programming style: experimenting with algorithms and alternative implementations is encouraged rather than punished. A description of SCL's overall structure as well as an overview of its classes is given. Important aspects of the work with SCL are discussed in the context of a sample program.

Algorithms↗
PubMed1996

A program for the user-independent computation of the correlation dimension and the largest Lyapunov exponent of heart rate dynamics from small data sets.

We propose a specially optimized computer program for the user-independent calculation of the correlation dimension D and the largest Lyapunov exponent L of heart rate dynamics on the basis of only 1024 electrocardiographically recorded RR intervals (heartbeat intervals). The validity of our program was established by analyzing a set of artificial standard signals. Our norm values of the correlation dimension (D = 5.37 +/- 0.62) and the largest Lyapunov exponent (L = 0.561 +/- 0.037 bits/beat) of RR dynamics, obtained from 79 healthy adults aged 26.3 +/- 4.8 years, were independent of gender and age; D and L correlated slightly with each other (Pearson correlation coefficient r = 0.26). Short-term reliability, tested for 25 of our subjects by two successive recordings, was fair: the intraclass correlation coefficients (ICCs) were 0.45 and 0.41 for D and L of RR dynamics, respectively. However, long-term reliability, tested for eight of our subjects by ten weekly recordings, was acceptable for L (ICC = 0.40) but not for D (ICC = 0.01). These results permit group comparisons on the basis of single measurements of L of RR dynamics. A reliable differentiation between young healthy individuals requires four measurements of L.

Adult↗
PubMed1987

Surveillance strategies: a primer.

A variety of acceptable surveillance methodologies have been described. CDC-type surveillance remains the standard, but a limited program may be most sensible for some. Surveillance by objective is an attractive concept and reports of its value are anticipated. For some, laboratory-based systems for identifying nosocomial infections and outbreaks have been highly effective but chart review is often still necessary. Regardless of the surveillance method chosen to anchor a program, the program should be flexible and dynamic, not static. Institutional needs should be assessed continually and the program should change as the problems change. Different strategies may be optimal at different times, and indeed many surveillance programs use a combination of elements. In our view adaptability and flexibility within a well-defined framework are qualities that improve not only responsiveness but also effectiveness.

Centers for Disease Control and Prevention, U.S.↗
PubMed1984

Gait analysis techniques. Rancho Los Amigos Hospital gait laboratory.

In the gait laboratory at Rancho Los Amigos Hospital, the emphasis is on patient testing to identify functional problems and determine the effectiveness of treatment programs. Footswitch stride analysis, dynamic EMG, energy-cost measurements, force plate, and instrumented motion analysis are the techniques most often used. Stride data define the temporal and distance factors of gait. We use this information to classify the patient's ability to walk and measure response to treatment programs. Inappropriate muscle action in the patient disabled by an upper motor neuron lesion is identified with dynamic EMG. Intramuscular wire electrodes are used to differentiate the action of adjacent muscles. We use the information to localize the source of abnormal function so that selection of treatment procedures is more precise. Force and motion data aid in determining the functional requirement and the muscular response necessary to meet the demand. Determining the optimum mode of locomotion and developing criteria for program planning have become more realistic with the aid of energy-cost measurements. Microprocessors and personal computer systems have made compact and reliable single-concept instrumentation available for basic gait analysis in the standard clinical environment at a modest cost. The more elaborate composite systems, however, still require custom instrumentation and engineering support.

Adult↗
PubMed2006

High-throughput method for the prediction of low-resolution, three-dimensional RNA structures.

Our aim is the high-throughput prediction of three-dimensional RNA structures at low resolution to answer questions posed by the RNA molecular biology. The strategy presented here is based on a computer program, called 3D-RNApredict, which implements and converts various structural data (RNA secondary structure, RNA motifs coordinates, experimental data) to create the input to the CYANA program (torsion-angle dynamics algorithm, TAD) which provides a fast engine for the 3D RNA structure calculation. The resultant RNA structure is refined using the X-PLOR program. The approach is amenable to automatization. Current predictions involve HIV-2 leader RNA domains and the sets of bacterial ncRNA.

Nucleic Acid Conformation↗
PubMedDate not supplied

Reassessing the cost-effectiveness of meningococcal serogroup C conjugate (MCC) vaccines using a transmission dynamic model.

BACKGROUND: The meningococcal serogroup C conjugate (MCC) vaccination program has successfully reduced morbidity and mortality from serogroup C disease in England and Wales, owing to high short-term vaccine effectiveness and substantial herd immunity. The latter effect was not accounted for in the previous economic analysis of the MCC program. METHODS: The authors applied a transmission dynamic model, which accounts for herd immunity, to reevaluate the cost-effectiveness of MCC vaccination. The direct and indirect benefits of the MCC vaccine strategy implemented in England and Wales were compared. The cost-effectiveness of alternative MCC vaccine strategies, including future changes to the current schedule, were evaluated. RESULTS: The authors found that including herd immunity improved the average cost-effectiveness ratio in all cases, although the extent depended on the vaccine strategy considered. Incremental analysis showed that those strategies that offered 1 dose early in the 2nd year of life dominated strategies that offered 3 doses of vaccine in infancy and that catch-up vaccination up to the age of 18 years was also highly attractive. Furthermore, the authors analyzed the effect of future changes to the routine vaccine schedule and predicted that shifting the age at routine vaccination from 2, 3, and 4 months (3 doses) to 12 months (1 dose) resulted in a net gain in the total number of cases prevented with only a few extra cases occurring in children under 1 year of age. This program dominated the current strategy. CONCLUSIONS: Models that do not include the indirect effects of vaccination will underestimate the impact of MCC vaccination and may lead to distorted decision making.

Child↗