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PubMed2006

Caring for patients with chronic heart failure: The trajectory model.

The purpose of this paper is to examine gaps in our understanding of the heart failure experience and describe the use of Trajectory of Chronic Illness Theory to bridge these gaps. New pharmacotherapeutic strategies have improved survival in heart failure, but research has consistently shown that clinical outcomes in these patients do not depend on physiologic variables alone. Psychological, behavioral, environmental, social and socioeconomic variables also contribute to a patient's ability to manage chronic illness. However, we have not yet identified the essential elements in helping patients engage in self-management and adhere to increasingly complex medical regimens. Theoretical models facilitate disciplinary integration, providing a comprehensive and cohesive foundation for building better science. The Trajectory of Chronic Illness Theory is particularly salient for heart failure because of its emphasis on patients' ability to manage a chronic illness. By using theory to explore gaps in our understanding of the heart failure experience, investigators may be able to develop more targeted interventions to help patients manage heart failure.

Adaptation, Psychological↗
PubMed2002

Ecdysone-regulated puff genes 2000.

The Ashburner model for the hormonal control of polytene chromosome puffing has provided a strong foundation for understanding the basic mechanisms of steroid-regulated gene expression (Cold Spring Harbor Symp. Quant. Biol. 38 (1974) 655). According to this model, the steroid hormone 20-hydroxyecdysone (referred here as ecdysone) directly induces the expression of a small set of early regulatory genes. These genes, in turn, induce a much larger set of late target genes that play a more direct role in controlling the biological responses to the hormone. The recent characterization of two early puff genes, E63-1 and E23, and three late puff genes, D-spinophilin, L63, and L82, provide further confirmation of the Ashburner model. In addition, these studies provide exciting new directions for our understanding of ecdysone signaling. Overexpression studies of E63-1 implicate this gene in directing calcium-dependent salivary gland glue secretion. In contrast, overexpression of E23 indicates that this ABC transporter family member may negatively regulate ecdysone signaling by actively transporting the hormone out of target cells. Finally, genetic studies of the L63 and L82 late genes reveal unexpected possible functions for ecdysone in controlling developmental timing and growth. This review surveys the recent characterization of these ecdysone-inducible genes and provides an overview of how they expand our understanding of ecdysone functions during development.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

Mental health research and philanthropy: possible partnerships?

Mental health research has received relatively little philanthropic support in Australia compared with other areas of health research. Philanthropic trusts do not generally provide recurrent funding or make grants for that perceived to be the responsibility of the state or the market. The emergence of 'strategic philanthropy' however, provides potential for mental health researchers to form partnerships with philanthropic foundations, particularly on initiatives that are focused on prevention and innovative and sustainable models with the capacity to 'go to scale' across the service system.

Financing, Organized↗
PubMed1997

National Kidney Foundation report on dialyzer reuse. Task Force on Reuse of Dialyzers, Council on Dialysis, National Kidney Foundation.

The Council on Dialysis of the National Kidney Foundation convened an expert panel to evaluate the current practice and literature related to the reuse of hemodialyzers. The panel reviewed and evaluated literature related to reuse since the last report of the National Kidney Foundation recommendations on reuse was published in 1988. The group sought to develop a consensus concerning the effect of reuse of hemodialyzers on mortality; the efficiency of delivered hemodialysis when reused hemodialyzers are used in the clinical setting; the clinical effects of reused dialyzers as compared with dialyzers not reused on intradialytic symptoms; infections in patients using reused dialyzers; and the effect of reused dialyzers on complement activation, cytokine production, and beta2-microglobulin metabolism and clearance. In addition, the panel reviewed the literature on the potential toxicity of germicides used in the processing of dialyzers for reuse as well as recent changes in federally mandated regulations concerning labeling of dialyzers for reuse, the monitoring of the reuse process, and the effectiveness of reused dialyzers to achieve a prescribed delivered clearance as estimated by urea kinetic modeling or by percent urea reduction. The National Kidney Foundation takes no position for or against dialyzer reuse. The principal reason for the practice of reuse is economical. In view of the uncertainties related to the safety and biological impact of reuse procedures, the task force recommends that a full discussion of the issue of reuse and its potential beneficial and detrimental effects be undertaken with each patient. There is no conclusive evidence to substantiate the notion that either morbidity or mortality associated with single use or reuse is different. Microbial contamination of the water used for dialyzer reprocessing increases patient morbidity. The chemical quality of water used for dialyzer reprocessing should, at least, fall within the same standards as those recommended for product water intended for hemodialysis. Dialyzers should not be reprocessed from patients who have tested positive for hepatitis B surface antigen. The effects of reprocessing high-flux dialyzers on beta2-microglobulin clearance are dependent on the reprocessing technique, the number of reuses, and the nature of the dialyzer membrane used. There are insufficient data on the effects of reuse on beta2-microglobulin behavior to make uniform recommendations. Untoward effects of reused dialyzers may still occur in spite of rigorous adherence to the AAMI guidelines. For example, use of the total cell volume method for assessing changes in small molecule clearances will not show the loss of performance attributable to dialysate shunting. For this reason, the measurement of Kt/V for urea as recommended by the AAMI or the determination of the urea reduction ratio (URR) is strongly recommended at least monthly to gauge the adequacy of the dialysis procedure. Given the significant fall in dialyzer efficiency for urea removal that can occur after repeated uses of a dialyzer, dialysis prescriptions in units practicing reuse should be designed to deliver a Kt/V or URR value that exceeds the dose used for patients treated with single-use dialyzers to make allowance for any possible reuse-induced reduction in dialyzer efficiency. Technicians and other personnel responsible for the reprocessing of dialyzers should receive proper training. These health care providers should be certified in reprocessing by an examining body so that professional competency can be assured.

Bacterial Infections↗
PubMed1990

A research-knowledge system (ARKS) for storing, managing, and modeling knowledge from the scientific literature.

Nursing knowledge and nursing data are the foundation for nursing practice. Domain knowledge that is stored in the literature of nursing and related disciplines, if not in memory, needs to be available to nurses during the process of clinical decision making. Although the electromechanical technology for delivering knowledge is available, conceptual technology lags far behind. An informatics solution to the conceptual problem is provided by knowledge engineering, the branch of informatics that addresses such problems by developing methods for restructuring knowledge from one form into a form that is more useful. The purpose of this article is to describe a research program for engineering nursing knowledge that has resulted in the development of such a tool, a prototype computer system for storing, managing, and modeling research-knowledge. The system is called ARKS, acronym for A Research-Knowledge System.

Computer Simulation↗
PubMed2004

Exploring rarity using a general model for distribution and abundance.

We describe a simple model for changes in the distribution and abundance of a metapopulation and use it to explore the conditions leading to different types of rarity. The model suggests that localized populations (those with low patch occupancy but high local abundance) arise from low dispersal, low heterogeneity in extant population size, and frequent local extinctions relative to the potential for recolonization. Scarce populations (with low distribution and abundance) arise when relative local extinction rate is low to moderate and heterogeneity is high or successful dispersal is relatively low. Sparse populations (widespread, but with low local abundance) arise when relative local extinction rate is very low and either spatial heterogeneity or mortality through unsuccessful dispersal is high. In sparse or common species, there may be unstable as well as stable equilibria, implying a threshold distribution and abundance for persistence. The model supports a general correlation between distribution and abundance and suggests that persistence may be threatened by dispersal rates being either too high or too low. The model provides a new perspective on rarity and suggests a simple theoretical foundation for understanding the population-dynamic mechanisms that determine distribution and abundance.

Animals↗
PubMed2005

Development of an epilepsy comprehensive care center: a Japanese model.

PURPOSE: To review the requirements of a comprehensive care center for people with epilepsy. METHODS: Twenty-seven years have passed since the foundation of the Japanese Epilepsy Center in Shizuoka. The development of this center is presented as a model of an epilepsy comprehensive care center. RESULTS: Between 1926 and 1947, the Shizuoka Higashi Hospital (the former name of SMIND) served as a tuberculosis hospital. In 1975, a proposal for a special center for the care of people with epilepsy was submitted to the Japanese government. An epilepsy center (the Center) was soon built, and the tuberculosis sanatorium ended its 50-year history. The facilities of the Center include an outpatient clinic, four inpatient wards with 200 beds, a day-care center for medical rehabilitation, and classrooms for elementary and junior high school children. The Center has modern diagnostic tools such as electroencephalography (EEG), closed-circuit TV-EEG (CCTVEEG), computed tomography (CT) scan, magnetic resonance imaging (MRI), single-photon emission CT (SPECT), and magnetoencephalography (MEG). Neurosurgery for intractable seizures has been conducted at the Center since 1983. Approximately 25,000 patients with epilepsy from all over Japan have been registered since 1975. Annually, approximately 5,000 outpatients and 600 inpatients attend the Center. As of March 2002, 500 patients had received resective surgery for epilepsy. Other activities in the Center include research and specialized training of professionals, including foreign nationals, in the treatment of epilepsy. CONCLUSIONS: The experience in Shizuoka suggests that management of epilepsy should be oriented toward psychological well-being, social rehabilitation, and seizure control.

Adolescent↗
PubMed2005

The interaction of attention and emotion.

We analyse emotions from the viewpoint of how emotion and attention interact in the brain. Much has been learnt about the brain structures involved in attention, especially in vision. In particular the manner in which attention functions as a high-level control system, able to make cognitive processing so effective, has been studied both at a global level by brain imaging (fMRI, PET, MEG and EEG), at a local single cell level in monkeys and lower animals, and computationally by a variety of models. The manner in which emotions impinge on this attention control system is not so well analysed, although numerous new results are now emerging from using the same tools. Here we use an engineering control approach to attention to model it in a global manner but with relatively sure local foundations at singe neuron level. The manner in which emotional value (as coded in amygdale and orbito-frontal cortex) can interact with the attention control circuitry is analysed using results of various experimental paradigms. A general model of this interaction is first developed and tested against a list of paradigms, and then more detailed computations are performed using more specific features of the attention control system and the limbic value coding. These computations are completed by a simulation of the emotional attentional blink, a demanding paradigm for any model of attention alone, but made more so by the presence of emotional value codes for stimuli. We conclude the paper with a general discussion of further avenues of research.

Animals↗
PubMed2005

Standards for statistical models used for public reporting of health outcomes: an American Heart Association Scientific Statement from the Quality of Care and Outcomes Research Interdisciplinary Writing Group: cosponsored by the Council on Epidemiology and Prevention and the Stroke Council. Endorsed by the American College of Cardiology Foundation.

With the proliferation of efforts to report publicly the outcomes of healthcare providers and institutions, there is a growing need to define standards for the methods that are being employed. An interdisciplinary writing group identified 7 preferred attributes of statistical models used for publicly reported outcomes. These attributes include (1) clear and explicit definition of an appropriate patient sample, (2) clinical coherence of model variables, (3) sufficiently high-quality and timely data, (4) designation of an appropriate reference time before which covariates are derived and after which outcomes are measured, (5) use of an appropriate outcome and a standardized period of outcome assessment, (6) application of an analytical approach that takes into account the multilevel organization of data, and (7) disclosure of the methods used to compare outcomes, including disclosure of performance of risk-adjustment methodology in derivation and validation samples.

American Heart Association↗
PubMed1999

The phase model of burnout: conceptual, theoretical, and practical issues.

This essay highlights major challenges and opportunities that highlight the products of over a decade of research and applications relying on the phase model. Nine points are developed, which rest upon progress with the phase model and also will further test the adequacy of the foundation it provides for more comprehensive work. To illustrate, the first of these points summarizes what we know with reasonable certainty, and what needs investigation, concerning cross-cultural replications; and a second point deals with the group locus of burnout. The relevance of this essay is substantial in the context of available research. Thus, the phase model isolates quite similar patterns of covariation in worldwide populations; and the phase operations also permit estimating what proportion of respondents have which degree of burnout, a capability beyond that of alternative operational definitions. Hence, the centrality of this effort to highlight sectors for further assessing the reliability and validity of the phase model.

Burnout, Professional↗
PubMed2001

Stress analysis of the distal locking screws for femoral interlocking nailing.

In femoral locked nailing, the distal locking screws are vulnerable to mechanical failure. Biomechanical studies have shown that the stress on these screws is substantially affected by the fit of the nail in the medullary canal. In this study, a "closed form" mathematical model based on elastic beam-column theory was developed to investigate how the nail-cortical contact, which was simulated by a linear elastic foundation, affected the stress on the distal locking screws. Providing data for the model was a construct of a fractured femur with an intramedullary locked nail loaded by an eccentric vertical load. The stress on the locking screw was analyzed as a function of the distance from the fracture to the locking screw in the distal fragment under two situations: with and without nail-cortical contact in the distal fragment. With nail-cortical contact, the screw stress decreased as the length of nail-cortical contact and the distance between the distal locking screw and the fracture site increased, but this stress contrarily increased when the nail reached the femoral region at which the screw length increased. The screw stress was much higher without nail-cortical contact than with contact and continued to increase as the nail was inserted further. The mathematical model developed here can be a convenient means of rapid stress evaluation and parametric analysis for locked femoral nailing. It may be used to improve the design of interlocking nails and surgical technique.

Biomechanical Phenomena↗
PubMed2000

Effective energy functions for protein structure prediction.

Protein structure prediction, fold recognition, homology modeling and design rely mainly on statistical effective energy functions. Although the theoretical foundation of such functions is not clear, their usefulness has been demonstrated in many applications. Molecular mechanics force fields, particularly when augmented by implicit solvation models, provide physical effective energy functions that are beginning to play a role in this area.

Animals↗
PubMed1991

Glynn and the conceptual development of the chemiosmotic theory: a retrospective and prospective view.

The origin and evolution of the chemiosmotic theory is described particularly in relation to Peter Mitchell's application of it to model oxidative phosphorylation. Much of the deployment, development and evaluation of the theory occurred at the independent laboratory of the Glynn Research Foundation; the value and future of such an institution is discussed. The role of models mediating between theories and phenomena is analyzed with regard to the growth of knowledge of chemiosmotic systems.

Biochemistry↗
PubMed2004

Combining FDI and AI approaches within causal-model-based diagnosis.

This paper presents a model-based diagnostic method designed in the context of process supervision. It has been inspired by both artificial intelligence and control theory. AI contributes tools for qualitative modeling, including causal modeling, whose aim is to split a complex process into elementary submodels. Control theory, within the framework of fault detection and isolation (FDI), provides numerical models for generating and testing residuals, and for taking into account inaccuracies in the model, unknown disturbances and noise. Consistency-based reasoning provides a logical foundation for diagnostic reasoning and clarifies fundamental assumptions, such as single fault and exoneration. The diagnostic method presented in the paper benefits from the advantages of all these approaches. Causal modeling enables the method to focus on sufficient relations for fault isolation, which avoids combinatorial explosion. Moreover, it allows the model to be modified easily without changing any aspect of the diagnostic algorithm. The numerical submodels that are used to detect inconsistency benefit from the precise quantitative analysis of the FDI approach. The FDI models are studied in order to link this method with DX component-oriented reasoning. The recursive on-line use of this algorithm is explained and the concept of local exoneration is introduced.

Algorithms↗
PubMed2005

Uniform scale-independent gene transfer to striated muscle after transvenular extravasation of vector.

BACKGROUND: The muscular dystrophies exemplify a class of systemic disorders for which widespread protein replacement in situ is essential for treatment of the underlying genetic disorder. Somatic gene therapy will require efficient, scale-independent transport of DNA-containing macromolecular complexes too large to cross the continuous endothelia under physiological conditions. Previous studies in large-animal models have revealed a trade-off between the efficiency of gene transfer and the inherent safety of the required surgical and pharmacological interventions to achieve this. METHODS AND RESULTS: Rats and dogs underwent limb or hemibody isolation via atraumatic tourniquet placement or myocardial isolation via heterotopic transplantation. Recombinant adenovirus (10(13) particles per kilogram) or recombinant adeno-associated virus (10(14) genome copies/kg) encoding the lacZ transgene was delivered through pressurized venous infusion without pharmacological mediators. Muscle exhibited almost 100% myofiber transduction in rats and dogs by X-galactosidase staining and significantly higher beta-galactosidase levels compared with nonpressurized delivery. No significant difference was seen in beta-galactosidase levels between 100- or 400-mm Hg groups. The <50-mm Hg group yielded inhomogeneous and significantly lower transgene expression. CONCLUSIONS: Uniform scale- and vector-independent skeletal and cardiac myofiber transduction is facilitated by pressurized venous infusion in anatomic domains isolated from the central circulation without pharmacological interference with cardiovascular homeostasis. We provide the first demonstration of uniform gene transfer to muscle fibers of an entire extremity in the dog, providing a firm foundation for further translational studies of efficacy in canine models for human diseases.

Animals↗
PubMed2002

A framework for operational modelling of hospital resources.

The provision of hospital resources, such as beds, operating theatres and nurses, is a matter of considerable public and political concern and has been the subject of widespread debate [1,2,31. The political element of healthcare emphasises the need for objective methods and tools to inform the debate and provide a better foundation for decision-making. There is considerable scope for operational models to be widely used for this purpose. An appreciation of the dynamics governing a hospital system, and the flow of patients through it, point towards the need for sophisticated capacity models reflecting the complexity, uncertainty, variability and limited resources. Working alongside managers and clinicians from participating hospitals, this paper proposes a generic framework for modelling of hospital resources in the light of perceived user-needs and real-life hospital processes. The proposed framework incorporates the need for patient classification techniques to be adopted, which forms a key differentiator between this approach and other attempts to produce practical capacity planning and management tools. Statistically and clinically meaningful patient groupings may then be fed into developed simulation models and individual patients from each group passed through the particular hospital system of concern. The effectiveness of the framework is demonstrated through the development and use of an integrated hospital capacity tool.

Algorithms↗
PubMed1992

Public-private partnerships: the Connecticut model for financing long-term care.

Responses to the growing crisis in long-term care financing have included efforts to negotiate partnerships between the private and public sectors for the purpose of developing innovative models for long-term care insurance. One such set of models has been encouraged by support from the Robert Wood Johnson Foundation's "Long Term Care Insurance Program" grants. The Connecticut Partnership for Long Term Care uses a cooperative approach to encourage the development of private sector long-term care insurance products that are integrated with Medicaid eligibility determinations. The Connecticut model is described, accompanied by a history of its development, and a comparison is made with other models currently under consideration by national policy analysts.

Connecticut↗
PubMed1977

[Principles for optimizing and guaging several processes in the technology of vaccine production. II. Modeling processes of thermal inactivation of microorganisms].

The paper treats of some problems pertinent to modelling of thermal inactivation of the microbes serving as a theoretical foundation for the achievement of guaranteed sterility of the equipment, communications and fluids. The principal attention is devoted to the problems of quantitative assessment of the efficacy of the mentioned processes. The advantages and the drawbacks of some deterministic and probability models which found application in microbiological laboratories are assessed. The expediency of orientation on a model proposing the use of characteristics of thermal resistance of the microorganisms and considering the heterogeneity of the actual populations by the thermoresistance index was demonstrated.

Bacillus↗