Biochemical systems theory and metabolic control theory: 2. the role of summation and connectivity relationships

Perhaps the major obstacle to recognizing the relatedness of Biochemical Systems Theory (BST) and a subsequently developed approach some have called Metabolic Control Theory (MCT) is the summation and connectivity relationships. These are the most visible and central features of the MCT approach to the understanding of intact biochemical systems, whereas in the BST approach they appear to be invisible and peripheral. Generalized versions of these relationships are shown to be inherent to BST, and it is shown how their role differs from that within MCT. The significance of summation and connectivity relationships is shown to be historical and secondary in the sense that one can understand fully the integrated behavior of complex biochemical systems in steady state with BST and never explicitly invoke these relationships. It also is shown that the summation and connectivity relationships in MCT have inherent limitations that make them inadequate as the basis for a general theory of biochemical systems. The results in this paper, together with those in the previous paper, clearly demonstrate that MCT is a special case of BST.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26551/1/0000090.pd

Biochemical systems theory and metabolic control theory: 1. fundamental similarities and differences

Biochemical Systems Theory (BST) was developed in the late 1960s to explicate the integrated behavior of intact biochemical systems--specific dynamic behavior as well as general principles of design--in relation to the properties of their underlying molecular elements. This approach was used successfully in a number of biochemical and other biological applications throughout the 1970s and 1980s. A related approach, Metabolic Control Theory (MCT), was proposed in the mid 1970s. Its developments generally have followed without reference the analogous developments in BST, and its proponents have treated the two approaches as if they were unrelated. Detailed comparison of the fundamental structures of BST and MCT shows that, although there are some superficial differences, both in fact are based upon the same underlying formalism. Molecular descriptions in MCT comprise a special case of those in BST. Systemic descriptions differ with respect to the level of aggregation assumed. The aggregation at the level of net increase or net decrease of each system constituent found in BST is shown to produce the more revealing and useful theory, and results presented elsewhere [41] suggest that this level of aggregation also provides a more accurate description of the system. At this fundamental level, MCT represents a special case of BST, for the content and range of validity of BST are more inclusive than those of MCT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26550/1/0000089.pd

Efficient solution of nonlinear models expressed in S-system canonical form

The S-system is emerging as a general canonical form for analysis of nonlinear models. Models expressed within this regularly structured system of nonlinear ordinary differential equations are obtained by applying either of two different strategies: (A) Direct derivation of an S-system utilizing the Power Law Formalism; or (B) exact recasting of an existing, well established model into S-system form. By capitalizing on the regular structure of S-systems, efficient formulas for numerical solution of this general class have been developed. For any S-system it can be shown that these formulas are more efficient than conventional multistep formulas of the same order. For implemented methods, the actual improvements in efficiency are considerably more than the minimum estimates. Preliminary tests show that time required for solution of S-systems is reduced by one or two orders of magnitude -- the relative improvement in efficiency increases with size and complexity of the problem, and with degree of accuracy required.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27485/1/0000528.pd

Self-reported diabetes is associated with self-management behaviour: a cohort study

<p>Abstract</p> <p>Background</p> <p>The purposes of this cohort study were to establish how frequently people with physician-diagnosed diabetes self-reported the disease, to determine factors associated with self-reporting of diabetes, and to evaluate subsequent differences in self-management behaviour, health care utilisation and clinical outcomes between people who do and do not report their disease.</p> <p>Methods</p> <p>We used a registry of physician-diagnosed diabetes as a reference standard. We studied respondents to a 2000/01 population-based health survey who were in the registry (n = 1,812), and we determined the proportion who reported having diabetes during the survey. Baseline factors associated with self-report and subsequent behavioural, utilisation and clinical differences between those who did and did not self-report were defined from the survey responses and from linkage with administrative data sources.</p> <p>Results</p> <p>Only 75% of people with physician-diagnosed diabetes reported having the disease. People who did self-report were more likely to be male, to live in rural areas, to have longer disease duration and to have received specialist physician care. People who did not report having diabetes in the survey were markedly less likely to perform capillary blood glucose monitoring in the subsequent two years (OR 0.05, 95% CI 0.02 to 0.08). They were also less likely to receive specialist physician care (OR 0.55, 95% CI 0.37 to 0.86), and were less likely to require hospital care for hypo- or hyperglycaemia (OR 0.09, 95% CI 0.01 to 0.28).</p> <p>Conclusion</p> <p>Many people with physician-diagnosed diabetes do not report having the disease, but most demographic and clinical features do not distinguish these individuals. These individuals are much less likely to perform capillary glucose monitoring, suggesting that their diabetes self-management is inadequate. Clinicians may be able to use the absence of glucose monitoring as a screening tool to identify people needing a detailed evaluation of their disease knowledge.</p

Dimensionless cosmology

Although it is well known that any consideration of the variations of fundamental constants should be restricted to their dimensionless combinations, the literature on variations of the gravitational constant $G$ is entirely dimensionful. To illustrate applications of this to cosmology, we explicitly give a dimensionless version of the parameters of the standard cosmological model, and describe the physics of Big Bang Neucleosynthesis and recombination in a dimensionless manner. The issue that appears to have been missed in many studies is that in cosmology the strength of gravity is bound up in the cosmological equations, and the epoch at which we live is a crucial part of the model. We argue that it is useful to consider the hypothetical situation of communicating with another civilization (with entirely different units), comparing only dimensionless constants, in order to decide if we live in a Universe governed by precisely the same physical laws. In this thought experiment, we would also have to compare epochs, which can be defined by giving the value of any {\it one} of the evolving cosmological parameters. By setting things up carefully in this way one can avoid inconsistent results when considering variable constants, caused by effectively fixing more than one parameter today. We show examples of this effect by considering microwave background anisotropies, being careful to maintain dimensionlessness throughout. We present Fisher matrix calculations to estimate how well the fine structure constants for electromagnetism and gravity can be determined with future microwave background experiments. We highlight how one can be misled by simply adding $G$ to the usual cosmological parameter set

Design and development of a complex narrative intervention delivered by text messages to reduce binge drinking among socially disadvantaged men

Background: Socially disadvantaged men are at high risk of suffering from alcohol-related harm. Disadvantaged groups are less likely to engage with health promotion. There is a need for interventions that reach large numbers at low cost and which promote high levels of engagement with the behaviour change process. The aim of this study was to design a theoretically and empirically based text message intervention to reduce binge drinking by socially disadvantaged men. Results: Following MRC guidance, the intervention was developed in four stages. Stage 1 developed a detailed behaviour change strategy based on existing literature and theory from several areas. These included the psychological theory that would underpin the intervention, alcohol brief interventions, text message interventions, effective behaviour change techniques, narratives in behaviour change interventions and communication theory. In addition, formative research was carried out. A logic model was developed to depict the pathways between intervention inputs, processes and outcomes for behaviour change. Stage 2 created a narrative which illustrated and modelled key steps in the strategy. Stage 3 rendered the intervention into a series of text messages and ensured that appropriate behavioural change techniques were incorporated. Stage 4 revised the messages to ensure comprehensive coverage of the behaviour change strategy and coherence of the narrative. It also piloted the intervention and made final revisions to it. Conclusions: The structured, systematic approach to design created a narrative intervention which had a strong theoretical and empirical basis. The use of a narrative helped make the intervention realistic and allowed key behaviour change techniques to be modelled by characters. The narrative was intended to promote engagement with the intervention. The intervention was rendered into a series of short text messages, and subsequent piloting showed they were acceptable in the target group. Delivery of an intervention by text message offers a low-cost, low-demand method that can reach large numbers of people. This approach provides a framework for the design of behaviour change interventions which could be used for interventions to tackle other health behaviours

Computational approaches for modeling human intestinal absorption and permeability

Human intestinal absorption (HIA) is an important roadblock in the formulation of new drug substances. Computational models are needed for the rapid estimation of this property. The measurements are determined via in vivo experiments or in vitro permeability studies. We present several computational models that are able to predict the absorption of drugs by the human intestine and the permeability through human Caco-2 cells. The training and prediction sets were derived from literature sources and carefully examined to eliminate compounds that are actively transported. We compare our results to models derived by other methods and find that the statistical quality is similar. We believe that models derived from both sources of experimental data would provide greater consistency in predictions. The performance of several QSPR models that we investigated to predict outside the training set for either experimental property clearly indicates that caution should be exercised while applying any of the models for quantitative predictions. However, we are able to show that the qualitative predictions can be obtained with close to a 70% success rate

Quality Measures for the Diagnosis and Non-Operative Management of Carpal Tunnel Syndrome in Occupational Settings

Introduction: Providing higher quality medical care to workers with occupationally associated carpal tunnel syndrome (CTS) may reduce disability, facilitate return to work, and lower the associated costs. Although many workers’ compensation systems have adopted treatment guidelines to reduce the overuse of unnecessary care, limited attention has been paid to ensuring that the care workers do receive is high quality. Further, guidelines are not designed to enable objective assessments of quality of care. This study sought to develop quality measures for the diagnostic evaluation and non-operative management of CTS, including managing occupational activities and functional limitations. Methods: Using a variation of the well-established RAND/UCLA Appropriateness Method, we developed draft quality measures using guidelines and literature reviews. Next, in a two-round modified-Delphi process, a multidisciplinary panel of 11 U.S. experts in CTS rated the measures on validity and feasibility. Results: Of 40 draft measures, experts rated 31 (78%) valid and feasible. Nine measures pertained to diagnostic evaluation, such as assessing symptoms, signs, and risk factors. Eleven pertain to non-operative treatments, such as the use of splints, steroid injections, and medications. Eleven others address assessing the association between symptoms and work, managing occupational activities, and accommodating functional limitations. Conclusions: These measures will complement existing treatment guidelines by enabling providers, payers, policymakers, and researchers to assess quality of care for CTS in an objective, structured manner. Given the characteristics of previous measures developed with these methods, greater adherence to these measures will probably lead to improved patient outcomes at a population level