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PubMedDate not supplied

Predicting metabolic control in diabetes: a pilot study using meta-analysis to estimate a linear model.

The purpose of this pilot study was to determine the feasibility of using data from replicated descriptive studies to test a four-variable model designed to explain metabolic control in diabetes. Predictors of metabolic control selected for this analysis were knowledge; health beliefs (and the subscales of barriers, commitment, cues, expectancies, impact on lifestyle, support, and susceptibility); and compliance/adherence. A total of 17 studies, published between 1982 and 1991, were located that met inclusion criteria. Findings indicated that health beliefs have direct and indirect effects on diabetes metabolic control, depending on the individual health belief subscale analyzed. For example, commitment to the benefits of therapy was found to have a statistically significant direct effect on metabolic control; barriers had a statistically significant indirect effect through compliance. The effects of knowledge were consistent throughout the five path models explored. An inverse direct effect was noted on metabolic control and a positive indirect effect was noted on metabolic control through compliance.

Attitude to Health↗

PubMed1993

Optimizing high-dose therapy using pharmacokinetic principles.

The oncologic literature of the past decade contains numerous articles supporting the concept of "dose intensity." The hypothesis that greater intensity of effective drug therapy can result in higher cure rates is supported by the results obtained in bone marrow transplantation for leukemia, lymphoma, and, possibly, breast carcinoma. Stem cell infusion overcomes the first level of the dose-limiting toxicities, ie, bone marrow suppression. This predictable toxicity develops in all patients. Second organ toxicities, such as renal, hepatic, or cardiopulmonary toxicity, occur in a less predictable manner. This variation in individual patient tolerance may be related to wide variations in drug concentration between patients while receiving the same dose. This interpatient variability has been well described for many oncologic agents, but is not unique to oncologic therapy. Important but incompletely defined relationships of importance to high-dose therapy include (1) the relationship of drug dose to concentration within patient groups and for the individual patient and (2) the relationship of drug concentration, or other related parameter such as area under the concentration versus time curve, to toxicity and outcome. Assuming such relationships can be defined, the value of using improved methods to select drug doses for an individual patient to achieve therapeutic goals needs to be explored. The purpose is to optimize therapy. In the bone marrow transplantation setting, the ideal is to provide the greatest drug exposure without undo risk of life-threatening second organ toxicity. To solve these problems, we need models that predict and allow us to control therapy in a much more precise manner than is currently possible. This review examines the concept of dose intensity, defines this concept in terms of plasma drug concentrations, and reviews methods that can aid the control of therapy in the individual patient. The potential importance of this methodology to the individual patient is discussed.

Antineoplastic Agents↗

PubMed1996

HIV seropositive gay men: understanding adoption of safe sexual practices.

The aim of this study was to determine the best predictors of safe sex practices among HIV seropositive gay men. A group of 96 homosexual men living with HIV completed a questionnaire that investigated theoretical constructs of the Ajzen's (1988) theory of planned behavior with respect to condom use for anal intercourse and sexual practices without anal intercourse. Other variables such as Triandis's (1977) construct of personal normative belief, psychological distress, and alcohol and drug use before sexual encounters were also investigated. Results indicated that the best predictor of intention to use condoms was perceived behavioral control. Personal normative belief was another important predictor of this intention. Although the best predictor of intention to have only sex without anal intercourse was perceived subjective norm, this intention was also significantly explained by perceived behavioral control. Moreover, perceived behavioral control was a significant predictor of having only sex without anal intercourse. Public health interventions among HIV seropositive gay men should aim mainly at increasing perception of behavioral control.

Adult↗

PubMed2006

Hyperhomocysteinemia correlates with insulin resistance and low-grade systemic inflammation in obese prepubertal children.

Obesity is an independent risk factor for the development of cardiovascular disease frequently associated with hypertension, dyslipemia, diabetes, and insulin resistance. Higher homocysteine (Hcy) levels are observed in the hyperinsulinemic obese adults and suggest that Hcy could play a role in the higher risk of cardiovascular disease in obesity. We analyzed total Hcy levels in obese prepubertal children and their possible association with both metabolic syndrome and various inflammatory biomarkers and leptin. We studied 43 obese children (aged 6-9 years) and an equal number of nonobese children, paired by age and sex. The obese subjects presented significantly elevated values for insulin (P = .003), C-reactive protein (P = .033), and leptin (P < .001). No significant differences were found in Hcy levels between the obese and nonobese children. However, Hcy concentration was significantly higher in the hyperinsulinemic obese children than in the normoinsulinemic group (P = .002). Using multivariant regression analysis, in the obese group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .001) and leptin (P partial = .02) are independent predictive factors for Hcy. In the control group, corrected for age and sex, the homeostasis model assessment for insulin resistance (P partial = .005) and leptin (P partial = .031) also are independent predictive factor for Hcy. Increased plasma Hcy, particularly in hyperinsulinemic obese children, may be causally involved in the pathogenesis of atherosclerosis and/or cardiovascular disease, both of which are common in obesity.

Anthropometry↗

PubMed2006

Systems analysis of effector caspase activation and its control by X-linked inhibitor of apoptosis protein.

Activation of effector caspases is a final step during apoptosis. Single-cell imaging studies have demonstrated that this process may occur as a rapid, all-or-none response, triggering a complete substrate cleavage within 15 min. Based on biochemical data from HeLa cells, we have developed a computational model of apoptosome-dependent caspase activation that was sufficient to remodel the rapid kinetics of effector caspase activation observed in vivo. Sensitivity analyses predicted a critical role for caspase-3-dependent feedback signalling and the X-linked-inhibitor-of-apoptosis-protein (XIAP), but a less prominent role for the XIAP antagonist Smac. Single-cell experiments employing a caspase fluorescence resonance energy transfer substrate verified these model predictions qualitatively and quantitatively. XIAP was predicted to control this all-or-none response, with concentrations as high as 0.15 microM enabling, but concentrations >0.30 microM significantly blocking substrate cleavage. Overexpression of XIAP within these threshold concentrations produced cells showing slow effector caspase activation and submaximal substrate cleavage. Our study supports the hypothesis that high levels of XIAP control caspase activation and substrate cleavage, and may promote apoptosis resistance and sublethal caspase activation in vivo.

Apoptosis↗

PubMed1993

Relating blood concentrations of tetrahydrocannabinol and metabolites to pharmacologic effects and time of marijuana usage.

Pharmacokinetic and pharmacodynamic analyses of marijuana data have provided new insights into the relationship of blood concentrations of tetrahydrocannabinol (THC) and metabolites to drug-induced effects. THC is rapidly absorbed and distributed to tissues; initial changes in blood concentrations are out of phase (hysteresis) with physiological and behavioral changes. Once blood/tissue equilibrium is established, a direct correlation of THC blood concentration and effect is observed. Various pharmacodynamic models provide concentration estimates in the range of 7-29 ng/ml for amount of THC in blood necessary for production of 50% of maximal subjective high effect. Also, models have been proposed for predicting the time of marijuana exposure from plasma concentrations of THC and THC-carboxy acid metabolite (THCCOOH). These models were based on data from a controlled clinical study of marijuana smoking. Such models allow prediction of the elapsed time since marijuana use based on analysis for cannabinoids from a single plasma sample and provide accompanying 95% confidence intervals around the prediction. These models may be beneficial to forensic scientists in their interpretation of cannabinoid blood data associated with accidents, criminal investigations, and traffic violations.

Dronabinol↗

PubMed2004

Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non-drug-using controls.

AIMS: To test a prediction of the discounting model of impulsiveness that discount rates would be positively associated with addiction. The delay-discount rate refers to the rate of reduction in the present value of a future reward as the delay to that reward increases. DESIGN AND MEASUREMENTS: We estimated participants' discount rates on the basis of their pattern of choices between smaller immediate rewards ($11-80) and larger, delayed rewards ($25-85; at delays from 1 week to 6 months) in a questionnaire format. Participants had a one-in-six chance of winning a reward that they chose on one randomly selected trial. PARTICIPANTS AND SETTING: Heroin (n = 27), cocaine (n = 41) and alcohol (n = 33) abusers and non-drug-using controls (n = 44) were recruited from advertisements. They were tested in a drug abuse research clinic at a medical school. FINDINGS: On average, the cocaine and heroin groups had higher rates than controls (both P < 0.001), but alcoholics did not (P = 0.44). Abstinence was associated with lower rates for heroin abusers (P = 0.03), but not for cocaine or alcohol abusers (both P > 0.50). CONCLUSIONS: These data suggest that discount rates vary with the preferred drug of abuse, and that high discount rates should be considered in the development of substance abuse prevention and treatment efforts.

Adult↗

PubMed1988

An approach to the interpretation of clinical data on the tumour control probability-dose relationship.

A conventional statistical model allows predicting the sterilisation rate as a function of dose. However, the computation requires data on biological parameters (proportion of clonogenic cells, survival per fraction, multiplication rate) which are inaccessible for human tumours. The curative dose 50% (TCD50) can be used as a synthesis of these parameters and its significance for the response-dose relationship of a population of tumours of uniform radiosensitivity is discussed. The slope of the dose-control curve provides vital information regarding the variation in radiocurability of the various individual tumours. The model allows the analysis of the clinical data and the separation of tumour subsets with different radiation responsiveness. It provides an evaluation of the benefit which could be obtained from the identification of the subsets and a guidance for the clinical, pathological and biological studies which relate to this identification. The change in the response-dose relationships with the tumour size cannot (usually) be explained by the cell number increase alone. Other possible factors of reduced radiocurability are discussed.

Cell Survival↗

PubMed1997

Developmental regulation across adulthood: primary and secondary control of age-related challenges.

This study addresses developmental regulation in adults at different ages. A conceptual model of optimization in primary and secondary control across the life span (OPS model) is presented, and predictions about age differences in developmental regulation are derived. Developmental goals, expectations about goal attainment and control, control strategies, life satisfaction, and age identification were assessed in a sample of 510 young, middle-aged, and old adults. At increasing age, the participants expressed (a) greater awareness of a reduced potential for growth and control. (b) increased focus on age-appropriate goals for primary control striving, (c) more goals directed at the avoidance of developmental losses and fewer goals aimed at developmental gains, and (d) a stronger tendency for compensatory secondary control, as shown in greater goal flexibility, more satisfaction with present life, and identification with younger age groups.

Adult↗

PubMed1984

Estimation of genetic trend in a selected population with and without the use of a control population.

Data from a selection experiment conducted with sheep at Massey University, New Zealand, were analyzed to obtain an evaluation of selection response. Selection was for heavy 14-mo greasy fleece weight. Approximately seven generations of selection were represented in the data. Three estimates of genetic superiority of the selected line to the control line were obtained. All three estimates were obtained from a mixed model evaluation using the individual animal model for predicting breeding values from own and relatives' records. The estimators were 1) deviation of selected line predicted yearly phenotypes from control line predicted yearly phenotypes, 2) deviation of the predicted yearly phenotype for the selected line from the year estimate in the control line and 3) the mean yearly breeding value from the analysis of the selected line only. The realized heritability using the first approach was .20. However, the control line was found to have a slight positive drift; hence, this estimate was biased downward. Using Approach 2, accounting for drift, the realized heritability was .23. The same realized heritability, .23, was obtained from an analysis of the selected line ignoring the control (Approach 3), when a prior heritability of .30 was assumed for the mixed model evaluation. The estimate of genetic trend from predicted breeding values in the latter approach is, however, quite dependent on the assumed heritability.

Animals↗

PubMed1967

Mathematical simulation of an aquatic snail population.

Techniques for controlling the intermediate snail hosts of schistosomiasis have had to be evaluated by field trials, since the complexity of snail population dynamics has so far made it impossible to predict the effects of these techniques and thereby avoid costly field testing.However, in laboratory studies with Biomphalaria glabrata it was found that the fecundity of these snails was directly proportional to F/NV, where F is the total amount of food in the habitat, N the number of snails, and V the volume of the habitat. The use of this fecundity variable together with data published on snail longevity and fecundity made it possible to construct a mathematical model of a snail population which may eventually be useful for evaluating snail control methods.For preliminary verification of the model, its predictions were compared with a published history of a population of Bulinus globosus in a small pond. The general agreement of the predicted and observed population data indicated that the basic structure of the model was sound.

Animals↗

PubMed1999

A behavior-based inverse kinematics algorithm to predict arm prehension postures for computer-aided ergonomic evaluation.

In this paper, the computational problem of inverse kinematics of arm prehension movements was investigated. How motions of each joint involved in arm movements can be used to control the end-effector (hand) position and orientation was first examined. It is shown that the inverse kinematics problem due to the kinematic redundancy in joint space is ill-posed only at the control of hand orientation but not at the control of hand position. Based upon this analysis, a previously proposed inverse kinematics algorithm (Wang et Verriest, 1998a) to predict arm reach postures was extended to a seven-DOF arm model to predict arm prehension postures using a separate control of hand position and orientation. The algorithm can be either in rule-based form or by optimization through appropriate choice of weight coefficients. Compared to the algebraic inverse kinematics algorithm, the proposed algorithm can handle the non-linearity of joint limits in a straightforward way. In addition, no matrix inverse calculation is needed, thus avoiding the stability and convergence problems often occurring near a singularity of the Jacobian. Since an end-effector motion-oriented method is used to describe joint movements, observed behaviors of arm movements can be easily implemented in the algorithm. The proposed algorithm provides a general frame for arm postural control and can be used as an efficient postural manipulation tool for computer-aided ergonomic evaluation.

Adult↗

PubMed1981

Alleviation of performance deficits of depression through thermal biofeedback training.

Explored thermal biofeedback as a method of reducing performance deficits associated with depression. A depressed and nondepressed control group and a depressed group given pretreatment with biofeedback were (N = 30) compared on their performance on an escape/avoidance task. As predicted by the learned helplessness model of depression, depressed controls showed significantly poorer performance than both other groups. The depressed biofeedback and nondepressed control groups did not differ from one another. Implications for alleviation of depression are discussed.

Achievement↗

PubMed1996

The applicability of the theory of planned behavior to abusive men's cessation of violent behavior.

This study examined the ability of Ajzen's (1988; 1991) Theory of Planned Behavior (TPB) to explain men's cessation of violent behavior. TPB suggests that a man's intention to abuse his female partner, and therefore his subsequent abusive behavior will be determined by: (1) his evaluation of possible outcomes of abusive behavior (attitudes toward behavior); (2) his perception of the expectations of others around him concerning violence and (3) the degree to which he believes he can control his abusive behavior. Pretest self-report measures from men and follow-up recidivism data based on partner report were available for 176 cases drawn from a previous study conducted by Harrell (1991). Reliable proxy measures for TPB variables (intentions/expectations to use violence, attitudes toward behavior, social norms, perceived behavioral control) were created. Regression analyses testing the TPB model provided modest support for prediction of intention to reabuse and subsequent abusive behavior. Of the TPB variables, perceived control appeared to be most important in understanding batterers' intentions to abuse and their subsequent abusive behavior. Refinement in measurements and the need for additional modifications to the model are discussed.

Adult↗

PubMed1988

A dynamic analysis of the ventilatory response to carbon dioxide inhalation in man.

1. The dynamics of the ventilatory response to carbon dioxide inhalation were studied in ten healthy young men using four different inspired fractions of carbon dioxide (FI, CO2) in air (0.015, 0.030, 0.045 and 0.060) successively increasing and decreasing stepwise. 2. Seven such different progressions were performed for each subject and each of seven different durations of the steps (t) ranging between 0.1 (i.e. one ventilatory cycle) and 10 min ('steady-state' conditions). The overall duration of one test (T) was taken as the sum of the seven successive FI, CO2 steps (t) plus one step, t, of air breathing. Thus, the values of T ranged between 0.8 (i.e. eight ventilatory cycles) and 80 min. Three subjects were tested twice. 3. We measured, as a function of T, the magnitude of the loops formed by the curves PA, CO2-VE and the value of the highest ventilatory response (VE max) to each progression. For all ten subjects, both functions had two maxima, one for T values of 2.6 or 8.0 min and one for T values of 24 or 40 min, and one minimum at T equal to 12 min. 4. The same measurements were made on tidal volume-response curves (PA, CO2-VT) and ventilatory frequency-response curves (PA, CO2-f) and yielded the same results except for the ventilatory frequency-response curves, for which we only found a statistically insignificant single maximum for T values of 24 or 40 min. 5. The locations of the maxima in loop magnitude and VE max were similar in duplicate tests in three subjects, whereas the quantitative values of these variables showed wide differences. 6. We compared our results with what is expected from the current linear dynamic model of ventilatory control submitted to the same forcing function: the first maximum in the loop magnitude is predicted by the model, but the second is not. The model shows no peak in the evolution of VE max. 7. We conclude that controlled system dynamics, which are the only ones included in dynamic models of ventilatory control, cannot by themselves account for our observations, and that one should take into consideration the dynamics of the controlling neuronal network.

Adult↗

PubMedDate not supplied

Design of a novel apparatus to study nitric oxide (NO) inhibition of platelet adhesion.

Nitric oxide (NO) is a simple biological molecule which inhibits adhesion and aggregation of platelets. A novel NO delivery device has been developed to quantitatively study the effects of NO concentration and flux on the adhesion of platelets to a surface. The slit-flow device is lined with a protein-coated membrane through which NO gas permeates into a perfusing platelet suspension. A model predicting spatial NO concentrations and fluxes within the flow slit was validated. At a wall shear rate of 250 s(-1), platelet adhesion was inhibited 87% relative to controls for exposures as low as 0.1 ppm NO. Corresponding model predictions of the aqueous NO concentration and fluxes at the surface were 0.15 nM, and between 0.5 and 1.1 nanomoles cm(-2) s(-1), respectively. Endothelial cells, which release NO to inhibit platelet adhesion in vivo, generate NO at an estimated flux similar to the above values. At a NO exposure of 0.02 ppm, platelet inhibition was only 10%. The delivery device is useful for other studies in which a knowledge of the spatial NO fluxes or concentrations is desired. Knowledge of these fluxes or concentrations is beneficial towards the design of biomaterials incorporating NO to inhibit platelet adhesion.

Biomedical Engineering↗

PubMed1990

A simple deterministic model for bancroftian filariasis transmission dynamics.

A differential equation model for bancroftian filariasis transmission dynamics is developed. Fluctuations of the mosquito vector population are related to environmental variables such as climate and vector control operations. Prevalence in the mosquito population and mean worm burden in the human population are considered. The behaviour of the model is compared with epidemiologic and entomological data from Pondicherry (South India). The model enables one to make predictions on the effect of future control operations.

Animals↗

PubMed2004

Pharmaceutical pricing, price controls, and their effects on pharmaceutical sales and research and development expenditures in the European Union.

BACKGROUND: Each country in the European Union (EU) currently employs direct price controls or permutations of direct price controls, such as reference pricing or limitations on returns to capital. Some countries also use volume controls. A new proposal that is being discussed would have all of the countries in the EU adopt uniform pricing for each pharmaceutical. OBJECTIVE: This paper analyzes the economic effects of free-market pricing individual-country price controls, and uniform EU price controls. METHODS: Microeconomic and mathematical models were used to simulate and predict probable economic outcomes in a comparative static setting. RESULTS: Price controls may be in the form of price ceilings or price floors. Both forms of price control generate deadweight economic losses in the short run and long run. A uniform EU price for each pharmaceutical sold there would have elements of a price ceiling in some of the countries and of a price floor in other countries. The deadweight loss incurred would be a function of the level at which the uniform price was set by the EU and the price elasticity of demand for each pharmaceutical in each country. CONCLUSIONS: Economic efficiency is maximized in both the short run and long run when prices are set in freely competitive markets. An additional important dimension of Ramsey pricing within a competitive context is that it generates funds for investment in pharmaceutical research and development, which enhances economic efficiency in the long run.

Cost Control↗