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Biomedical subjects

R Boston

Publications and source records attributed to R Boston.

10 recordsLinked to original sources

Balancing needs, efficiency, and functionality in the provision of modeling software: a perspective of the NIH WinSAAM Project.

The development of new software or the refinement of existing software for new operating environments each calls for judicious balancing. On the one hand, we strive for simplicity, predictability, and operational protection as it is well recognized that software with these attributes will attract an audience of satisfied users. But, on the other hand, these attributes do not conjure a sense of power, efficiency, or flexibility, and these other properties are also appreciated by users, albeit a somewhat different group of users. The goal is to achieve a blend which isolates critical functionality, flexible control, and user support while meeting the needs of the broadest collection of serious users. In this chapter, we discuss the issues impacting the migration of SAAM to the Windows environment, the NIH WinSAAM Project, and we outline the steps taken to ensure its feasibility. In addition, we describe a new paradigm for software development and use which ensures the durability of the software for modeling.

Computer Simulation

Hemodynamic factors affecting uterine artery Doppler waveform pulsatility in sheep.

Quantitative analysis of vascular resistance from the Doppler time-velocity waveform relies on measuring arterial pulsatility. However, input pressure waveform pulsatility, impedance, and resistance have all been found to effect artery flow waveform pulsatility in circulatory mathematic models and in umbilical sheep preparations in vivo. The present study used an in vivo sheep preparation to determine that embolization of the uteroplacental circulation and maternal angiotensin II administration caused changes in the uterine Doppler time-velocity waveform pulsatility that were dependent on input pressure waveform pulsatility, fundamental impedance, and resistance changes. Uteroplacental vascular embolization increased vascular resistance and the uterine artery Doppler waveform resistive index; the mean component of flow (mean pressure/resistance) decreased. Decreased uterine artery Doppler resistive index occurred despite angiotensin II-induced vasoconstriction and increased vascular resistance because the pulse component of flow (pulse pressure/impedance) decreased.

Angiotensin II

Glucose metabolism in severe malaria: minimal model analysis of the intravenous glucose tolerance test incorporating a stable glucose label.

Basal plasma glucose is usually increased in uncomplicated malaria, implying insulin resistance. If the infection progresses, the risk of hypoglycemia will increase as host glucose production becomes insufficient for host/parasite demand. To assess the relative contribution of insulin-mediated and non-insulin-mediated glucose disposal to plasma glucose levels in severe malaria, we studied six healthy controls (two males and four females; mean age, 38 years) and eight patients with complicated falciparum malaria (five males and three females; mean age, 31 years) who had a frequently sampled intravenous glucose tolerance test (FSIVGTT) in which 10% of the dextrose bolus was 6,6-D2-glucose. The minimal model was applied to native and labeled plasma glucose and serum insulin profiles over 4 hours postinjection. Basal plasma glucose concentrations in the patients were significantly greater than in the controls (median [range], 6.1 [2.1 to 8.5] v 4.3 [3.9 to 4.7] mmol/L, P = .03). Malaria-associated insulin resistance was confirmed by a lower insulin sensitivity index (SI) in patients (5.6 [2.4 to 17.4] v 16.0 [2.5 to 22.3] x 10(-4).min-1 per microU/mL in controls, P = .026). Glucose effectiveness ([SG] the ability of glucose to reduce its own plasma concentration) was higher in the patients (0.015 [0.006 to 0.024] v 0.008 [0.007 to 0.010] min-1 in controls, p = .019). Glucose disappearance at basal concentration was increased by a median of 42% in severe malaria patients, with the insulin-independent component comprising 81%, versus 67% in controls. Indices of beta-cell function were normal in malaria patients. These data demonstrate that basal plasma glucose utilization is increased approximately 50% in severe malaria, consistent with previously published isotope-turnover studies. Altered SG plays a major role. Prevention and treatment of early hypoglycemia should be based on adequate glucose replacement. Strategies that reduce insulin secretion or effects appear to be of minor importance.

Adolescent

Using models to explore whole-body metabolism and accessing models through a model library.

A model is a mathematical representation of a system that can be used to explore the system in a number of ways: to determine the system's internal connections, to calculate properties of the system such as flow rates and pool sizes, and to make predictions about the system's behavior under different conditions. The use of modeling to explore whole-body metabolism is demonstrated using a compartmental model of zinc kinetics as an example. Because models are useful tools for exploring systems, a facility called a "model library" is being established on the Internet to provide access to working versions of published models.

Animals

Passive transfer of immune serum reduces the L1/adult ratio of worms recovered from the intestines of Strongyloides stercoralis-infected gerbils.

In Strongyloides stercoralis-infected gerbils it had been observed previously that the ratio of first-stage larvae to adult worms decreases after 3 wk of infection. Serum obtained from gerbils after this decrease in fecundity, but before worms were expelled, was transferred passively to other infected gerbils during the peak of worm fecundity. The immune serum caused a significant decrease in the L1/adult ratio but had no effect on the number of uterine eggs, the length, or the intestinal and ovarian ultrastructure of adult worms. Apparently a factor(s) in the immune serum either killed eggs, after oviposition, or the hatched larvae, without damaging the adult worms.

Animals

Rest potential--cooperative selectivity.

It is often necessary to determine the selectivity and cooperativity constants of ions and other substances which are selectively and cooperatively adsorbed at surface sites of biological cells. A computer program based on the Levenberg-Marquardt method is given to determine the selectivity and cooperativity constants from the non-linear equation for the resting potential.

Adsorption

EMSA: a SAAM service for the estimation of population parameters based on model fits to identically replicated experiments.

This paper presents a new technique for the aggregation of models to produce population parameter estimates based on a set of identically replicated experiments. After describing the theoretical basis for the technique we discuss tactical and strategic issues associated with its implementation in the SAAM software. Finally, we demonstrate its utility in the aggregation of models fitted to four simulated experiments.

Algorithms

Suppression by diets rich in fish oil of very low density lipoprotein production in man.

The highly polyunsaturated fatty acids in fish oils lower the plasma triglyceride concentration. We have studied the effect of a diet rich in fish oil on the rate of production of the triglyceride-transporting very low density lipoprotein (VLDL). Seven subjects, five normal and two with hypertriglyceridemia received up to 30% of daily energy needs from a fish oil preparation that was rich in eicosapentaenoic acid and docosahexaenoic acid, omega-3 fatty acids with five and six double bonds, respectively. Compared with a diet similarly enriched with safflower oil (in which the predominant fatty acid is the omega-6 linoleic acid, with two double bonds), the fish oil diet lowered VLDL lipids and B apoprotein concentrations profoundly. High density lipoprotein lipids and A1 apoprotein were also lowered, but the effect on low density lipoprotein (LDL) concentration was inconsistent. The daily production or flux of VLDL apoprotein B, calculated from reinjected autologous 125I-labeled lipoprotein, was substantially less in six subjects studied after 3 wk of fish oil, compared with after safflower oil. This effect on flux was more consistent than that on the irreversible fractional removal rate, which was increased in the four normolipidemic but inconsistent in the hypertriglyceridemic subjects. This suggests that fish oil reduced primarily the production of VLDL. The daily production of VLDL triglyceride, calculated from the kinetics of the triglyceride specific radioactivity-time curves after [3H]glycerol was injected, also showed very substantial reductions in five subjects studied. The marked suppression in VLDL apoprotein B and VLDL triglyceride formation was found not to be due to diminished plasma total free fatty acid or plasma eicosapentaenoic flux, calculated during constant infusions of [14C]eicosapentaenoic acid and [3H]oleic acid in four subjects. In two subjects there was presumptive evidence for substantial independent influx of LDL during the fish oil diet, based on the precursor-product relationship between the intermediate density lipoprotein and LDL apoprotein B specific radioactivity-time curves.

Adult