Total, average and marginal rates of basal heat production during human growth.

Our goal was to examine how total, average (heat production rate per unit mass) and marginal (the increase in the heat production rate per unit increase in mass) rates of basal heat production changed as mass increased in growing humans. Specifically, our hypotheses were that the marginal basal heat production rate did not decrease monotonically as humans grew; and that an energetically optimal mass, one at which the average basal heat production rate of a growing human was minimal, existed. Marginal rates of heat production were estimated and six potential models to describe the effect of mass during human growth on basal heat production rate were evaluated using a large, meticulously curated, dataset from the literature. Marginal rates of heat production were quadratically related to body mass during growth; they declined initially, reached a minimum, and then increased. This suggested that the relationship between basal heat production rate and mass was cubic. Of the six potential models evaluated, a three-parameter cubic polynomial best described the data. Marginal rates of heat production were minimal for 56-kg females and 62-kg males. Basal heat production rates per unit mass of a growing human were minimal (i.e., energetically optimal) for 83-kg females and 93-kg males; the average masses of U.S. adults have been increasing and approaching these optima over the last 60 yr.

A computational model of feedback-mediated hematopoietic stem cell differentiation in vitro.

Hematopoietic stem cells (HSCs) play an important physiological role as regulators of all blood and immune cell populations, and are of clinical importance for bone marrow transplants. Regulating HSC biology in vitro for clinical applications requires improved understanding of biological inducers of HSC lineage specification. A significant challenge for controlled HSC expansion and differentiation is the complex network of molecular crosstalk between multiple bone marrow niche components influencing HSC biology. We describe a biology-driven computational approach to model cell kinetics in vitro to gain new insight regarding culture conditions and intercellular signaling networks. We further investigate the balance between self-renewal and differentiation that drives early and late hematopoietic progenitor populations. We demonstrate that changing the feedback driven by cell-secreted biomolecules alters lineage specification in early progenitor populations. Using a first order deterministic model, we are able to predict the impact of media change frequency on cell kinetics, as well as distinctions between primitive long-term HSCs and differentiated myeloid progenitors. Integrating the computational model and sensitivity analyses we identify critical culture parameters for regulating HSC proliferation and myeloid lineage specification. Our analysis suggests that accurately modeling the kinetics of hematopoietic sub-populations in vitro requires direct contributions from early progenitor differentiation along with the more traditionally considered intermediary oligopotent progenitors. While consistent with recent in vivo results, this work suggests the need to revise our perspective on HSC lineage engineering in vitro for expansion of discrete hematopoietic populations.

Progressive limit feeding to maximize profit in the feedlot1.

Our objective was to examine the potential of limit feeding that keeps a previously growing animal at a constant size (termed progressive limit feeding) to maximize profit using a 3D surface to integrate the effects of animal size, feeding rate, and time in the feedlot. The constant size contours of the surface were determined using a combination of results. We used data from a study of growing beef cattle being fed to maintain specified sizes coupled with modern growth rate data for animals fed ad libitum in a feedlot. These feed rate contours were best-fit declining exponentials. They shared the same exponent and they originated on the ad libitum curve, thus defining the entire possible growth surface. The asymptotes of these exponentials coincided with the interspecies mean for the metabolic body size of mature animals. This surface also demonstrated the phenomenon of compensatory growth. We proved that the most profitable growth path across this surface is of a particular form under realistic assumptions. Specifically, we proved that the profit maximizing growth path in the feedlot began with a period of progressive limit feeding and then allowed ad libitum feeding to the same market time as experienced by the standard continuous ad libitum fed animal. The opportunity cost of holding the progressively limit-fed animal longer in the feedlot than the animal fed ad libitum quickly overpowered any profit gained by limit feeding. Consequently the progressively limit-fed animal on the optimal feeding path at sale time was slightly smaller but potentially more profitable than the animal fed ad libitum, both slaughtered at the same time. It may also have an economically favorable body composition. Thus we have demonstrated a process for maximizing profit in the feedlot. The approach involved developing a growth surface to integrate the effects of progressive limit feeding and subsequent compensatory growth. After refinement this same process could be applied to other livestock.

Energy and materials conservation: applying pioneering research and techniques to current non-energy materials conservation issues.

The research of the Energy Research Group (ERG) at the University of Illinois at Urbana-Champaign through the 1970s and early 1980s has recurring bouts of popularity. That research traced the flow of various energy types from nature to the final product or service, using modified economic input-output analysis. That information allowed for a comparison of alternative uses of products and services that delivered the same demand. The goal of the study was to identify the energy-conserving potential of the alternatives. Interest in that research has risen and fallen with the price of energy through three cycles now, with the current interest also encompassing materials conservation. Although the specific numerical results of this work are dated, the process by which the analysis was conducted creates, at least, a suggestion for future analysis in the arena of materials research. A review of the ERG history, including techniques pioneered for investigating the potential for energy conservation and some of the ancillary lessons learned along the way, may be of some use to those working on issues of materials conservation today. In the coming years, the most relevant research will include assessment of the socio-economic-ecological impact of technological materials conservation policies.

Simulated comparison of topical and oral formulations of 5-aminosalicylate for the treatment of ulcerative colitis.

BACKGROUND: 5-Aminosalicylate (5-ASA) formulations are approved for the treatment of ulcerative colitis (UC). Determination of the colonic pharmacokinetics of 5-ASA is challenging. A dynamic model of 5-ASA colonic amounts after oral delayed-release 5-ASA (Asacol), oral extended delayed-release 5-ASA (Lialda), 5-ASA enema (Rowasa), foam and suppositories (Canasa) was developed to determine the colonic kinetics of these agents. METHODS: We created a model with Stella software. Colonic 5-ASA in the right, transverse, descending, sigmoid colon, and rectum were estimated for adults after recommended doses of the above formulations. Simulations of active mild/moderate UC and in remission were performed and compared using Student's t-test for differences in means. RESULTS: For UC in remission, the highest amounts of 5-ASA were from Asacol in the right and transverse colon (P < 0.01), Lialda in the descending and sigmoid colon (P < 0.01), and Rowasa in the rectum (P < 0.01). For active UC, sigmoid amounts were highest with foam (P < 0.01), and rectal amounts highest with Rowasa (P < 0.01). Differences in rectosigmoid amounts of 5-ASA from enemas and suppositories for UC in remission occurred based on the relationship between the timing of administration relative to the daily bowel movement (P < 0.01). CONCLUSIONS: Compared to Asacol, Lialda results in higher 5-ASA amounts in the left colon. Asacol with Rowasa provides highest 5-ASA amounts across the entire colon. Higher 5-ASA amounts from topical formulations occur when the insertion occurs soon after the daily bowel movement. This model provides a rationale for further investigation.

The role of input-output analysis of energy and ecologic systems. In the early development of ecological economics--a personal perspective.

A summary is provided of the early history of research on the flow of nonrenewable energy resources through the economy and of the flow of renewable energy resources through a natural ecosystem. The techniques are similar, and many specific applications are provided. A combined economic and ecological technique is also defined. The early history and people of the International Society Ecological Economic are cited.

A dynamic model of once-daily 5-aminosalicylic acid predicts clinical efficacy.

New once daily mesalamine formulations may improve adherence to medication usage. Response to Asacol and other forms of 5-aminosalicyclic acid (5-ASA) is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon. Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration. In our study, the model simulated Asacol distribution in the healthy colon, and during quiescent and active ulcerative colitis. An Asacol dosage of 800 mg, three times a day, was compared to 2400 mg given once a day. Under ideal conditions, the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3% between single and multiple doses. Despite changes in motility and defection rates, the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10% between dosing regimens. Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate. In active colitis, sigmoid 5-ASA concentration becomes negligible. Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.

A computer simulation of the prevention of the transmission of Toxoplasma gondii on swine farms using a feline T. gondii vaccine.

Transmission of Toxoplasma gondii on swine farms was investigated using a deterministic dynamic computer simulation model. A primary focus was to evaluate a feline T. gondii vaccine. Animal populations (swine and cats) were compartmentalized based on the stage of T. gondii infection. Simulations were run under conditions of closed and equilibrium population size. Model parameters were varied in a factorial experimental design to test the following hypotheses: T. gondii infection in finishing pigs decreases with (1) vaccination of susceptible cats, (2) an increase in the proportion of cats captured for vaccination, (3) a decrease in the initial number of cats, (4) a decrease in the initial T. gondii prevalence in cats and (5) a decrease in oocyst-survival time. Seeding conditions included a total of 10, 20, 30, 40 or 50 cats, initial T. gondii prevalences in cats of 30, 60 or 90%, vaccination of 0, 50 or 75% of the cats and two vaccination schedules (the field schedule from a prior trial and a weaning-vaccination schedule). Simulations were run at oocyst-survival times of 52, 39 and 26 weeks. T. gondii prevalence in finishing pigs was recorded every week for 10 years. The probability of elimination of T. gondii from finishing pigs increased with a decrease in the number of cats and a decrease in oocyst-survival time. The last-year average prevalence was used as the outcome in a multiple linear regression analysis. Decreased T. gondii prevalence in finishing pigs was the result of a decrease in the initial number of cats on the farm (squared semipartial correlation coefficient (sr(2))=47%), decreased oocyst survival (sr(2)=35%), using the weaning-vaccination schedule (sr(2)=7%) and vaccination versus non-vaccination (sr(2)=5%). Unexpectedly, the initial T. gondii prevalence in cats had no effect on T. gondii prevalence in finishing pigs. The simulation supports the field trial indicating vaccine effectiveness. However, vaccination had less impact on decreasing T. gondii infection in finishing pigs than a decrease in the number of farm cats.