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What is the cost of a healthy diet in terms of achieving RDAs?

OBJECTIVE: Assessing how the Italian average food pattern would be affected in terms of consumption structure and expenditure by the adoption of nutritional prescriptions. DESIGN: A linear programming model with nutritional and food habits constraints was employed to generate a pattern following recommended daily allowances (RDAs) and nutritional guidelines provided for the Italian population. SETTING: Food consumption data from ISTAT Household Budget Survey of Italian population. SUBJECTS: Italian families investigated by the Family Budget Survey of the National Institute of Statistics. RESULTS: Compared to actual behaviour, the pattern generated by the model implies an increased consumption of vegetables, pasta, rice and fresh fish, and a decreased consumption of meats, bread, sugars and cakes, and especially fats and oils. At given prices, total expenditure is lower than actual expenditure. CONCLUSIONS: Differences between actual behaviour and the generated pattern are consistent with long-term trends in food consumption. The adoption of RDAs is unlikely to result in an increased food expenditure.

Budgets↗

13C NMR evidence for pyruvate kinase flux attenuation underlying suppressed acid formation in Bacillus subtilis.

When batch and continuous Bacillus subtilis cultures are provided with a small amount of citrate, acid production ceases, carbon yield increases by more than 2-fold, and the productivity of recombinant protein increases. It has been hypothesized that pyruvate kinase activity is attenuated, which in turn lowers glucose flux and minimizes the acid overflow prompted by low Krebs cycle capacity. To complement existing enzyme activity, linear programming, and metabolite pool studies, (13)C NMR studies were performed. Atom mapping and isotopomer mapping matrix methods were used to select the best glucose label. "Best" was defined such that the NMR spectra of glutamate associated with metabolizing labeled glucose via the different candidate metabolic trafficking scenarios would differ considerably in fine structure (e.g., relative singlet intensities). When experiments were performed with 1-(13)C glucose, the observed NMR spectra corresponded well to the one predicted to arise when the metabolic trafficking occurs according to a pyruvate kinase attenuation scenario. This evidence further fortifies the prospects for successfully basing a metabolic engineering strategy on reducing pyruvate kinase activity to better match glycolytic and Krebs cycle capacities.

Bacillus subtilis↗

Optimal design of protein production plants with time and size factor process models.

In this work we propose an optimization model for the design of a biotechnological multiproduct batch plant. A first level of detail posynomial model is constructed for each unit, as well as decisions regarding the structural optimization of the plant. A particular feature of this model is that it contains composite units in which semicontinuous items operate on the material contained by batch items. This occurs in the purification steps, in particular with the microfilters operating between retentate and permeate vessels, and with the homogenizer and ultrafilters operating on the material contained in a batch holding vessel. Also, the unit models rely on batch operating time expressions that depend on both the batch size and the size of semicontinuous items. The model takes into account all of the available options to increase the efficiency of the batch plant design: unit duplication in-phase and out-of-phase and intermediate storage tanks. The resulting mathematical model for the minimization of the plant capital cost is a mixed integer non-linear program (MINLP), which is solved to global optimality with an implementation of the outer approximation/ equality relaxation/ augmented penalty (OA/ER/AP) method. A plant that produces four recombinant proteins in eight processing stages is used to illustrate the proposed approach. An interesting feature of this example is that it represents an attempt to standardize a plant for the production of both therapeutic and nontherapeutic proteins; the model applied is generic and can thus be applied to any such modular plant. Results indicate that the best solution in terms of minimal capital cost contains no units in parallel and with intermediate storage tank allocation.

Algorithms↗

Cell surface electrochemical heterogeneity of the Fe(III)-reducing bacteria Shewanella putrefaciens.

Acid-base titration experiments and electrostatic force microscopy (EFM) were used to investigate the cell surface electrochemical heterogeneity of the Fe(III)-reducing bacteria, Shewanella putrefaciens. The acid-base titrations extended from pH 4 to 10, and the titration data were fit using a linear programming pKa spectrum approach. Overall, a five-site model accounted for the observed titration behavior with the most acidic sites corresponding to carboxylic groups and phosphodiester groups, intermediate sites phosphoryl groups, and two basic sites equivalent to amine or hydroxyl groups. The pH for the point of zero charge on the bacteria was 5.4. In EFM images of cells rinsed in solutions at pH 4.0, 7.0, and 8.0, a pronounced increase in small (< or = 100 nm diameter) high contrast patches was observed on the cells with increasing pH. The pH dependence of EFM image contrast paralleled the pattern of cell surface charge development inferred from the titration experiments; however, quantitative analysis of high contrast regions in the EFM images yielded lower surface charge values than those anticipated from the titration data. For example at pH 7, the calculated surface charge of high contrast regions in EFM images of the bacterial cells was -0.23 microC/cm2 versus -20.0 microC/cm2 based on the titration curve. The differences in surface charge estimates between the EFM images and titration data are consistent not only with charge development throughout the entire volume of the bacterial cell wall (i.e., in association with functional groups that are not directly exposed at the cell surface) but also with the presence of a thin structural layer of water containing charge-compensating counterions. In combination, the pKa spectra and EFM data demonstrate that a particularly high degree of electrochemical heterogeneity exists within the cell wall and at the cell surface of S. putrefaciens.

Cell Membrane↗

QALYs and the integration of claims in health-care rationing.

The paper argues against the polarization of the health economics literature into pro- and anti-QALY camps. In particular, we suggest that a crucial distinction should be made between the QALY measure as a metric of health, and QALY maximization as an applied social choice rule. We argue against the rule but for the measure and that the appropriate conceptualization of health-care rationing decisions should see the main task as the integration of competing and possibly incommensurable normative claim types. We identify the main types as consequences, rights, social contracts, individual votes and community values and note situations in which the contribution of each claim type is limited. We go on to show that the integration of (at least some of) these claim types can be formalized within the mathematical framework provided by non-linear programming.

Attitude to Health↗

Changing incidence of lobular carcinoma in situ of the breast.

Estimating the incidence of lobular carcinoma in situ (LCIS) of the breast is challenging because it lacks both clinical and mammographic signs and is usually an incidental finding in breast biopsies performed for other reasons. In general, population-based studies are believed to provide the most accurate measures, but few documenting changes in LCIS incidence rates over time have been reported. Age-adjusted age-specific LCIS incidence rates among women with no prior history of in situ or invasive breast carcinoma from 1978 to 1998 were obtained from nine population-based cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) Program. Linear trends were evaluated using negative binomial regression. Overall, LCIS incidence rates increased fourfold (95% confidence interval, 2.9-5.6) over the study period. Specifically, they rose from 0.90/100,000 person-years in 1978-80 to 2.83/100,000 person-years in 1987-89, but then increased only modestly up to 1996-98 where the incidence rate was 3.19/100,000 person-years. However, among women 50-79 years of age, LCIS incidence rates increased continuously over the study's duration. In 1996-98, 50-59 year-olds had the highest incidence rate (11.47/100,000 person-years) and experienced the greatest absolute increase in incidence over the study period (9.48/100,000 person-years). LCIS incidence rates have steadily increased from 1978 to 1998 only among postmenopausal women. Further research is required to assess what factors are contributing to these trends.

Adult↗

Cataract surgery and effectiveness. 2. An index approach for the measurement of output and efficiency of cataract surgery at different surgery departments.

PURPOSE: To describe a model for comparing the performance of cataract surgery among ophthalmology departments in terms of economic efficiency. METHODS: An index approach for the measurement of outcome of cataract surgery is modeled. The index approach uses information about activities and difficulties in daily life as well as visual acuity and age. The change in activities and difficulties after surgery is expressed by changes in distances, and an overall index score is calculated as ratios of values to distances. Values to distances are estimated as solutions to linear programming problems. Index scores are calculated for two groups of patients, those with an ocular co-morbidity and those without. Economic efficiency is also estimated by use of an index approach. In the estimation of efficiency we use the calculated index scores of outcome of surgery as a measure of output of the ophthalmology department. Four different departments providing cataract surgery are compared. RESULTS: The studied departments showed differences to a great extent when traditional measures of cataract surgery outcomes were used. These differences changed when the outcomes were compared by use of index scores. When economic efficiency was calculated the difference between the departments was further reduced and only one department was considered inefficient according to the model. CONCLUSION: An index approach was used to study outcomes of cataract surgery and economic efficiency in four departments. This approach takes into account the complexity of cost in relation to feasible outcome. The ranking between the departments described by traditional methods turned out differently using the model.

Cataract Extraction↗

The use of spectral analysis to determine regional cerebral glucose utilization with positron emission tomography and [18F]fluorodeoxyglucose: theory, implementation, and optimization procedures.

A method for kinetic analysis of dynamic positron emission tomography (PET) data by linear programming that allows identification of the components of a measured PET signal without predefining a compartmental model has recently been proposed by Cunningham and co-workers. The method identifies a small subset of functions from a large input set of feasible functions that best fits the time course of total radioactivity measured by PET. To investigate in detail the properties of this technique, we applied it to PET studies with [18F]fluorodeoxyglucose, a tracer with well-characterized kinetic properties. We examined dynamically acquired data over various time intervals in many brain regions and found that the number of components identified by the method is stable and consistent with the presence of kinetic heterogeneity in every region. We optimized the method for determination of regional rates of glucose utilization; calculated rates were found to be somewhat dependent upon the treatment of noise in the measured tissue data and upon the time interval in which the data were collected. The application of a numerical filter to remove noise in the data resulted in values for regional cerebral glucose utilization that were stable with time and consistent with rates determined by the other established techniques. Based on the results of the current study, we expect that the spectral analysis technique will prove to be a highly flexible tool for kinetic analysis of other tracer compounds; it is capable of producing low-variance, time-stable estimates of physiological parameters when optimized for time interval of application, input spectrum of components, and processing of noise in the data.

Adult↗

Fat synthesis in adipose tissue. An examination of stoichiometric constraints.

The requirement for net balance of synthesis, degradation and transport for all intermediates in the pathways from glucose to fat imposes constraints on the balance of fluxes between different pathways. Linear programming has been used to examine the interactions between these constraints on metabolism in adipocytes and the requirement for efficiency in the conversion of glucose into fat. The circumstances under which excessive ATP synthesis would accompany this conversion have been investigated.

Adipose Tissue↗

A hospital throughput model in the context of long waiting lists.

In a public health system, one of the problems is the size of the waiting list for admission to hospital. This research involves establishing a method of analysing the general surgery waiting list problem at hospital and district level. While there are many aspects to such a study, this paper concentrates on a linear programming model to plan the aggregate throughput of the general surgical department. Preliminary results from applying the techniques to actual health districts in the United Kingdom are reported.

Appointments and Schedules↗

Solving the combined zoning and location problem for several emergency units.

This paper discusses methods for the solution of the combined zoning and location problem for several emergency units. This is a stochastic optimization problem. The stochastic aspects include ordered preference of servers. A constraint of equal workload for the servers is also dealt with. Non-linear programming techniques are adapted for its solution.

Ambulances↗

Analysis of optimality in natural and perturbed metabolic networks.

An important goal of whole-cell computational modeling is to integrate detailed biochemical information with biological intuition to produce testable predictions. Based on the premise that prokaryotes such as Escherichia coli have maximized their growth performance along evolution, flux balance analysis (FBA) predicts metabolic flux distributions at steady state by using linear programming. Corroborating earlier results, we show that recent intracellular flux data for wild-type E. coli JM101 display excellent agreement with FBA predictions. Although the assumption of optimality for a wild-type bacterium is justifiable, the same argument may not be valid for genetically engineered knockouts or other bacterial strains that were not exposed to long-term evolutionary pressure. We address this point by introducing the method of minimization of metabolic adjustment (MOMA), whereby we test the hypothesis that knockout metabolic fluxes undergo a minimal redistribution with respect to the flux configuration of the wild type. MOMA employs quadratic programming to identify a point in flux space, which is closest to the wild-type point, compatibly with the gene deletion constraint. Comparing MOMA and FBA predictions to experimental flux data for E. coli pyruvate kinase mutant PB25, we find that MOMA displays a significantly higher correlation than FBA. Our method is further supported by experimental data for E. coli knockout growth rates. It can therefore be used for predicting the behavior of perturbed metabolic networks, whose growth performance is in general suboptimal. MOMA and its possible future extensions may be useful in understanding the evolutionary optimization of metabolism.

Biomass↗

Multisurface method of pattern separation for medical diagnosis applied to breast cytology.

Multisurface pattern separation is a mathematical method for distinguishing between elements of two pattern sets. Each element of the pattern sets is comprised of various scalar observations. In this paper, we use the diagnosis of breast cytology to demonstrate the applicability of this method to medical diagnosis and decision making. Each of 11 cytological characteristics of breast fine-needle aspirates reported to differ between benign and malignant samples was graded 1 to 10 at the time of sample collection. Nine characteristics were found to differ significantly between benign and malignant samples. Mathematically, these values for each sample were represented by a point in a nine-dimensional space of real variables. Benign points were separated from malignant ones by planes determined by linear programming. Correct separation was accomplished in 369 of 370 samples (201 benign and 169 malignant). In the one misclassified malignant case, the fine-needle aspirate cytology was so definitely benign and the cytology of the excised cancer so definitely malignant that we believe the tumor was missed on aspiration. Our mathematical method is applicable to other medical diagnostic and decision-making problems.

Biopsy, Needle↗

Protein, essential amino acids and glycine requirements of the growing gosling (Anser cireneus).

The dietary requirements for protein and amino acids of the growing gosling (0-7 weeks) were calculated according to body composition, maintenance needs and the absorption rate of amino acids from feeds. The diets were formulated by least-cost linear programming, using the calculated requirements for amino acids, with or without minimal glycine + serine requirements. The diets formulated without minimal requirements of glycine + serine were supplemented with various amounts of glycine, and fed to growing goslings. The calculated requirements for protein and essential amino acids were lower than those suggested for growing broilers and turkeys. The requirements (g/MJ metabolizable energy) at 0-2, 2-4 and 4-7 weeks of age respectively, were: lysine 0.88, 0.48, 0.43; methionine + cystine 0.48, 0.38, 0.29; protein 14.5, 9.3, 7.6. The goslings did not respond to glycine supplementation of the diet.

Amino Acids, Essential↗

Effective energy: a concept of energy utilization applied across species.

An energy system is described in which, in both single-stomached and ruminant animals, the heat increment of feeding is considered to be linearly related to five measurable quantities. For both kinds of animals three of the quantities, with their heat increments in parentheses, are urinary N (wu; kJ/g), faecal organic matter (wd; kJ/g) and positive protein retention (wp; kJ/g). In ruminants the other two, with their heat increments in parentheses, are CH4 energy (wm; kJ/kJ) and positive lipid retention (w1; kJ/g); in single-stomached animals they are positive lipid retention from feed lipid (wII; kJ/g), and positive lipid retention not from feed lipid (wI; kJ/g). Data from suitable experiments on steers, pigs and chickens were used to test the system and to estimate wu 29.2, wd 3.80, wp 36.5, wm 0.616, wI 16.4 and wII 4.4. The values for wu, wd, wm and (wI - wII) allow an energy scale, called effective energy, to be defined for both single-stomached animals and ruminants. On this energy scale the values of wp and wI, together with the heats of combustion of protein and lipid of 23.8 and 39.6 kJ/g respectively, allow the energy requirement to be expressed as (MH + 50PR + 56LR) for both kinds of animal, where PR and LR are the rates of positive protein and lipid retention (g/d), and MH is the maintenance heat production (kJ/d) which can be estimated as 0.96 of the fasting heat production. The effective energy (EE) yielded to a ruminant animal by a feed ingredient can be estimated as EE (MJ/kg organic matter) = 1.15ME - 3.84 - 4.67DCP, where ME is the metabolizable energy value (MJ/kg organic matter) and DCP is the digested crude protein content (kg/kg organic matter) with both measured at maintenance. Alternatively, EE can be estimated as EE (MJ/kg) = GE (d - 0.228) - 4.67DCP, where GE is the gross energy (MJ/kg) and d is the energy digestibility (MJ/MJ) also measured at maintenance. The EE yielded to a single-stomached animal can be estimated as EE (kJ/g) = 1.17ME - 4.2CP - 2.44, where ME (kJ/g) is measured at, or corrected to, zero N-retention and CP (g/g) is the crude protein (N x 6.25) content of the feed ingredient. The system is simpler for ruminants, and more accurate for both kinds of animal, than those now in use. As effective energy values can be tabulated for ingredients, and are additive to the extent that ME values are additive, they can be used to formulate diets using linear programming.

Animal Nutritional Physiological Phenomena↗

The large-scale separation of peroxisomes, mitochondria, and lysosomes from the livers of rats injected with triton WR-1339. Improved isolation procedures, automated analysis, biochemical and morphological properties of fractions.

Improved, largely automated methods are described for the purification and analysis o peroxisomes, lysosomes, and mitochondria from the livers of rats injected with Triton WR-1339. With these new methods, it has become possible to obtain, in less than 6 hr and with reliable reproducibility, mitochondria practically free of contaminants, as well as the rarer cytoplasmic particles in amounts (about 100 mg of protein) and in a state of purity (95%) that make them suitable for detailed biochemical studies. The results obtained so far on these preparations have made more conclusive and precise previous estimates of the biochemical and morphological properties of the three groups of cytoplasmic particles. In addition, peroxisomes were found to contain essentially all the L-alpha-hydroxy acid oxidase of the liver, as well as a small, but significant fraction of its NADP-linked isocitrate dehydrogenase activity. Another small fraction of the latter enzyme is present in the mitochondria, the remainder being associated with the cell sap. The mitochondrial localization of the metabolically active cytoplasmic DNA could be verified. The relative content of the fractions in mitochondria, whole peroxisomes, peroxisome cores, lysosomes, and endoplasmic reticulum was estimated independently by direct measurements on electron micrographs, and by linear programming (based on the assumption that the particles are biochemically homogeneous) of the results of enzyme assays. The two types of estimates agreed very well, except for one fraction in which low cytochrome oxidase activity was associated with mitochondrial damage.

Acid Phosphatase↗

Uniform depth dose distribution for biological irradiation using negative pions.

A simple, flexible technique has been developed to generate uniform depth dose profiles for the biomedical pion beam at TRIUMF using dynamic momentum control and linear programming. Either the entrance dose or the irradiation time required for a certain dose over the uniform region can be minimised. The dynamic momentum control can operate automatically under computer control even with a highly unstable beam. Cell survival profiles have been obtained for this uniform dose distribution using the gelatin technique. The RBE increases with increasing depth through the uniform dose region.

Animals↗

A practical approach to inverse planning for high-precision dose escalated conformal prostate radiotherapy.

The problem of choosing the best gantry angles and beam weights for dose-escalated conformal prostate treatment planning is formulated using a mixed-integer linear programming approach, to account for tumour dose homogeneity and dose-volume constraints. The formulation allows the number of beams to be restricted and for some of the beams to be compulsory. The present planning algorithm interfaces with and utilizes the three-dimensional planning capabilities of a commercial treatment planning system. A case study is illustrated, which represents a particularly challenging planning problem due to a large planning target volume and an unusually small bladder. Treatment plans with different numbers of beams are generated to compare with each other and with the standard six-field plan. Significant improvement is shown in the reduction of hot regions within the femoral heads and rectal wall, while not unduly compromising homogeneity constraints for the tumour.

Humans↗