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PubMed2002

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↗

PubMed2001

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↗

PubMed1994

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↗

PubMed2006

A novel approach for accurate prediction of spontaneous passage of ureteral stones: support vector machines.

The objective of this study was to optimally predict the spontaneous passage of ureteral stones in patients with renal colic by applying for the first time support vector machines (SVM), an instance of kernel methods, for classification. After reviewing the results found in the literature, we compared the performances obtained with logistic regression (LR) and accurately trained artificial neural networks (ANN) to those obtained with SVM, that is, the standard SVM, and the linear programming SVM (LP-SVM); the latter techniques show an improved performance. Moreover, we rank the prediction factors according to their importance using Fisher scores and the LP-SVM feature weights. A data set of 1163 patients affected by renal colic has been analyzed and restricted to single out a statistically coherent subset of 402 patients. Nine clinical factors are used as inputs for the classification algorithms, to predict one binary output. The algorithms are cross-validated by training and testing on randomly selected train- and test-set partitions of the data and reporting the average performance on the test sets. The SVM-based approaches obtained a sensitivity of 84.5% and a specificity of 86.9%. The feature ranking based on LP-SVM gives the highest importance to stone size, stone position and symptom duration before check-up. We propose a statistically correct way of employing LR, ANN and SVM for the prediction of spontaneous passage of ureteral stones in patients with renal colic. SVM outperformed ANN, as well as LR. This study will soon be translated into a practical software toolbox for actual clinical usage.

Algorithms↗

PubMed1986

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↗

PubMed1983

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↗

PubMed1985

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↗

PubMed2005

At the boundary between reduced density-matrix and density-functional theories.

Here, we revisit the problem of finding the ground-state energy of an N-fermion fluid under an external field, with molecular structure as the ultimate target. Density-functional methods only have to deal with electron density, but require an empirical functional; reduced density-matrix methods involve a matrix on pair space and do give exact bounds, but require very complex linear programming to achieve their results. The polydensity representation that we introduce has the advantage of dealing only with densities, requires no empirical information, and also gives exact bounds; the major problem is that of accumulating and utilizing conditions on the densities that iteratively improve their realizability in the class of N-fermion systems. We indicate several directions along these lines and make some primitive applications.

Journal Article↗

PubMed2005

Deconvolution of the relaxations associated with local and segmental motions in poly(methacrylate)s containing dichlorinated benzyl moieties in the ester residue.

The relaxation behavior of poly(2,3-dichlorobenzyl methacrylate) is studied by broadband dielectric spectroscopy in the frequency range of 10(-1)-10(9) Hz and temperature interval of 303-423 K. The isotherms representing the dielectric loss of the glassy polymer in the frequency domain present a single absorption, called beta process. At temperatures close to Tg, the dynamical alpha relaxation already overlaps with the beta process, the degree of overlapping increasing with temperature. The deconvolution of the alpha and beta relaxations is facilitated using the retardation spectra calculated from the isotherms utilizing linear programming regularization parameter techniques. The temperature dependence of the beta relaxation presents a crossover associated with a change in activation energy of the local processes. The distance between the alpha and beta peaks, expressed as log(fmax;beta/fmax;alpha) where fmax is the frequency at the peak maximum, follows Arrhenius behavior in the temperature range of 310-384 K. Above 384 K, the distance between the peaks remains nearly constant and, as a result, the a onset temperature exhibited for many polymers is not reached in this system. The fraction of relaxation carried out through the alpha process, without beta assistance, is larger than 60% in the temperature range of 310-384 K where the so-called Williams ansatz holds.

Journal Article↗

PubMed2002

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↗

PubMed1990

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↗

PubMed2004

Candidate metabolic network states in human mitochondria. Impact of diabetes, ischemia, and diet.

The human mitochondrial metabolic network was recently reconstructed based on proteomic and biochemical data. Linear programming and uniform random sampling were applied herein to identify candidate steady states of the metabolic network that were consistent with the imposed physico-chemical constraints and available experimental data. The activity of the mitochondrion was studied under four metabolic conditions: normal physiologic, diabetic, ischemic, and dietetic. Pairwise correlations between steady-state reaction fluxes were calculated in each condition to evaluate the dependence among the reactions in the network. Applying constraints on exchange fluxes resulted in predictions for intracellular fluxes that agreed with experimental data. Analyses of the steady-state flux distributions showed that the experimentally observed reduced activity of pyruvate dehydrogenase in vivo could be a result of stoichiometric constraints and therefore would not necessarily require enzymatic inhibition. The observed changes in the energy metabolism of the mitochondrion under diabetic conditions were used to evaluate the impact of previously suggested treatments. The results showed that neither normalized glucose uptake nor decreased ketone body uptake have a positive effect on the mitochondrial energy metabolism or network flexibility. Taken together, this study showed that sampling of the steady-state flux space is a powerful method to investigate network properties under different conditions and provides a basis for in silico evaluations of effects of potential disease treatments.

Adenosine Triphosphate↗

PubMed1983

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↗

PubMed1994

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↗

PubMed2006

Evaluation of an application for making palmtop computers accessible to individuals with intellectual disabilities.

BACKGROUND: Palmtop computers provide a promising mobile platform to address barriers to computer-based supports for people with intellectual disabilities. This study evaluated a specially designed interface to make navigation and features of palmtop computers more accessible to users with intellectual disabilities. METHOD: The specialised cognitively accessible interface was compared with a standard Windows CE interface. Participants completed a structured set of navigation/computer use tasks using both the experimental and control conditions. Measurements included the amount of assistance needed and errors made in completing the navigation/computer use tasks. RESULTS: Participants (N = 32) made significantly fewer errors (p<.001) and required significantly fewer prompts (p<.001) while using the specialised software interface compared to the mainstream Windows interface. CONCLUSIONS: The research demonstrates the feasibility of using special software design methods, such as linear program flows, error minimisation and the incorporation of repetition and consistency, to improve access to palmtop computers for individuals with intellectual disabilities. Issues related to designing cognitively accessible interfaces are discussed.

Adolescent↗

PubMed1968

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↗

PubMed1979

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↗

PubMed2001

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↗