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An inexact two-stage mixed integer linear programming method for solid waste management in the City of Regina.

In this study, an interval-parameter two-stage mixed integer linear programming (ITMILP) model is developed for supporting long-term planning of waste management activities in the City of Regina. In the ITMILP, both two-stage stochastic programming and interval linear programming are introduced into a general mixed integer linear programming framework. Uncertainties expressed as not only probability density functions but also discrete intervals can be reflected. The model can help tackle the dynamic, interactive and uncertain characteristics of the solid waste management system in the City, and can address issues concerning plans for cost-effective waste diversion and landfill prolongation. Three scenarios are considered based on different waste management policies. The results indicate that reasonable solutions have been generated. They are valuable for supporting the adjustment or justification of the existing waste flow allocation patterns, the long-term capacity planning of the City's waste management system, and the formulation of local policies and regulations regarding waste generation and management.

Canada↗

[Non-linear model of glottic vibration. Potential clinical implications].

Glottic vibration is governed by a certain number of physical laws which in general correspond, as far as myo-elastic theory is concerned, with the laws of passive vibration of an elastic body under the influence of the expired air. Some of these laws are non-linear, especially those that deal with the exchange of energy between the expired air and the vocal folds. This non-linearity is specially important when it comes to the key concepts of the phonatory threshold and the passive synchronisation of the vocal cords. Based on their experimental work, which has been presented previously, the authors propose a mixed model, which is both linear and non-linear, like the oscillators of Van der Pool. This model is known as Slip-Stick.

Glottis↗

T2-prepared steady-state free precession blood oxygen level-dependent MR imaging of myocardial perfusion in a dog stenosis model.

PURPOSE: To assess the ability of a T2-prepared steady-state free precession blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging sequence to depict changes in myocardial perfusion during stress testing in a dog stenosis model. MATERIALS AND METHODS: Study was approved by the institutional Animal Care and Use Committee. A hydraulic occluder was placed in the left circumflex coronary artery (LCX) in 10 dogs. Adenosine was administered intravenously to increase coronary blood flow, and stenosis was achieved in the LCX with the occluder. A T2-prepared two-dimensional steady-state free precession sequence was used for BOLD imaging at a spatial resolution of 1.5 x 1.2 x 5.0 mm3, and first-pass perfusion images were acquired for visual comparison. Microspheres were injected to provide regional perfusion information. Mixed-effect regression analysis was performed to assess normalized MR signal intensity ratios and microsphere-measured perfusion differences. For the same data, 95% prediction intervals were calculated to determine the smallest perfusion change detectable. Means +/- standard deviations were calculated for myocardial regional comparison data. A two-tailed Student t test was used to determine if significant differences (P < .01) existed between different myocardial regions. RESULTS: Under maximal adenosine stress, MR clearly depicted stenotic regions and showed regional signal differences between the left anterior descending coronary artery (LAD)-fed myocardium and the stenosed LCX-fed myocardium. Visual comparisons with first-pass images were also excellent. Regional MR signal intensity differences between LAD and LCX-fed myocardium (1.24 +/- 0.08) were significantly different (P < .01) from differences between LAD and septal-fed myocardium (1.02 +/- 0.07), which was in agreement with microsphere-measured flow differences (LAD/LCX, 3.38 +/- 0.83; LAD/septal, 1.26 +/- 0.49). The linear mixed-effect regression model showed good correlation (R = 0.79) between MR differences and microsphere-measured flow differences. CONCLUSION: On T2-prepared steady-state free precession BOLD MR images in dogs, signal intensity differences were linearly related to flow differences in myocardium, with a high degree of correlation. SUPPLEMENTAL MATERIAL: radiology.rsnajnls.org/cgi/content/full/236/2/503/DC1

Animals↗

Physician-based activity counseling: intervention effects on mediators of motivational readiness for physical activity.

In theory-based interventions for behavior change, there is a need to examine the effects of interventions on the underlying theoretical constructs and the mediating role of such constructs. These two questions are addressed in the Physically Active for Life study, a randomized trial of physician-based exercise counseling for older adults. Three hundred fifty-five patients participated (intervention n = 181, control n = 174; mean age = 65.6 years). The underlying theories used were the Transtheoretical Model, Social Cognitive Theory and the constructs of decisional balance (benefits and barriers), self-efficacy, and behavioral and cognitive processes of change. Motivational readiness for physical activity and related constructs were assessed at baseline, 6 weeks, and 8 months. Linear or logistic mixed effects models were used to examine intervention effects on the constructs, and logistic mixed effects models were used for mediator analyses. At 6 weeks, the intervention had significant effects on decisional balance, self-efficacy, and behavioral processes, but these effects were not maintained at 8 months. At 6 weeks, only decisional balance and behavioral processes were identified as mediators of motivational readiness outcomes. Results suggest that interventions of greater intensity and duration may be needed for sustained changes in mediators and motivational readiness for physical activity among older adults.

Aged↗

Checking linearity of non-parametric component in partially linear models with an application in systemic inflammatory response syndrome study.

Two tests are proposed for checking the linearity of nonparametric function in partially linear models. The first one is based on a Crámer-von Mises statistic. This test can detect the local alternative converging to the null at the parametric rate 1/square root n. A bootstrap resample technique is provided to calculate the critical values. The second one is constructed in a penalized spline framework along with linear mixed-effects (LME) modeling. This is an extension likelihood ratio test for testing zero variance of random effects in LME models. Simulation experiments are conducted to explore the numerical performance of two tests. It is observed that two tests have good level properties, and the first test has a substantially superior power property over the second test in a variety of cases. A real data set is analysed with the proposed tests.

Humans↗

An investigation of factors contributing to styrene and styrene-7,8-oxide exposures in the reinforced-plastics industry.

During the manufacturing of reinforced plastics, large amounts of styrene and trace quantities of styrene-7,8-oxide (SO) are released. Since previous work suggests that inhalation of even small amounts of SO might be an important health risk, we investigated several possible factors contributing to styrene and SO exposure during the manufacture of reinforced plastics. Factors related to job type, worker and the type and quantity of styrene-containing resins were investigated using mixed-effects multiple linear regression models. Overall, SO exposure levels were positively correlated with styrene exposure levels. However, this correlation was statistically significant only among hand laminators who had the highest exposures to both styrene and SO. An important factor for predicting both styrene and SO concentrations was the type of resin used, while the quantity of resin consumed was predictive of styrene but not of SO exposure. Since So exposure appears to be associated with factors other than coexposure to styrene, more effort should be placed on investigating emissions of SO per se. The type of mixed-models regression analysis employed in this study can be used for clarifying the underlying patterns for exposures to styrene and SO as well as for evaluating preventive measures.

Carcinogens↗

Pharmacokinetic/pharmacodynamic modelling of GnRH antagonist degarelix: a comparison of the non-linear mixed-effects programs NONMEM and NLME.

In this paper, the two non-linear mixed-effects programs NONMEM and NLME were compared for their use in population pharmacokinetic/pharmacodynamic (PK/PD) modelling. We have described the first-order conditional estimation (FOCE) method as implemented in NONMEM and the alternating algorithm in NLME proposed by Lindstrom and Bates. The two programs were tested using clinical PK/PD data of a new gonadotropin-releasing hormone (GnRH) antagonist degarelix currently being developed for prostate cancer treatment. The pharmacokinetics of intravenous administered degarelix was analysed using a three compartment model while the pharmacodynamics was analysed using a turnover model with a pool compartment. The results indicated that the two algorithms produce consistent parameter estimates. The bias and precision of the two algorithms were further investigated using a parametric bootstrap procedure which showed that NONMEM produced more accurate results than NLME together with the nlmeODE package for this specific study.

Algorithms↗

Continuous growth of mean tumor diameter in a subset of grade II gliomas.

Serial magnetic resonance images of 27 patients with untreated World Health Organization grade II oligodendrogliomas or mixed gliomas were reviewed retrospectively to study the kinetics of tumor growth before anaplastic transformation. Analysis of the mean tumor diameters over time showed constant growth. Linear regression, using a mixed model, found an average slope of 4.1mm per year (95% confidence interval, 3.8-4.4mm/year). Untreated low-grade oligodendrogliomas or mixed gliomas grow continuously during their premalignant phase, and their pattern of growth can be predicted within a relatively narrow range. These findings could be of interest to optimize patients management and follow-up.

Adult↗

Simple model for mixing at accelerated fluid interfaces with shear and compression

A simple model was recently described for predicting linear and nonlinear mixing at an unstable planar interface between two fluids of different density subjected to an arbitrary time-dependent variable acceleration history [J. D. Ramshaw, Phys. Rev. E 58, 5834 (1998)]. Here we generalize this model to include the Kelvin-Helmholtz (KH) instability resulting from a tangential velocity discontinuity delta u, as well as the effects of a uniform anisotropic compression or expansion of the mixing layer as a whole. The model consists of a second-order nonlinear ordinary differential equation of motion for the half-width h of the mixing layer. This equation is derived by combining the wavelength renormalization hypothesis used in the earlier model with a suitable expression for the rate of change of the kinetic energy of the mixing layer. The resulting generalized model contains no additional free parameters, and reduces to the previous model in the absence of tangential velocities and compression. It also reduces in the linear regime to the correct linearized stability equation for an accelerated shear layer with compression [J. D. Ramshaw, Phys. Rev. E 61, 1486 (2000)]. For a pure incompressible KH instability in the nonlinear regime, the model predicts that h = eta magnitude of delta u t, where eta = [alpha(2 - theta)/square root of theta(1 - theta)]square root of rho 1 rho 2/(rho 1 + rho 2), and alpha and theta are parameters appearing in the nonlinear Rayleigh-Taylor and Richtmyer-Meshkov growth laws. For equal densities and the same parameter values previously used to match variable-acceleration experimental data, we find eta = 0.10, in close agreement with experimental data for free shear layers.

Journal Article↗

Estimation of population pharmacokinetic parameters of saquinavir in HIV patients with the MONOLIX software.

In nonlinear mixed-effects models, estimation methods based on a linearization of the likelihood are widely used although they have several methodological drawbacks. Kuhn and Lavielle (Comput. Statist. Data Anal. 49:1020-1038 (2005)) developed an estimation method which combines the SAEM (Stochastic Approximation EM) algorithm, with a MCMC (Markov Chain Monte Carlo) procedure for maximum likelihood estimation in nonlinear mixed-effects models without linearization. This method is implemented in the Matlab software MONOLIX which is available at http://www.math.u-psud.fr/~lavielle/monolix/logiciels. In this paper we apply MONOLIX to the analysis of the pharmacokinetics of saquinavir, a protease inhibitor, from concentrations measured after single dose administration in 100 HIV patients, some with advance disease. We also illustrate how to use MONOLIX to build the covariate model using the Bayesian Information Criterion. Saquinavir oral clearance (CL/F) was estimated to be 1.26 L/h and to increase with body mass index, the inter-patient variability for CL/F being 120%. Several methodological developments are ongoing to extend SAEM which is a very promising estimation method for population pharmacockinetic/pharmacodynamic analyses.

Administration, Oral↗

Mandibular advancement decreases pressures in the tissues surrounding the upper airway in rabbits.

The pharyngeal airway can be considered as an airway luminal shape formed by surrounding tissues, contained within a bony enclosure formed by the mandible, skull base, and cervical vertebrae. Mandibular advancement (MA), a therapy for obstructive sleep apnea, is thought to increase the size of this bony enclosure and to decrease the pressure in the upper airway extraluminal tissue space (ETP). We examined the effect of MA on upper airway airflow resistance (Rua) and ETP in a rabbit model. We studied 11 male, supine, anesthetized, spontaneously breathing New Zealand White rabbits in which ETP was measured via pressure transducer-tipped catheters inserted into the tissues surrounding the lateral (ETPlat) and anterior (ETPant) pharyngeal wall. Airflow, measured via surgically inserted pneumotachograph in series with the trachea, and tracheal pressure were recorded while graded MA at 75 degrees and 100 degrees to the horizontal was performed using an external traction device. Data were analyzed using a linear mixed-effects statistical model. We found that MA at 100 degrees increased mouth opening from 4.7 +/- 0.4 to 6.6 +/- 0.4 (SE) mm (n = 7; P < 0.004), whereas mouth opening did not change from baseline (4.0 +/- 0.2 mm) with MA at 75 degrees . MA at both 75 degrees and 100 degrees decreased mean ETPlat and ETPant by approximately 0.1 cmH2O/mm MA (n = 7-11; all P < 0.0005). However, the fall in Rua (measured at 20 ml/s) with MA was greater for MA at 75 degrees (approximately 0.03 mmH2O.ml(-1).s.mm(-1)) than at 100 degrees (approximately 0.01 mmH2O.ml(-1).s.mm(-1); P < 0.02). From these findings, we conclude that MA decreases ETP and is more effective in reducing Rua without mouth opening.

Airway Obstruction↗

Complex gastrointestinal surgery: impact of provider experience on clinical and economic outcomes.

BACKGROUND: Commonly performed elective gastrointestinal surgical procedures are carried out with low morbidity and mortality in hospitals throughout the United States. Complex operative procedures on the alimentary tract are performed with a relatively low frequency and are associated with higher mortality. Volume and experience of the surgical provider team have been correlated with better clinical and economic outcomes for one complex gastrointestinal surgical procedure, pancreaticoduodenectomy. This study evaluated whether provider volume and experience were important factors influencing clinical and economic outcomes for a variety of complex gastrointestinal surgical procedures in one state. STUDY DESIGN: Complex high-risk gastrointestinal surgical procedures were defined as those with statewide in-hospital mortality of > or = 5%, frequency of greater than 200 per year in the state, and requiring special surgical skill and expertise. Six procedures met these criteria. Using publicly available discharge data, all patients discharged from Maryland hospitals from July 1989 to June 1997 with a primary procedure code for one of the six study procedures were selected. Hospitals were classified into one of six groups based on the average number of study procedures per year: 10 or less; 11 to 20; 21 to 50; 51 to 100; 101 to 200; and 201 or more procedures per year. A hospital was included if at least one procedure was performed there during the study period. No providers fell within the 51 to 100, and 101 to 200 groups, so all analyses were performed for the remaining four volume groups that were classified, respectively, as minimal (10 or fewer procedures), low (11 to 20 procedures), medium (21 to 50 procedures), and high-volume groups (201 or more procedures). Poisson regression was used to assess the relationship between in-hospital mortality and hospital volume after case-mix adjustment. Multiple linear regression models were used to assess differences in average length-of-stay and average total hospital charges among hospital volume groups. We further analyzed mortality, length-of-stay, and charges at the procedural level to understand these subgroups of complex gastrointestinal patients. We also examined the relationship between provider volume and outcomes for malignant versus benign diagnosis groups. RESULTS: Complex gastrointestinal surgical procedures were performed on 4,561 patients in Maryland from July 1989 through June 1997. The study population averaged 61.6 years of age, was 55% male, 71% Caucasian, and had predominantly Medicare as a payment source. After case-mix adjustment, patients who underwent complex gastrointestinal surgical procedures at the medium-, low-, and minimal-volume provider groups had a 2.1, 3.3, and 3.2 times greater risk of in-hospital death, respectively, than patients at the high-volume provider (p < 0.001 for all comparisons); longer lengths-of-stay, 16.1, 15.7, and 15.5 days at the low-, medium-, and minimal-volume groups, respectively, versus 14.0 days for the high-volume provider (p < 0.001 for all comparisons). Similarly, adjusted charges at the high-volume provider were, on average, 14% less than those of the low-volume group, which had the next lowest charges. Although mortality rates differed by procedure type, for each procedure, mortality increased as provider volume decreased, following the pattern found in the aggregate analysis. After case-mix adjustment, the risk of in-hospital death for patients with malignant diagnoses was significantly higher for the medium-, low-, and minimal-volume groups compared with patients at the high-volume provider, relative risk of 3.1, 4.0, and 4.2, respectively, (p < 0.001 for all comparisons). CONCLUSIONS: This study demonstrates that increased hospital experience is associated with a marked decrease in hospital mortality. The decreased mortality at the high-volume provider was also associated with shorter lengths-of-stay and lower hospital char

Clinical Competence↗

The assessment of biomarkers in sentinel cattle for monitoring vanadium exposure.

Various potential biomarkers were sampled for vanadium every 3-4 months from Bos indicus beef cattle farmed extensively immediately adjacent (high exposure (HE) group) and two km away (low exposure (LE) group) from a vanadium processing plant, respectively. Vanadium intake (mg vanadium kg(-1) bwt d(-1)) was modelled using environmental and physiological data as inputs. The vanadium intake ranged from 0.57 to 5.44 mg vanadium kg(-1) bwt d(-1) in the HE group and 0.41 to 2.61 mg vanadium kg(-1) bwt d(-1) in the LE group over a five-year period of monitoring. Samples collected from live sentinel animals over the five-year period included caudal coccygeal vertebrae, tail-switch hair, milk, urine, faeces, rib-bone biopsies and a wide range of blood clinical pathology and haematological parameters. The data was analysed for differences in response between the HE and LE groups. Where differences were found, a linear mixed-effects regression model was fitted to model the relationship between the exposure dose and the response variable. The model included the effects of age, duration of exposure and response, and allowed the prediction of the exposure dose given these inputs. Moreover, forty-two adult cattle were slaughtered over the five years. A wide range of tissue samples, rumen content and whole blood were taken from the cattle at slaughter for vanadium determination. In live animals, a difference in response was found between the HE group and LE group with respect to serum albumin (n = 36), monocyte (n = 36) and thrombocyte (n = 36) counts, and hair (n = 2) and faeces (n = 34) vanadium concentrations. No difference in vanadium concentrations could be shown for urine (n = 36), the traditional occupational health biomarker. Regression models are described for serum albumin, monocyte counts, faeces and hair, which showed the most promise as biomarkers. Average concentrations of vanadium in the tissues of slaughtered cattle ranged from 0.08 to 2.94 mg kg(-1) (wet-weight basis) and rumen content contained 16.67 mg kg(-1). Significant correlations were found between the exposure dose (end-dose) just prior to slaughter and the concentrations of vanadium in the coccygeal vertebrae, liver, diaphragm and rib-bone in descending order of magnitude. Other tissues showed poor correlation to the end-dose. Tissue levels of vanadium in healthy cattle include a much wider range than is currently reflected in the literature. The best tissue from slaughter animals for assessing chronic vanadium exposure is probably the liver.

Animals↗

Improving diabetes processes of care in managed care.

OBJECTIVE: To evaluate the impact of systematic patient evaluation and patient and provider feedback on the processes and intermediate outcomes of diabetes care in Independent Practice Association model internal medicine practices. RESEARCH DESIGN AND METHODS: Nine practices providing care to managed care patients were randomly assigned as intervention or comparison sites. Intervention-site subjects had Annual Diabetes Assessment Program (ADAP) assessments (HbA(1c), blood pressure, lipids, smoking, retinal photos, urine microalbumin, and foot examination) at years 1 and 2. Comparison-site subjects had ADAP assessments at year 2. At Intervention sites, year 1 ADAP results were reviewed with subjects, mailed to providers, and incorporated into electronic medical records with guideline-generated suggestions for treatment and follow-up. Medical records were evaluated for both groups for the year before both the year 1 and year 2 ADAP assessments. Processes and intermediate outcomes were compared using linear and logistic mixed hierarchical models. RESULTS: Of 284 eligible subjects, 103 of 173 (60%) at the Intervention sites and 71 of 111 (64%) at the comparison sites participated; 83 of 103 (81%) of the intervention-site subjects returned for follow-up at year 2. Performance of the six recommended assessments improved in intervention-site subjects at year 2 compared with year 1 (5.8 vs. 4.3, P = 0.0001) and compared with comparison-site subjects at year 2 (4.2, P = 0.014). No significant changes were noted in intermediate outcomes. CONCLUSIONS: The ADAP significantly improved processes of care but not intermediate outcomes. Additional interventions are needed to improve intermediate outcomes.

Aged↗

Asymmetry and gender effect in functionally lateralized cortical regions: a proton MRS imaging study.

PURPOSE: to compare metabolite concentrations and ratios in gray matter regions known for their anatomical/functional asymmetry and evaluate gender effect. MATERIALS AND METHODS: Proton MRS imaging was performed at 1.5 T with TR/TE 2300/280 msec in 20 healthy right-handed subjects (mean age 29.6 +/- 5.3 years, 10 men). Concentrations of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr), and the peak area ratios NAA/Cho, NAA/Cr, and Cho/Cr were evaluated in hippocampal and parahippocampal gyri, thalamus, insula, Broca's and Wernicke's areas (and corresponding contralateral areas), primary and secondary visual areas, temporal, inferior parietal, cingulate, supplemental motor, dorsolateral prefrontal, and sensorimotor areas. Linear mixed-effects regression models were used for statistical analyses. RESULTS: NAA concentration and NAA/Cho were higher in the left thalamus by 21.9% and 20%, respectively (both P < 0.001). NAA concentration was 13% higher in the region contralateral to Wernicke's area (P < 0.02). No gender differences were found. CONCLUSION: Metabolite concentrations and ratios were symmetric and gender independent in most brain regions, however small hemispheric side differences in the thalamus and in Wernicke's area were found.

Adult↗

Criticality in a dynamic mixed system.

We suggest a dynamic generalization of the simplest static hierarchical mixed model introduced by Shnirman and Blanter [Phys. Rev. Lett. 81, 5445 (1998); Phys. Rev. E. 60, 5111 (1998). We show that the stationary solution of the dynamic mixed model (DMM) demonstrates, in general, a linear form of the magnitude-frequency relation and may be considered a self-organized critical system. The dynamic mixed model demonstrates three principal kinds of system behavior: stability, catastrophe, and scale invariance. We show that the catastrophic area exists for all parameters of the mixture, and obtain three analytical expressions for boundary conditions of the stability and the scale invariance domains. As in the static model scale invariance appears as a result of a strong heterogeneity of the mixture. We describe how the magnitude-frequency relation reflects parameters of the heterogeneity and healing conditions for different domains of system behavior. Deviation of the DMM from the static mixed model and possible applications to earthquake prediction are discussed.

Journal Article↗

Effects of occupational noise exposure on blood pressure.

We measured 24-hour ambulatory blood pressure and 16-hour noise exposure continuously for 20 automobile workers, and used linear mixed-effects regression models to estimate transient and sustained effects of noise exposure on blood pressure. The occupational noise levels of the high-exposure workers with 85 +/- 8 dBA were significantly higher than those of the low-exposure workers with 59 +/- 4 dBA (P < 0.05). We found a significant difference of 16 +/- 6 mm Hg in sleep-time systolic blood pressure (SBP) existed between 2 exposure groups, and a marginal increase of 1 mm Hg SBP per 1-dBA increase in occupational noise exposure at a 60-minute lag time during work (P = 0.07). Occupational noise exposure had both transient and sustained effects on workers' SBP.

Adult↗

[Analysis of environmentally-conditioned and genetic influences on the frequency of hip joint dysplasia in German Shepherd dogs].

The importance of environmental and genetic influences on the frequency of hip dysplasia was studied in 10,595 German shepherd dogs. Systematic effects were analysed using mixed linear and mixed nonlinear threshold models. Following effects were regarded in the models applied: sire and mother of the dog as random effects, age at x-raying, sex, birth year and season of the x-rayed dogs, litter size, percentage of x-rayed dogs in each litter and sex ratio of the litter as fixed effects. Sire, mother, sex and age at x-raying showed significant influence on the occurrence of hip dysplasia. The heritability estimates in a hierarchical data design (sire, mother within sire) for the polychotomous trait hip dysplasia were for full sibs h2 = 0.30, for maternal half sibs h2 = 0, 48, and for paternal half sibs h2 = 0.11. Only the heritability estimates of the paternal half sibs seem to be reliable because kennel and breeder effects are confounded with the mother effect. Analysing the frequency of hip dysplasia as all-or-none traits, the heritability estimates were usually lowered by 50%. Selection programmes to reduce frequency of hip dysplasia can be improved if the estimation of breeding values with respect to environmental effects and frequency of hip dysplasia in all relatives will be implemented.

Analysis of Variance↗