Model-Based Estimates of Right Whale Habitat Use in the Gulf of Maine

Balancing human uses of the marine environment with the recovery of protected species requires accurate information on when and where species of interest are likely to be present. Here, we describe a system that can produce useful estimates of right whale Eubalaena glacialis presence and abundance on their feeding grounds in the Gulf of Maine. The foundation of our system is a coupled physical-biological model of the copepod Calan us finmarchicus, the preferred prey of right whales. From the modeled prey densities, we can estimate when whales will appear in the Great South Channel feeding ground. Based on our experience with the system, we consider how the relationship between right whales and copepods changes across spatial scales. The scale-dependent relationship between whales and copepods provides insight into how to improve future estimates of the distribution of right whales and other pelagic predators.

Plant diversity effects on the water balance of an experimental grassland

In the literature, contrasting effects of plant species richness on the soil water balance are reported. Our objective was to assess the effects of plant species and functional richness and functional identity on soil water contents and water fluxes in the experimental grassland of the Jena Experiment. The Jena Experiment comprises 86 plots on which plant species richness (0, 1, 2, 4, 8, 16, and 60) and functional group composition (zero to four functional groups: legumes, grasses, tall herbs, and small herbs) were manipulated in a factorial design. We recorded meteorological data and soil water contents of the 0·0–0·3 and 0·3–0·7 m soil layers and calculated actual evapotranspiration (ETa), downward flux (DF), and capillary rise with a soil water balance model for the period 2003–2007. Missing water contents were estimated with a Bayesian hierarchical model. Species richness decreased water contents in subsoil during wet soil conditions. Presence of tall herbs increased soil water contents in topsoil during dry conditions and decreased soil water contents in subsoil during wet conditions. Presence of grasses generally decreased water contents in topsoil, particularly during dry phases; increased ETa and decreased DF from topsoil; and decreased ETa from subsoil. Presence of legumes, in contrast, decreased ETa and increased DF from topsoil and increased ETa from subsoil. Species richness probably resulted in complementary water use. Specific functional groups likely affected the water balance via specific root traits (e.g. shallow dense roots of grasses and deep taproots of tall herbs) or specific shading intensity caused by functional group effects on vegetation cover. Copyright © 2013 John Wiley & Sons, Ltd.

Homeless access to dental health care: Creation of a dental service model

This project involved developing a model for planning a dental emergency treatment center that could function as an embedded component of a shelter for the homeless population. The dental services provided by such a clinic should include treatment for tooth pain, dental caries or cavities, chipped or broken teeth, broken partials, abscessed teeth, emergency cleanings, periodontal disease or gum disease and fillings. These are the dental services that are most often sought by homeless people in hospital emergency rooms.^ The underlying assumption for this project was that the oral health needs of the homeless community can most effectively be addressed by implementing small dental clinics in existing facilities that provide shelter and other services for this population. The model described in this project identifies oral health care services that would be provided by the clinic, facility (physical plant) requirements and associated infrastructure to operate an embedded dental clinic, methods for obtaining funding, strategies of recruiting dental professionals to staff the facility, and methods to assess the outcomes of the embedded clinic strategy. As an example, this project describes a strategy for developing such an embedded clinic at San Antonio Metropolitan Ministries SAMM shelter based on recommendations from community health care leaders, managers of homeless shelters, members of the homeless community and dental professionals^

(Table 1) Correlation of precipitation and winter mass balance (bw) at Storbreen, Norway

Measurements of winter balance (bw) and summer balance (bs) have been carried out at Storbreen since 1949. Here we apply a simple mass balance model to study the climate sensitivity and to reconstruct the mass balance series prior to 1949. The model is calibrated and validated with data from an automatic weather station (AWS) operating in the ablation zone of Storbreen since 2001. Regression analysis revealed that bw was best modelled using precipitation data southwest of the glacier. Results from the model compared well with reported mass balance values for the period 1949-2006, obtained correlations (r) for bw and bs varied between 0.83 and 0.87 depending on model set up. Reconstruction of the mass balance series for the period 1924/1925-1948/1949 suggested a cumulative mass deficit of c. 30 m w.e. mainly due to highly negative summer balances, but also lower bw than the average for 1949-2006. Calculated change in specific mass balance for a ±1°C change in air temperature was ±0.55 m w.e., whereas a ±10 % increase in precipitation represented a change of ± 0.20 m w.e. Model results further indicated that for a 2°C warming, the ablation season will be extended by c. 30 days and that the period of ice melt at the AWS location will increase from c. 40 to c. 80 days.

Realistic detailed balance study of the quantum efficiency of quantum dot solar cells

An attractive but challenging technology for high efficiency solar energy conversion is the intermediate band solar cell (IBSC), whose theoretical efficiency limit is 63%, yet which has so far failed to yield high efficiencies in practice. The most advanced IBSC technology is that based on quantum dots (QDs): the QD-IBSC. In this paper, k·p calculations of photon absorption in the QDs are combined with a multi-level detailed balance model. The model has been used to reproduce the measured quantum efficiency of a real QD-IBSC and its temperature dependence. This allows the analysis of individual sub-bandgap transition currents, which has as yet not been possible experimentally, yielding a deeper understanding of the failure of current QD-IBSCs. Based on the agreement with experimental data, the model is believed to be realistic enough to evaluate future QD-IBSC proposals.

Land cover dynamics and climate change implications on water resources in South Pacific Costa Rica

Water is fundamental to human life and the availability of freshwater is often a constraint on human welfare and economic development. Consequently, the potential effects of global changes on hydrology and water resources are considered among the most severe and vital ones. Water scarcity is one of the main problems in the rural communities of Central America, as a result of an important degradation of catchment areas and the over-exploitation of aquifers. The present Thesis is focused on two critical aspects of global changes over water resources: (1) the potential effects of climate change on water quantity and (2) the impacts of land cover and land use changes on the hydrological processes and water cycle. Costa Rica is among the few developing countries that have recently achieved a land use transition with a net increase in forest cover. Osa Region in South Pacific Costa Rica is an appealing study site to assess water supply management plans and to measure the effects of deforestation, forest transitions and climate change projections reported in the region. Rural Community Water Supply systems (ASADAS) in Osa are dealing with an increasing demand of freshwater due to the growing population and the change in the way of life in the rural livelihoods. Land cover mosaics which have resulted from the above mentioned processes are characterized by the abandonment of marginal farmland with the spread over these former grasslands of high return crops and the expansion of secondary forests due to reforestation initiatives. These land use changes have a significant impact on runoff generation in priority water-supply catchments in the humid tropics, as evidenced by the analysis of the Tinoco Experimental Catchment in the Southern Pacific area of Costa Rica. The monitoring system assesses the effects of the different land uses on the runoff responses and on the general water cycle of the basin. Runoff responses at plot scale are analyzed for secondary forests, oil palm plantations, forest plantations and grasslands. The Oil palm plantation plot presented the highest runoff coefficient (mean RC=32.6%), twice that measured under grasslands (mean RC=15.3%) and 20-fold greater than in secondary forest (mean RC=1.7%). A Thornthwaite-type water balance is proposed to assess the impact of land cover and climate change scenarios over water availability for rural communities in Osa Region. Climate change projections were obtained by the downscaling of BCM2, CNCM3 and ECHAM5 models. Precipitation and temperature were averaged and conveyed by the A1B, A2 and B1 IPCC climate scenario for 2030, 2060 and 2080. Precipitation simulations exhibit a positive increase during the dry season for the three scenarios and a decrease during the rainy season, with the highest magnitude (up to 25%) by the end of the 21st century under scenario B1. Monthly mean temperature simulations increase for the three scenarios throughout the year with a maximum increase during the dry season of 5% under A1B and A2 scenarios and 4% under B1 scenario. The Thornthwaite-type Water Balance model indicates important decreases of water surplus for the three climate scenarios during the rainy season, with a maximum decrease on May, which under A1B scenario drop up to 20%, under A2 up to 40% and under B1 scenario drop up to almost 60%. Land cover scenarios were created taking into account current land cover dynamics of the region. Land cover scenario 1 projects a deforestation situation, with forests decreasing up to 15% due to urbanization of the upper catchment areas; land cover scenario 2 projects a forest recovery situation where forested areas increase due to grassland abandonment on areas with more than 30% of slope. Deforestation scenario projects an annual water surplus decrease of 15% while the reforestation scenario projects a water surplus increase of almost 25%. This water balance analysis indicates that climate scenarios are equal contributors as land cover scenarios to future water resource estimations.

Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis

Hydroxychloroquine (HCQ) is an antimalarial drug that is also used as a second-line treatment of rheumatoid arthritis (RA). Clinically, the use of HCQ is characterized by a long delay in the onset of action, and withdrawal of treatment is often a result of inefficacy rather than from toxicity. The slow onset of action can be attributed to the pharmacokinetics (PK) of HCQ, and wide interpatient variability is evident. Tentative relationships between concentration and effect have been made, but to date, no population PK model has been developed for HCQ. This study aimed to develop a population PK model including an estimation of the oral bioavailability of HCQ. In addition, the effects of the coadministration of methotrexate on the PK of HCQ were examined. Hydroxychloroquine blood concentration data were combined from previous pharmacokinetic studies in patients with rheumatoid arthritis. A total of 123 patients were studied, giving the data cohort from four previously published studies. Two groups of patients were included: 74 received hydroxychloroquine (HCQ) alone, and 49 received HCQ and methotrexate (MTX). All data analyses were carried out using the NONMEM program. A one-compartment PK model was supported, rather than a three-compartment model as previously published, probably because of the clustering of concentrations taken at the end of a dosing interval. The population estimate of bioavailability of 0.75 (0.07), n = 9, was consistent with literature values. The parameter values from the final model were: (Cl) over bar = 9.9 +/- 0.4 L/h, (V) over bar 605 +/- 91 L, (k(d)) over bar = 0.77 +/- 0.22 hours(-1), (t(tag)) over bar = 0.44 +/- 0.02 hours. Clearance was not affected by the presence of MTX, and, hence, steady-state drug concentrations and maintenance dosage requirements were similar. A population PK model was successfully developed for HCQ.

Population pharmacokinetic analysis of mycophenolic acid in renal transplant recipients following oral administration of mycophenolate mofetil

Aim To develop a population pharmacokinetic model for mycophenolic acid in adult kidney transplant recipients, quantifying average population pharmacokinetic parameter values, and between- and within-subject variability and to evaluate the influence of covariates on the pharmacokinetic variability. Methods Pharmacokinetic data for mycophenolic acid and covariate information were previously available from 22 patients who underwent kidney transplantation at the Princess Alexandra Hospital. All patients received mycophenolate mofetil 1 g orally twice daily. A total of 557 concentration-time points were available. Data were analysed using the first-order method in NONMEM (version 5 level 1.1) using the G77 FORTRAN compiler. Results The best base model was a two-compartment model with a lag time (apparent oral clearance was 271 h(-1), and apparent volume of the central compartment 981). There was visual evidence of complex absorption and time-dependent clearance processes, but they could not be successfully modelled in this study. Weight was investigated as a covariate, but no significant relationship was determined. Conclusions The complexity in determining the pharmacokinetics of mycophenolic acid is currently underestimated. More complex pharmacokinetic models, though not supported by the limited data collected for this study, may prove useful in the future. The large between-subject and between-occasion variability and the possibility of nonlinear processes associated with the pharmacokinetics of mycophenolic acid raise questions about the value of the use of therapeutic monitoring and limited sampling strategies.

Toward better outcomes with tacrolimus therapy: Population pharmacokinetics and individualized dosage prediction in adult liver transplantation

Patient outcomes in transplantation would improve if dosing of immunosuppressive agents was individualized. The aim of this study is to develop a population pharmacokinetic model of tacrolimus in adult liver transplant recipients and test this model in individualizing therapy. Population analysis was performed on data from 68 patients. Estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F) using the nonlinear mixed effects model program (NONMEM). Factors screened for influence on these parameters were weight, age, sex, transplant type, biliary reconstructive procedure, postoperative day, days of therapy, liver function test results, creatinine clearance, hematocrit, corticosteroid dose, and interacting drugs. The predictive performance of the developed model was evaluated through Bayesian forecasting in an independent cohort of 36 patients. No linear correlation existed between tacrolimus dosage and trough concentration (r(2) = 0.005). Mean individual Bayesian estimates for CL/F and V/F were 26.5 8.2 (SD) L/hr and 399 +/- 185 L, respectively. CL/F was greater in patients with normal liver function. V/F increased with patient weight. CL/F decreased with increasing hematocrit. Based on the derived model, a 70-kg patient with an aspartate aminotransferase (AST) level less than 70 U/L would require a tacrolimus dose of 4.7 mg twice daily to achieve a steady-state trough concentration of 10 ng/mL. A 50-kg patient with an AST level greater than 70 U/L would require a dose of 2.6 mg. Marked interindividual variability (43% to 93%) and residual random error (3.3 ng/mL) were observed. Predictions made using the final model were reasonably nonbiased (0.56 ng/mL), but imprecise (4.8 ng/mL). Pharmacokinetic information obtained will assist in tacrolimus dosing; however, further investigation into reasons for the pharmacokinetic variability of tacrolimus is required.

Modelling nucleation in wet granulation

Nucleation is the first stage in any granulation process where binder liquid first comes into contact with the powder. This paper investigates the nucleation process where binder liquid is added to a fine powder with a spray nozzle. The dimensionless spray flux approach of Hapgood et al. (Powder Technol. 141 (2004) 20) is extended to account for nonuniform spray patterns and allow for overlap of nuclei granules rather than spray drops. A dimensionless nuclei distribution function which describes the effects of the design and operating parameters of the nucleation process (binder spray characteristics, the nucleation area ratio between droplets and nuclei and the powder bed velocity) on the fractional surface area coverage of nuclei on a moving powder bed is developed. From this starting point, a Monte Carlo nucleation model that simulates full nuclei size distributions as a function of the design and operating parameters that were implemented in the dimensionless nuclei distribution function is developed. The nucleation model was then used to investigate the effects of the design and operating parameters on the formed nuclei size distributions and to correlate these effects to changes of the dimensionless nuclei distribution function. Model simulations also showed that it is possible to predict nuclei size distributions beyond the drop controlled nucleation regime in Hapgood's nucleation regime map. Qualitative comparison of model simulations and experimental nucleation data showed similar shapes of the nuclei size distributions. In its current form, the nucleation model can replace the nucleation term in one-dimensional population balance models describing wet granulation processes. Implementation of more sophisticated nucleation kinetics can make the model applicable to multi-dimensional population balance models.

Kinetic study of the thermal degradation of high density polyethylene

The thermal degradation of high density polyethylene has been modelled by the random breakage of polymer bonds, using a set of population balance equations. A model was proposed in which the population balances were lumped into representative sizes so that the experimentally determined molecular weight distribution of the original polymer could be used as the initial condition. This model was then compared to two different cases of the unlumped population balance which assumed unimolecular initial distributions of 100 and 500 monomer units, respectively. The model that utilised the experimentally determined molecular weight distribution was found to best describe the experimental data. The model fits suggested a second mechanism in addition to random breakage at slow reaction rates. (c) 2005 Elsevier Ltd. All rights reserved.

Population pharmacokinetics of itraconazole and its active metabolite hydroxy-itraconazole in paediatric cystic fibrosis and bone marrow transplant patients

Objective: The objective of the study was to characterise the population pharmacokinetic properties of itraconazole and its active metabolite hydroxyitraconazole in a representative paediatric population of cystic fibrosis and bone marrow transplant (BMT) patients and to identify patient characteristics influencing the pharmacokinetics of itraconazole. The ultimate goals were to determine the relative bioavailability between the two oral formulations (capsules vs oral solution) and to optimise dosing regimens in these patients. Methods: All paediatric patients with cystic fibrosis or patients undergoing BMT at The Royal Children's Hospital, Brisbane, QLD, Australia, who were prescribed oral itraconazole for the treatment of allergic bronchopulmonary aspergillosis (cystic fibrosis patients) or for prophylaxis of any fungal infection (BMT patients) were eligible for the study. Blood samples were taken from the recruited patients as per an empirical sampling design either during hospitalisation or during outpatient clinic visits. ltraconazole and hydroxy-itraconazole plasma concentrations were determined by a validated high-performance liquid chromatography assay with fluorometric detection. A nonlinear mixed-effect modelling approach using the NONMEM software to simultaneously describe the pharmacokinetics of itraconazole and its metabolite. Results: A one-compartment model with first-order absorption described the itraconazole data, and the metabolism of the parent drug to hydroxy-itraconazole was described by a first-order rate constant. The metabolite data also showed one-compartment characteristics with linear elimination. For itraconazole the apparent clearance (CLitraconazole) was 35.5 L/hour, the apparent volume of distribution (V-d(itraconazole)) was 672L, the absorption rate constant for the capsule formulation was 0.0901 h(-1) and for the oral solution formulation was 0.96 h-1. The lag time was estimated to be 19.1 minutes and the relative bioavailability between capsules and oral solution (F-rel) was 0.55. For the metabolite, volume of distribution, V-m/(F (.) f(m)), and clearance, CL/(F (.) fm), were 10.6L and 5.28 L/h, respectively. The influence of total bodyweight was significant, added as a covariate on CLitraconazoie/F and V-d(itraconazole)/F (standardised to a 70kg person) using allometric three-quarter power scaling on CLitraconazole/F, which therefore reflected adult values. The unexplained between-subject variability (coefficient of variation %) was 68.7%, 75.8%, 73.4% and 61.1% for CLitraconazoie/F, Vd(itraconazole)/F, CLm/(F (.) fm) and F-rel, respectively. The correlation between random effects of CLitraconazole and Vd((itraconazole)) was 0.69. Conclusion: The developed population pharmacokinetic model adequately described the pharmacokinetics of itraconazole and its active metabolite, hydroxy-itraconazole, in paediatric patients with either cystic fibrosis or undergoing BMT. More appropriate dosing schedules have been developed for the oral solution and the capsules to secure a minimum therapeutic trough plasma concentration of 0.5 mg/L for these patients.

Right ventricle extraction by low level and model-based algorithm

In this paper we present an algorithm as the combination of a low level morphological operation and model based Global Circular Shortest Path scheme to explore the segmentation of the Right Ventricle. Traditional morphological operations were employed to obtain the region of interest, and adjust it to generate a mask. The image cropped by the mask is then partitioned into a few overlapping regions. Global Circular Shortest Path algorithm is then applied to extract the contour from each partition. The final step is to re-assemble the partitions to create the whole contour. The technique is deemed quite reliable and robust, as this is illustrated by a very good agreement between the extracted contour and the expert manual drawing output.

A priori prediction of aggregation efficiency and rate constant for fluidized bed melt granulation

This paper presents a predictive aggregation rate model for spray fluidized bed melt granulation. The aggregation rate constant was derived from probability analysis of particle–droplet contact combined with time scale analysis of droplet solidification and granule–granule collision rates. The latter was obtained using the principles of kinetic theory of granular flow (KTGF). The predicted aggregation rate constants were validated by comparison with reported experimental data for a range of binder spray rate, binder droplet size and operating granulator temperature. The developed model is particularly useful for predicting particle size distributions and growth using population balance equations (PBEs).

Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients

Aims - To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation. Methods - The present study retrospectively examined tacrolimus whole blood pre-dose concentrations (n = 628) of 43 children during their first year post-liver transplantation. Population pharmacokinetic analysis was performed using the non-linear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance and influential covariates. Results - The final model identified time post-transplantation and CYP3A5*1 allele as influential covariates on tacrolimus apparent clearance according to the following equation: TVCL = 12.9 x (Weight/13.2)0.35 x EXP (-0.0058 x TPT) x EXP (0.428 x CYP3A5) where TVCL is the typical value for apparent clearance, TPT is time post-transplantation in days and the CYP3A5 is 1 where *1 allele is present and 0 otherwise. The population estimate and inter-individual variability (%CV) of tacrolimus apparent clearance were found to be 0.977 l h−1 kg−1 (95% CI 0.958, 0.996) and 40.0%, respectively, while the residual variability between the observed and predicted concentrations was 35.4%. Conclusion Tacrolimus apparent clearance was influenced by time post-transplantation and CYP3A5 genotypes. The results of this study, once confirmed by a large scale prospective study, can be used in conjunction with therapeutic drug monitoring to recommend tacrolimus dose adjustments that take into account not only body weight but also genetic and time-related changes in tacrolimus clearance.