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At least 433 records · Page 24

Comparative Approach of MRI-Based Brain Tumor Segmentation and Classification Using Genetic Algorithm

The detection of a brain tumor and its classification from modern imaging modalities is a primary concern, but a time-consuming and tedious work was performed by radiologists or clinical supervisors. The accuracy of detection and classification of tumor stages performed by radiologists is depended on their experience only, so the computer-aided technology is very important to aid with the diagnosis accuracy. In this study, to improve the performance of tumor detection, we investigated comparative approach of different segmentation techniques and selected the best one by comparing their segmentation score. Further, to improve the classification accuracy, the genetic algorithm is employed for the automatic classification of tumor stage. The decision of classification stage is supported by extracting relevant features and area calculation. The experimental results of proposed technique are evaluated and validated for performance and quality analysis on magnetic resonance brain images, based on segmentation score, accuracy, sensitivity, specificity, and dice similarity index coefficient. The experimental results achieved 92.03% accuracy, 91.42% specificity, 92.36% sensitivity, and an average segmentation score between 0.82 and 0.93 demonstrating the effectiveness of the proposed technique for identifying normal and abnormal tissues from brain MR images. The experimental results also obtained an average of 93.79% dice similarity index coefficient, which indicates better overlap between the automated extracted tumor regions with manually extracted tumor region by radiologists.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparative Study of the Effect of Magnetic Nanoparticle CoFe{sub 2}O{sub 4} on Fluctuation-Induced Conductivity of Y-123 and Y-358 Superconductors

In this study, a comparative investigation of the electrical conductivity fluctuations in nano-CoFe{sub 2}O{sub 4} added to Y{sub 3}Ba{sub 5}Cu{sub 8}O{sub 18±x} (Y-358) and YBa{sub 2}Cu{sub 3}O{sub 7−d} (Y-123) products is performed. All products were made using the solid-state reaction process. X-ray powder diffraction (XRD) analyses confirmed the formation of different phases. Scanning electron microscope (SEM) analysis shows the reduction of grain size with increasing the quantity of nano-CoFe{sub 2}O{sub 4} particles for both the Y-123 and Y-358 samples. The decrease of grain size is more accentuated in the case of the Y-358 samples compared with the Y-123 ones. The data of conductivity fluctuations are examined in terms of the derivative of the electrical resistivity with respect to temperature and the logarithmic derivative of the conductivity with regard to temperature. The results illustrate the existence of a transition with two stages; intragrain and intergrain. It is demonstrated that the addition of CoFe{sub 2}O{sub 4} nanoparticles affects the electrical conductivity fluctuations, the values of the critical exponents, and the fluctuation dimensionality in YBCO systems.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

A Comparative Study on Formability of the Third-Generation Automotive Medium-Mn Steel and 22MnB5 Steel

Third-generation advanced automotive medium-Mn steel, which can replace 22MnB5 steel, was newly developed to improve the lightweight and crashworthiness of automobile. Studies on the formability and simulation method of medium-Mn steel have just been initiated. In this study, finite element simulation models of square-cup deep drawing were established based on various material property experiments and validated by experiments. The effects of blank holder force (BHF), fillet radii of tools (die and punch) on the maximum drawing depth (MDD), thickness distribution of the formed products, and the microstructure before and after forming were investigated and compared with those on 22MnB5 steel. Results show that the MDD of the two steels decreased with increased BHF but increased with the fillet radius of punch; however, the fillet radius of die showed no significant effect on the MDD for both steels. Compared with hot-formed 22MnB5 steel, the martensitic transformation of the hot-formed medium-Mn steel is rarely influenced by the process parameters; thus, it holds the complete, fine-grained, and uniform martensitic microstructure. Moreover, the medium-Mn has better formability, lower initial blank temperature, and smaller impact of BHF and fillet radius of tools on the hot-formed product. Thus, a theoretical basis for the replacement of 22MnB5 steel by medium-Mn steel in hot forming process is provided.

36 MATERIALS SCIENCE↗

Atmospheric Pressure Ionization Using a High Voltage Target Compared to Electrospray Ionization

A new atmospheric pressure ionization (API) source, viz. UniSpray, was evaluated for mass spectrometry (MS) analysis of pharmaceutical compounds by head-to-head comparison with electrospray ionization (ESI) on the same high-resolution MS system. The atmospheric pressure ionization source is composed of a grounded nebulizer spraying onto a high voltage, cylindrical stainless steel target. Molecules are ionized in a similar fashion to electrospray ionization, predominantly producing protonated or deprotonated species. Adduct formation (e.g., proton and sodium adducts) and in-source fragmentation is shown to be almost identical between the two sources. The performance of the new API source was compared with electrospray by infusion of a mix of 22 pharmaceutical compounds with a wide variety of functional groups and physico-chemical properties (molecular weight, logP, and pKa) in more than 100 different conditions (mobile phase strength, solvents, pH, and flow rate). The new API source shows an intensity gain of a factor 2.2 compared with ESI considering all conditions on all compounds tested. Finally, some hypotheses on the ionization mechanism, similarities, and differences with ESI, are discussed. .

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Comparative analysis of image binarization methods for crack identification in concrete structures

Surface cracks in concrete structures are critical indicators of structural damage and durability. Manual visual inspection, the most commonly used method in practice, is inefficient from cost, time, accuracy, and safety perspectives. A promising alternative is computer vision-based methods that can automatically extract crack information from images. Image binarization, developed for text detection, is appropriate for crack identification, as texts and cracks are similar, consisting of distinguishable lines and curves. However, standardizing crack identification using image binarization is challenging, because binarization depends on the method and associated parameters. We investigate image binarization for crack identification, focusing on optimal parameter determination and comparative performance evaluation for five common binarization methods. Crack images are prepared to obtain optimal parameters by minimizing errors in estimated crack widths. Subsequently, comparative analysis is conducted using crack images with different conditions based on three performance evaluation criteria: crack width and length measurement accuracy and computation time.

36 MATERIALS SCIENCE↗

Individualized Positron Emission Tomography–Based Isotoxic Accelerated Radiation Therapy Is Cost-Effective Compared With Conventional Radiation Therapy: A Model-Based Evaluation

Purpose: To evaluate long-term health effects, costs, and cost-effectiveness of positron emission tomography (PET)-based isotoxic accelerated radiation therapy treatment (PET-ART) compared with conventional fixed-dose CT-based radiation therapy treatment (CRT) in non-small cell lung cancer (NSCLC). Methods and Materials: Our analysis uses a validated decision model, based on data of 200 NSCLC patients with inoperable stage I-IIIB. Clinical outcomes, resource use, costs, and utilities were obtained from the Maastro Clinic and the literature. Primary model outcomes were the difference in life-years (LYs), quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness and cost/utility ratio (ICER and ICUR) of PET-ART versus CRT. Model outcomes were obtained from averaging the predictions for 50,000 simulated patients. A probabilistic sensitivity analysis and scenario analyses were carried out. Results: The average incremental costs per patient of PET-ART were €569 (95% confidence interval [CI] €−5327-€6936) for 0.42 incremental LYs (95% CI 0.19-0.61) and 0.33 QALYs gained (95% CI 0.13-0.49). The base-case scenario resulted in an ICER of €1360 per LY gained and an ICUR of €1744 per QALY gained. The probabilistic analysis gave a 36% probability that PET-ART improves health outcomes at reduced costs and a 64% probability that PET-ART is more effective at slightly higher costs. Conclusion: On the basis of the available data, individualized PET-ART for NSCLC seems to be cost-effective compared with CRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparative Assessment of Liver Tumor Motion Using Cine–Magnetic Resonance Imaging Versus 4-Dimensional Computed Tomography

Purpose: To compare the extent of tumor motion between 4-dimensional CT (4DCT) and cine-MRI in patients with hepatic tumors treated with radiation therapy. Methods and Materials: Patients with liver tumors who underwent 4DCT and 2-dimensional biplanar cine-MRI scans during simulation were retrospectively reviewed to determine the extent of target motion in the superior–inferior, anterior–posterior, and lateral directions. Cine-MRI was performed over 5 minutes. Tumor motion from MRI was determined by tracking the centroid of the gross tumor volume using deformable image registration. Motion estimates from 4DCT were performed by evaluation of the fiducial, residual contrast (or liver contour) positions in each CT phase. Results: Sixteen patients with hepatocellular carcinoma (n=11), cholangiocarcinoma (n=3), and liver metastasis (n=2) were reviewed. Cine-MRI motion was larger than 4DCT for the superior–inferior direction in 50% of patients by a median of 3.0 mm (range, 1.5-7 mm), the anterior–posterior direction in 44% of patients by a median of 2.5 mm (range, 1-5.5 mm), and laterally in 63% of patients by a median of 1.1 mm (range, 0.2-4.5 mm). Conclusions: Cine-MRI frequently detects larger differences in hepatic intrafraction tumor motion when compared with 4DCT most notably in the superior–inferior direction, and may be useful when assessing the need for or treating without respiratory management, particularly in patients with unreliable 4DCT imaging. Margins wider than the internal target volume as defined by 4DCT were required to encompass nearly all the motion detected by cine-MRI for some of the patients in this study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to achieve additional benefit with dose escalation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Compared to Intensity Modulated Radiation Therapy

Purpose: The clinical significance of magnetic resonance imaging (MRI) changes after radiation therapy (RT) in children with ependymoma is not well defined. We compared imaging changes following proton beam radiation therapy (PBRT) to those after photon-based intensity modulated RT (IMRT). Methods and Materials: Seventy-two patients with nonmetastatic intracranial ependymoma who received postoperative RT (37 PBRT, 35 IMRT) were analyzed retrospectively. MRI images were reviewed by 2 neuroradiologists. Results: Sixteen PBRT patients (43%) developed postradiation MRI changes at 3.8 months (median) with resolution by 6.1 months. Six IMRT patients (17%) developed changes at 5.3 months (median) with 8.3 months to resolution. Mean age at radiation was 4.4 and 6.9 years for PBRT and IMRT, respectively (P=.06). Age at diagnosis (>3 years) and time of radiation (≥3 years) was associated with fewer imaging changes on univariate analysis (odds ratio [OR]: 0.35, P=.048; OR: 0.36, P=.05). PBRT (compared to IMRT) was associated with more frequent imaging changes, both on univariate (OR: 3.68, P=.019) and multivariate (OR: 3.89, P=.024) analyses. Seven (3 IMRT, 4 PBRT) of 22 patients with changes had symptoms requiring intervention. Most patients were treated with steroids; some PBRT patients also received bevacizumab and hyperbaric oxygen therapy. None of the IMRT patients had lasting deficits, but 2 patients died from recurrent disease. Three PBRT patients had persistent neurological deficits, and 1 child died secondarily to complications from radiation necrosis. Conclusions: Postradiation MRI changes are more common with PBRT and in patients less than 3 years of age at diagnosis and treatment. It is difficult to predict causes for development of imaging changes that progress to clinical significance. These changes are usually self-limiting, but some require medical intervention, especially those involving the brainstem.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Targeting Myeloid-derived Suppressor Cells and Programmed Death Ligand 1 Confers Therapeutic Advantage of Ablative Hypofractionated Radiation Therapy Compared With Conventional Fractionated Radiation Therapy

Ablative hypofractionated radiation therapy (AHFRT) presents a therapeutic advantage compared with conventional fractionated radiation therapy (CFRT) for primary and oligometastatic cancers. However, the underlying mechanisms remain largely unknown. In the present study, we compared the immune alterations in response to AHFRT versus CFRT and examined the significance of immune regulations contributing to the efficacy of AHFRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A comparative study of diffraction of shallow-water waves by high-level IGN and GN equations

This work is on the nonlinear diffraction analysis of shallow-water waves, impinging on submerged obstacles, by two related theories, namely the classical Green–Naghdi (GN) equations and the Irrotational Green–Naghdi (IGN) equations, both sets of equations being at high levels and derived for incompressible and inviscid flows. Recently, the high-level Green–Naghdi equations have been applied to some wave transformation problems. The high-level IGN equations have also been used in the last decade to study certain wave propagation problems. However, past works on these theories used different numerical methods to solve these nonlinear and unsteady sets of differential equations and at different levels. Moreover, different physical problems have been solved in the past. Therefore, it has not been possible to understand the differences produced by these two sets of theories and their range of applicability so far. We are thus motivated to make a direct comparison of the results produced by these theories by use of the same numerical method to solve physically the same wave diffraction problems. We focus on comparing these two theories by using similar codes; only the equations used are different but other parts of the codes, such as the wave-maker, damping zone, discretion method, matrix solver, etc., are exactly the same. This way, we eliminate many potential sources of differences that could be produced by the solution of different equations. The physical problems include the presence of various submerged obstacles that can be used for example as breakwaters or to represent the continental shelf. A numerical wave tank is created by placing a wavemaker on one end and a wave absorbing beach on the other. The nonlinear and unsteady sets of differential equations are solved by the finite-difference method. The results are compared with different equations as well as with the available experimental data.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Comparative study of optical and structural properties of electrospun 1-dimensional CaYAl{sub 3}O{sub 7}:Eu{sup 3+} nanofibers and bulk phosphor

We report the optical and structural studies of Eu{sup 3+}-doped 1-dimensional CaYAl{sub 3}O{sub 7} nano-fiber phosphor. CaYAl{sub 3}O{sub 7}:Eu{sup 3+} phosphors were synthesized by electrospinning technique and the pristine nano-fibers were annealed at 900 °C to form well crystallized uniform fibers. Under ultraviolet excitation, the CaYAl{sub 3}O{sub 7}:Eu{sup 3+} exhibited red emission, due to transitions in the 4f states of Eu{sup 3+}. In order to explore the difference between the quantum efficiency of nano-fiber and bulk CaYAl{sub 3}O{sub 7}:Eu{sup 3+} phosphor, detailed structural and optical analyses were carried out. The structural analysis of the CaYAl{sub 3}O{sub 7}:Eu{sup 3+} nano-fibers indicates that the structural environment surrounding the dopant Eu{sup 3+} ion was more unstable in nano-fiber when compared to a bulk sample. Decay curves for both the samples when fitted with double exponential decay model indicate that the nano-fiber has shorter decay time, arising from the larger contribution from the non-radiative decay, due to defect levels introduced in the host lattice. - Highlights: • Synthesis of red nano-phosphor through electrospinning • Luminescence properties of bulk and nano-phosphors are compared. • Inferior emission intensity of the nano-phosphor is analyzed using MEM. • Charge cloud around nano-phosphor was found to be oblique.

36 MATERIALS SCIENCE↗

Structural, negative thermal expansion and photocatalytic properties of ZrV{sub 2}O{sub 7}: a comparative study between fibers and powders

Novel ZrV{sub 2}O{sub 7} microfibers with diameters about 1–3 μm were synthesized using a sol–gel technique. For comparison, ZrV{sub 2}O{sub 7} powders were prepared by the same method. The resultant structures were studied by X-ray diffraction, field-emission scanning electron microscopy and transmission electron microscopy. The results indicated that both the pure ZrV{sub 2}O{sub 7} microfibers and powders could be synthesized by the sol–gel technique. The thermal expansion property of the as-prepared ZrV{sub 2}O{sub 7} microfibers and powders was characterized by a thermal mechanical analyzer, both the fibers with cylindrical morphology and irregular powders with average size between 100 and 200 nm showed negative thermal expansion between 150 °C and 600 °C. The photocatalytic activity of the microfibers was compared to that of powders under UV radiations. The band gap of ZrV{sub 2}O{sub 7} microfibers decreased and its absorption edge exhibited red shift. The microfibers also had a higher surface area compared with the powders, resulting in considerably higher photocatalytic characteristics. The large surface area and the enhanced photocatalytic activity of the ZrV{sub 2}O{sub 7} microfibers also offer potential applications in sensors and inorganic ion exchangers. - Graphical abstract: (a and c) SEM photos of ZrV{sub 2}O{sub 7} powders and fibers. (b and d) TEM images of ZrV{sub 2}O{sub 7} powders and fibers. (e) Thermal expansion curves of ZrV{sub 2}O{sub 7} powders and fibers. (f) Degradation curves of ZrV{sub 2}O{sub 7} powders and ZrV{sub 2}O{sub 7} fibers. - Highlights: • Novel ZrV{sub 2}O{sub 7} fibers could be synthesized using sol–gel technique. • ZrV{sub 2}O{sub 7} powders with irregular shape are also prepared for comparison. • Both ZrV{sub 2}O{sub 7} microfibers and powders exhibit negative thermal expansion property. • ZrV{sub 2}O{sub 7} microfibers show outstanding photocatalytic activity under UV irradiation. • This synthesis technique can be easily extended to many other functional fibers.

36 MATERIALS SCIENCE↗

Sample preparation methods for scanning electron microscopy of homogenized Al-Mg-Si billets: A comparative study

Characterization of Mg-Si precipitates is crucial for optimizing the homogenization heat treatment of Al-Mg-Si alloys. Although sample preparation is key for high quality scanning electron microscopy imaging, most common methods lead to dealloying of Mg-Si precipitates. In this article we systematically evaluate different sample preparation methods: mechanical polishing, etching with various reagents, and electropolishing using different electrolytes. We demonstrate that the use of a nitric acid and methanol electrolyte for electropolishing a homogenized Al-Mg-Si alloy prevents the dissolution of Mg-Si precipitates, resulting in micrographs of higher quality. This preparation method is investigated in depth and the obtained scanning electron microscopy images are compared with transmission electron micrographs: the shape and size of Mg-Si precipitates appear very similar in either method. The scanning electron micrographs allow proper identification and measurement of the Mg-Si phases including needles with lengths of roughly 200 nm. These needles are β″ precipitates as confirmed by high resolution transmission electron microscopy. - Highlights: •Secondary precipitation in homogenized 6xxx Al alloys is crucial for extrudability. •Existing sample preparation methods for SEM are improvable. •Electropolishing with nitric acid/methanol yields superior quality in SEM. •The obtained micrographs are compared to TEM micrographs.

36 MATERIALS SCIENCE↗

A dosimetric comparative study: Volumetric modulated arc therapy vs intensity-modulated radiation therapy in the treatment of nasal cavity carcinomas

The purpose of this study was to evaluate the differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in the treatment of nasal cavity carcinomas. The treatment of 10 patients, who had completed IMRT treatment for resected tumors of the nasal cavity, was replanned with the Philips Pinnacle{sup 3} Version 9 treatment-planning system. The IMRT plans used a 9-beam technique whereas the VMAT (known as SmartArc) plans used a 3-arc technique. Both types of plans were optimized using Philips Pinnacle{sup 3} Direct Machine Parameter Optimization algorithm. IMRT and VMAT plans' quality was compared by evaluating the maximum, minimum, and mean doses to the target volumes and organs at risk, monitor units (MUs), and the treatment delivery time. Our results indicate that VMAT is capable of greatly reducing treatment delivery time and MUs compared with IMRT. The reduction of treatment delivery time and MUs can decrease the effects of intrafractional uncertainties that can occur because of patient movement during treatment delivery. VMAT's plans further reduce doses to critical structures that are in close proximity to the target volume.

61 RADIATION PROTECTION AND DOSIMETRY↗

Dosimetric advantages of intensity-modulated proton therapy for oropharyngeal cancer compared with intensity-modulated radiation: A case-matched control analysis

A potential advantage of intensity-modulated proton therapy (IMPT) over intensity-modulated (photon) radiation therapy (IMRT) in the treatment of oropharyngeal carcinoma (OPC) is lower radiation dose to several critical structures involved in the development of nausea and vomiting, mucositis, and dysphagia. The purpose of this study was to quantify doses to critical structures for patients with OPC treated with IMPT and compare those with doses on IMRT plans generated for the same patients and with a matched cohort of patients actually treated with IMRT. In this study, 25 patients newly diagnosed with OPC were treated with IMPT between 2011 and 2012. Comparison IMRT plans were generated for these patients and for additional IMRT-treated controls extracted from a database of patients with OPC treated between 2000 and 2009. Cases were matched based on the following criteria, in order: unilateral vs bilateral therapy, tonsil vs base of tongue primary, T-category, N-category, concurrent chemotherapy, induction chemotherapy, smoking status, sex, and age. Results showed that the mean doses to the anterior and posterior oral cavity, hard palate, larynx, mandible, and esophagus were significantly lower with IMPT than with IMRT comparison plans generated for the same cohort, as were doses to several central nervous system structures involved in the nausea and vomiting response. Similar differences were found when comparing dose to organs at risks (OARs) between the IMPT cohort and the case-matched IMRT cohort. In conclusion, these findings suggest that patients with OPC treated with IMPT may experience fewer and less severe side effects during therapy. This may be the result of decreased beam path toxicities with IMPT due to lower doses to several dysphagia, odynophagia, and nausea and vomiting–associated OARs. Further study is needed to evaluate differences in long-term disease control and chronic toxicity between patients with OPC treated with IMPT in comparison to those treated with IMRT.

61 RADIATION PROTECTION AND DOSIMETRY↗

Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model

Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1 or 6 h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED{sub 50} values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1 h; > 200 fold at 6 h) than with tiotropium (1.5 and 4.2 fold at 1 h; 4.6 and 5.5 fold at 6 h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M{sub 2} muscarinic receptor occupancy, which predicted significantly higher M{sub 2} receptor blockade at ED{sub 50} doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. - Highlights: • We use an in vivo rat model to study CV safety of inhaled muscarinic antagonists. • We integrate protein and receptor binding and PK of tiotropium and glycopyrrolate. • At ED{sub 50} doses for bronchoprotection we model systemic M{sub 2} receptor occupancy. • Glycopyrrolate demonstrates lower M{sub 2} occupancy at bronchoprotective doses. • Glycopyrrolate demonstrates an improved CV safety profile, versus tiotropium.

60 APPLIED LIFE SCIENCES↗

Droplet Nucleation: Physically-Based Parameterization and Comparative Evaluation

One of the greatest sources of uncertainty in simulations of climate and climate change is the influence of aerosols on the optical properties of clouds. The root of this influence is the droplet nucleation process. Droplet nucleation involves the simultaneous condensational growth of an aerosol population until maximum supersaturation is achieved and a subset of the particles are large enough to grow spontaneously into cloud droplets. Numerical models of droplet nucleation are capable of representing much of the complexity of the process, but at a computational cost that limits their application to simulations of hours or days. Parameterizations of droplet nucleation are designed to quickly estimate the number nucleated as a function of the primary controlling parameters: the cooling rate and the size distribution of aerosol number and hygroscopicity. Here we compare and contrast the key assumptions used in developing each of the most popular parameterizations and compare the performance of each under a variety of conditions. In general we find that the more complex parameterizations perform well under a wider variety of conditions, but all parameterizations perform well under the most common conditions. We then discuss the various applications of the parameterizations to cloud-resolving, regional and global models to study aerosol effects on clouds at a wide range of spatial and temporal scales. We conclude with a summary of the outstanding challenges remaining for further development.

54 ENVIRONMENTAL SCIENCES↗