The effect of flow field & geometry on the dynamic contact angle

A number of recent experiments suggest that, at a given wetting speed, the dynamic contact angle formed by an advancing liquid-gas interface with a solid substrate depends on the flow field and geometry near the moving contact line. In the present work, this effect is investigated in the framework of an earlier developed theory that was based on the fact that dynamic wetting is, by its very name, a process of formation of a new liquid-solid interface (newly “wetted” solid surface) and hence should be considered not as a singular problem but as a particular case from a general class of flows with forming or/and disappearing interfaces. The results demonstrate that, in the flow configuration of curtain coating, where a liquid sheet (“curtain”) impinges onto a moving solid substrate, the actual dynamic contact angle indeed depends not only on the wetting speed and material constants of the contacting media, as in the so-called slip models, but also on the inlet velocity of the curtain, its height, and the angle between the falling curtain and the solid surface. In other words, for the same wetting speed the dynamic contact angle can be varied by manipulating the flow field and geometry near the moving contact line. The obtained results have important experimental implications: given that the dynamic contact angle is determined by the values of the surface tensions at the contact line and hence depends on the distributions of the surface parameters along the interfaces, which can be influenced by the flow field, one can use the overall flow conditions and the contact angle as a macroscopic multiparametric signal-response pair that probes the dynamics of the liquid-solid interface. This approach would allow one to investigate experimentally such properties of the interface as, for example, its equation of state and the rheological properties involved in the interface’s response to an external torque, and would help to measure its parameters, such as the coefficient of sliding friction, the surface-tension relaxation time, and so on.

Boundary integral methods in high frequency scattering

In this article we review recent progress on the design, analysis and implementation of numerical-asymptotic boundary integral methods for the computation of frequency-domain acoustic scattering in a homogeneous unbounded medium by a bounded obstacle. The main aim of the methods is to allow computation of scattering at arbitrarily high frequency with finite computational resources.

The calculation of force constants and normal coordinates III: constrained force fields for the methyl halides

A method is discussed for imposing any desired constraint on the force field obtained in a force constant refinement calculation. The application of this method to force constant refinement calculations for the methyl halide molecules is reported. All available data on the vibration frequencies, Coriolis interaction constants and centrifugal stretching constants of CH3X and CD3X molecules were used in the refinements, but despite this apparent abundance of data it was found that constraints were necessary in order to obtain a unique solution to the force field. The results of unconstrained calculations, and of three different constrained calculations, are reported in this paper. The constrained models reported are a Urey—Bradley force field, a modified valence force field, and a constraint based on orbital-following bond-hybridization arguments developed in the following paper. The results are discussed, and compared with previous results for these molecules. The third of the above models is found to reproduce the observed data better than either of the first two, and additional reasons are given for preferring this solution to the force field for the methyl halide molecules.

Comparison of energy evaluation systems and a mechanistic model for milk production by dairy cattle offered fresh grass-based diets

Grass-based diets are of increasing social-economic importance in dairy cattle farming, but their low supply of glucogenic nutrients may limit the production of milk. Current evaluation systems that assess the energy supply and requirements are based on metabolisable energy (ME) or net energy (NE). These systems do not consider the characteristics of the energy delivering nutrients. In contrast, mechanistic models take into account the site of digestion, the type of nutrient absorbed and the type of nutrient required for production of milk constituents, and may therefore give a better prediction of supply and requirement of nutrients. The objective of the present study is to compare the ability of three energy evaluation systems, viz. the Dutch NE system, the agricultural and food research council (AFRC) ME system, and the feed into milk (FIM) ME system, and of a mechanistic model based on Dijkstra et al. [Simulation of digestion in cattle fed sugar cane: prediction of nutrient supply for milk production with locally available supplements. J. Agric. Sci., Cambridge 127, 247-60] and Mills et al. [A mechanistic model of whole-tract digestion and methanogenesis in the lactating dairy cow: model development, evaluation and application. J. Anim. Sci. 79, 1584-97] to predict the feed value of grass-based diets for milk production. The dataset for evaluation consists of 41 treatments of grass-based diets (at least 0.75 g ryegrass/g diet on DM basis). For each model, the predicted energy or nutrient supply, based on observed intake, was compared with predicted requirement based on observed performance. Assessment of the error of energy or nutrient supply relative to requirement is made by calculation of mean square prediction error (MSPE) and by concordance correlation coefficient (CCC). All energy evaluation systems predicted energy requirement to be lower (6-11%) than energy supply. The root MSPE (expressed as a proportion of the supply) was lowest for the mechanistic model (0.061), followed by the Dutch NE system (0.082), FIM ME system (0.097) and AFRCME system(0.118). For the energy evaluation systems, the error due to overall bias of prediction dominated the MSPE, whereas for the mechanistic model, proportionally 0.76 of MSPE was due to random variation. CCC analysis confirmed the higher accuracy and precision of the mechanistic model compared with energy evaluation systems. The error of prediction was positively related to grass protein content for the Dutch NE system, and was also positively related to grass DMI level for all models. In conclusion, current energy evaluation systems overestimate energy supply relative to energy requirement on grass-based diets for dairy cattle. The mechanistic model predicted glucogenic nutrients to limit performance of dairy cattle on grass-based diets, and proved to be more accurate and precise than the energy systems. The mechanistic model could be improved by allowing glucose maintenance and utilization requirements parameters to be variable. (C) 2007 Elsevier B.V. All rights reserved.

An integrated mathematical model to evaluate nutrient partition in dairy cattle between the animal and its environment

In the past decade, a number of mechanistic, dynamic simulation models of several components of the dairy production system have become available. However their use has been limited due to the detailed technical knowledge and special software required to run them, and the lack of compatibility between models in predicting various metabolic processes in the animal. The first objective of the current study was to integrate the dynamic models of [Brit. J. Nutr. 72 (1994) 679] on rumen function, [J. Anim. Sci. 79 (2001) 1584] on methane production, [J. Anim. Sci. 80 (2002) 2481 on N partition, and a new model of P partition. The second objective was to construct a decision support system to analyse nutrient partition between animal and environment. The integrated model combines key environmental pollutants such as N, P and methane within a nutrient-based feed evaluation system. The model was run under different scenarios and the sensitivity of various parameters analysed. A comparison of predictions from the integrated model with the original simulation models showed an improvement in N excretion since the integrated model uses the dynamic model of [Brit. J. Nutr. 72 (1994) 6791 to predict microbial N, which was not represented in detail in the original model. The integrated model can be used to investigate the degree to which production and environmental objectives are antagonistic, and it may help to explain and understand the complex mechanisms involved at the ruminal and metabolic levels. A part of the integrated model outputs were the forms of N and P in excreta and methane, which can be used as indices of environmental pollution. (C) 2004 Elsevier B.V All rights reserved.

Gaining acceptability for the Bayesian decision-theoretic approach in dose-escalation studies

There has recently been increasing demand for better designs to conduct first-into-man dose-escalation studies more efficiently, more accurately and more quickly. The authors look into the Bayesian decision-theoretic approach and use simulation as a tool to investigate the impact of compromises with conventional practice that might make the procedures more acceptable for implementation. Copyright © 2005 John Wiley & Sons, Ltd.

The double triangular test in practice

The double triangular test was introduced twenty years ago, and the purpose of this paper is to review applications that have been made since then. In fact, take-up of the method was rather slow until the late 1990s, but in recent years several clinical trial reports have been published describing its use in a wide range of therapeutic areas. The core of this paper is a detailed account of five trials that have been published since 2000 in which the method was applied to studies of pancreatic cancer, breast cancer, myocardial infarction, epilepsy and bedsores. Before those accounts are given, the method is described and the history behind its evolution is presented. The future potential of the method for sequential case-control and equivalence trials is also discussed. Copyright © 2004 John Wiley & Sons, Ltd.

Decision-making in a phase II clinical trial: a new approach combining Bayesian and frequentist concepts

The aim of a phase H clinical trial is to decide whether or not to develop an experimental therapy further through phase III clinical evaluation. In this paper, we present a Bayesian approach to the phase H trial, although we assume that subsequent phase III clinical trials will hat,e standard frequentist analyses. The decision whether to conduct the phase III trial is based on the posterior predictive probability of a significant result being obtained. This fusion of Bayesian and frequentist techniques accepts the current paradigm for expressing objective evidence of therapeutic value, while optimizing the form of the phase II investigation that leads to it. By using prior information, we can assess whether a phase II study is needed at all, and how much or what sort of evidence is required. The proposed approach is illustrated by the design of a phase II clinical trial of a multi-drug resistance modulator used in combination with standard chemotherapy in the treatment of metastatic breast cancer. Copyright (c) 2005 John Wiley & Sons, Ltd.

Comparison of sample size formulae for 2x2 cross-over designs applied to bioequivalence studies

We consider the comparison of two formulations in terms of average bioequivalence using the 2 × 2 cross-over design. In a bioequivalence study, the primary outcome is a pharmacokinetic measure, such as the area under the plasma concentration by time curve, which is usually assumed to have a lognormal distribution. The criterion typically used for claiming bioequivalence is that the 90% confidence interval for the ratio of the means should lie within the interval (0.80, 1.25), or equivalently the 90% confidence interval for the differences in the means on the natural log scale should be within the interval (-0.2231, 0.2231). We compare the gold standard method for calculation of the sample size based on the non-central t distribution with those based on the central t and normal distributions. In practice, the differences between the various approaches are likely to be small. Further approximations to the power function are sometimes used to simplify the calculations. These approximations should be used with caution, because the sample size required for a desirable level of power might be under- or overestimated compared to the gold standard method. However, in some situations the approximate methods produce very similar sample sizes to the gold standard method. Copyright © 2005 John Wiley & Sons, Ltd.

Evaluation of a sequential global test of improved recovery following stroke as applied to the ICTUS trial of citicoline

The International Citicoline Trial in acUte Stroke is a sequential phase III study of the use of the drug citicoline in the treatment of acute ischaemic stroke, which was initiated in 2006 in 56 treatment centres. The primary objective of the trial is to demonstrate improved recovery of patients randomized to citicoline relative to those randomized to placebo after 12 weeks of follow-up. The primary analysis will take the form of a global test combining the dichotomized results of assessments on three well-established scales: the Barthel Index, the modified Rankin scale and the National Institutes of Health Stroke Scale. This approach was previously used in the analysis of the influential National Institute of Neurological Disorders and Stroke trial of recombinant tissue plasminogen activator in stroke. The purpose of this paper is to describe how this trial was designed, and in particular how the simultaneous objectives of taking into account three assessment scales, performing a series of interim analyses and conducting treatment allocation and adjusting the analyses to account for prognostic factors, including more than 50 treatment centres, were addressed. Copyright (C) 2008 John Wiley & Sons, Ltd.

From a discrete to a continuum model of cell dynamics in one dimension

Multiscale modeling is emerging as one of the key challenges in mathematical biology. However, the recent rapid increase in the number of modeling methodologies being used to describe cell populations has raised a number of interesting questions. For example, at the cellular scale, how can the appropriate discrete cell-level model be identified in a given context? Additionally, how can the many phenomenological assumptions used in the derivation of models at the continuum scale be related to individual cell behavior? In order to begin to address such questions, we consider a discrete one-dimensional cell-based model in which cells are assumed to interact via linear springs. From the discrete equations of motion, the continuous Rouse [P. E. Rouse, J. Chem. Phys. 21, 1272 (1953)] model is obtained. This formalism readily allows the definition of a cell number density for which a nonlinear "fast" diffusion equation is derived. Excellent agreement is demonstrated between the continuum and discrete models. Subsequently, via the incorporation of cell division, we demonstrate that the derived nonlinear diffusion model is robust to the inclusion of more realistic biological detail. In the limit of stiff springs, where cells can be considered to be incompressible, we show that cell velocity can be directly related to cell production. This assumption is frequently made in the literature but our derivation places limits on its validity. Finally, the model is compared with a model of a similar form recently derived for a different discrete cell-based model and it is shown how the different diffusion coefficients can be understood in terms of the underlying assumptions about cell behavior in the respective discrete models.

Action following the discovery of a global association between the whole genome and adverse event risk in a clinical drug-development programme

Observation of adverse drug reactions during drug development can cause closure of the whole programme. However, if association between the genotype and the risk of an adverse event is discovered, then it might suffice to exclude patients of certain genotypes from future recruitment. Various sequential and non-sequential procedures are available to identify an association between the whole genome, or at least a portion of it, and the incidence of adverse events. In this paper we start with a suspected association between the genotype and the risk of an adverse event and suppose that the genetic subgroups with elevated risk can be identified. Our focus is determination of whether the patients identified as being at risk should be excluded from further studies of the drug. We propose using a utility function to? determine the appropriate action, taking into account the relative costs of suffering an adverse reaction and of failing to alleviate the patient's disease. Two illustrative examples are presented, one comparing patients who suffer from an adverse event with contemporary patients who do not, and the other making use of a reference control group. We also illustrate two classification methods, LASSO and CART, for identifying patients at risk, but we stress that any appropriate classification method could be used in conjunction with the proposed utility function. Our emphasis is on determining the action to take rather than on providing definitive evidence of an association. Copyright (C) 2008 John Wiley & Sons, Ltd.