Visualising and controlling the flow in biomolecular systems at and between multiple scales:from atoms to hydrodynamics at different locations in time and space

A novel framework for modelling biomolecular systems at multiple scales in space and time simultaneously is described. The atomistic molecular dynamics representation is smoothly connected with a statistical continuum hydrodynamics description. The system behaves correctly at the limits of pure molecular dynamics (hydrodynamics) and at the intermediate regimes when the atoms move partly as atomistic particles, and at the same time follow the hydrodynamic flows. The corresponding contributions are controlled by a parameter, which is defined as an arbitrary function of space and time, thus, allowing an effective separation of the atomistic 'core' and continuum 'environment'. To fill the scale gap between the atomistic and the continuum representations our special purpose computer for molecular dynamics, MDGRAPE-4, as well as GPU-based computing were used for developing the framework. These hardware developments also include interactive molecular dynamics simulations that allow intervention of the modelling through force-feedback devices.

A hybrid molecular dynamics/fluctuating hydrodynamics method for modelling liquids at multiple scales in space and time

A new 3D implementation of a hybrid model based on the analogy with two-phase hydrodynamics has been developed for the simulation of liquids at microscale. The idea of the method is to smoothly combine the atomistic description in the molecular dynamics zone with the Landau-Lifshitz fluctuating hydrodynamics representation in the rest of the system in the framework of macroscopic conservation laws through the use of a single "zoom-in" user-defined function s that has the meaning of a partial concentration in the two-phase analogy model. In comparison with our previous works, the implementation has been extended to full 3D simulations for a range of atomistic models in GROMACS from argon to water in equilibrium conditions with a constant or a spatially variable function s. Preliminary results of simulating the diffusion of a small peptide in water are also reported.

Spatial pattern analysis of beta-amyloid (A beta) deposits in Alzheimer disease by linear regression

The spatial patterns of discrete beta-amyloid (Abeta) deposits in brain tissue from patients with Alzheimer disease (AD) were studied using a statistical method based on linear regression, the results being compared with the more conventional variance/mean (V/M) method. Both methods suggested that Abeta deposits occurred in clusters (400 to <12,800 mu m in diameter) in all but 1 of the 42 tissues examined. In many tissues, a regular periodicity of the Abeta deposit clusters parallel to the tissue boundary was observed. In 23 of 42 (55%) tissues, the two methods revealed essentially the same spatial patterns of Abeta deposits; in 15 of 42 (36%), the regression method indicated the presence of clusters at a scale not revealed by the V/M method; and in 4 of 42 (9%), there was no agreement between the two methods. Perceived advantages of the regression method are that there is a greater probability of detecting clustering at multiple scales, the dimension of larger Abeta clusters can be estimated more accurately, and the spacing between the clusters may be estimated. However, both methods may be useful, with the regression method providing greater resolution and the V/M method providing greater simplicity and ease of interpretation. Estimates of the distance between regularly spaced Abeta clusters were in the range 2,200-11,800 mu m, depending on tissue and cluster size. The regular periodicity of Abeta deposit clusters in many tissues would be consistent with their development in relation to clusters of neurons that give rise to specific neuronal projections.

Incremental nature of anterior eye grading scales determined by objective image analysis

Aim: To use previously validated image analysis techniques to determine the incremental nature of printed subjective anterior eye grading scales. Methods: A purpose designed computer program was written to detect edges using a 3 × 3 kernal and to extract colour planes in the selected area of an image. Annunziato and Efron pictorial, and CCLRU and Vistakon-Synoptik photographic grades of bulbar hyperaemia, palpebral hyperaemia roughness, and corneal staining were analysed. Results: The increments of the grading scales were best described by a quadratic rather than a linear function. Edge detection and colour extraction image analysis for bulbar hyperaemia (r2 = 0.35-0.99), palpebral hyperaemia (r2 = 0.71-0.99), palpebral roughness (r2 = 0.30-0.94), and corneal staining (r2 = 0.57-0.99) correlated well with scale grades, although the increments varied in magnitude and direction between different scales. Repeated image analysis measures had a 95% confidence interval of between 0.02 (colour extraction) and 0.10 (edge detection) scale units (on a 0-4 scale). Conclusion: The printed grading scales were more sensitive for grading features of low severity, but grades were not comparable between grading scales. Palpebral hyperaemia and staining grading is complicated by the variable presentations possible. Image analysis techniques are 6-35 times more repeatable than subjective grading, with a sensitivity of 1.2-2.8% of the scale.

Measuring the degree of spatial correlation between histological features in thin sections of brain tissue

Histological features visible in thin sections of brain tissue, such as neuronal perikarya, blood vessels, or pathological lesions may exhibit a degree of spatial association or correlation. In neurodegenerative disorders such as AD, Pick's disease, and CJD, information on whether different types of pathological lesion are spatially correlated may be useful in elucidating disease pathogenesis. In the present article the statistical methods available for studying spatial association in histological sections are reviewed. These include tests of interspecific association between two or more histological features using χ2 contingency tables, measurement of 'complete' and 'absolute' association, and more complex methods that use grids of contiguous samples. In addition, the use of correlation matrices and stepwise multiple regression methods are described. The advantages and limitations of each method are reviewed and possible future developments discussed.

Measuring the degree of spatial correlation between pathological lesions in Alzheimer's disease

The pathological lesions characteristic of Alzheimer's disease (AD), viz., senile plaques (SP) and neurofibrillary tangles (NFT) may not be randomly distributed with reference to each other but exhibit a degree of sptial association or correlation, information on the degree of association between SP and NFT or between the lesions and normal histological features, such as neuronal perikarya and blood vessels, may be valuable in elucidating the pathogenesis of AD. This article reviews the statistical methods available for studying the degree of spatial association in histological sections of AD tissue. These include tests of interspecific association between two or more histological features using chi-square contingency tables, measurement of 'complete' and 'absolute' association, and more complex methods that use grids of contiguous samples. In addition, analyses of association using correlation matrices and stepwise multiple regression methods are described. The advantages and limitations of each method are reviewed and possible future developments discussed.

Redefining neuromarketing as an integrated science of influence

Multiple transformative forces target marketing, many of which derive from new technologies that allow us to sample thinking in real time (i.e., brain imaging), or to look at large aggregations of decisions (i.e., big data). There has been an inclination to refer to the intersection of these technologies with the general topic of marketing as “neuromarketing”. There has not been a serious effort to frame neuromarketing, which is the goal of this paper. Neuromarketing can be compared to neuroeconomics, wherein neuroeconomics is generally focused on how individuals make “choices”, and represent distributions of choices. Neuromarketing, in contrast, focuses on how a distribution of choices can be shifted or “influenced”, which can occur at multiple “scales” of behavior (e.g., individual, group, or market/society). Given influence can affect choice through many cognitive modalities, and not just that of valuation of choice options, a science of influence also implies a need to develop a model of cognitive function integrating attention, memory, and reward/aversion function. The paper concludes with a brief description of three domains of neuromarketing application for studying influence, and their caveats.

Data analysis methods in optometry Part 7: multiple linear regression

Multiple regression analysis is a complex statistical method with many potential uses. It has also become one of the most abused of all statistical procedures since anyone with a data base and suitable software can carry it out. An investigator should always have a clear hypothesis in mind before carrying out such a procedure and knowledge of the limitations of each aspect of the analysis. In addition, multiple regression is probably best used in an exploratory context, identifying variables that might profitably be examined by more detailed studies. Where there are many variables potentially influencing Y, they are likely to be intercorrelated and to account for relatively small amounts of the variance. Any analysis in which R squared is less than 50% should be suspect as probably not indicating the presence of significant variables. A further problem relates to sample size. It is often stated that the number of subjects or patients must be at least 5-10 times the number of variables included in the study.5 This advice should be taken only as a rough guide but it does indicate that the variables included should be selected with great care as inclusion of an obviously unimportant variable may have a significant impact on the sample size required.

Adherence to antiepileptic medicines in children:a multiple-methods assessment involving dried blood spot sampling

Purpose - To evaluate adherence to prescribed antiepileptic drugs (AEDs) in children with epilepsy using a combination of adherence-assessment methods. Methods - A total of 100 children with epilepsy (≤17 years old) were recruited. Medication adherence was determined via parental and child self-reporting (≥9 years old), medication refill data from general practitioner (GP) prescribing records, and via AED concentrations in dried blood spot (DBS) samples obtained from children at the clinic and via self- or parental-led sampling in children's own homes. The latter were assessed using population pharmacokinetic modeling. Patients were deemed nonadherent if any of these measures were indicative of nonadherence with the prescribed treatment. In addition, beliefs about medicines, parental confidence in seizure management, and the presence of depressed mood in parents were evaluated to examine their association with nonadherence in the participating children. Key Findings - The overall rate of nonadherence in children with epilepsy was 33%. Logistic regression analysis indicated that children with generalized epilepsy (vs. focal epilepsy) were more likely (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.37–15.81) to be classified as nonadherent as were children whose parents have depressed mood (OR 3.6, 95% CI 1.16–11.41). Significance - This is the first study to apply the novel methodology of determining adherence via AED concentrations in clinic and home DBS samples. The present findings show that the latter, with further development, could be a useful approach to adherence assessment when combined with other measures including parent and child self-reporting. Seizure type and parental depressed mood were strongly predictive of nonadherence.

Investigation of assessment methods for final year optometry undergraduates

This retrospective study was designed to investigate the factors that influence performance in examinations comprised of multiple-choice questions (MCQs), short-answer questions (SAQs), and essay questions in an undergraduate population. Final year optometry degree examination marks were analyzed for two separate cohorts. Direct comparison found that students performed better in MCQs than essays. However, forward stepwise regression analysis of module marks compared with the overall score showed that MCQs were the least influential, and the essay or SAQ mark was a more reliable predictor of overall grade. This has implications for examination design.

On the use of likert-type scales in multilevel data:Influence on aggregate variables

In multilevel analyses, problems may arise when using Likert-type scales at the lowest level of analysis. Specifically, increases in variance should lead to greater censoring for the groups whose true scores fall at either end of the distribution. The current study used simulation methods to examine the influence of single-item Likert-type scale usage on ICC(1), ICC(2), and group-level correlations. Results revealed substantial underestimation of ICC(1) when using Likert-type scales with common response formats (e.g., 5 points). ICC(2) and group-level correlations were also underestimated, but to a lesser extent. Finally, the magnitude of underestimation was driven in large part to an interaction between Likert-type scale usage and the amounts of within- and between-group variance. © Sage Publications.

Integrated project evaluation and selection using multiple-attribute decision-making technique

The evaluation and selection of industrial projects before investment decision is customarily done using marketing, technical and financial information. Subsequently, environmental impact assessment and social impact assessment are carried out mainly to satisfy the statutory agencies. Because of stricter environment regulations in developed and developing countries, quite often impact assessment suggests alternate sites, technologies, designs, and implementation methods as mitigating measures. This causes considerable delay to complete project feasibility analysis and selection as complete analysis requires to be taken up again and again till the statutory regulatory authority approves the project. Moreover, project analysis through above process often results sub-optimal project as financial analysis may eliminate better options, as more environment friendly alternative will always be cost intensive. In this circumstance, this study proposes a decision support system, which analyses projects with respect to market, technicalities, and social and environmental impact in an integrated framework using analytic hierarchy process, a multiple-attribute decision-making technique. This not only reduces duration of project evaluation and selection, but also helps select optimal project for the organization for sustainable development. The entire methodology has been applied to a cross-country oil pipeline project in India and its effectiveness has been demonstrated. © 2005 Elsevier B.V. All rights reserved.

Analysis of computer communication systems by use of digital signal processing methods

Queueing theory is an effective tool in the analysis of canputer camrunication systems. Many results in queueing analysis have teen derived in the form of Laplace and z-transform expressions. Accurate inversion of these transforms is very important in the study of computer systems, but the inversion is very often difficult. In this thesis, methods for solving some of these queueing problems, by use of digital signal processing techniques, are presented. The z-transform of the queue length distribution for the Mj GY jl system is derived. Two numerical methods for the inversion of the transfom, together with the standard numerical technique for solving transforms with multiple queue-state dependence, are presented. Bilinear and Poisson transform sequences are presented as useful ways of representing continuous-time functions in numerical computations.

When do conservation planning methods deliver? Quantifying the consequences of uncertainty

The rapid global loss of biodiversity has led to a proliferation of systematic conservation planning methods. In spite of their utility and mathematical sophistication, these methods only provide approximate solutions to real-world problems where there is uncertainty and temporal change. The consequences of errors in these solutions are seldom characterized or addressed. We propose a conceptual structure for exploring the consequences of input uncertainty and oversimpli?ed approximations to real-world processes for any conservation planning tool or strategy. We then present a computational framework based on this structure to quantitatively model species representation and persistence outcomes across a range of uncertainties. These include factors such as land costs, landscape structure, species composition and distribution, and temporal changes in habitat. We demonstrate the utility of the framework using several reserve selection methods including simple rules of thumb and more sophisticated tools such as Marxan and Zonation. We present new results showing how outcomes can be strongly affected by variation in problem characteristics that are seldom compared across multiple studies. These characteristics include number of species prioritized, distribution of species richness and rarity, and uncertainties in the amount and quality of habitat patches. We also demonstrate how the framework allows comparisons between conservation planning strategies and their response to error under a range of conditions. Using the approach presented here will improve conservation outcomes and resource allocation by making it easier to predict and quantify the consequences of many different uncertainties and assumptions simultaneously. Our results show that without more rigorously generalizable results, it is very dif?cult to predict the amount of error in any conservation plan. These results imply the need for standard practice to include evaluating the effects of multiple real-world complications on the behavior of any conservation planning method.

Data methods in optometry. Part 6: fitting a regression line to data

1. Fitting a linear regression to data provides much more information about the relationship between two variables than a simple correlation test. A goodness of fit test of the line should always be carried out. Hence, r squared estimates the strength of the relationship between Y and X, ANOVA whether a statistically significant line is present, and the ‘t’ test whether the slope of the line is significantly different from zero. 2. Always check whether the data collected fit the assumptions for regression analysis and, if not, whether a transformation of the Y and/or X variables is necessary. 3. If the regression line is to be used for prediction, it is important to determine whether the prediction involves an individual y value or a mean. Care should be taken if predictions are made close to the extremities of the data and are subject to considerable error if x falls beyond the range of the data. Multiple predictions require correction of the P values. 3. If several individual regression lines have been calculated from a number of similar sets of data, consider whether they should be combined to form a single regression line. 4. If the data exhibit a degree of curvature, then fitting a higher-order polynomial curve may provide a better fit than a straight line. In this case, a test of whether the data depart significantly from a linear regression should be carried out.