Using simulation techniques to investigate methods to determine resistance of helminths to anthelmintic treatment

The widespread and increasing resistance of internal parasites to anthelmintic control is a serious problem for the Australian sheep and wool industry. As part of control programmes, laboratories use the Faecal Egg Count Reduction Test (FECRT) to determine resistance to anthelmintics. It is important to have confidence in the measure of resistance, not only for the producer planning a drenching programme but also for companies investigating the efficacy of their products. The determination of resistance and corresponding confidence limits as given in anthelmintic efficacy guidelines of the Standing Committee on Agriculture (SCA) is based on a number of assumptions. This study evaluated the appropriateness of these assumptions for typical data and compared the effectiveness of the standard FECRT procedure with the effectiveness of alternative procedures. Several sets of historical experimental data from sheep and goats were analysed to determine that a negative binomial distribution was a more appropriate distribution to describe pre-treatment helminth egg counts in faeces than a normal distribution. Simulated egg counts for control animals were generated stochastically from negative binomial distributions and those for treated animals from negative binomial and binomial distributions. Three methods for determining resistance when percent reduction is based on arithmetic means were applied. The first was that advocated in the SCA guidelines, the second similar to the first but basing the variance estimates on negative binomial distributions, and the third using Wadley’s method with the distribution of the response variate assumed negative binomial and a logit link transformation. These were also compared with a fourth method recommended by the International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) programme, in which percent reduction is based on the geometric means. A wide selection of parameters was investigated and for each set 1000 simulations run. Percent reduction and confidence limits were then calculated for the methods, together with the number of times in each set of 1000 simulations the theoretical percent reduction fell within the estimated confidence limits and the number of times resistance would have been said to occur. These simulations provide the basis for setting conditions under which the methods could be recommended. The authors show that given the distribution of helminth egg counts found in Queensland flocks, the method based on arithmetic not geometric means should be used and suggest that resistance be redefined as occurring when the upper level of percent reduction is less than 95%. At least ten animals per group are required in most circumstances, though even 20 may be insufficient where effectiveness of the product is close to the cut off point for defining resistance.

Closed-form solutions for low-rank non-rigid reconstruction

Recovering the motion of a non-rigid body from a set of monocular images permits the analysis of dynamic scenes in uncontrolled environments. However, the extension of factorisation algorithms for rigid structure from motion to the low-rank non-rigid case has proved challenging. This stems from the comparatively hard problem of finding a linear “corrective transform” which recovers the projection and structure matrices from an ambiguous factorisation. We elucidate that this greater difficulty is due to the need to find multiple solutions to a non-trivial problem, casting a number of previous approaches as alleviating this issue by either a) introducing constraints on the basis, making the problems nonidentical, or b) incorporating heuristics to encourage a diverse set of solutions, making the problems inter-dependent. While it has previously been recognised that finding a single solution to this problem is sufficient to estimate cameras, we show that it is possible to bootstrap this partial solution to find the complete transform in closed-form. However, we acknowledge that our method minimises an algebraic error and is thus inherently sensitive to deviation from the low-rank model. We compare our closed-form solution for non-rigid structure with known cameras to the closed-form solution of Dai et al. [1], which we find to produce only coplanar reconstructions. We therefore make the recommendation that 3D reconstruction error always be measured relative to a trivial reconstruction such as a planar one.

Exact evaluation of Gaussian path integrals involving non-local potentials

An exact expression for the calculation of gaussian path integrals involving non-local potentials is given. Its utility is demonstrated by using it to evaluate a path integral arising in the study of an electron gas in a random potential.

A Nonlinear System Under Combined Periodic and Random Excitation

The anharmonic oscillator under combined sinusoidal and white noise excitation is studied using the Gaussian closure approximation. The mean response and the steady-state variance of the system is obtained by the WKBJ approximation and also by the Fokker Planck equation. The multiple steadystate solutions are obtained and their stability analysis is presented. Numerical results are obtained for a particular set of system parameters. The theoretical results are compared with a digital simulation study to bring out the usefulness of the present approximate theory.

Strategic Analysis: A key factor in developing horticultural supply chains in transitional Asian economies

Globalisation is set to have a major impact on world horticultural production and distribution of fruit and vegetables throughout the world. In contrast to developing countries such as China, production and consumption of fresh fruit and vegetables in most developed countries is relatively static. For developed countries, we are starting to see consolidation in the number of farms producing fruit and vegetables with falling or static prices and real farm incomes. Global supply chains are now dominated by a few large multi-national retailers supplied by preferred trans-national distribution companies. The major competitive advantages that are emerging are consistency of supply of high quality product over an extended season and the control of genetic resources and their marketing. To capture these new competitive advantages, new strategic analyses and planning processes must be implemented. In the past, strategic analyses and planning has been undertaken on an ad hoc basis without accurate global intelligence. In the future, working ‘on the supply chain’ will become equally, if not more important, than working ‘in the supply chain’. A revised approach to strategic planning, which encompasses and adjusts for the changes caused by globalisation, is urgently needed. A new 6-step strategic analyses process is described.

Accelerating Pseudo-Marginal MCMC using Gaussian Processes

Pseudo-marginal methods such as the grouped independence Metropolis-Hastings (GIMH) and Markov chain within Metropolis (MCWM) algorithms have been introduced in the literature as an approach to perform Bayesian inference in latent variable models. These methods replace intractable likelihood calculations with unbiased estimates within Markov chain Monte Carlo algorithms. The GIMH method has the posterior of interest as its limiting distribution, but suffers from poor mixing if it is too computationally intensive to obtain high-precision likelihood estimates. The MCWM algorithm has better mixing properties, but less theoretical support. In this paper we propose to use Gaussian processes (GP) to accelerate the GIMH method, whilst using a short pilot run of MCWM to train the GP. Our new method, GP-GIMH, is illustrated on simulated data from a stochastic volatility and a gene network model.

Invited paper Application of the least mean fourth (LMF) adaptive algorithm to signals associated with gaussian noise

This paper considers the applicability of the least mean fourth (LM F) power gradient adaptation criteria with 'advantage' for signals associated with gaussian noise, the associated noise power estimate not being known. The proposed method, as an adaptive spectral estimator, is found to provide superior performance than the least mean square (LMS) adaptation for the same (or even lower) speed of convergence for signals having sufficiently high signal-to-gaussian noise ratio. The results include comparison of the performance of the LMS-tapped delay line, LMF-tapped delay line, LMS-lattice and LMF-lattice algorithms, with the Burg's block data method as reference. The signals, like sinusoids with noise and stochastic signals like EEG, are considered in this study.

Modeling growth of hydrogen bubbles in aluminum castings using the level-set method

A new approach is proposed to solve for the growth as well as the movement of hydrogen bubbles during solidification in aluminum castings. A level-set methodology has been adopted to handle this multiphase phenomenon. A microscale domain is considered and the growth and movement of hydrogen bubbles in this domain has been studied. The growth characteristics of hydrogen bubbles have been evaluated under free growth conditions in a melt having a hydrogen input caused b solidification occurring around the microdomain.

The impact of inter-fraction set-up errors on the probability of pulmonary and cardiac complication in left-sided breast cancer patients

Purpose This study evaluated the impact of patient set-up errors on the probability of pulmonary and cardiac complications in the irradiation of left-sided breast cancer. Methods and Materials Using the CMS XiO Version 4.6 (CMS Inc., St Louis, MO) radiotherapy planning system's NTCP algorithm and the Lyman -Kutcher-Burman (LKB) model, we calculated the DVH indices for the ipsilateral lung and heart and the resultant normal tissue complication probabilities (NTCP) for radiation-induced pneumonitis and excess cardiac mortality in 12 left-sided breast cancer patients. Results Isocenter shifts in the posterior direction had the greatest effect on the lung V20, heart V25, mean and maximum doses to the lung and the heart. Dose volume histograms (DVH) results show that the ipsilateral lung V20 tolerance was exceeded in 58% of the patients after 1cm posterior shifts. Similarly, the heart V25 tolerance was exceeded after 1cm antero-posterior and left-right isocentric shifts in 70% of the patients. The baseline NTCPs for radiation-induced pneumonitis ranged from 0.73% - 3.4% with a mean value of 1.7%. The maximum reported NTCP for radiation-induced pneumonitis was 5.8% (mean 2.6%) after 1cm posterior isocentric shift. The NTCP for excess cardiac mortality were 0 % in 100% of the patients (n=12) before and after setup error simulations. Conclusions Set-up errors in left sided breast cancer patients have a statistically significant impact on the Lung NTCPs and DVH indices. However, with a central lung distance of 3cm or less (CLD <3cm), and a maximum heart distance of 1.5cm or less (MHD<1.5cm), the treatment plans could tolerate set-up errors of up to 1cm without any change in the NTCP to the heart.

Normative values for corneal nerve morphology assessed using corneal confocal microscopy: A multinational normative data set

OBJECTIVE Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters. RESEARCH DESIGN AND METHODS A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis. RESULTS There was a significant linear age-dependent decrease in CNFD (-0.164 no./mm(2) per year for men, P < 0.01, and -0.161 no./mm(2) per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm(2) per year for men, P = 0.26, and -0.050 no./mm(2) per year for women, P = 0.78). CNFL decreased in men (-0.045 mm/mm(2) per year, P = 0.07) and women (-0.060 mm/mm(2) per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter. CONCLUSIONS This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.

Set theoretic operations on polygons using the scan-grid approach

This paper describes an algorithm to compute the union, intersection and difference of two polygons using a scan-grid approach. Basically, in this method, the screen is divided into cells and the algorithm is applied to each cell in turn. The output from all the cells is integrated to yield a representation of the output polygon. In most cells, no computation is required and thus the algorithm is a fast one. The algorithm has been implemented for polygons but can be extended to polyhedra as well. The algorithm is shown to take O(N) time in the average case where N is the total number of edges of the two input polygons.

Bi-criteria single machine scheduling problem with a learning effect: Aneja-Nair method to obtain the set of optimal sequences

In this paper, we consider the bi-criteria single machine scheduling problem of n jobs with a learning effect. The two objectives considered are the total completion time (TC) and total absolute differences in completion times (TADC). The objective is to find a sequence that performs well with respect to both the objectives: the total completion time and the total absolute differences in completion times. In an earlier study, a method of solving bi-criteria transportation problem is presented. In this paper, we use the methodology of solvin bi-criteria transportation problem, to our bi-criteria single machine scheduling problem with a learning effect, and obtain the set of optimal sequences,. Numerical examples are presented for illustrating the applicability and ease of understanding.

Responses in carcass lean pH at 24 hours post-mortem in lines of Large White pigs selected for growth rate on a fixed ration over a set time

A restricted maximum likelihood analysis applied to an animal model showed no significant differences (P > 0.05) in pH value of the longissimus dorsi measured at 24 h post-mortem (pH24) between high and low lines of Large White pigs selected over 4 years for post-weaning growth rate on restricted feeding. Genetic and phenotypic correlations between pH24 and production and carcass traits were estimated using all performance testing records combined with the pH24 measurements (5.05-7.02) on slaughtered animals. The estimate of heritability for pH24 was moderate (0.29 ± 0.18). Genetic correlations between pH24 and production or carcass composition traits, except for ultrasonic backfat (UBF), were not significantly different from zero. UBF had a moderate, positive genetic correlation with pH24 (0.24 ± 0.33). These estimates of genetic correlations affirmed that selection for increased growth rate on restricted feeding is likely to result in limited changes in pH24 and pork quality since the selection does not put a high emphasis on reduced fatness.

Analysis of randomly time varying systems by gaussian closure technique

The Gaussian probability closure technique is applied to study the random response of multidegree of freedom stochastically time varying systems under non-Gaussian excitations. Under the assumption that the response, the coefficient and the excitation processes are jointly Gaussian, deterministic equations are derived for the first two response moments. It is further shown that this technique leads to the best Gaussian estimate in a minimum mean square error sense. An example problem is solved which demonstrates the capability of this technique for handling non-linearity, stochastic system parameters and amplitude limited responses in a unified manner. Numerical results obtained through the Gaussian closure technique compare well with the exact solutions.