Protection of live bacteria from bile acid toxicity using bile acid adsorbing resins

We previously demonstrated that a dry, room temperature stable formulation of a live bacterial vaccine was highly susceptible to bile, and suggested that this will lead to significant loss of viability of any live bacterial formulation released into the intestine using an enteric coating or capsule. We found that bile and acid tolerance is very rapidly recovered after rehydration with buffer or water, raising the possibility that rehydration in the absence of bile prior to release into the intestine might solve the problem of bile toxicity to dried cells. We describe here a novel formulation that combines extensively studied bile acid adsorbent resins with the dried bacteria, to temporarily adsorb bile acids and allow rehydration and recovery of bile resistance of bacteria in the intestine before release. Tablets containing the bile acid adsorbent cholestyramine release 250-fold more live bacteria when dissolved in a bile solution, compared to control tablets without cholestyramine or with a control resin that does not bind bile acids. We propose that a simple enteric coated oral dosage form containing bile acid adsorbent resins will allow improved live bacterial delivery to the intestine via the oral route, a major step towards room temperature stable, easily administered and distributed vaccine pills and other bacterial therapeutics

The value of badger populations and control of tuberculosis in cattle in England and Wales: A note

This note reports on the results of a choice experiment survey of 400 people in England and Wales, conducted to estimate the value that society places on changes to the size of the badger population. The study was undertaken in the context of the possible need to reduce the badger population by culling to help control bovine tuberculosis in cattle. The study found that people were concerned about the problem of bovine tuberculosis in cattle, which was reflected in their willingness to pay to control the disease, and gave a relatively low value to changes in the size of the badger population (within limits). However, people did not like the idea of a policy that intentionally killed large numbers of badgers and had a relatively very high willingness to pay not to have such a policy.

Unravelling the rationale of 'overgrazing' and stocking rates in the beef production systems of Central Brazil using a bi-criteria compromise programming model

In Central Brazil, the long-term sustainability of beef cattle systems is under threat over vast tracts of farming areas, as more than half of the 50 million hectares of sown pastures are suffering from degradation. Overgrazing practised to maintain high stocking rates is regarded as one of the main causes. High stocking rates are deliberate and crucial decisions taken by the farmers, which appear paradoxical, even irrational given the state of knowledge regarding the consequences of overgrazing. The phenomenon however appears inextricably linked with the objectives that farmers hold. In this research those objectives were elicited first and from their ranking two, ‘asset value of cattle (representing cattle ownership)' and ‘present value of economic returns', were chosen to develop an original bi-criteria Compromise Programming model to test various hypotheses postulated to explain the overgrazing behaviour. As part of the model a pasture productivity index is derived to estimate the pasture recovery cost. Different scenarios based on farmers' attitudes towards overgrazing, pasture costs and capital availability were analysed. The results of the model runs show that benefits from holding more cattle can outweigh the increased pasture recovery and maintenance costs. This result undermines the hypothesis that farmers practise overgrazing because they are unaware or uncaring about overgrazing costs. An appropriate approach to the problem of pasture degradation requires information on the economics, and its interplay with farmers' objectives, for a wide range of pasture recovery and maintenance methods. Seen within the context of farmers' objectives, some level of overgrazing appears rational. Advocacy of the simple ‘no overgrazing' rule is an insufficient strategy to maintain the long-term sustainability of the beef production systems in Central Brazil.

Unravelling the rationale of 'overgrazing' and stocking rates in the beef production systems of Central Brazil using a bi-criteria compromise programming model

In Central Brazil, the long-term, sustainability of beef cattle systems is under threat over vast tracts of farming areas, as more than half of the 50 million hectares of sown pastures are suffering from. degradation. Overgrazing practised to maintain high stocking rates is regarded as one of the main causes. High stocking rates are deliberate and crucial decisions taken by the farmers, which appear paradoxical, even irrational given the state of knowledge regarding the consequences of overgrazing. The phenomenon however appears inextricably linked with the objectives that farmers hold. In this research those objectives were elicited first and from their ranking two, 'asset value of cattle (representing cattle ownership and 'present value of economic returns', were chosen to develop an original bi-criteria Compromise Programming model to test various hypotheses postulated to explain the overgrazing behaviour. As part of the model a pasture productivity index is derived to estimate the pasture recovery cost. Different scenarios based on farmers' attitudes towards overgrazing, pasture costs and capital availability were analysed. The results of the model runs show that benefits from holding more cattle can outweigh the increased pasture recovery and maintenance costs. This result undermines the hypothesis that farmers practise overgrazing because they are unaware or uncaring caring about overgrazing costs. An appropriate approach to the problem of pasture degradation requires information on the economics,and its interplay with farmers' objectives, for a wide range of pasture recovery and maintenance methods. Seen within the context of farmers' objectives, some level of overgrazing appears rational. Advocacy of the simple 'no overgrazing' rule is an insufficient strategy to maintain the long-term sustainability of the beef production systems in Central Brazil. (C) 2004 Elsevier Ltd. All rights reserved.

Potential economic impacts of terminator technologies: policy implications for developing countries

The terminator gene can render seeds sterile, so forcing farmers to purchase fresh seed every year. It is a technological solution to the problem of market failure that could increase the appropriability of R&D investment more effectively than intellectual property rights legislation or patents. This paper shows that appropriability should be more than tripled and that this leads to greater private R&D investment, which may be expected to double or triple. This would bring open-pollinating varieties into line with F1 hybrids, for which seed cannot be saved. In turn, the increased investment should raise yield increases to levels similar to those for hybrid crops. Thus, there are benefits to set against the possible ecological and environmental costs and the clear distributional and social consequences. The paper discusses the way the seed market is developing, the possible impacts, especially from a developing country viewpoint, and considers the policy changes that are needed.

Inbreeding depression and founder diversity among captive and free-living populations of the endangered pink pigeon Columba mayeri

The endemic pink pigeon has recovered from less than 20 birds in the mid-1970s to 355 free-living individuals in 2003. A major concern for the species' recovery has been the potential genetic problem of inbreeding. Captive pink pigeons bred for reintroduction were managed to maximise founder representation and minimise inbreeding. In this paper, we quantify the effect of inbreeding on survival and reproductive parameters in captive and wild populations and quantify DNA sequence variation in the mitochondrial d-loop region for pink pigeon founders. Inbreeding affected egg fertility, squab, juvenile and adult survival, but effects were strongest in highly inbred birds (F≥0.25). Inbreeding depression was more apparent in free-living birds where even moderate levels of inbreeding affected survival, although highly inbred birds were equally compromised in both captive and wild populations. Mitochondrial DNA haplotypic diversity in pink pigeon founders is low, suggesting that background inbreeding is contributing to low fertility and depressed productivity in this species, as well as comparable survival of some groups of non-inbred and nominally inbred birds. Management of wild populations has boosted population growth and may be required long-term to offset the negative effects of inbreeding depression and enhance the species' survival.

Asymptotic normality in mixtures of power series distributions

The problem of estimating the individual probabilities of a discrete distribution is considered. The true distribution of the independent observations is a mixture of a family of power series distributions. First, we ensure identifiability of the mixing distribution assuming mild conditions. Next, the mixing distribution is estimated by non-parametric maximum likelihood and an estimator for individual probabilities is obtained from the corresponding marginal mixture density. We establish asymptotic normality for the estimator of individual probabilities by showing that, under certain conditions, the difference between this estimator and the empirical proportions is asymptotically negligible. Our framework includes Poisson, negative binomial and logarithmic series as well as binomial mixture models. Simulations highlight the benefit in achieving normality when using the proposed marginal mixture density approach instead of the empirical one, especially for small sample sizes and/or when interest is in the tail areas. A real data example is given to illustrate the use of the methodology.

Estimation following selection of the largest of two normal means

This paper considers the problem of estimation when one of a number of populations, assumed normal with known common variance, is selected on the basis of it having the largest observed mean. Conditional on selection of the population, the observed mean is a biased estimate of the true mean. This problem arises in the analysis of clinical trials in which selection is made between a number of experimental treatments that are compared with each other either with or without an additional control treatment. Attempts to obtain approximately unbiased estimates in this setting have been proposed by Shen [2001. An improved method of evaluating drug effect in a multiple dose clinical trial. Statist. Medicine 20, 1913–1929] and Stallard and Todd [2005. Point estimates and confidence regions for sequential trials involving selection. J. Statist. Plann. Inference 135, 402–419]. This paper explores the problem in the simple setting in which two experimental treatments are compared in a single analysis. It is shown that in this case the estimate of Stallard and Todd is the maximum-likelihood estimate (m.l.e.), and this is compared with the estimate proposed by Shen. In particular, it is shown that the m.l.e. has infinite expectation whatever the true value of the mean being estimated. We show that there is no conditionally unbiased estimator, and propose a new family of approximately conditionally unbiased estimators, comparing these with the estimators suggested by Shen.

Estimation of population growth or decline in genetically monitored populations

This article introduces a new general method for genealogical inference that samples independent genealogical histories using importance sampling (IS) and then samples other parameters with Markov chain Monte Carlo (MCMC). It is then possible to more easily utilize the advantages of importance sampling in a fully Bayesian framework. The method is applied to the problem of estimating recent changes in effective population size from temporally spaced gene frequency data. The method gives the posterior distribution of effective population size at the time of the oldest sample and at the time of the most recent sample, assuming a model of exponential growth or decline during the interval. The effect of changes in number of alleles, number of loci, and sample size on the accuracy of the method is described using test simulations, and it is concluded that these have an approximately equivalent effect. The method is used on three example data sets and problems in interpreting the posterior densities are highlighted and discussed.

Chromatographic alignment of LC-MS and LC-MS/MS datasets by genetic algorithm feature extraction

Liquid chromatography-mass spectrometry (LC-MS) datasets can be compared or combined following chromatographic alignment. Here we describe a simple solution to the specific problem of aligning one LC-MS dataset and one LC-MS/MS dataset, acquired on separate instruments from an enzymatic digest of a protein mixture, using feature extraction and a genetic algorithm. First, the LC-MS dataset is searched within a few ppm of the calculated theoretical masses of peptides confidently identified by LC-MS/MS. A piecewise linear function is then fitted to these matched peptides using a genetic algorithm with a fitness function that is insensitive to incorrect matches but sufficiently flexible to adapt to the discrete shifts common when comparing LC datasets. We demonstrate the utility of this method by aligning ion trap LC-MS/MS data with accurate LC-MS data from an FTICR mass spectrometer and show how hybrid datasets can improve peptide and protein identification by combining the speed of the ion trap with the mass accuracy of the FTICR, similar to using a hybrid ion trap-FTICR instrument. We also show that the high resolving power of FTICR can improve precision and linear dynamic range in quantitative proteomics. The alignment software, msalign, is freely available as open source.

Enhancing dominant modes in nonstationary time series by means of the symbolic resonance analysis

We present the symbolic resonance analysis (SRA) as a viable method for addressing the problem of enhancing a weakly dominant mode in a mixture of impulse responses obtained from a nonlinear dynamical system. We demonstrate this using results from a numerical simulation with Duffing oscillators in different domains of their parameter space, and by analyzing event-related brain potentials (ERPs) from a language processing experiment in German as a representative application. In this paradigm, the averaged ERPs exhibit an N400 followed by a sentence final negativity. Contemporary sentence processing models predict a late positivity (P600) as well. We show that the SRA is able to unveil the P600 evoked by the critical stimuli as a weakly dominant mode from the covering sentence final negativity. (c) 2007 American Institute of Physics. (c) 2007 American Institute of Physics.

Use of auditory cues for wayfinding assistance in virtual environment: music aids route decision

This paper addresses the crucial problem of wayfinding assistance in the Virtual Environments (VEs). A number of navigation aids such as maps, agents, trails and acoustic landmarks are available to support the user for navigation in VEs, however it is evident that most of the aids are visually dominated. This work-in-progress describes a sound based approach that intends to assist the task of 'route decision' during navigation in a VE using music. Furthermore, with use of musical sounds it aims to reduce the cognitive load associated with other visually as well as physically dominated tasks. To achieve these goals, the approach exploits the benefits provided by music to ease and enhance the task of wayfinding, whilst making the user experience in the VE smooth and enjoyable.

Performance of asynchronous channel assignment scheme in non-uniform and dynamic topology WLANs

Dense deployments of wireless local area networks (WLANs) are fast becoming a permanent feature of all developed cities around the world. While this increases capacity and coverage, the problem of increased interference, which is exacerbated by the limited number of channels available, can severely degrade the performance of WLANs if an effective channel assignment scheme is not employed. In an earlier work, an asynchronous, distributed and dynamic channel assignment scheme has been proposed that (1) is simple to implement, (2) does not require any knowledge of the throughput function, and (3) allows asynchronous channel switching by each access point (AP). In this paper, we present extensive performance evaluation of this scheme when it is deployed in the more practical non-uniform and dynamic topology scenarios. Specifically, we investigate its effectiveness (1) when APs are deployed in a nonuniform fashion resulting in some APs suffering from higher levels of interference than others and (2) when APs are effectively switched `on/off' due to the availability/lack of traffic at different times, which creates a dynamically changing network topology. Simulation results based on actual WLAN topologies show that robust performance gains over other channel assignment schemes can still be achieved even in these realistic scenarios.

Effectiveness of asynchronous channel assignment scheme in heterogeneous WLANs

Due to their popularity, dense deployments of wireless local area networks (WLANs) are becoming a common feature of many cities around the world. However, with only a limited number of channels available, the problem of increased interference can severely degrade the performance of WLANs if an effective channel assignment scheme is not employed. Previous studies on channel assignment in WLANs almost always assume that all access points (AP) employ the same channel assignment scheme which is clearly unrealistic. On the other hand, to the best of our knowledge, the interaction between different channel assignment schemes has also not been studied before. Therefore, in this paper, we investigate the effectiveness of our earlier proposed asynchronous channel assignment scheme in these heterogeneous WLANs scenarios. Simulation results show that our proposed scheme is still able to provide robust performance gains even in these scenarios.

Impact of interference on throughput in dense WLANs with multiple APs

The popularity of wireless local area networks (WLANs) has resulted in their dense deployments around the world. While this increases capacity and coverage, the problem of increased interference can severely degrade the performance of WLANs. However, the impact of interference on throughput in dense WLANs with multiple access points (APs) has had very limited prior research. This is believed to be due to 1) the inaccurate assumption that throughput is always a monotonically decreasing function of interference and 2) the prohibitively high complexity of an accurate analytical model. In this work, firstly we provide a useful classification of commonly found interference scenarios. Secondly, we investigate the impact of interference on throughput for each class based on an approach that determines the possibility of parallel transmissions. Extensive packet-level simulations using OPNET have been performed to support the observations made. Interestingly, results have shown that in some topologies, increased interference can lead to higher throughput and vice versa.