The current status of anticoagulant resistance in rats and mice in the UK

Introduction: Resistance to anticoagulants in Norway rats (Rattus norvegicus) and house mice (Mus domesticus) has been studied in the UK since the early 1960s. In no other country in the world is our understanding of resistance phenomena so extensive and profound. Almost every aspect of resistance in the key rodent target species has been examined in laboratory and field trials and results obtained by independent researchers have been published. It is the principal purpose of this document to present a short synopsis of this information. More recently, however, the development of genetical techniques has provided a definitive means of detection of resistant genotypes among pest rodent populations. Preliminary information from a number of such surveys will also be presented. Resistance in Norway rats: A total of nine different anticoagulant resistance mutations (single nucleotide polymorphisms or SNPs) are found among Norway rats in the UK. In no other country worldwide are present so many different forms of Norway rat resistance. Among these nine SNPs, five are known to confer on rats that carry them a significant degree of resistance to anticoagulant rodenticides. These mutations are: L128Q, Y139S, L120Q, Y139C and Y139F. The latter three mutations confer, to varying degrees, practical resistance to bromadiolone and difenacoum, the two second-generation anticoagulants in predominant use in the UK. It is the recommendation of RRAG that bromadiolone and difenacoum should not be used against rats carrying the L120Q, Y139C and Y139F mutations because this will promote the spread of resistance and jeopardise the long-term efficacy of anticoagulants. Brodifacoum, flocoumafen and difethialone are effective against these three genotypes but cannot presently be used because of the regulatory restriction that they can only be applied against rats that are living and feeding predominantly indoors. Our understanding of the geographical distribution of Norway rat resistance in incomplete but is rapidly increasing. In particular, the mapping of the focus of L120Q Norway rat resistance in central-southern England by DNA sequencing is well advanced. We now know that rats carrying this resistance mutation are present across a large part of the counties of Hampshire, Berkshire and Wiltshire, and the resistance spreads into Avon, Oxfordshire and Surrey. It is also found, perhaps as outlier foci, in south-west Scotland and East Sussex. L120Q is currently the most severe form of anticoagulant resistance found in Norway rats and is prevalent over a considerable part of central-southern England. A second form of advanced Norway rat resistance is conferred by the Y139C mutation. This is noteworthy because it occurs in at least four different foci that are widely geographically dispersed, namely in Dumfries and Galloway, Gloucestershire, Yorkshire and Norfolk. Once again, bromadiolone and difenacoum are not recommended for use against rats carrying this genotype and a concern of RRAG is that continued applications of resisted active substances may result in Y139C becoming more or less ubiquitous across much of the UK. Another type of advanced resistance, the Y139F mutation, is present in Kent and Sussex. This means that Norway rats, carrying some degree of resistance to bromadiolone and difenacoum, are now found from the south coast of Kent, west into the city of Bristol, to Yorkshire in the north-east and to the south-west of Scotland. This difficult situation can only deteriorate further where these three genotypes exist and resisted anticoagulants are predominantly used against them. Resistance in house mice: House mouse is not so well understood but the presence in the UK of two resistant genotypes, L128S and Y139C, is confirmed. House mice are naturally tolerant to anticoagulants and such is the nature of this tolerance, and the presence of genetical resistance, that house mice resistant to the first-generation anticoagulants are considered to be widespread in the UK. Consequently, baits containing warfarin, sodium warfarin, chlorophacinone and coumatetralyl are not approved for use against mice. This regulatory position is endorsed by RRAG. Baits containing brodifacoum, flocoumafen and difethialone are effective against house mice and may be applied in practice because house mouse infestations are predominantly indoors. There are some reports of resistance among mice in some areas to the second-generation anticoagulant bromadiolone, while difenacoum remains largely efficacious. Alternatives to anticoagulants: The use of habitat manipulation, that is the removal of harbourage, denial of the availability of food and the prevention of ingress to structures, is an essential component of sustainable rodent pest management. All are of importance in the management of resistant rodents and have the advantage of not selecting for resistant genotypes. The use of these techniques may be particularly valuable in preventing the build-up of rat infestations. However, none can be used to remove any sizeable extant rat infestation and for practical reasons their use against house mice is problematic. Few alternative chemical interventions are available in the European Union because of the removal from the market of zinc phosphide, calciferol and bromethalin. Our virtual complete reliance on the use of anticoagulants for the chemical control of rodents in the UK, and more widely in the EU, calls for improved schemes for resistance management. Of course, these might involve the use of alternatives to anticoagulant rodenticides. Also important is an increasing knowledge of the distribution of resistance mutations in rats and mice and the use of only fully effective anticoagulants against them.

Rhodosporidium toruloides cultivated in NaCl-enriched glucose-based media: adaptation dynamics and lipid production

In the present report and for the first time in the international literature, the impact of the addition of NaCl upon growth and lipid production on the oleaginous yeast Rhodosporidium toruloides was studied. Moreover, equally for first time, lipid production by R. toruloides was performed under non-aseptic conditions. Therefore, the potentiality of R. toruloides DSM 4444 to produce lipid in media containing several initial concentrations of NaCl with glucose employed as carbon source was studied. Preliminary batch-flask trials with increasing amounts of NaCl revealed the tolerance of the strain against NaCl content up to 6.0% (w/v). However, 4.0% (w/v) of NaCl stimulated lipid accumulation for this strain, by enhancing lipid production up to 71.3% (w/w) per dry cell weight. The same amount of NaCl was employed in pasteurized batch-flask cultures in order to investigate the role of the salt as bacterial inhibiting agent. The combination of NaCl and high glucose concentrations was found to satisfactorily suppress bacterial contamination of R. toruloides cultures under these conditions. Batch-bioreactor trials of the yeast in the same media with high glucose content (up to 150 g/L) resulted in satisfactory substrate assimilation, with almost linear kinetic profile for lipid production, regardless of the initial glucose concentration imposed. Finally, fed-batch bioreactor cultures led to the production of 37.2 g/L of biomass, accompanied by 64.5% (w/w) of lipid yield. Lipid yield per unit of glucose consumed received the very satisfactory value of 0.21 g/g, a value amongst the highest ones in the literature. The yeast lipid produced contained mainly oleic acid and to lesser extent palmitic and stearic acids, thus constituting a perfect starting material for “second generation” biodiesel

What do patients want to know? An empirical approach to explanation generation and validation

This article describes an empirical, user-centred approach to explanation design. It reports three studies that investigate what patients want to know when they have been prescribed medication. The question is asked in the context of the development of a drug prescription system called OPADE. The system is aimed primarily at improving the prescribing behaviour of physicians, but will also produce written explanations for indirect users such as patients. In the first study, a large number of people were presented with a scenario about a visit to the doctor, and were asked to list the questions that they would like to ask the doctor about the prescription. On the basis of the results of the study, a categorization of question types was developed in terms of how frequently particular questions were asked. In the second and third studies a number of different explanations were generated in accordance with this categorization, and a new sample of people were presented with another scenario and were asked to rate the explanations on a number of dimensions. The results showed significant differences between the different explanations. People preferred explanations that included items corresponding to frequently asked questions in study 1. For an explanation to be considered useful, it had to include information about side effects, what the medication does, and any lifestyle changes involved. The implications of the results of the three studies are discussed in terms of the development of OPADE's explanation facility.

Military doctrine, command philosophy and the generation of fighting power: genesis and theory

Military doctrine is one of the conceptual components of war. Its raison d’être is that of a force multiplier. It enables a smaller force to take on and defeat a larger force in battle. This article’s departure point is the aphorism of Sir Julian Corbett, who described doctrine as ‘the soul of warfare’. The second dimension to creating a force multiplier effect is forging doctrine with an appropriate command philosophy. The challenge for commanders is how, in unique circumstances, to formulate, disseminate and apply an appropriate doctrine and combine it with a relevant command philosophy. This can only be achieved by policy-makers and senior commanders successfully answering the Clausewitzian question: what kind of conflict are they involved in? Once an answer has been provided, a synthesis of these two factors can be developed and applied. Doctrine has implications for all three levels of war. Tactically, doctrine does two things: first, it helps to create a tempo of operations; second, it develops a transitory quality that will produce operational effect, and ultimately facilitate the pursuit of strategic objectives. Its function is to provide both training and instruction. At the operational level instruction and understanding are critical functions. Third, at the strategic level it provides understanding and direction. Using John Gooch’s six components of doctrine, it will be argued that there is a lacunae in the theory of doctrine as these components can manifest themselves in very different ways at the three levels of war. They can in turn affect the transitory quality of tactical operations. Doctrine is pivotal to success in war. Without doctrine and the appropriate command philosophy military operations cannot be successfully concluded against an active and determined foe.

A comparison of photoinduced poling and thermal poling of azo‐dye‐doped polymer films for second order nonlinear optical applications

Photoinduced poling (PIP) is a new technique which allows the room‐temperature preparation of guest/host polymer films exhibiting significant polar order for nonlinear optical applications. We report a comparison of this novel technique with the conventional electrode poling procedure performed at the glass transition temperature of the polymer using disperse red 1/poly(methylmethacrylate) films. In particular, in situ second harmonic generation measurements show that levels of polar order achieved using these two techniques are similar. In contrast, the stability of the polar order is reduced by up to 20 times in terms of the decay time constant in films prepared using PIP although the stability is very dependent upon the temperature at which the poling was performed.

Review of the formulation of present‐generation stratospheric chemistry‐climate models and associated external forcings

The goal of the Chemistry‐Climate Model Validation (CCMVal) activity is to improve understanding of chemistry‐climate models (CCMs) through process‐oriented evaluation and to provide reliable projections of stratospheric ozone and its impact on climate. An appreciation of the details of model formulations is essential for understanding how models respond to the changing external forcings of greenhouse gases and ozonedepleting substances, and hence for understanding the ozone and climate forecasts produced by the models participating in this activity. Here we introduce and review the models used for the second round (CCMVal‐2) of this intercomparison, regarding the implementation of chemical, transport, radiative, and dynamical processes in these models. In particular, we review the advantages and problems associated with approaches used to model processes of relevance to stratospheric dynamics and chemistry. Furthermore, we state the definitions of the reference simulations performed, and describe the forcing data used in these simulations. We identify some developments in chemistry‐climate modeling that make models more physically based or more comprehensive, including the introduction of an interactive ocean, online photolysis, troposphere‐stratosphere chemistry, and non‐orographic gravity‐wave deposition as linked to tropospheric convection. The relatively new developments indicate that stratospheric CCM modeling is becoming more consistent with our physically based understanding of the atmosphere.

Dynamic game soundtrack generation in response to a continously varying emotional trajectory

Dynamic soundtracking presents various practical and aesthetic challenges to composers working with games. This paper presents an implementation of a system addressing some of these challenges with an affectively-driven music generation algorithm based on a second order Markov-model. The system can respond in real-time to emotional trajectories derived from 2-dimensions of affect on the circumplex model (arousal and valence), which are mapped to five musical parameters. A transition matrix is employed to vary the generated output in continuous response to the affective state intended by the gameplay.