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.

Dissecting the brain`s fear system reveals the hypothalamus is critical for responding in subordinate conspecific intruders

Effective defense against natural threats in the environment is essential for the survival of individual animals. Thus, instinctive behavioral responses accompanied by fear have evolved to protect individuals from predators and from opponents of the same species (dominant conspecifics). While it has been suggested that all perceived environmental threats trigger the same set of innately determined defensive responses, we tested the alternate hypothesis that different stimuli may evoke differentiable behaviors supported by distinct neural circuitry. The results of behavioral, neuronal immediate early gene activation, lesion, and neuroanatomical experiments indicate that the hypothalamus is necessary for full expression of defensive behavioral responses in a subordinate conspecific, that lesions of the dorsal premammillary nucleus drastically reduce behavioral measures of fear in these animals, and that essentially separate hypothalamic circuitry supports defensive responses to a predator or a dominant conspecific. It is now clear that differentiable neural circuitry underlies defensive responses to fear conditioning associated with painful stimuli, predators, and dominant conspecifics and that the hypothalamus is an essential component of the circuitry for the latter two stimuli.

The mitochondrial transcription factor A functions in mitochondrial base excision repair

Mitochondrial transcription factor A (TFAM) is an essential component of mitochondrial nucleoids TFAM plays an important role in mitochondrial transcription and replication TFAM has been previously reported to inhibit nucleotide excision repair (NER) in vitro but NER has not yet been detected in mitochondria, whereas base excision repair (BER) has been comprehensively characterized in these organelles The BER proteins are associated with the inner membrane in mitochondria and thus with the mitochondrial nucleoid, where TFAM is also situated However, a function for TFAM in BER has not yet been investigated This study examines the role of TFAM in BER In vitro studies with purified recombinant TFAM indicate that it preferentially binds to DNA containing 8-oxoguanines, but not to abasic sites, uracils, or a gap in the sequence TFAM inhibited the in vitro incision activity of 8-oxoguanine DNA glycosylase (OGG1), uracil-DNA glycosylase (UDG), apurinic endonuclease 1 (APE1), and nucleotide incorporation by DNA polymerase gamma (pol gamma) On the other hand, a DNA binding-defective TFAM mutant, L58A, showed less inhibition of BER in vitro Characterization of TFAM knockdown (KD) cells revealed that these lysates had higher 8oxoG incision activity without changes in alpha OGG1 protein levels TFAM KD cells had mild resistance to menadione and increased damage accumulation in the mtDNA when compared to the control cells In addition, we found that the tumor suppressor p53, which has been shown to interact with and alter the DNA binding activity of TFAM, alleviates TFAM-Induced inhibition of BER proteins Together, the results suggest that TFAM modulates BER in mitochondria by virtue of its DNA binding activity and protein interactions Published by Elsevier B V

"Den dag vi slutar bli bättre, slutar vi vara bra" : Ledarskapets inverkan på medarbetares motivation till ständiga förbättringar

Syfte - Syftet med studien är att få en djupare insikt i sambandet mellan ledarskap och de faktorer som bidrar till ökat engagemang hos medarbetarna i arbetet med ständiga förbättringar. Studien riktar sig mot ett mellanstort industriföretag som implementerat lean production. Design/ metod - I vår undersökning valde vi att göra en kvalitativ fallstudie. Data samlades in i ett svenskt industriföretag. Totalt har 7 intervjuer genomförts. Undersökningsresultat - Resultatet vi kom fram till är att medarbetarna är i låg utsträckning delaktiga i förbättringsarbetet. Tidigare forskning visar att medarbetare som är delaktiga i beslut är också mer engagerade i arbetet. Metodkritik – Resultatet speglar enbart subjektiva bedömningar och de studerade variablerna bygger på respondenternas uppfattningar. Framtida forskning bör inkludera mer objektiva mått. Praktiska konsekvenser - Studien ger belägg till att medarbetarnas engagemang och motivation i förbättringsarbetet kan ökas genom att göra dem mer delaktiga. Forskning visar att medarbetare som får information och får delta i beslut känner större delaktighet i arbetet. Kunskapsbidrag - I den befintliga litteraturen hävdas det att ledarskapet är en viktig komponent för att öka medarbetarnas engagemang. Lite har dock skrivits om hur ledarskapet kan motivera medarbetarna till ständiga förbättringar i en organisation som arbetar i lean production. Nyckelord:

Towards a Protocol for the Attachment of Semantic Descriptions to Grid Services

Service discovery in large scale, open distributed systems is difficult because of the need to filter out services suitable to the task at hand from a potentially huge pool of possibilities. Semantic descriptions have been advocated as the key to expressive service discovery, but the most commonly used service descriptions and registry protocols do not support such descriptions in a general manner. In this paper, we present a protocol, its implementation and an API for registering semantic service descriptions and other task/user-specific metadata, and for discovering services according to these. Our approach is based on a mechanism for attaching structured and unstructured metadata, which we show to be applicable to multiple registry technologies. The result is an extremely flexible service registry that can be the basis of a sophisticated semantically-enhanced service discovery engine, an essential component of a Semantic Grid.

Towards a Protocol for the Attachment of Metadata to Service Descriptions and its Use in Semantic Discovery

Service discovery in large scale, open distributed systems is difficult because of the need to filter out services suitable to the task at hand from a potentially huge pool of possibilities. Semantic descriptions have been advocated as the key to expressive service discovery, but the most commonly used service descriptions and registry protocols do not support such descriptions in a general manner. In this paper, we present a protocol, its implementation and an API for registering semantic service descriptions and other task/user-specific metadata, and for discovering services according to these. Our approach is based on a mechanism for attaching structured and unstructured metadata, which we show to be applicable to multiple registry technologies. The result is an extremely flexible service registry that can be the basis of a sophisticated semantically-enhanced service discovery engine, an essential component of a Semantic Grid.

Light Coverage on Colby College Campus

Outdoor lighting is an essential component for nighttime safety on college campuses. Outdoor lighting on Colby College campus is not uniform, leaving some areas with minimal light. The purpose of this project is to analytically evaluate if and where major walkways on Colby College have inadequate lighting. While we were unable to define inadequate lighting, we found that most paths on campus do appear to be well lit, while in general open spaces on campus have the lowest light levels.

Influência da suplementação de retinol palmitato sobre os níveis de vitamina A no leite de puérperas saudáveis

The tendency towards reduction of serum retinol levels, an existing placental barrier and the increase of retinol demand, are factors that place puerperal and lactating women at risk for Vitamin A deficiency. This micronutrient is an essential component of vital processes such as differentiation, cellular proliferation, and apoptosis. The objective of this study is to evaluate the effect of palmitate retinol supplementation (100.000UI) upon the milk retinollevels in puerperal women at the Januário Cicco University Maternity Hospital. This intervention has been adopted by the Ministry of Health since 2002. The longitudinal experiment was conducted with 106 puerperal women (68 comprised the supplemented group and 38 the control group). The High Performance Liquid Chromatography (HPLC) method was used to dose the retinol of the milk and serum samples, and the creamtocrit method to determine the milk fat levels. The retinol means for the colostrums were 99.0 ± 64.4 ug/dL and 160.1 ± 94,4 ug/dl 6 hours afier supplementation; 68.9 ± 33.5 ug/dL for the transitional milk, and 30.6 ± 15.2 ug/dL for the mature milk of the supplemented group. Ali the difterences between means were statistically significant. The difterence between retinol means in the control group were also significant, with these being greater in the colostrum, 88.6 ± 62.1 ug/dL with 61.9 ± 30.1 ug/dl in the transition milk and 32.9 ±32.9 ± 17.6 ug/dL in the mature milk. No significant difference was observed in the retinol means of the three types ot milk in the supplemented group when compared to their respective means in the control group. The prevalence in serum (35.1 % and 81.1 % for the cutting point 20 ug/dL, respectively) and in milk (51.4%) revealed vitamin A deficiency as a public health problem. COlostrum, transition, and mature milk tats varied similarly in the supplemented group (1,92 ± 0,96; 3,25 ± 1,27 and 3,31 ± 1,36 grams) and in the control group (1,87 ± 1,14; 3,25 ± 1,31 and 3,36 ± 1,67 grams), with an observed difference between the colostrum/transition milk and the colostrum/mature milk fats. No difference was observed between the groups. The study showed that the 200.000UI supplementation was not sufficient to increase the milk retinol to the desired levels nor to meet the demands of the mothers with deprived hepatic reserves. It is suggested that another similar dose be offered within 30 days or less, and within 2 months post-partum, while continual/y monitoring for possible pregnancy

Aplicação de enxofre em cobertura e qualidade fisiológica de sementes de feijão

A qualidade fisiológica das sementes pode ser afetada pelo estado nutricional das plantas, destacando-se, dentre os nutrientes, o fornecimento de enxofre, constituinte essencial dos aminoácidos. O trabalho objetivou avaliar os efeitos da adubação sulfatada em cobertura sobre a qualidade fisiológica de sementes de feijão cv. Pérola. O delineamento experimental utilizado foi em blocos casualizados, com quatro repetições. Os tratamentos foram constituídos por cinco doses de enxofre (0, 20, 40, 60 e 80 kg ha-1) em cobertura, na forma de sulfato de amônio, 22 dias após a emergência das plântulas. Avaliou-se a qualidade fisiológica das sementes logo após a colheita mediante testes de germinação e vigor. A aplicação de enxofre, em cobertura, aumentou o vigor das sementes, avaliado pelo teste de envelhecimento acelerado; contudo, houve redução do desenvolvimento inicial das plântulas com acréscimo da dose de S em cobertura até 50 a 60 kg ha-1.

Analytical Validation of Quantitative High-Performance Liquid Chromatographic Methods in Pharmaceutical Analysis: A Practical Approach

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

As origens históricas do Zaratustra nietzcheano: o espelho de Zaratustra, a correção do mais fatal dos erros e a superação da morte de Deus

Through a careful examination of the relationship between Zoroastrianism and the Western tradition, and a detailed and critical reading of the writings of Nietzsche, this work aims at showing to what extent the character Zarathustra , his discourses and poetical-philosophical thoughts, and related passages from many distinct Nietzschean works, directly or undirectly reflect a philosophy that harvests contributions from the Zoroastrian tradition or its headways (in the Judeo-Greco-Christian tradition, and furthermore in the whole Western philosophical tradition). Supplied with this provisions, and with the interpretation cast upon them, Nietzschean philosophy questions the entire Western tradition of thought, and proposes its replacement by a new attitude towards life. This work also intends to show the way the Nietzschean Zarathustra was built up, in the writings of the German philosopher, together with the idea of making, out of the namesake character of the ancient Iranian prophet (Zarathushtra or Zoroaster, the founder of Zoroastrianism), the herald of that important text that intended to bring the German language to its highest perfection , clumping together, and leading to a prophetic-poetic climax consonant with the meaning of the Earth , Nietzsche s key ideas about the rectification of the most fatal of errors and about the death of God . An elaborate investigation has been pursued after the reasons and manners of the building up of Nietzsche s Zarathustra mirroring its Iranian namesake (sections 1.1 to 1.6), and a survey of the works of Nietzsche has suggested unquestionable relations with the Zoroastrian tradition, mostly through the Jewish, Greek or Christian repercussions of this tradition. These relations have been put in context, in many framings (sections 2.1 to 2.3.2), in the ambit of the most fatal of errors - the - creation of morals in the very occasion of its transposition to metaphysics (Ecce Homo, Why I am a destiny , 3). Through an evaluation of the possible circumstances and repercussions of the death of God , the relations between Nietzsche s writings and Zoroastrian tradition have been investigated (sections 3.1 to 3.7), allowing the understanding of this event as an essential component, and tragic outcome, of the rectification of the most fatal of errors

Desenvolvimento formal de aplicações para smartcards

Smart card applications represent a growing market. Usually this kind of application manipulate and store critical information that requires some level of security, such as financial or confidential information. The quality and trustworthiness of smart card software can be improved through a rigorous development process that embraces formal techniques of software engineering. In this work we propose the BSmart method, a specialization of the B formal method dedicated to the development of smart card Java Card applications. The method describes how a Java Card application can be generated from a B refinement process of its formal abstract specification. The development is supported by a set of tools, which automates the generation of some required refinements and the translation to Java Card client (host) and server (applet) applications. With respect to verification, the method development process was formalized and verified in the B method, using the Atelier B tool [Cle12a]. We emphasize that the Java Card application is translated from the last stage of refinement, named implementation. This translation process was specified in ASF+SDF [BKV08], describing the grammar of both languages (SDF) and the code transformations through rewrite rules (ASF). This specification was an important support during the translator development and contributes to the tool documentation. We also emphasize the KitSmart library [Dut06, San12], an essential component of BSmart, containing models of all 93 classes/interfaces of Java Card API 2:2:2, of Java/Java Card data types and machines that can be useful for the specifier, but are not part of the standard Java Card library. In other to validate the method, its tool support and the KitSmart, we developed an electronic passport application following the BSmart method. We believe that the results reached in this work contribute to Java Card development, allowing the generation of complete (client and server components), and less subject to errors, Java Card applications.

Transporte coletivo em Natal/RN: uma abordagem geográfica

This paper focuses public bus service as an essential component to urban dynamics in Natal, RN. Thereby, the approach of public bus service in Natal City, capital of Rio Grande do Norte State, has as analytical category the concept of territory used, in which techniques are seen as space elements allowing man and nature interact together. The result of this interaction, systematically analyzed in different historical phases, makes space to a geographical assessment of the theme. On a second moment, it is investigated how public bus system came to be and how it functions today in Natal City. In this sense, this paper looks for the main elements that contributed to explain the subject under investigation. For example, how public bus service has accompanied Natal s socio-spatial changes, and eventually, the use of territory carried out in the context of public bus system. These questions are highlighted in this paper because they play a fundamental role to an explanation about public bus circulation, urban vehicle policies and how they affect the use of territory nowadays.

Efeitos da fisioterapia respiratória convencional versus aumento do fluxo expiratório na saturação de O2, freqüência cardíaca e freqüência respiratória, em prematuros no período pós-extubação

INTRODUÇÃO: Recém-nascidos (RN) prematuros apresentam elevada morbidade respiratória e necessidade de ventilação mecânica, assim, a fisioterapia respiratória é parte integrante da assistência neonatal. Objetivo: Comparar os efeitos da fisioterapia respiratória convencional (FRC) versus aumento do fluxo expiratório (AFE), na saturação de O2 (SpO2), freqüência cardíaca (FC) e na freqüência respiratória (FR) em prematuros no período pós-extubação. Método: Ensaio clínico randomizado realizado na UTI Neonatal do Hospital das Clínicas de BotucatuUNESP, comparando duas técnicas fisioterapêuticas, aplicadas em recém-nascidos prematuros, nas primeiras 48 horas pós-extubação. Para a análise estatística foram utilizados o teste t Student, Mann-Whitney, Qui-quadrado e o teste exato de Fisher, com nível de significância em 5%. Resultados: Os dois grupos de estudo: Grupo FRC (n= 20) e grupo AFE (n= 20), não diferiram quanto à idade gestacional (média de 28 semanas) e peso de nascimento (média de 1100 gramas). em ambos os grupos a síndrome do desconforto respiratório (SDR) foi o principal diagnóstico. A mediana da idade no início da fisioterapia foi de sete dias no grupo AFE e 11 dias na FRC. Ambas as técnicas produziram aumento significativo da SpO2 aos 10 e 30 minutos, sem alterações na FR. A FC aumentou significativamente após a FRC e não se alterou após o AFE. Conclusão: Os resultados sugerem que o AFE é menos estressante que a FRC e pode ser aplicado em prematuros no período pós-extubação. Nestes recém-nascidos o AFE parece ser seguro e benéfico a curto prazo.

Higher salt preference in heart failure patients

Heart failure (HF) is a complex syndrome that involves changes in behavioral, neural and endocrine regulatory systems. Dietary salt restriction along with pharmacotherapy is considered an essential component in the effective management of symptomatic HF patients. However, it is well recognized that HF patients typically have great difficulty in restricting sodium intake. We hypothesized that under HF altered activity in systems that normally function to regulate body fluid and cardiovascular homeostasis could produce an increased preference for the taste of salt. Therefore, this study was conducted to evaluate the perceived palatability (defined as salt preference) of food with different concentrations of added salt in compensated chronically medicated HF patients and comparable control subjects. Healthy volunteers (n = 25) and medicated, clinically stable HF patients (n = 38, NYHA functional class II or III) were interviewed and given an evaluation to assess their preferences for different amounts of saltiness. Three salt concentrations (0.58, 0.82, and 1.16 g/100 g) of bean soup were presented to the subjects. Salt preference for each concentration was quantified using an adjective scale (unpleasant, fair or delicious). Healthy volunteers preferred the soup with medium salt concentration (p = 0.042), HF patients disliked the low concentration (p < 0.001) and preferred the high concentration of salted bean soup (p < 0.001). When compared to healthy volunteers, HF patients demonstrated a significantly greater preference for the soup with a high salt concentration (p = 0.038). It is concluded that medicated, compensated patients under chronic treatment for HF have an increased preference for salt. (C) 2011 Elsevier Ltd. All rights reserved,