Molecular mechanisms of cocaine reward: Combined dopamine and serotonin transporter knockouts eliminate cocaine place preference

Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET). Cocaine reward/reinforcement has been linked to actions at DAT or to blockade of SERT. However, knockouts of neither DAT, SERT, or NET reduce cocaine reward/reinforcement, leaving substantial uncertainty about cocaine's molecular mechanisms for reward. Conceivably, the molecular bases of cocaine reward might display sufficient redundancy that either DAT or SERT might be able to mediate cocaine reward in the other's absence. To test this hypothesis, we examined double knockout mice with deletions of one or both copies of both the DAT and SERT genes. These mice display viability, weight gain, histologic features, neurochemical parameters, and baseline behavioral features that allow tests of cocaine influences. Mice with even a single wild-type DAT gene copy and no SERT copies retain cocaine reward/reinforcement, as measured by conditioned place-preference testing. However, mice with no DAT and either no or one SERT gene copy display no preference for places where they have previously received cocaine. The serotonin dependence of cocaine reward in DAT knockout mice is thus confirmed by the elimination of cocaine place preference in DAT/SERT double knockout mice. These results provide insights into the brain molecular targets necessary for cocaine reward in knockout mice that develop in their absence and suggest novel strategies for anticocaine medication development.

Esquemas cognitivos, sintomas de ansiedade e depressão em mulheres de um Programa de Cessação de Tabagismo

O tabagismo é um problema de saúde pública em todo o mundo. Entre as mulheres, devido ao aumento da prevalência comparada aos homens, o tabagismo feminino tem merecido atenção. Para o enfrentamento, é necessário entender o fenômeno e criar estratégias mais adequadas que incluam aspectos emocionais e sociais da dependência do tabagismo. Este estudo buscou descrever os esquemas cognitivos, sintomas de ansiedade e depressão de 112 mulheres que procuraram tratamento para cessação do tabagismo e sua relação com o insucesso do tratamento. A coleta de dados incluiu roteiro de entrevista estruturada e escalas validadas para a população brasileira que têm o objetivo de avaliar os esquemas cognitivos, sintomas de ansiedade e de depressão, e aspectos da dependência do cigarro. O conhecimento de fatores emocionais envolvidos no tabagismo e sua cessação podem ser úteis às ações de apoio à mudança comportamental do fumante. Objetivo: Descrever o perfil psicológico de mulheres que buscam cessação do tabagismo quanto aos esquemas cognitivos, sintomas de ansiedade e depressão antes e depois do tratamento com Terapia Cognitivo- Comportamental em grupo, e analisar fatores que contribuem para o desfecho de cessação. O desenho do estudo foi longitudinal e transversal. Para avaliar os esquemas cognitivos, o Questionário de Esquemas de Young em sua forma curta foi utilizado. Os grupos de terapia cognitivo-comportamental foram realizados concomitantes ao cuidado usual por médicos do estudo. Esses profissionais foram treinados no protocolo do estudo e o seguimento foi realizado por telefone por um membro do estudo independente e cego. Resultados: Os resultados forneceram evidências de que esquemas cognitivos tiveram relação significativa com os sintomas de depressão e ansiedade, com a adesão e os resultados do tratamento (cessação do tabagismo)

O papel do terceiro facilitador na conciliação de conflitos previdenciários

A conciliação judicial de conflitos previdenciários envolve, em geral, uma proposta de acordo baseada na renúncia pelo indivíduo de parte dos valores do benefício em atraso em um processo no qual a decisão contrária ao entendimento do Instituto Nacional do Segurado Social (INSS) é muito provável. Como regra, há um notório desequilíbrio de poder envolvendo, de um lado, um litigante ocasional (indivíduo) e, de outro, um litigante habitual (INSS). O presente trabalho pretende discutir qual o papel do terceiro facilitador nesse contexto, de modo a legitimar a prática existente e avançar para uma mudança de paradigma. Para tanto, parte-se da tese de que a conciliação deve ser adequada ao conflito que se pretende tratar, cabendo ao terceiro facilitador atuar de acordo com as peculiaridades desse conflito. Desse modo, propõe-se que, para o tratamento do conflito previdenciário, o conceito de conciliador deve ser entendido em termos amplos, abrangendo não apenas o conciliador leigo, mas também o juiz conciliador e o Judiciário como conciliador interinstitucional. Embora cada uma dessas atuações possua características próprias, sustenta-se que o ponto em comum é o respeito a um devido processo legal mínimo que possibilite a existência de uma base adequada de poder e que permita, assim, a tomada de uma decisão informada pelas partes. Dessa forma, a flexibilidade instrumental própria da conciliação não impediria o estabelecimento de parâmetros mínimos da atuação do conciliador. Por isso, tendo como limite a tomada de uma decisão informada, o conciliador atuaria por meio de estratégias variadas, aproximando-se e distanciando-se das partes, com maior ou menor interferência, de acordo com as características do caso apresentado. Conclui-se que, com a atuação conjunta e coordenada das diversas espécies de conciliador é possível aprimorar qualitativamente a conciliação de conflitos previdenciários.

Reducing visual deficits caused by refractive errors in school and preschool children: results of a pilot school program in the Andean region of Apurimac, Peru

Background: Refractive error is defined as the inability of the eye to bring parallel rays of light into focus on the retina, resulting in nearsightedness (myopia), farsightedness (Hyperopia) or astigmatism. Uncorrected refractive error in children is associated with increased morbidity and reduced educational opportunities. Vision screening (VS) is a method for identifying children with visual impairment or eye conditions likely to lead to visual impairment. Objective: To analyze the utility of vision screening conducted by teachers and to contribute to a better estimation of the prevalence of childhood refractive errors in Apurimac, Peru. Design: A pilot vision screening program in preschool (Group I) and elementary school children (Group II) was conducted with the participation of 26 trained teachers. Children whose visual acuity was<6/9 [20/30] (Group I) and≤6/9 (Group II) in one or both eyes, measured with the Snellen Tumbling E chart at 6 m, were referred for a comprehensive eye exam. Specificity and positive predictive value to detect refractive error were calculated against clinical examination. Program assessment with participants was conducted to evaluate outcomes and procedures. Results: A total sample of 364 children aged 3–11 were screened; 45 children were examined at Centro Oftalmológico Monseñor Enrique Pelach (COMEP) Eye Hospital. Prevalence of refractive error was 6.2% (Group I) and 6.9% (Group II); specificity of teacher vision screening was 95.8% and 93.0%, while positive predictive value was 59.1% and 47.8% for each group, respectively. Aspects highlighted to improve the program included extending training, increasing parental involvement, and helping referred children to attend the hospital. Conclusion: Prevalence of refractive error in children is significant in the region. Vision screening performed by trained teachers is a valid intervention for early detection of refractive error, including screening of preschool children. Program sustainability and improvements in education and quality of life resulting from childhood vision screening require further research.

Invited commentary: Gender regimes in health systems

In short, what Elisa Chilet has found in her recent thesis dissertation entitled 'Gender bias in clinical research, pharmaceutical marketing and the prescription of drugs', a review of which is published in this issue of the journal, is a significant amount of gender bias.

Gender and health inequalities: intersections with other relevant axes of oppression

The risk of disease, disability, and mortality as well as access to health services are unfairly distributed among the population, with certain groups bearing an unequally larger burden of ill health and poorer access to care due to gender, sexual identity/orientation, ethnic background, or class. According to the WHO Commission on Social Determinants of Health (CSDH), these health inequalities emanate from socioeconomic and political factors (governance, cultural values, macroeconomic policies), which generate a set of socioeconomic positions in society according to which populations are stratified based on gender, ethnicity, education, income, or other factors. These societal inequalities influence people’s material and psychosocial circumstances as well as behavioral and biological factors, which in turn impact on health inequalities. Tackling gender, race/ethnic, and socioeconomic inequalities in society is thus recognized as the most powerful action to cope with unequal health risks distribution, and social innovations focusing on these ‘root causes’ are needed in order to prevent and stop endemic social inequalities and social exclusion in health within low-income as well as high-income countries. Increasing existing knowledge and making visible the health status of the most vulnerable and invisible groups are critical in order to contribute to this imperative challenge.

Register of the Inferior Court, 1759-1763

Contains the Inferior Court's register of debtor's cases heard for the Mayor's Court for the following counties: Orange County, Suffolk County, Westchester County, Ulster County, Duchess County, and Queens County, in New York state. The register, kept by William Wickham, cites parties to the action, sentencing, court costs, and has a name index at the end.

In-house lawyers of NRAs may not represent their clients before the European Court of Justice: A case note on UKE (2011). Research Papers in Law, 3/2011

From the Introduction. It is not frequent for a National Regulation Authority (NRA) to bring an action against the Commission decision and, cynically speaking, case Prezes Urzędu Komunikacji Elektronicznej2 v Commission3 shows that the avoidance of a sweeping retaliation may be one of the reasons for it. The General Court followed the Commission‟s argument that, notwithstanding the peculiarities of the employment conditions of the Polish Regulator‟s legal counsel giving it virtually full independence, as well as the fact that the Polish law itself does not differentiate between in-house counsel and third party attorneys, the claim should be rejected on the grounds of inadmissibility. The GC based its judgment on Art 19 of the Statute of the Court of Justice4, which requires that, with the exception of the Member States' Governments and the EU Institutions, parties to the dispute must be represented by a lawyer. In so doing, the Court explicitly referred to the infamous Akzo Nobel Chemicals and Akcros Chemicals v Commission5 and EREF v Commission6. Most importantly, the Court stated that the lawyers representing Prezes Urzędu Komunikacji Elektronicznej (UKE) are bound to enjoy a degree of independence inferior to that of lawyers who are not linked to their clients by an employment contract7.

La réforme Dodd-Frank des produits dérivés de gré à gré : vers un modèle mondial?

Suite à la crise financière de 2008 les pays du G20 se sont interrogés sur la transparence des marchés, la stabilité du système et une façon de réguler les risques posés par le nouvel environnement économique. Les produits dérivés de gré à gré ont été identifiés et des engagements ont été pris en faveur de nouvelles régulations des dérivés de gré à gré et la gestion des risques sous-jacents. Les régulateurs ont donc adopté chacun à leur tour un cadre législatif régulant les dérivés de gré à gré tout en déployant un effort international d'harmonisation et de reconnaissance des contreparties assujetties à des régimes équivalents. Les autorités canadiennes en valeurs mobilières ont publié des projets de règlements. Nous nous interrogerons sur ce nouveau cadre réglementaire des dérivés de gré à gré élaboré par les autorités canadiennes en valeurs mobilières, prenant en considération les spécificités canadiennes et les acteurs actifs sur leur territoire. Notre étude traite de ces projets de règlements et de la difficulté d'encadrer les marchés des dérivés de gré à gré qui par définition ne comportent pas de plateformes de négociation ou de lieu géographique et de frontières mais se caractérisent surtout par le lien contractuel entre les parties et l'identification de ces parties. L'élaboration d'un nouveau cadre pour les dérivés de gré à gré qui régule les transactions transfrontières semble très délicat à traiter et les possibles conflits et chevauchements de lois seront inévitables. Confrontés à des définitions divergentes de contreparties locales, les parties à une opération seront condamnées à un risque de qualification en vertu des règlements nationaux sur les dérivés de gré à gré. Une concertation pourrait être renforcée et la détermination de l'autorité compétente ainsi que les concepts de contreparties locales, succursales ou filiales pourraient être harmonisés.

LMX à distance : analyse qualitative et développement d’une échelle de mesure

Notre recherche a pour objectif général de proposer l’adaptation du concept de la relation d’échange superviseur-subordonné (leader-member exchange ou LMX) à la nouvelle réalité du travail à distance. Il s’agit d’étudier la relation d’échange qui se développe entre le superviseur et le subordonné travaillant à distance. Plus précisément, nous visons à définir et à développer une échelle de mesure valide et fiable du concept du LMX à distance. Jusqu’à présent, aucune définition de cette relation d’échange superviseur-subordonné n'a été proposée et aucune échelle de mesure n'a été développée. Dans l’étude que nous proposons, la notion de la distance n’est pas considérée comme un élément contextuel, mais plutôt un élément indissociable du concept lui-même, contrairement à certaines études qui ont examiné la distance comme modérateur de la relation entre le LMX et ses résultantes (Bligh et Riggio, 2012; Brunelle, 2013). À cet effet, cette étude constitue la première sur le sujet. Étant donné l'importance du LMX à distance pour les travailleurs à distance et dont le nombre atteindrait plus de 50 % d’ici 2020 (ITIF, CAS et CoreNet Global), il est primordial de comprendre et d'analyser la relation d’échange superviseur-subordonné à distance afin de mieux comprendre sa nature et son processus de développement, ce qui permettra aux parties de la dyade superviseur-subordonné de mieux s’adapter à cette nouvelle réalité de travail et de développer des relations d’échanges de qualité. Cette recherche aidera les superviseurs travaillant à distance à mieux gérer leur potentiel humain. Pour cerner ce sujet de recherche, nous avons fait une revue approfondie de la littérature traitant du LMX traditionnel et de la notion de distance, et ce, afin de pouvoir proposer une définition du concept du LMX à distance. En outre, nous avons fait appel aux recommandations de la littérature portant sur la psychométrie et nous avons réalisé une étude exploratoire de nature qualitative pour développer son échelle de mesure. Nous avons donc effectué des entrevues individuelles semi-dirigées auprès de trente professeurs d’une université canadienne. Ces entrevues ont été analysées avec le logiciel qualitatif spécialisé Nvivo et ont permis de présenter une première échelle de mesure du LMX à distance composée de sept dimensions et de 27 indicateurs. En somme, nous avons tenu à acquérir une meilleure compréhension de ce phénomène qui est très répandu dans les organisations modernes et à offrir une plateforme théorique et pratique que les chercheurs pourront utiliser pour enrichir leurs connaissances sur le concept du LMX à distance. Enfin, notre étude permettra aux superviseurs et aux subordonnés de comprendre l'importance de développer et de maintenir des relations de qualité conduisant à des résultats organisationnels et personnels positifs.

The Judicial Dimension of the European Neighbourhood Policy. EU Diplomacy Paper 08/2013, November 2013

In this paper, the expression “neighbourhood policy” of the European Union (EU) is understood in a broad way which includes the members of the European Free Trade Association (EFTA) contracting parties to the European Economic Area (EEA), the EFTA State Switzerland, candidate states, the countries of the European Neighbour-hood Policy (ENP), and Russia. The European Court of Justice (ECJ) is the centre of gravity in the judicial dimension of this policy. The innermost circle of integration after the EU itself comprises the EFTA States who are party to the European Economic Area. With the EFTA Court, they have their own common court. The existence of two courts – the ECJ and the EFTA Court – raises the question of homogeneity of the case law. The EEA homogeneity rules resemble the ones of the Lugano Convention. The EFTA Court is basically obliged to follow or take into account relevant ECJ case law. But even if the ECJ has gone first, there may be constellations where the EFTA Court comes to the conclusion that it must go its own way. Such constellations may be given if there is new scientific evidence, if the ECJ has left certain questions open, where there is relevant case law of the European Court of Human Rights or where, in light of the specific circumstances of the case, there is room for “creative homogeneity”. However, in the majority of its cases the EFTA Court is faced with novel legal questions. In such cases, the ECJ, its Advocates General and the Court of First Instance make reference to the EFTA Court’s case law. The question may be posed whether the EEA could serve as a model for other regional associations. For the ENP states, candidate States and Russia this is hard to imagine. Their courts will to varying degrees look to the ECJ when giving interpretation to the relevant agreements. The Swiss Government is – at least for the time being – unwilling to make a second attempt to join the EEA. The European Commission has therefore proposed to the Swiss to dock their sectoral agreements with the EU to the institutions of the EFTA pillar, the EFTA Surveillance Authority (ESA) and the EFTA Court. Switzerland would then negotiate the right to nominate a member of the ESA College and of the EFTA Court. The Swiss Government has, however, opted for another model. Swiss courts would continue to look to the ECJ, as they did in the past, and conflicts should also in the future be resolved by diplomatic means. But the ECJ would play a decisive role in dispute settlement. It would, upon unilateral request of one side, give an “authoritative” interpretation of EU law as incorporated into the relevant bilateral agreement. In a “Non-Paper” which was drafted by the chief negotiators, the interpretations of the ECJ are even characterised as binding. The decision-making power would, however, remain with the Joint Committees where Switzerland could say no. The Swiss Government assumes that after a negative decision by the ECJ it would be able to negotiate a compromise solution with the Commission without the ECJ being able to express itself on the outcome. The Government has therefore not tried to emphasise that the ECJ would not be a foreign court. Whether the ECJ would accept its intended role, is an open question. And if it would, the Swiss Government would have to explain to its voters that Switzerland retains the freedom to disregard such a binding decision and that for this reason the ECJ is not only no foreign court, but no adjudicating court at all.

Italy and the EU in historical perspective. ACES Working Papers, August 2009

This paper will deal with relations between Italy and the European Communities in a historical perspective. It will take into consideration both exogenous and endogenous variables. As regards the exogenous, relations with the United States are of particular relevance. As for the endogenous, the focus will be on the way political parties have perceived the process of European integration. Here, one can distinguish three periods: from the origins to the late 1970s; from the late 1970s to the mid 1990s and from the mid 1990s to today. The first period was characterized by the opposition of the left to European and Atlantic integration, on the basis of ideological contraposition; the second witnessed a shared consensus by all political parties on integration - especially European; in the latest period, domestic political divisions at times lead parties to oppose European integration.

PALESTINIAN REFUGEES-HOW CAN A DURABLE SOLUTION BE ACHIEVED? CEPS Middle East Working Paper No. 6, July 2003

From the Introduction. The refugee question is at the core of the conflict between Israel and the Palestinians. Palestinians were first displaced as a direct consequence of the 1948 war and its aftermath. Twenty years later, another wave of Palestinian refugees was created as a consequence of the war during which Israel occupied the West Bank and the Gaza Strip. The purpose of the present paper is to: • deliver a critical analysis of past approaches to deal with the refugee issue in the various attempts to resolve the conflict between Israel and the Palestinians; • discuss lessons to be learned from the settlement and its implementation mechanisms in Bosnia and Herzegovina; and • propose a direction for a long-term strategy for the international community that avoids past pitfalls and could ultimately lead both parties to an agreement.

The Eurozone crisis and the erosion of democratic legitimacy: Lessons from the gold standard. ACES Cases No. 2013.3

This paper makes four propositions. First, it argues that the euro’s institutional design makes it function like the interwar gold exchange standard during periods of stress. Just like the gold exchange standard during the 1930s, the euro created a ‘core’ of surplus countries and a ‘periphery’ of deficit countries. The latter have to sacrifice their internal domestic economic equilibrium in order to restore their external equilibrium, and therefore have no choice but to respond to balance of payments crises by a series of deflationary spending, price and wage cuts. The paper’s second claim is that the euro’s institutional design and the EU’s response to its ‘sovereign debt crisis’ during 2010-13 deepened the recession in the Eurozone periphery, as EMU leaders focused almost exclusively on austerity measures and structural reforms and paid only lip service to the need to rebalance growth between North and South. As Barry Eichengreen argued in Golden Fetters, the rigidity of the gold standard contributed to the length and depth of the Great Depression during the 1930s, but also underscored the incompatibility of the system with legitimate national democratic government in places like Italy, Germany, and Spain, which is the basis for the paper’s third proposition: the euro crisis instigated a crisis of democratic government in Southern Europe underlining that democratic legitimacy still mainly resides within the borders of nation states. By adopting the euro, EMU member states gave up their ability to control major economic policy decisions, thereby damaging their domestic political legitimacy, which in turn dogged attempts to enact structural reforms. Evidence of the erosion of national democracy in the Eurozone periphery can be seen in the rise of anti-establishment parties, and the inability of traditional center-left and center-right parties to form stable governments and implement reforms. The paper’s fourth proposition is that the euro’s original design and the Eurozone sovereign debt crisis further widened the existing democratic deficit in the European Union, as manifested in rising anti-EU and anti-euro sentiment, as well as openly Eurosceptic political movements, not just in the euro periphery, but also increasingly in the euro core.

THE KYOTO PROTOCOL AND THE WTO: INSTITUTIONAL EVOLUTION AND ADAPTATION. CEPS Policy Brief No. 28/December

Overview. Questions about the interface between the multilateral climate regime embodied in the Kyoto Protocol and the multilateral trade regime embodied in the World Trade Organisation (WTO) have become especially timely since the fall of 2001. At that time, ministerial-level meetings in Marrakech and Doha agreed to advance the agendas, respectively, for the implementation of the Kyoto Protocol and for negotiations on further agreements at the WTO. There have been concerns that each of these multilateral arrangements could constrain the effectiveness of the other, and these concerns will become more salient with the entry into force of the Kyoto Protocol. There are questions about whether and how the rights and obligations of the members of the WTO and the parties to the Protocol may conflict. Of particular concern is whether provisions in the Protocol, as well as government policies and business activities undertaken in keeping with those provisions, may conflict with the WTO non-discrimination principles of national treatment and most-favoured nation treatment. The WTO agreements that are potentially relevant to climate change issues include many of the individual Uruguay Round agreements and subsequent agreements as well. The principal elements of the Kyoto Protocol that are particularly relevant are its provisions concerning emissions trading, the Clean Development Mechanism, Joint Implementation, enforcement, and parties’ policies and measures. In combination, therefore, there are numerous potential points of intersection between the elements of the Kyoto Protocol and the WTO agreements. Previous studies have clarified many issues, as they have focused on particular aspects of the regimes’ relationships. Yet, some analyses suggest that the two regimes are largely compatible and even mutually reinforcing, while others suggest that there are significant conflicts between them. Those and other studies are referenced in the ‘suggestions for further reading’ section at the end of the paper.1 The present paper seeks to expand on those studies by providing additional breadth and depth to understanding of the issues. The analysis gives special attention to key issues on the agenda – i.e. issues that are particularly problematic because of the likelihood of occurrence of specific conflicts and the significance of their economic and/or political consequences. The paper adopts a modified ‘triage’ approach, which classifies points of intersection as (a) highly problematic and clearly in need of further attention, (b) perhaps problematic but less urgent, and (c) apparently not problematic, at least at this point in time. The principal conclusions are that: · The missions and objectives of the two regimes are largely compatible, and their operations are potentially mutually reinforcing in several respects. · Some provisions of the multilateral agreements that may superficially seem at odds are not likely to become particularly problematic in practice. · ‘Domestic policies and measures’ that governments may undertake in the context of the Protocol could pose difficult issues in the context of WTO dispute cases. · Recent WTO agreements and dispute cases acknowledge the legitimacy of the ‘precautionary principle’ and are thus consistent with the environmental protection objectives of the Protocol. · The relative newness of the climate regime creates opportunities for institutional adaptation, as compared with the constraints of tradition in the trade-investment regime. · The prospect of largely independent evolutionary paths for the two regimes poses a series of issues about future international regime design and management, which may require new institutional arrangements. In sum, the present paper thus finds that although there are some areas of interaction that are problematic, the two regimes may nevertheless co-exist in relative harmony in other respects –more like ‘neighbours’ than either ‘friends’ or ‘foes’, as Krist (2001) has suggested.