Development and validation of AMANDA, a new algorithm for selecting highly relevant regions in Molecular Interaction Fields

Descriptors based on Molecular Interaction Fields (MIF) are highly suitable for drug discovery, but their size (thousands of variables) often limits their application in practice. Here we describe a simple and fast computational method that extracts from a MIF a handful of highly informative points (hot spots) which summarize the most relevant information. The method was specifically developed for drug discovery, is fast, and does not require human supervision, being suitable for its application on very large series of compounds. The quality of the results has been tested by running the method on the ligand structure of a large number of ligand-receptor complexes and then comparing the position of the selected hot spots with actual atoms of the receptor. As an additional test, the hot spots obtained with the novel method were used to obtain GRIND-like molecular descriptors which were compared with the original GRIND. In both cases the results show that the novel method is highly suitable for describing ligand-receptor interactions and compares favorably with other state-of-the-art methods.

Clinical Utility of the 2 New Scales of the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA): A Naturalistic, Prospective Study in a Psychiatric Unit for Adolescents.

OBJECTIVES: The goal of this study was to assess the clinical usefulness of the emotional symptoms (Emo) and externalizing problems (Ext) scales compared with the Total score on the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA). METHODS: The HoNOSCA was rated at admission and discharge for 260 adolescent inpatients. The primary outcomes assessed were (a) the sensitivity of the 3 HoNOSCA scores to clinical improvement; and (b) the between diagnoses discriminative value of these scores. RESULTS: Analyses of variances [2 (time: admission vs. discharge) ×5 (diagnostic groups)] revealed a main effect of time for the 3 scores, a main effect of the diagnostic group for the Total and Ext scores, and an interaction effect between time and diagnosis for the Emo score. A moderate correlation was observed between the change in Ext and Emo scores between admission and discharge. DISCUSSION: These 2 new scales of the HoNOSCA demonstrated good clinical utility and the ability to assess different aspects of clinical improvements. A significant discriminative value of both scores was observed. SIGNIFICANT OUTCOMES: The clinical utility of the 2 new scales on the HoNOSCA was established. These 2 new scales provided a sensitive measure of clinical outcome for assessing improvement between admission and discharge on a psychiatric inpatient unit for adolescents, regardless of diagnostic group, and captured additional information about clinical improvements. Adolescents with psychosis and conduct disorders presented with higher externalizing symptoms than those with other disorders, as rated on the HoNOSCA, at admission and discharge. The Emo score differentiated between clinical improvement in patients with psychosis versus eating disorders. LIMITATIONS: The sample in this study represented a homogeneous population of adolescent inpatients, so that further research is needed before these findings can be generalized to outpatients. In addition, the small number of patients in some diagnostic groups did not allow for their inclusion in some of the statistical analyses.

On the institution of the moral subject: on the commander and the commanded in Nietzsche's discussion of law

The article discusses how Nietzsche understands the institution of law and morals in distinction to Kant and the Christian tradition. It argues that Nietzsche to a large extent is inspired by the paradigm-shift toward a evolutionary biological thinking introduced by several of his peers in the late 19th century, among else F. A. Lange, who sees this shift as a sobering scientific-materialistic alternative to Kant. In Nietzsche, the Kantian moral imperative is replaced with a notion of a morality emerging thanks to historical, or pre-historical, civilizational processes, imposed on a feebleminded human without any inherent rational dispositions to obey Law. It is also a process, which rather than universalizing the human, splits it in a duality where one part obeys old immediate self-interests and another part obeys new 'commands,' having been shouted 'into the ear' by a so-called 'commander.' The compliance with law takes two radically different forms in Nietzsche: servile and mediocre individuals need to be exposed to discipline and punishment in order to adopt Law; while so-called 'sovereign' individuals are able to impose law upon themselves. The figure of the 'sovereign' has consequently been an issue for vigorous debate in especially the Anglo-Saxon tradition of Nietzsche research, since his apparent 'respect for law' and 'sense of duty' reiterate typical Kantian qualities. Relating to these discussions, I suggest that Nietzsche's 'sovereign' (in one context) is identical his 'commander' (in other contexts). When the 'sovereign' as such imposes law upon himself and others, his act is conventional and arbitrary (like language in Saussure), and is rather irrational than rational as in Kant. His will is not a good will, nor a rational will with a vision of human autonomy. His command of himself and others is a performative, thus without truth-value (like illocutionary speech-acts in Austin and Searle).

Pausing at the river's edge : a narrative inquiry into the practice of a reading teacher /

In this narrative self-study I retell and connect the stories ofmy personal journey with literacy from childhood to the present. I use narrative as both methodology and method as I story my life experiences and my personal encounters with literacy. The heart ofmy reflections comes from the pages of personal journals written and storied over many years of trying to make meaning of powerful literacy experiences in my life. Now, in going back through the stories and reconstructing meaning, I make connections between the memories along the journey and the place from which I now tell my story. The interpretations I construct give voice to beliefs 1 have lived by and illuminations to moments in time that I have come to see with new eyes as I have engaged in this inquiry. The journey and self-reflection within the pages of this inquiry provide understanding of the driving force behind my personal passion for literacy. I am better able to understand my motivations and share the stories that validate my personal and professional path through time.

Le rôle de l’évaluation économique dans la pratique des médecins de famille = The role of economic evaluation in the practice of family physicians

L’évaluation économique en santé consiste en l’analyse comparative d’alternatives de services en regard à la fois de leurs coûts et de leurs conséquences. Elle est un outil d’aide à la décision. La grande majorité des décisions concernant l’allocation des ressources sont prises en clinique; particulièrement au niveau des soins primaires. Puisque chaque décision est associée à un coût d’opportunité, la non-prise en compte des considérations économiques dans les pratiques des médecins de famille peut avoir un impact important sur l’efficience du système de santé. Il existe peu de connaissances quant à l’influence des évaluations économiques sur la pratique clinique. L’objet de la thèse est de comprendre le rôle de l’évaluation économique dans la pratique des médecins de famille. Ses contributions font l’objet de quatre articles originaux (philosophique, théorique, méthodologique et empirique). L’article philosophique suggère l’importance des questions de complexité et de réflexivité en évaluation économique. La complexité est la perspective philosophique, (approche générale épistémologique) qui sous-tend la thèse. Cette vision du monde met l’attention sur l’explication et la compréhension et sur les relations et les interactions (causalité interactive). Cet accent sur le contexte et le processus de production des données souligne l’importance de la réflexivité dans le processus de recherche. L’article théorique développe une conception nouvelle et différente du problème de recherche. L’originalité de la thèse réside également dans son approche qui s’appuie sur la perspective de la théorie sociologique de Pierre Bourdieu; une approche théorique cohérente avec la complexité. Opposé aux modèles individualistes de l’action rationnelle, Bourdieu préconise une approche sociologique qui s’inscrit dans la recherche d’une compréhension plus complète et plus complexe des phénomènes sociaux en mettant en lumière les influences souvent implicites qui viennent chaque jour exercer des pressions sur les individus et leurs pratiques. L’article méthodologique présente le protocole d’une étude qualitative de cas multiples avec niveaux d’analyse imbriqués : les médecins de famille (niveau micro-individuel) et le champ de la médecine familiale (niveau macro-structurel). Huit études de cas furent réalisées avec le médecin de famille comme unité principale d’analyse. Pour le niveau micro, la collecte des informations fut réalisée à l’aide d’entrevues de type histoire de vie, de documents et d’observation. Pour le niveau macro, la collecte des informations fut réalisée à l’aide de documents, et d’entrevues de type semi-structuré auprès de huit informateurs clés, de neuf organisations médicales. L’induction analytique fut utilisée. L’article empirique présente l’ensemble des résultats empiriques de la thèse. Les résultats montrent une intégration croissante de concepts en économie dans le discours officiel des organisations de médecine familiale. Cependant, au niveau de la pratique, l'économisation de ce discours ne semble pas être une représentation fidèle de la réalité puisque la très grande majorité des participants n'incarnent pas ce discours. Les contributions incluent une compréhension approfondie des processus sociaux qui influencent les schèmes de perception, de pensée, d’appréciation et d’action des médecins de famille quant au rôle de l’évaluation économique dans la pratique clinique et la volonté des médecins de famille à contribuer à une allocation efficiente, équitable et légitime des ressources.

Placing defects at the heart of high quality new homes: a learning perspective

The UK new-build housing sector is facing dual pressures to expand supply, whilst delivering against tougher planning and Building Regulation requirements; predominantly in the areas of sustainability. The sector is currently responding by significantly scaling up production and incorporating new technical solutions into new homes. This trajectory of up-scaling and technical innovation has been of research interest; but this research has primarily focus on the ‘upstream’ implications for house builders’ business models and standardised design templates. There has been little attention, though, to the potential ‘downstream’ implications of the ramping up of supply and the introduction of new technologies for build quality and defects. This paper contributes to our understanding of the ‘downstream’ implications through a synthesis of the current UK defect literature with respect to new-build housing. It is found that the prevailing emphasis in the literature is limited to the responsibility, pathology and statistical analysis of defects (and failures). The literature does not extend to how house builders individually and collectively, in practice, collect and learn from defects information. The paper concludes by describing an ongoing collaborative research programme with the National House Building Council (NHBC) to: (a) understand house builders’ localised defects analysis procedures, and their current knowledge feedback loops to inform risk management strategies; and, (b) building on this understanding, design and test action research interventions to develop new data capture, learning processes and systems to reduce targeted defects.

The human-resource management practice of retail branding: an ethnography within Oxfam trading division

Purpose – While the charity retail literature emphasizes the richness of human resource practices among charity retailers, it rarely makes the link between these practices and their interest for establishing charity retailers' brands. Simultaneously, while the retail branding literature increasingly emphasizes the central role of human resource practices for retail branding, it rarely explains how retailers should conduct such practices. The purpose of this study is to test the recent model proposed by Burt and Sparks in 2002 (the “fifth generation of retail branding”) which proposes that a retail brand depends on the alignment between a retailer's substance (vision and culture) and its perceived image by customers. Design/methodology/approach – The research is based on an ethnographic study conducted within the Oxfam Trading Division, GB from October to December 2002. Findings – The study supports the Burt and Spark's model and makes explicit the practice of human resource for branding. The study demonstrates that it was the alignment between the vision of Oxfam's top management and its new customer‐oriented culture, two elements of its core substance mediated to customers by store employees, which has enabled an improved customers' perception of the brand. The study also seeks to elaborate upon the Burt and Spark's model by specifying an ascending feedback loop starting from customers' perception of Oxfam brand and enabling the creation of a suitable culture and vision again mediated by store employees. Research limitations/implications – New research should explore whether and how retailers create synergies between human resource and marketing functions to sustain their brand image. Practical implications – If the adoption of business practices by charity retailers is often discussed, this study highlights that commercial retailers could usefully transfer human resource best practices from leading charity retailers to develop their retail brand. Originality/value – The paper is of value to commercial retailers.

Conflicts of law and the mutual recognition of same-sex unions in the EU

My thesis uses legal arguments to demonstrate a requirement for recognition of same-sex marriages and registered partnerships between EU Member States. I draw on the US experience, where arguments for recognition of marriages void in some states previously arose in relation to interracial marriages. I show how there the issue of recognition today depends on conflicts of law and its interface with US constitutional freedoms against discrimination. I introduce the themes of the importance of domicile, the role of the public policy exception, vested rights, and relevant US constitutional freedoms. Recognition in the EU also depends on managing the tension between private international law and freedoms guaranteed by higher norms, in this case the EU Treaties and the European Convention on Human Rights. I set out the inconsistencies between various private international law systems and the problems this creates. Other difficulties are caused by the use of nationality as a connecting factor to determine personal capacity, and the overuse of the public policy exception. I argue that EU Law can constrain the use of conflicts law or public policy by any Member State where these are used to deny effect to same-sex unions validly formed elsewhere. I address the fact that family law falls only partly within Union competence, that existing EU Directives have had limited success at achieving full equality and that powers to implement new measures have not been used to their full potential. However, Treaty provisions outlawing discrimination on grounds of nationality can be interpreted so as to require recognition in many cases. Treaty citizenship rights can also be interpreted favourably to mandate recognition, once private international law is itself recognised as an obstacle to free movement. Finally, evolving interpretations of the European Convention on Human Rights may also support claims for cross-border recognition of existing relationships.

Compliance to law and effectiveness of the rule of law in Brazil

The goal of this paper is to debate the degree of effectiveness of the rule of law in Brazil, through a survey measuring perceptions, attitudes and habits of Brazilians in regard to compliance to law. The survey conducted in Brazil is based on the study conducted by Tom R. Tyler in the United States, entitled Why People Obey the Law? (New Haven, CT: Yale University Press, 1990). The main argument of Tyler´s study is that people obey the law when they believe it’s legitimate, and not because they fear punishment. We test the same argument in Brazil, relying on five indicators: (i) behavior, which depicts the frequency with which respondents declared to have engaged in conducts in disobedience to the law; (ii) instrumentality, measuring perception of losses associated with the violation of the law, specially fear of punishment; (iii) morality, measuring perception of how much is right or wrong to engage in certain conducts in violation of the law; (iv) social control, which measures perception of social disapproval of certain types of behavior in violation of the law, and (v) legitimacy, which measures the perception of respect to the law and to some authorities. Results indicate that fear of sanctions is not the strongest drive in compliance to law, but more than legitimacy, indicators of morality and social control are the strongest in explaining why people obey the law in Brazil.

The role of law and public-private collaboration in promoting innovative firms in Brazil: the case of the BNDES and the “criatec fund”

This paper presents the result of a qualitative empirical research about the “Criatec Fund”, a venture capital fund, privately managed and directed to innovative firms, that was created in 2007 by the Brazilian Development Bank (BNDES). The paper discusses the role of law in the implementation of the Criatec Fund in three different legal dimensions: structural, regulatory and contractual. Based on interviews, this paper tries to test some hypothesis previously formulated by some scholars that studied new financial policies created by the BNDES. This study explains the institutional arrangements of this seed capital policy and the role of flexible legal instruments in the execution of this peculiar type of publicprivate partnership. It also poses some questions to the “law and development agenda” based on some insights from the economic sociology of law.

Políticas de conteúdo local: crescimento econômico e rule of law

As chamadas Políticas de Conteúdo Local (“PCLs”) fazem parte de um grupo de políticas desenvolvimentistas adotadas em todo o mundo com o objetivo de maximizar os benefícios sociais e econômicos decorrentes de determinadas atividades econômicas. Neste trabalho, analisaram-se, principalmente, as PCLs relativas à extração e produção de petróleo e gás. O instituto é juridicamente polêmico, uma vez que, além de ser difícil de definir, é instrumentalizado por diversos atos normativos diferentes. Tal situação agrava-se com o fato de que o desenho de cada PCL pode sugerir ou impor diversas medidas de implementação diferentes, com impactos nas diferentes áreas do Direito. Considerando este cenário, aponta-se que o principal objetivo deste trabalho é a análise de transplantes ao nosso ordenamento jurídico de PCLs bem-sucedidas em ordenamentos jurídicos estrangeiros. Para isso, demonstrou-se, em um primeiro momento, que o instituto das PCLs deve ser reinterpretado à luz da Constituição vigente. Isso porque as PCLs foram criadas em uma época em que a escola desenvolvimentista principal era a keynesiana, que foi substituída atualmente pela escola do Rule of Law. Embora nosso ordenamento jurídico tenha acompanhado essa evolução (através de Emendas Constitucionais e adoção de determinadas leis), as PCLs não acompanharam e, por isso, precisam sofrer essa releitura. Nesse sentido, extraíram-se da Lei quatro elementos principais que as PCLs devem preencher para estar em consonância com o Rule of Law: (A) Benefícios aos Consumidores Finais; (B) Sustentabilidade; (C) Transetorialidade; e (D) Ampliação do Mercado de Trabalho. Em sequência, classificaram-se as diversas PCLs mapeadas, exemplificando cada uma. Ao longo da classificação, apontaram-se três critérios que facilitam a identificação das maiores dificuldades jurídicas em cada transplante: (A) Canal; (B) Natureza; e (C) Instrumento. Por fim, quatro PCLs estrangeiras bem-sucedidas foram escolhidas para uma análise mais aprofundada: a Kazakhstan Contract Agency, no Cazaquistão, a Petro Arctic Supplier Asssociation, na Noruega, o Australian Industry Participation Plan na Austrália e o Nigerian Oil & Gas Content Industry Development Act, na Nigéria. Para cada uma, é dedicada uma análise especial. As análises são seguidas pela Conclusão.

Theory and practice of industrial policy: evidence from the Latin American experience

Includes bibliography