bluuebunny/crossref_metadata_2025 huggingface dataset:
Children and Domestic Violence: Constructing a Policy Problem in Australia and New Zealand
Authors: Powell Anastasia , Murray Suellen
Published: December 2008

The intersection of public policy and legislation addressing children and domestic violence is fraught with complexity. Domestic violence responses, child protection responses and family law responses, all potentially collide where a child witnesses or experiences domestic violence. These responses not only operate with different purposes and assumptions, but also construct the problem of domestic violence in different ways. This article is based on the preliminary findings of a larger research project exploring the history of domestic violence policy in Australia. Drawing on Bacchi's (1999) `what's the problem represented to be?' approach we consider how children's experiences of domestic violence are named and framed in Australian and New Zealand law and policy. In identifying and making apparent these particular understandings, and considering the implications of these meanings for current responses, we seek to open up debates on the future direction of domestic violence policy and legislation concerned with children.
Critique of Abel on Popular Justice and the Alexandra Treason Trial
Authors: Hund John
Published: December 2008

Popular justice as a field of study is marked by profound conceptual confusion and is regarded by many as an imbroglio of misunderstanding. In this critique I present reasons for believing that this problem has its roots in Richard L. Abel's influential theory of `informal justice'. I show that this term as used by Abel is a logically confused malapropism for popular justice which is based on a fundamental category mistake that vitiates his definitional apparatus (his `general theory') of popular justice from top to bottom. This critique shows that his self-styled `contradictions of informal justice' are artefacts of his own general theory of popular justice and are not based on anything inherently contradictory in the nature of popular justice itself. An additional criticism is that Abel's general theory is a one-sided `lawyer's theory' of justice which excludes by definitional fiat the most basic kind of popular justice of all. This critique concludes by showing how these defects along with other factors have caused Abel to fundamentally misconstrue the Alexandra Treason Trial and to obscure the roles played by popular justice and sociology in this important South African jurisprudential event.
Feeling Good: the Ethopolitics of Pleasure; Psychoactive Substance Use and Public Health and Criminal Justice Governance: Therapeutic Jurisprudence and the Drug Courts in the USA
Authors: Mackenzie Robin
Published: December 2008

The drug courts in the United States exemplify how mechanisms of inclusion and exclusion are mediated by complex cultural constructions of ways in which we may `feel good' rather than mad, bad, sad or sick. I argue that such mechanisms, and public health initiatives which seek to persuade us to choose specific means to enhance our health while eschewing others, are engaging an ethopolitics of moralized pleasures associated with the trope of addiction. Technologies of pleasure associated with current public health initiatives encouraging us to manage our risky neurochemical selves are, in some senses, homologous with the practices of the drug courts in the United States. In both, normalization is anchored in the management of pleasures, while notions of addiction support neo-liberal governance strategies. The rhetoric of salvationary narratives is drawn upon as a device of purification which decontextualizes debate, marginalizing counter-theories
India and the Great Powers
Authors: Rajagopalan Rajesh , Sahni Varun
Published: December 2008

Six propositions drive this article. First, India's relations with the great powers as they evolve over the next two decades are going to be conditioned by India's own emergence as a great power. Second, it will take at least 15 to 20 years for a balance to re-emerge in the contemporary hegemonic system; hence, India's emergence will be simultaneous with the relative decline of the United States (US). Third, Indian policy makers and analysts need to think structurally about India's external relations, especially with the US and China. Fourth, India's relations with the great powers are inseparable from the broader issue of emerging Asian balances and security architectures. Fifth, India needs to keep a keen eye on other major powers, among whom Russia, Japan, the European Union (EU) and Brazil will be particularly important. Finally, while building its capabilities along a broad spectrum, India must not lose sight of the normative component that is inherent in great power status.
India and the United States
Authors: Bajpai Kanti
Published: December 2008

A grand strategic partnership between India and the United States (US) can be constructed at five levels—the planetary, the global, the international, the continental and the regional. The focus, conventionally, is on the last three levels. Planetary and global changes, however, confront both countries with huge challenges. India and the US must find ways to cooperate in dealing with climate change and resource depletion, as also with a revolution in human affairs that promises emancipation but could end in reaction and violence. As two continental-sized, pluralistic democracies, they have unique strengths in building a better world.
India and Russia
Authors: Chenoy Anuradha M.
Published: December 2008

India is seeking a greater role for itself in the international system. This aspiration is based on the view that India is a stable democracy with significant human and material resources; it is an increasingly important economic power; it has an established record as a responsible and law abiding state; and it has consistently voiced the concerns of the developing countries as a leader of the non-aligned group. Indian foreign policy makers argue that at this stage of ‘take off’ as a great power India needs to re-invent itself. For this proposed new role India requires new allies and partnerships, including with the dominant superpower, the United States of America (US). The US has stated that it will make India into a great power. What is the US interest in India? How will this new interest and tie-up affect India's traditional partners like Russia? This article seeks to analyse the old model of relations that India enjoyed with Russia. This model is now being given up. Its place is being taken by an Indo-US strategic partnership. How different is this new model strategic relationship in comparison to the Indo-Soviet/Russian relationship? Some of these issues are addressed in this article.
Venus and the Porcupine
Authors: Kavalski Emilian
Published: December 2008

This article brings together the diverse suggestions on the nascent strategic partnership between the European Union (EU) and India. Apart from focusing on popular and policy perceptions, this inquiry undertakes a discursive assessment of key documents defi ning the institutional and ideational frameworks of relations between Brussels and New Delhi. Such narrative analysisallows for innovative tracing of the genealogy, distinct grammars and contradictions of their interactions. Thus, while many of the commentaries on the emerging agency of the EU and India are primarily aimed at making an empirical contribution, this investigation offers a theoretically-informed refl ection on their debates. The contention is that an analytical observation can elicit underlying patterns that tend to remain occluded by the focus on trade fi gures, commercial output or military capabilities.
India and Japan
Authors: Paul Joshy M.
Published: December 2008

The relationship between Japan and India has been influenced by the international power configuration over time. In the early post-War period, both countries embraced idealistic moor-ings about how the world should be. In due course of time, the United States (US) alliance system put Japan in the western camp of Cold War power politics while India followed a policy of non-alignment. However, with the end of the Cold War and the transformation of Asia into a composite power playground, India and Japan have developed a much closer relationship. The relative decline of America's strategic interest towards the East Asian region and the changing dynamics of security in Asia have forced Japan to search for new partners in Asia, culminat-ing in the present strategic partnership with India. It is in this context that this article probes Indo-Japanese relations by analysing their economic, political and strategic facets.
South Africa in the Contemporary International Economy
Authors: Shrivastava Meenal
Published: December 2008

New Economy cannot be characterised by the high technological applications to production, distribution and consumption alone. Its other salient dimension is South-South economic and political alliances. In the evolving international political economy, a small group of middleincome developing countries are actively challenging established international structures and regimes. While the success of IBSA (India, Brazil, South Africa) as an economic or ideological strategy of the South is far from proven, its impact on South Africa-India relations in particular is tangible. Since South Africa occupies a unique position in Africa, the analysis follows a detailed layout of the South African economy since 1994. This article assesses South Africa's trajectory of economic development by analysing local, regional and global contexts within which the South African economy operates in order to understand the unique position of South Africa on the continent and in the global South. The article also explores the impact of these changing contexts on the South Africa-India bilateral relationship, within and beyond IBSA.
Brazil–India Relations
Authors: Hirst Mo´nica
Published: December 2008

Relations between Brazil and India seem to be blooming recently, favoured by a mix of domestic and international developments. Together with an expanded terrain of common interests in multilateral political and economic matters, both countries share the trend of perceiving bilateralism as a stimulating and useful learning process. Furthermore, they have assumed a leading role in the process of revival of South-South diplomacy in world affairs. Brazil and India have become major actors in recent proposals aimed at simultaneously promoting a renewed configuration of multilateral institutions and innovative inter-state coalition building among developing countries. The India, Brazil, South Africa (IBSA) initiative is part of this strategy. However, time and maturity are still needed to assert that Brazil-India bilateral ties and converging interests will build up as a relevant dimension for each other's international insertion as well as for an effective renewal of South-South relations in the twenty-first century.
Addressing the Challenge of Preparing Australian Pre-service Primary Teachers in Environmental Education
Authors: Kennelly Julie , Taylor Neil , Maxwell T. W.
Published: December 2008

Concerns have been raised for some time about the preparation of Australian teachers in the area of environmental education. Few tertiary institutions that undertake teacher education in Australia have specific units or modules dedicated to environmental education. This article reports on an evaluation of such a dedicated unit recently introduced to the BEd (Primary) award at an Australian university. Students were surveyed pre- and post-instruction and the findings indicate that most participants felt more confident about teaching environmental education. This was largely attributed to improved pedagogical content knowledge and an appreciation of how to integrate environmental education into the everyday learning of their students. The efficacy of this unit in terms of the motivation and confidence of student-teachers regarding environmental education lends support to those who call for more specific environmental education content in teacher education courses.
Delivering Education for Sustainable Development through the MESA Partnership
Authors: Ogbuigwe Akpezi
Published: December 2008

Mainstreaming Environment and Sustainability in African Universities Part-nership (MESA) is a programme which grew out of the coming together, in 2004, of a number of African universities met with the United Nations Environment Programme (UNEP), UNESCO and several African regional environment and education projects to assess the status of environment and sustainability education in Africa and to develop a programme to help universities integrate environment, economics, health, poverty and development into a meaningful learning experience. The programme seeks to offer opportunities for collaborative projects among universities, govern-ments, civil society, communities and the private sector. This article shares the ex-periences of the first phase of the programme—which ran from 2004 to 2007—focusing on the findings of an evaluation of this phase by UNEP in early 2007.
Participatory approaches to promote healthy lifestyles among Turkish and Moroccan women in Amsterdam
Authors: Wagemakers Annemarie , Corstjens Renée , Koelen Maria , Vaandrager Lenneke , van't Riet Hilda , Dijkshoorn Henriëtte
Published: December 2008

Although it is recognized that community health promotion succeeds or fails by level of participation, effectiveness and benefits of community programs are underestimated, because participation is seldom monitored and evaluated. In the Dutch “Healthy Lifestyle Westerpark” program in Amsterdam, participation was both the main working principle and the main goal.

Between 2003 and 2006, the Municipal Health Service (MHS) carried out a qualitative study on the background of overweight in Turkish and Moroccan women aged 25 to 45 years and on possibilities for promoting health with and for the target group. The aim of the program was to increase the women's participation and to evaluate participation levels in all phases. The research aim of this paper is to contribute to the development of participatory methods.

Needs assessment and intervention development phases resulted in implementation of aerobic lessons and nutrition interventions. In the evaluation phase, participation levels were measured using Pretty's typology in focus groups.

Results show that women appreciate participating in the program. Increase in physical activity was not measured. Women's knowledge about healthy food increased, women changed behavior by buying healthier food ingredients and women continued to participate.

Participatory approaches facilitate participation at the desired level in the different phases of the program. Participatory approaches are time-consuming but worthwhile. Pretty's typology is useful to measure degree of participation, although methods can be improved and the meaning of participation should be reconsidered.

The added value of this article is twofold: 1. it demonstrates that participatory methods and tools both facilitate and evaluate participation, and 2. it shows how to evaluate the degree of participation. (Promot Educ, 2008; 15 (4): pp. 17-23)
The dynamics of community and NGO partnership: primary health care experiences in rural Mali
Authors: Solomon Yodit , Ballif-Spanvill Bonnie , Ward Carol , Fuhriman Addie , Widdision-Jones Kacey
Published: December 2008

Utilizing ethnographic research methods, this case study examines the experiences of an NGO-sponsored health care program in rural Mali. The findings indicate that while, in principle, the organization operates from an alternative development base, it has been unable to decentralize the decision-making process and facilitate community dialogue and participation. Numerous problems resulted, including superficial forms of local participation, lack of community ownership, non-remuneration of health workers and midwives, inadequate training, and ultimately, limited program gains. The analyses highlight the complexity and dynamic nature of health program implementation in a developing context, and suggest several factors important to project success. These include drawing on diverse local perspectives, promoting broad-based participation, and providing culturally appropriate ways to include all community members, particularly women.
Provision of essential obstetric care (EOC): a sine qua non to reducing maternal mortality rate in Nigeria
Authors: Ibekwe Perpetus C. , Ibekwe Rosemary O.
Published: December 2008

Nigeria's maternal mortality rate has been on the increase even after the launching of the Safe Motherhood Initiative (SMI) 16 years ago. The causes of this increase are well known, and mainly result from inability of a health system to deal effectively with complications, especially during or shortly after childbirth. Shortage of health professionals and health facilities equipped to offer EOC and emergency obstetric care 24 hours a day are significantly related to quality of care and maternal mortality rates. Since the Primary Health Care (PHC) level is usually the first contact point for the majority of our women, it must be able to deliver the essential services in full and make appropriate referrals when necessary. From available statistics, provision of EOC services in Nigeria has been deplorable. Deficient areas within the health system concerning EOC services are highlighted and suggestions made on how to improve and sustain services.

It is concluded that provision of effective and efficient EOC facilities and services will play a key role in maternal mortality reduction, not only in Nigeria but in most developing regions of the world. (Promot Educ, 2008; 15 (4): pp. 50-52)
Beyond SARS: ethnic community organization's role in public health — a Toronto experience
Authors: Weizhen Dong
Published: December 2008

The SARS outbreak in Toronto was a public health crisis. It was particularly frightening to the Chinese-Canadians, because of the origin of the deadly disease. The Chinese-Canadian community organizations launched various activities to help the Chinese-Canadians as well as other Asian-Canadian communities to fight against SARS and its social side-effects. From launching the SARS Supporting Line, distributing health promotional material, disseminating SARS related information, paying tribute to frontline health workers, and promoting local business, to fundraising for SARS related research; they played an active role in easing the public's anxiety, especially for the Chinese-Canadians in the great Toronto area.

The culturally diverse population brought problems as well as solutions. Ethnic groups have expertise in almost all areas, including people with leadership skills. The Toronto Chinese community's experience in combating SARS is a good example. The Chinese-Canadian community organizations' activities during the SARS outbreak demonstrate that ethnic minority organizations can play an important role in public health, especially in a public health crisis, and beyond. (Promot Educ, 2008; 15 (4): pp. 53-55)
Making it Sane: Using Narrative to Explore Theory in a Mental Health Consumer-Run Organization
Authors: Brown Louis D.
Published: December 2008

My previous research led to the development of a theoretical model explaining the processes by which people can benefit from consumer-run organizations (CROs). This study builds on that work by exploring the ability of the conceptual framework to capture the complexity of seven diverse life history narratives from participants at one CRO. To construct life history narratives, I used data from participant observation and a series of in-depth, minimally structured interviews. Application of the proposed conceptual framework to the narratives provides a consistent structure that organizes the experiences of informants into meaningful components. This application of the framework to the data also enables an exploration of the framework's ability to account for the lives of all informants. This analysis leads to conclusions on the conceptual framework's ability to explain how people benefit from CROs.
Using Student-Centered Cases in the Classroom
Authors: Foster Pacey , Carboni Inga
Published: December 2008

This article addresses the concern that business schools are not adequately developing the practical leadership skills that are required in the real world of management. The article begins by discussing the limitations of traditional case methods for teaching behavioral skills. This approach is contrasted with an alternative case method drawn from action inquiry (AI) that uses ongoing student cases to develop more effective leadership behaviors. The student-centered case approach is distinguished from traditional case teaching by tracing an important similarity between AI and Socratic pedagogy. A leadership workshop for evening MBAs that uses AI pedagogy to help students improve their leadership behaviors at work and in the class is also described. The article concludes with a discussion of the significant benefits and challenges associated with helping students develop new leadership behaviors.
HIV-Unrelated Benign Lymphoepithelial Cyst of the Parotid Glands Containing Lymphoepithelial Lesion—Like Structures: A Report of 3 Cases
Authors: Kojima Masaru , Nakamura Naoya , Matsuda Hazuki , Kaba Sadayuki , Itoh Hideaki , Masawa Nobuhide
Published: December 2008

Benign lymphoepithelial cyst (BLC) of the salivary gland is uncommon. Among report of these lesions, there were no previous cases of lymphoepithelial lesion (LeL) in human immunodeficiency virus type-1 (HIV-1) unrelated BLC. This study reports 3 cases of HIV-unrelated BLC containing LeL-like structures. Pathologically, 3 lesions were characterized by cuboidal epithelial-lined, cystic spaces, numerous lymphoid follicles, and dense lymphoplasmacytoid infiltrate. Moreover, small lymphocytes invaded the epithelial clusters forming LeL-like structures. Histological findings of 3 lesions resembled marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. However, staining with CD3, CD5, and CD20 demonstrated the mixed nature of small lymphocytes invading the epithelial clusters (LeLlike structures). Moreover, there were no CD43+ B-lymphocytes in any of the cases. The polytypic nature of B-lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. The 3 cases indicate that HIV-unrelated BLC should be added to the differential diagnosis of MALT-type lymphoma involving the parotid glands.
Experiments in risk and criminal justice
Authors: O'Malley Pat
Published: December 2008

Risk has not been regarded positively in most social theory and critical criminology, especially in the light of Beck's `risk society' thesis. This paper argues that such criticism is misplaced. Risk is an extremely variable governmental technology, and many of the targets of criticism are shaped by the contemporary political environment. The same environment has given a similar negative cast to other approaches to security. There are ways of deploying risk, such as drug harm minimization strategies, that offer considerable promise for linking risk to security, and more broadly to issues of social justice. However, abstract calls for harm minimizing security suffer exactly the same problems that confront generalizing about risk-based security. This paper suggests that we could use a governmental analytic to construct a strategic knowledge of risk, both through the analysis of existing approaches (such as harm minimization and restorative justice) and by using this to generate experiments in risk, security and justice.
The Maximizer: Clarifying Merton's theories of anomie and strain
Authors: Murphy Daniel S. , Robinson Mathew B.
Published: December 2008

Robert Merton's (1957) theories of anomie and strain are among the most widely examined theories of criminality. Messner and Rosenfeld's (1994) theory of institutional anomie built on Merton's conception of anomie, delineating how specific institutions lead to conditions of anomie and criminality. Cloward and Ohlin's (1961) theory of differential opportunity built upon Merton's strain theory, underscoring the fact that those involved in illegitimate means of opportunity require a set of learned skills as do those involved in legitimate means. In this tradition, the present paper further expands Merton's theories of anomie and strain, suggesting that Merton's categories of conformist and innovator are not mutually exclusive. In fact, some individuals combine both legitimate and illegitimate means of opportunity in pursuit of the American Dream. The Maximizer, the authors suggest, merges elements of both the conformist and the innovator (i.e. legitimate and illegitimate means). The present paper explores the justification for merging legitimate and illegitimate means of opportunity in pursuit of the American Dream.
Developing a peace education curriculum for Vietnamese primary schools
Authors: Conley Tyler Melissa H. , Bretherton Diane , Halafoff Anna , Nietschke Yung
Published: December 2008

In 2003, the International Conflict Resolution Centre at the University of Melbourne, Australia, produced a primary school teaching manual for UNESCO Vietnam. The finished manual included lesson plans and materials for a five year, 50 lesson peace education course. The manual is one of the first examples of a systematic core national curriculum in peace education worldwide. Development of the Teaching Manual posed a number of challenges including differences in language, culture, government and education system. To meet these challenges, a participatory action research approach was central in the project's development and curriculum design. This case study is offered as a model for effective cross-cultural curriculum development of peace education materials. In particular, the use of games and reflective materials and the use of UNESCO's peace keys are outlined as innovative outcomes of the project.
The International Baccalaureate and its Diploma Programme online
Authors: Bunnell Tristan
Published: December 2008

The International Baccalaureate Organisation (IBO) celebrated its 40th Anniversary in 2008. Following almost four decades of rapid growth the IBO embarked on a strategic planning exercise in 2004. One outcome is that the IBO seeks to widen access to its Diploma Programme (IBDP), and one avenue being followed is online provision. There have been two pre-pilot IBDP Online (IBDPO) experiments involving six schools in five countries. September 2008 saw the start of a four-year pilot phase, involving initially 75 students from a minimum of 13 schools worldwide. The IBO has identified a potential demand in the future of about 6000 students. This article charts the development of the IBDPO project and offers an insight into three possible future scenarios and some of the key challenges likely to be faced.
Misalignment detection and enabling of seam tracking for friction stir welding
Authors: Fleming P. A. , Lammlein D. H. , Wilkes D. M. , Cook G. E. , Strauss A. M. , Delapp D. R. , Hartman D. A.
Published: December 2008

This paper describes a technique for determining the position of a friction stir welding (FSW) tool with respect to the weld seam during welding. Forces are used as a feedback signal, and a general regression neural network is trained to predict offset position given weld forces. Experimental results demonstrate the accuracy of the developed position predictor. This technique is proposed for online misalignment detection or as a position estimator for in-process tracking of the weld seam for FSW and robotic FSW.
Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo
Authors: Bruno Benedetto , Rotta Marcello , Patriarca Francesca , Mattei Daniele , Allione Bernardino , Carnevale-Schianca Fabrizio , Sorasio Roberto , Rambaldi Alessandro , Casini Marco , Parma Matteo , Bavaro Pasqua , Onida Francesco , Busca Alessandro , Castagna Luca , Benedetti Edoardo , Iori Anna Paola , Giaccone Luisa , Palumbo Antonio , Corradini Paolo , Fanin Renato , Maloney David , Storb Rainer , Baldi Ileana , Ricardi Umberto , Boccadoro Mario
Published: December 2008

Despite recent advances, allografting remains the only potential cure for myeloma. From July 1999 to June 2005, 100 newly diagnosed patients younger than 65 years were enrolled in a prospective multicenter study. First-line treatment included vincristin, adriamycin, and dexamethasone (VAD)–based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m2) followed by a single dose of nonmyeloablative total body irradiation and allografting from an human leukocyte antigen (HLA)–identical sibling. Primary end points were the overall survival (OS) and event-free survival (EFS) from diagnosis. After a median follow-up of 5 years, OS was not reached, and EFS was 37 months. Incidences of acute and chronic graft-versus-host disease (GVHD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) before allografting was associated with achievement of posttransplantation CR (hazard ratio [HR] 2.20, P = .03) and longer EFS (HR 0.33, P < .01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplantation approach allows prolonged survival and long-term disease control in patients with reduced tumor burden at the time of allografting. We are currently investigating the role of “new drugs” in intensifying pretransplantation cytoreduction and posttransplantation graft-versus-myeloma effects to further improve clinical outcomes. (http://ClinicalTrials.gov; NCT-00702247.)
LAD-1/variant syndrome is caused by mutations in FERMT3
Authors: Kuijpers Taco W. , van de Vijver Edith , Weterman Marian A. J. , de Boer Martin , Tool Anton T. J. , van den Berg Timo K. , Moser Markus , Jakobs Marja E. , Seeger Karl , Sanal Özden , Ünal Sule , Çetin Mualla , Roos Dirk , Verhoeven Arthur J. , Baas Frank
Published: December 2008

Leukocyte adhesion deficiency-1/variant (LAD1v) syndrome presents early in life and manifests by infections without pus formation in the presence of a leukocytosis combined with a Glanzmann-type bleeding disorder, resulting from a hematopoietic defect in integrin activation. In 7 consanguineous families, we previously established that this defect was not the result of defective Rap1 activation, as proposed by other investigators. In search of the genetic defect, we carried out homozygosity mapping in 3 of these patients, and a 13-Mb region on chromosome 11 was identified. All 7 LAD1v families share the same haplotype, in which 3 disease-associated sequence variants were identified: a putative splice site mutation in CALDAGGEF1 (encoding an exchange factor for Rap1), an intronic 1.8-kb deletion in NRXN2, and a premature stop codon (p.Arg509X) in FERMT3. Two other LAD1v patients were found to carry different stop codons in FERMT3 (p.Arg573X and p.Trp229X) and lacked the CALDAGGEF1 and NRXN2 mutations, providing convincing evidence that FERMT3 is the gene responsible for LAD1v. FERMT3 encodes kindlin-3 in hematopoietic cells, a protein present together with integrins in focal adhesions. Kindlin-3 protein expression was undetectable in the leukocytes and platelets of all patients tested. These results indicate that the LAD1v syndrome is caused by truncating mutations in FERMT3.
IDEA: Interactive Display for Evolutionary Analyses
Authors: Simons Rain , Mahurkar Anup , Crabtree Jonathan , Badger Jonathan H , Carlton Jane M , Silva Joana C
Published: December 2008

Background

The availability of complete genomic sequences for hundreds of organisms promises to make obtaining genome-wide estimates of substitution rates, selective constraints and other molecular evolution variables of interest an increasingly important approach to addressing broad evolutionary questions. Two of the programs most widely used for this purpose are codeml and baseml, parts of the PAML (Phylogenetic Analysis by Maximum Likelihood) suite. A significant drawback of these programs is their lack of a graphical user interface, which can limit their user base and considerably reduce their efficiency.

Results

We have developed IDEA (Interactive Display for Evolutionary Analyses), an intuitive graphical input and output interface which interacts with PHYLIP for phylogeny reconstruction and with codeml and baseml for molecular evolution analyses. IDEA's graphical input and visualization interfaces eliminate the need to edit and parse text input and output files, reducing the likelihood of errors and improving processing time. Further, its interactive output display gives the user immediate access to results. Finally, IDEA can process data in parallel on a local machine or computing grid, allowing genome-wide analyses to be completed quickly.

Conclusion

IDEA provides a graphical user interface that allows the user to follow a codeml or baseml analysis from parameter input through to the exploration of results. Novel options streamline the analysis process, and post-analysis visualization of phylogenies, evolutionary rates and selective constraint along protein sequences simplifies the interpretation of results. The integration of these functions into a single tool eliminates the need for lengthy data handling and parsing, significantly expediting access to global patterns in the data.
Multi-label literature classification based on the Gene Ontology graph
Authors: Jin Bo , Muller Brian , Zhai Chengxiang , Lu Xinghua
Published: December 2008

Background

The Gene Ontology is a controlled vocabulary for representing knowledge related to genes and proteins in a computable form. The current effort of manually annotating proteins with the Gene Ontology is outpaced by the rate of accumulation of biomedical knowledge in literature, which urges the development of text mining approaches to facilitate the process by automatically extracting the Gene Ontology annotation from literature. The task is usually cast as a text classification problem, and contemporary methods are confronted with unbalanced training data and the difficulties associated with multi-label classification.

Results

In this research, we investigated the methods of enhancing automatic multi-label classification of biomedical literature by utilizing the structure of the Gene Ontology graph. We have studied three graph-based multi-label classification algorithms, including a novel stochastic algorithm and two top-down hierarchical classification methods for multi-label literature classification. We systematically evaluated and compared these graph-based classification algorithms to a conventional flat multi-label algorithm. The results indicate that, through utilizing the information from the structure of the Gene Ontology graph, the graph-based multi-label classification methods can significantly improve predictions of the Gene Ontology terms implied by the analyzed text. Furthermore, the graph-based multi-label classifiers are capable of suggesting Gene Ontology annotations (to curators) that are closely related to the true annotations even if they fail to predict the true ones directly. A software package implementing the studied algorithms is available for the research community.

Conclusion

Through utilizing the information from the structure of the Gene Ontology graph, the graph-based multi-label classification methods have better potential than the conventional flat multi-label classification approach to facilitate protein annotation based on the literature.
Tissue remodeling: a mating-induced differentiation program for the Drosophilaoviduct
Authors: Kapelnikov Anat , Rivlin Patricia K , Hoy Ronald R , Heifetz Yael
Published: December 2008

Background

In both vertebrates and invertebrates, the oviduct is an epithelial tube surrounded by visceral muscles that serves as a conduit for gamete transport between the ovary and uterus. While Drosophila is a model system for tubular organ development, few studies have addressed the development of the fly's oviduct. Recent studies in Drosophila have identified mating-responsive genes and proteins whose levels in the oviduct are altered by mating. Since many of these molecules (e.g. Muscle LIM protein 84B, Coracle, Neuroglian) have known roles in the differentiation of muscle and epithelia of other organs, mating may trigger similar differentiation events in the oviduct. This led us to hypothesize that mating mediates the last stages of oviduct differentiation in which organ-specific specializations arise.

Results

Using electron- and confocal-microscopy we identified tissue-wide post-mating changes in the oviduct including differentiation of cellular junctions, remodeling of extracellular matrix, increased myofibril formation, and increased innervation. Analysis of once- and twice-mated females reveals that some mating-responsive proteins respond only to the first mating, while others respond to both matings.

Conclusion

We uncovered ultrastructural changes in the mated oviduct that are consistent with the roles that mating-responsive proteins play in muscle and epithelial differentiation elsewhere. This suggests that mating triggers the late differentiation of the oviduct. Furthermore, we suggest that mating-responsive proteins that respond only to the first mating are involved in the final maturation of the oviduct while proteins that remain responsive to later matings are also involved in maintenance and ongoing function of the oviduct. Taken together, our results establish the oviduct as an attractive system to address mechanisms that regulate the late stages of differentiation and maintenance of a tubular organ.
Genomic NGFBvariation and multiple sclerosis in a case control study
Authors: Akkad Denis A , Kruse Niels , Arning Larissa , Gold Ralf , Epplen Jörg T
Published: December 2008

Background

Nerve growth factor β (NGFB) is involved in cell proliferation and survival, and it is a mediator of the immune response. ProNGF, the precursor protein of NGFB, has been shown to induce cell death via interaction with the p75 neurotrophin receptor. In addition, this neurotrophin is differentially expressed in males and females. Hence NGFB is a good candidate to influence the course of multiple sclerosis (MS), much like in the murine model of experimental autoimmune encephalomyelitis (EAE).

Methods

Ten single nucleotide polymorphisms (SNPs) were genotyped in the NGFB gene in up to 1120 unrelated MS patients and 869 controls. Expression analyses were performed for selected MS patients in order to elucidate the possible functional relevance of the SNPs.

Results

Significant association of NGFB variations with MS is evident for two SNPs. NGFB mRNA seems to be expressed in sex- and disease progression-related manner in peripheral blood mononuclear cells.

Conclusion

NGFB variation and expression levels appear as modulating factors in the development of MS.
Thyroid Transcription Factor 1 Is an Independent Prognostic Factor for Patients With Stage I Lung Adenocarcinoma
Authors: Anagnostou Valsamo K. , Syrigos Konstantinos N. , Bepler Gerold , Homer Robert J. , Rimm David L.
Published: December 2008

Purpose

Thyroid transcription factor 1 (TTF1) is a transcription factor that regulates the expression of multiple genes involved in lung development. It is preferentially expressed in adenocarcinomas of the lung and has been investigated as a potential prognostic parameter in patients with lung cancer, with conflicting results. We quantitatively assessed TTF1 protein expression in two large and independent data sets to investigate the impact of TTF1 nuclear expression on patient survival.

Patients and Methods

Automated quantitative analysis, a fluorescent-based method for analysis of in situ protein expression, was used to assess a series of cell lines to find the threshold of detection of TTF1 expression. Then two independent cohorts (176 and 237 cases, respectively) were measured by the same technique, and TTF1 expression was correlated with survival.

Results

Tumors expressed TTF1 in 45% and 58% of the cases in each cohort. TTF1 was consistently expressed in adenocarcinomas (n = 61 and 73; Spearman ρ = 0.313 and 0.4 for the first and second set, respectively; P < .0001) independent of their differentiation and stage. Survival analysis showed that patients with stage I adenocarcinoma with TTF1 expression had a longer median overall survival than those without expression (n = 43, 44.3 v 26.2 months, P = .05 for the first cohort; n = 87; 49.7 v 38.5 months, P = .03 for the second cohort) Multivariate analysis revealed an independent lower risk of death for patients with stage I adenocarcinoma with TTF1-expressing tumors (hazard ratio = 0.479, 95% CI, 0.235 to 0.977; P = .043).

Conclusion

TTF1 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of patients with stage I lung adenocarcinoma.
Addition of Bevacizumab to Fluorouracil-Based First-Line Treatment of Metastatic Colorectal Cancer: Pooled Analysis of Cohorts of Older Patients From Two Randomized Clinical Trials
Authors: Kabbinavar Fairooz F. , Hurwitz Herbert I. , Yi Jing , Sarkar Somnath , Rosen Oliver
Published: December 2008

Purpose

Colorectal cancer (CRC) occurs predominantly in older persons. To provide more statistical power to assess risk/benefit in older patients, we examined the clinical benefit of bevacizumab (BV) plus fluorouracil-based chemotherapy in first-line metastatic CRC (mCRC) treatment in patients aged ≥ 65 years, using data pooled from two placebo-controlled studies.

Patients and Methods

Pooled efficacy data for 439 patients ≥ 65 years old randomized to BV plus chemotherapy (n = 218) or placebo plus chemotherapy (n = 221) in study 1 and study 2 were retrospectively analyzed on an intent-to-treat basis for overall survival (OS), progression-free survival (PFS), and objective response. Safety analysis was based on reports of targeted adverse events in treated patients.

Results

Median OS with BV plus chemotherapy was 19.3 v 14.3 months with placebo plus chemotherapy (hazard ratio [HR] = 0.70; 95% CI, 0.55 to 0.90; P = .006). Patients treated with BV plus chemotherapy had a median PFS of 9.2 v 6.2 months for placebo plus chemotherapy patients (HR = 0.52; 95% CI, 0.40 to 0.67; P < .0001). The objective response rate was 34.4% with BV plus chemotherapy versus 29.0% with placebo plus chemotherapy (difference not statistically significant). Rates of BV-associated adverse events in the pooled BV plus chemotherapy group were consistent with those reported in the overall populations for the two studies.

Conclusion

Analysis of pooled patient cohorts age ≥ 65 years from two similar trials in mCRC indicates that adding bevacizumab to fluorouracil-based chemotherapy improved OS and PFS, similar to the benefits in younger patients. Also, the risks of treatment do not seem to exceed those in younger patients with mCRC.
Lymphedema in Breast Cancer Survivors: Incidence, Degree, Time Course, Treatment, and Symptoms
Authors: Norman Sandra A. , Localio A. Russell , Potashnik Sheryl L. , Simoes Torpey Heather A. , Kallan Michael J. , Weber Anita L. , Miller Linda T. , DeMichele Angela , Solin Lawrence J.
Published: December 2008

Purpose

To examine the incidence, degree, time course, treatment, and symptoms of lymphedema in breast cancer survivors.

Methods

We conducted a 5-year, population-based prospective study of 631 randomly selected Philadelphia and Delaware County, Pennsylvania female residents with incident breast cancer who were diagnosed from 1999 to 2001. Using a questionnaire previously validated against physical therapists’ measurement-based clinical criteria, we assigned a score indicating the degree of lymphedema (none, mild, or moderate/severe) to each month of follow-up based on the respondent's perceived differences in hand/arm size. Standard survival analysis methods permitted maximum use of follow-up.

Results

Five-year cumulative incidence of lymphedema was 42 (42%) per 100 women. Among the 238 affected women, lymphedema first occurred within 2 years of diagnosis in 80% and within 3 years in 89%. Among 433 women observed for 3 years, 23% reported no more than mild lymphedema, 12% reported moderate/severe lymphedema, and 2% reported chronically moderate/severe lymphedema. Women with mild lymphedema were more than three times more likely to develop moderate/severe lymphedema than women with no lymphedema. Thirty-seven percent of women with mild lymphedema and 68% with moderate/severe lymphedema received treatment. Increasing proportions of women with increasing degree of lymphedema reported symptoms (eg, jewelry too tight, tired/thick/heavy arm). Symptoms present before the first occurrence of lymphedema were associated with a higher probability of later lymphedema (eg, hazard ratio for jewelry too tight = 7.37; 95% CI, 4.26 to 12.76).

Conclusion

Lymphedema after breast cancer is common but mostly mild. Subtle differences in self-reported hand/arm size and symptoms can be early signs of progressing lymphedema.
Metastatic Sarcomatoid Renal Cell Carcinoma Treated With Vascular Endothelial Growth Factor–Targeted Therapy
Authors: Golshayan Ali Reza , George Saby , Heng Daniel Y. , Elson Paul , Wood Laura S. , Mekhail Tarek M. , Garcia Jorge A. , Aydin Hakan , Zhou Ming , Bukowski Ronald M. , Rini Brian I.
Published: December 2008

Purpose

Metastatic renal cell carcinoma (mRCC) with sarcomatoid differentiation is an aggressive disease that is associated with poor outcomes to chemotherapy or immunotherapy. The utility of vascular endothelial growth factor (VEGF)–targeted therapy in patients with this disease is unknown.

Patients and Methods

Patients who had mRCC with sarcomatoid features in the primary tumor and who were treated with VEGF-targeted therapy were retrospectively identified. Pathology slides were reviewed to determine the percentage of sarcomatoid differentiation. Objective response rate, percentage of tumor burden shrinkage, progression-free survival (PFS), and overall survival (OS) were determined.

Results

Forty-three patients who had sarcomatoid mRCC were identified. The median percentage of sarcomatoid features was 14% (range, 3% to 90%). Patients were treated with either sunitinib (49%), sorafenib (28%), bevacizumab (19%), or sunitinib plus bevacizumab (5%). Partial responses were observed in eight patients (19%); 21 patients (49%) had stable disease; and 14 patients (33%) had progressive disease as their best response. Partial responses were limited to patients who had underlying clear-cell histology and less than 20% sarcomatoid elements. Median tumor shrinkage was −2% (range, −85% to 127%), and 53% achieved some degree of tumor shrinkage on therapy. Median PFS and OS were estimated to be 5.3 months and 11.8 months, respectively.

Conclusion

Patients who have mRCC and sarcomatoid differentiation can demonstrate objective responses and tumor shrinkage to VEGF-targeted therapy. Patients who have clear-cell histology and a lower percentage of sarcomatoid differentiation may have better outcomes with VEGF-targeted therapy.