bluuebunny/crossref_metadata_2025 huggingface dataset:
Living in the Shadow of Cain Echoes of a Developing Tradition in James 5:1-6
Authors: Byron John
Published: July 2006

Behind the statements in James 5:1-6 is an echo of the Cain and Abel story. While it has been recognized that Abel served as an archetype for righteousness and unjust suffering, it is sometimes overlooked that Cain fulfilled a similar role. Beginning with the writings of Josephus and Philo and continuing through to the Midrashim, Cain was portrayed as an archetype for those who oppress the poor and the righteous for self-gain. Just as James accuses the wealthy of using dishonest means to retain the wages of the poor, so also Cain was accused of increasing his property and possessions through robbery and force. The enigmatic statements in 5:6 represent an indictment against the wealthy and declaring that they are guilty of the sin of Cain.
Pathways to friendship in the lives of people with psychosis: Incorporating narrative into experimental research
Authors: Stayner David , Staeheli Martha , Davidson Larry
Published: July 2006

This paper explores the role of friendship in the lives of people with psychiatric disabilities through the use of narrative. We suggest that the use of phenomenologically based investigation in experimental or other traditional research designs provides a more in-depth and complex view of the lives of people with serious mental illness. We offer the example of the Partnership Project, which provides people with psychiatric disabilities a consumer or non-consumer "partner" with whom to enjoy community activities and spend a weekly stipend. Through the lens of narrative, we examine the ways that friendship differs between people matched with either a consumer or non-consumer partner and delve into the importance of connection and friendship in the lives of people with psychiatric disabilities.
Phenomenology and Contemporary Clinical Practice: Introduction to Special Issue
Authors: Davidson Larry
Published: July 2006

This special issue reconsiders the contributions that phenomenology can make to the development and practice of a clinical science of psychology. In it, we suggest that earlier attempts to apply phenomenological principles were influenced heavily by psychoanalysis, with few, if any, alternative versions of a "depth" psychology available on which to draw in reframing the nature of psychopathology and its treatment. We suggest that this lingering presence of psychoanalysis runs counter to the founding principles of phenomenological method and offer a few examples of a constructive alternative grounded in Husserl's transcendental phenomenology. Borrowing from Mohanty, we offer this approach as a respectful—as opposed to suspicious—phenomenology, and begin to outline ways in which a transcendentally-grounded psychology reconceptualizes both clinical research and practice, from the initial intake interview and interpretation of interview data to the aims and strategies of psychological interventions.
,,Only darkness in the Goldeneh Medina?" Die Lower East Side in der US-amerikanischen Kinder- und Jugendliteratur
Authors: Pohl Jana
Published: July 2006

The paper deals with the Lower East Side as a site of memory in children's literature in the United States. Contemporary children's books depict the Lower East Side in migration narratives about Eastern European Jews who came to America around the turn of the last century. They do so both verbally and visually by incorporating an often reproduced photograph that has come to symbolize the imaginary place. The Lower East Side is a Jewish site of immigrant poverty, crowded tenement houses, and sweat shops. In the examples given, it is used to dismantle the image of the Goldeneh Medina.
Coordinating Philanthropy for Peace
Authors: Greenberg Melanie
Published: July 2006

Collaboration at many levels – between governments, non-governmental organizations, regional groups, and academic disciplines – will create the fabric from which a durable peace can be established in the post-9/11 era. Private foundations, even without the vast resources of government agencies, can play an important catalytic role in encouraging collaboration across the spectrum of peacebuilding. Transaction costs and barriers to negotiation can make collaboration difficult for foundations and grantees, but the potential gains from collaboration overcome the costs of time and the risks of uncertainty inherent in collaborative ventures. Foundations can be especially helpful in establishing collaborations linking theory and practice (especially in the area of evaluation); in bringing together grantees in particular geographical areas; and in helping disseminate best practices and lessons learned from peacebuilding experiences. Foundations can create an even stronger voice for peacebuilding if foundation leaders are willing to join together as effectively in the peace and security area as they do in areas such as the environment and public health.
Putting the "Up" in Bottom-up Peacebuilding: Broadening the Concept of Peace Negotiations
Authors: Hemmer Bruce , Graham John , Garb Paula , Phillips Marlett
Published: July 2006

A new theory of how nations negotiate is described wherein peoples negotiate, not just political leaders, and the negotiations of the latter are affected by the former. We draw on theories and concepts from Track Two diplomacy, citizen peacebuilding, civic democratization, and social movements to develop an integrated theory of how peoples negotiate. That is, we demonstrate how citizen peacebuilders create the democratic, social, cultural and human capital necessary to effectively engage national level politics by first building peace and democracy at the grassroots and in local politics. Further, we describe the development of a "peacebuilding organism" involving specialized citizen peacebuilding organizations that coordinate to produce mutually reinforcing growth toward peace and democracy at all levels of society. This gives peace a deep-rooted momentum that transforms political resistance. This theory is applied to explain peace movement development in Bosnia-Herzegovina. We close by considering implications of this theory for optimizing international assistance.
Trading for Security: Military Alliances and Economic Agreements*
Authors: Long Andrew G. , Leeds Brett Ashley
Published: July 2006

The authors appraise a well-known argument connecting economics and security in international relations: military allies are likely to trade more with one another than non-allies. A review of alliance treaties and diplomatic history suggests that, under certain conditions, states may tie together alliance agreements and economic agreements. When states explicitly link alliance agreements with economic cooperation, one would expect to see increased economic exchange coinciding with coordinated security policies. This article evaluates whether the linking of economic and security agreements accounts for a positive relationship between alliances and trade among European states before World War II and produces evidence in support of this argument. Trade among allies who have specified economic cooperation in their alliance agreements is higher than trade among non-allied states and higher than trade among allies who have not promised economic cooperation. In contrast, trade among allies without specific economic provisions in their treaties is statistically no different from trade among non-allies. Thus, the positive empirical relationship between alliances and trade that the authors find in pre-WWII Europe is a result of only a specific subset of all military alliances, namely, those treaties that stipulate economic cooperation between the allies. This study advances our understanding of the alliance–trade relationship by focusing attention on the joint negotiation of cooperation in different issue-areas.
Systemic Patterns in Bullying and Victimization
Authors: Chan John H.F.
Published: July 2006

Using a new non-anonymous questionnaire and a nomination method by which victims were asked to name their aggressors, Chan (2002) collated the responses from individual victims to produce name-clusters that were studied for systemic patterns of bullying and victimization within the whole-school community. Three such patterns emerged: serial bullying, multiple victimization and the familial pattern in bullying. Serial bullying is the situation where one perpetrator preys on two or more victims, often traversing a broad range of classes and grades to target his/her victims. Although relatively fewer in number, this group of serial bullies was found to be responsible for a sizeable percentage of the bullying problems in the schools sampled. The data obtained support the notion that concentrating intervention efforts on this group will reap tremendous payoffs, by effectively eliminating the origin of much of the school's various forms of violence. The converse of serial bullying is multiple victimization, that is, more than one perpetrator can converge on one victim. The reasons why some children are chronically victimized and attract attack from multiple sources was discussed in the context of personality dispositions, peer-relational and family-relational factors, as well as its developmental links with workplace victim status in adulthood. The third pattern studied by Chan (2002) involved cases where children in the same family (i.e. siblings) turned up being named as bullies by their peers. Family influences (e.g. rearing practices, parental modelling) on aggressive behaviour in children have long been known. But transmission of influences between siblings, through acting as ‘key pathogens’ and/or ‘partners in crime’ is also responsible for the aggregation of delinquent behaviour. The familial pattern in bullying found in Chan's (2002) study is consistent with such transmission pathways. The ability to reveal the hidden patterns of interaction and links amongst bullies and victims in the context of the whole-school community attests to the significance and practical use of the SLS peer nomination method of asking victims to name the perpetrators of bullying. It makes possible the tracking of bullies and victims beyond class boundaries, thereby providing information that goes beyond individual data and incidence rates. What is more important, intervention and treatment can be more effectively implemented in a systems-wide approach, when there is integrated information from various key sources.
Arthroscopic Rotator Interval Closure
Authors: Plausinis Derek , Bravman Jonathan T. , Heywood Christian , Kummer Frederick J. , Kwon Young W. , Jazrawi Laith M.
Published: July 2006

Background

The effect of arthroscopic rotator interval closure on glenohumeral motion and translation is not well understood, nor is the ideal location or number of sutures required for closure.

Hypothesis

The number of arthroscopic rotator interval closure sutures and their placement will have a significant effect on glenohumeral range of motion and anterior-posterior translation.

Study Design

Controlled laboratory study.

Methods

Using a custom testing apparatus, the authors measured range of motion in 12 fresh-frozen cadaveric shoulders; anteriorposterior translation in adduction and neutral rotation was measured in 9. Specimens were initially tested without sutures and then tested after 3 interval closures using a random sequence of (1) an isolated medial suture at the level of the glenoid, (2) an isolated lateral suture 1 cm lateral to the glenoid, or (3) both sutures followed by removal of all sutures.

Results

Analysis of variance demonstrated that interval closure had a significant effect on decreasing flexion (mean, 6°), external rotation (mean, 10°), and anterior translation (mean, 3 mm) of the adducted shoulder. There was no significant difference between the 3 interval closures in any of the tests.

Conclusion

Arthroscopic interval closure produced significant decreases in range of motion and anterior-posterior translation. The effects of single lateral or medial suture closures were similar to the use of 2 sutures.

Clinical Relevance

This study suggests that the initial effect of arthroscopic rotator interval closure on anterior translation of the shoulder will be similar whether 1 or 2 sutures are used. In vivo studies are necessary to determine if the effect of these 2 methods would be the same over time.
Social Engagement and Depressive Symptoms in Late Life
Authors: Glass Thomas A. , De Leon Carlos F. Mendes , Bassuk Shari S. , Berkman Lisa F.
Published: July 2006

Objectives: The purpose is to investigate whether social engagement protects against depressive symptoms in older adults. Method: Three waves of data from a representative cohort study of community-dwelling adults aged 65 years and above from the New Haven Established Populations for the Epidemiologic Study of the Elderly are examined using random effects models. Results: Social engagement (an index combining social and productive activity) is associated with lower CES-D scores after adjustment for age, sex, time, education, marital status, health and functional status, and fitness activities. This association is generally constant with time, suggesting a cross-sectional association. In addition, social engagement is associated with change in depressive symptoms, but only among those with CES-D scores below 16 at baseline. Discussion: Social engagement is independently associated with depressive symptoms cross-sectionally. A longitudinal association is seen only among those not depressed at baseline.
Investigating Differences Among Older Adults' Access to Specialized Rehabilitation Services
Authors: Neufeld Stewart , Lysack Cathy
Published: July 2006

The purpose of this study was to (a) describe rehabilitation in-patients aged 65 and older who received specialized occupational therapy home evaluation services and (b) examine these data for evidence of inequalities based on patient gender, race, age, and health insurance status. An archival review was conducted of all in-patient admissions (2,767) to a large urban rehabilitation hospital who were 65 years and older and eligible to receive a home evaluation. Logistic regression was used to predict the likelihood of receiving an occupational therapy home evaluation. Analysis showed that 9.7% of subjects received an in-home evaluation and those who did had significantly longer rehabilitation hospital stays (p < 0.0001) and were significantly more dependent at discharge as measured by the Functional Independence Measure (p < 0.0001) than those who did not. We found no evidence of inequalities on the basis of gender, race, age, and health insurance type after controlling for the level of functional independence of patients. Although this study found little evidence of inequalities, it does raise several critical policy questions including “How many rehabilitation in-patients should receive a home evaluation?” and “How should rehabilitation services be allocated?”
Questions and the exercise of power
Authors: Wang Jinjun
Published: July 2006

This article argues that ‘ideal dialogue’, which is free from power, is unattainable and unrealistic, and power is inherent in all dialogues. It focuses on the exploration of questions as a possible means to exercise power in both casual conversation and institutional dialogue. Comparatively speaking, power tends to be overt in institutional dialogue and covert in casual conversation and questions exercise power in different ways in both forms of verbal interaction respectively. On the basis of data analysis, it is pointed out that the immediate allocation of turn-taking and the temporary topic control result in the latency of questions as a powerful means in casual conversation. The prominence of questions as a powerful means centers on three factors, that is, notably unequal distribution of questions producing the unequal allocation of turn-taking, dominant questions controlling both local and global topics, and Yes/No questions and Wh-questions exercising power in different degrees.
‘I’m very careful about that’: narrative and agency of men in prison
Authors: McKendy John P.
Published: July 2006

My research is based on lifestory interviews I conducted with men in prison for violent crimes. Having been deemed fitting objects of punishment, they were enjoined to speak of themselves as responsible, self-possessed agents who could have acted differently. Yet narrating their lived-through experiences, many struggled to convey their own victimization, suffering and powerlessness. Strewn throughout their narratives I found fragments, gaps, inconsistencies, false starts, pauses, switches between discourses, self-interruptions and frame breaks. This ‘narrative debris’ is evidence of the way the prison experience, and the language associated with it, make it difficult for these men to talk in direct ways about their situation. Not being able to talk directly about this means they are less likely to be able to think about it, which in turn means that they are less likely to see it as their responsibility. What is paradoxical, of course, is that it is the official discourse of the prison - which explicitly desires them to take such responsibility - that makes it so difficult for them to do so.
Antecedents and Consequences of Group-Based Guilt: The Effects of Ingroup Identification
Authors: Doosje Bertjan E. J. , Branscombe Nyla R. , Spears Russell , Manstead Antony S. R.
Published: July 2006

Effects of ingroup identification on antecedents and consequences of group-based guilt were examined in two experiments. In the first study, ingroup identification was unrelated to guilt when the negative historical information was said to come from an outgroup source, but was positively related when the same information was said to come from an ingroup source. Among high identifiers it is difficult to dismiss negative information when the source is one's own ingroup. In the second study, people who are low in identification were more in favor of acknowledging the negative aspects of their group's history as a way of alleviating feelings of guilt. We discuss the implications of these results for coming to terms with the legacy of a negative ingroup past.
Horizontal Hostility: Multiple Minority Groups and Differentiation from the Mainstream
Authors: White Judith B. , Schmitt Michael T. , Langer Ellen J.
Published: July 2006

Three studies examined minority group members' attitudes toward other, similar minority groups. We predicted that minority group members would differentiate between multiple outgroups with asymmetric horizontal hostility(White & Langer, 1999), a pattern of expressing relatively unfavorable attitudes toward an outgroup that is similar to and more mainstream than the minority ingroup. We replicated White and Langer's pattern of horizontal hostility among members of minority political parties in Greece (Study 1). When the mainstream majority was made a salient part of the intergroup context, vegetarians' attitudes toward vegans became more positive, and vegans' attitudes toward vegetarians more negative (Study 2). In Study 3, mainstream salience made Dartmouth College students' relative evaluations of a similar, more mainstream college more negative, whereas priming a superordinate minority identity made them more positive. Results suggest that asymmetric horizontal hostility results from the motivation to differentiate one's minority ingroup from a similar, more mainstream group in comparative contexts anchored by the mainstream majority outgroup.
Separating Status from Power as an Antecedent of Intergroup Perception
Authors: Boldry Jennifer G. , Gaertner Lowell
Published: July 2006

Status and power covary such that higher status groups are typically higher power groups. This research explored the effect of status on intergroup perception controlling for power. Experiment 1 manipulated the relative status of social groups and explicitly provided the groups equal power. Experiment 2 manipulated status and power orthogonally. Multiple measures yielded consistent patterns indicating that status affected perceived group centrality and variability independent of power. The patterns were consistent with a strategic intergroup comparison account as suggested by social identity theory. Specifically, the effect of status on intergroup perception varied with the relevance and valence of the dimension of comparison in a manner that balanced social reality with a positive social identity.
Social Compensation: Fact or Social-Comparison Artifact?
Authors: Todd Andrew R. , Seok Dong-Heon , Kerr Norbert L. , Messé Lawrence A.
Published: July 2006

The use of coactors as non-group controls in prior social compensation research has left open the possibility that the effect might artifactually have resulted from a confound between work condition (Coaction vs. Collective) and the opportunity to make performance comparisons. A direct empirical test of this alternative, artifactual explanation is reported. Its results contradict that explanation and suggest that the use of coactors as controls has, if anything, resulted in an underestimation of the magnitude of the social compensation effect. It is argued that multiple alternative non-group performance baselines can be informative for analyzing group motivation effects.
Enterococcal colonization of the gastro-intestinal tract: role of biofilm and environmental oligosaccharides
Authors: Creti Roberta , Koch Stefanie , Fabretti Francesca , Baldassarri Lucilla , Huebner Johannes
Published: July 2006

Background

Biofilm formation in E. faecalis is presumed to play an important role in a number of enterococcal infections. We have previously identified a genetic locus provisionally named bop that is involved in maltose metabolism and biofilm formation. A transposon insertion into the second gene of the locus (bopB) resulted in loss of biofilm formation, while the non-polar deletion of this gene, together with parts of the flanking genes (bopA and bopC) resulted in increased biofilm formation. A polar effect of the transposon insertion on a transcriptional regulator (bopD) was responsible for the reduced biofilm formation of the transposon mutant.

Results

The amount of biofilm formed is related to the presence of maltose or glucose in the growth medium. While the wild-type strain was able to produce biofilm in medium containing either glucose or maltose, two mutants of this locus showed opposite effects. When grown in medium containing 1% glucose, the transposon mutant showed reduced biofilm formation (9%), while the deletion mutant produced more biofilm (110%) than the wild-type. When grown in medium containing 1% maltose, the transposon mutant was able to produce more biofilm than the wild-type strain (111%), while the deletion mutant did not produce biofilm (4%). Biofilm formation was not affected by the presence of several other sugar sources. In a gastrointestinal colonization model, the biofilm-negative mutant was delayed in colonization of the mouse intestinal tract.

Conclusion

The biofilm-positive phenotype of the wild-type strain seems to be associated with colonization of enterococci in the gut and the presence of oligosaccharides in food may influence biofilm formation and therefore colonization of enterococci in the gastrointestinal system.
Comparative evaluation of the treatment efficacy of suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer cell lines and primary ovarian cancer cells from patients
Authors: Sonnemann Jürgen , Gänge Jennifer , Pilz Sabine , Stötzer Christine , Ohlinger Ralf , Belau Antje , Lorenz Gerd , Beck James F
Published: July 2006

Background

In most patients with ovarian cancer, diagnosis occurs after the tumour has disseminated beyond the ovaries. In these cases, post-surgical taxane/platinum combination chemotherapy is the "gold standard". However, most of the patients experience disease relapse and eventually die due to the emergence of chemotherapy resistance. Histone deacetylase inhibitors are novel anticancer agents that hold promise to improve patient outcome.

Methods

We compared a prototypic histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), and paclitaxel for their treatment efficacy in ovarian cancer cell lines and in primary patient-derived ovarian cancer cells. The primary cancer cells were isolated from malignant ascites collected from five patients with stage III ovarian carcinomas. Cytotoxic activities were evaluated by Alamar Blue assay and by caspase-3 activation. The ability of SAHA to kill drug-resistant 2780AD cells was also assessed.

Results

By employing the cell lines OVCAR-3, SK-OV-3, and A2780, we established SAHA at concentrations of 1 to 20 μM to be as efficient in inducing cell death as paclitaxel at concentrations of 3 to 300 nM. Consequently, we treated the patient-derived cancer cells with these doses of the drugs. All five isolates were sensitive to SAHA, with cell killing ranging from 21% to 63% after a 72-h exposure to 20 μM SAHA, while four of them were resistant to paclitaxel (i.e., <10% cell death at 300 nM paclitaxel for 72 hours). Likewise, treatment with SAHA led to an increase in caspase-3 activity in all five isolates, whereas treatment with paclitaxel had no effect on caspase-3 activity in three of them. 2780AD cells were responsive to SAHA but resistant to paclitaxel.

Conclusion

These ex vivo findings raise the possibility that SAHA may prove effective in the treatment of paclitaxel-resistant ovarian cancer in vivo.
Streptococcal Receptor Polysaccharides: Recognition Molecules for Oral Biofilm Formation
Authors: Yoshida Yasuo , Palmer Robert J , Yang Jinghua , Kolenbrander Paul E , Cisar John O
Published: July 2006

Background

Strains of viridans group streptococci that initiate colonization of the human tooth surface typically coaggregate with each other and with Actinomyces naeslundii, another member of the developing biofilm community. These interactions generally involve adhesin-mediated recognition of streptococcal receptor polysaccharides (RPS). The objective of our studies is to understand the role of these polysaccharides in oral biofilm development.

Methods

Different structural types of RPS have been characterized by their reactions with specific antibodies and lectin-like adhesins. Streptococcal gene clusters for RPS biosynthesis were identified, sequenced, characterized and compared. RPS-producing bacteria were detected in biofilm samples using specific antibodies and gene probes.

Results

Six different types of RPS have been identified from representative viridans group streptococci that coaggregate with A. naeslundii. Each type is composed of a different hexa- or heptasaccharide repeating unit, the structures of which contain host-like motifs, either GalNAcβ1-3Gal or Galβ1-3GalNAc. These motifs account for RPS-mediated recognition, whereas other features of these polysaccharides are more closely associated with RPS antigenicity. The RPS-dependent interaction of S. oralis with A. naeslundii promotes growth of these bacteria and biofilm formation in flowing saliva. Type specific differences in RPS production have been noted among the resident streptococcal floras of different individuals, raising the possibility of RPS-based differences in the composition of oral biofilm communities.

Conclusion

The structural, functional and molecular properties of streptococcal RPS support a recognition role of these cell surface molecules in oral biofilm formation.
Child health inequities in developing countries: differences across urban and rural areas
Authors: Fotso Jean-Christophe
Published: July 2006

Objectives

To document and compare the magnitude of inequities in child malnutrition across urban and rural areas, and to investigate the extent to which within-urban disparities in child malnutrition are accounted for by the characteristics of communities, households and individuals.

Methods

The most recent data sets available from the Demographic and Health Surveys (DHS) of 15 countries in sub-Saharan Africa (SSA) are used. The selection criteria were set to ensure that the number of countries, their geographical spread across Western/Central and Eastern/Southern Africa, and their socioeconomic diversities, constitute a good yardstick for the region and allow us to draw some generalizations. A household wealth index is constructed in each country and area (urban, rural), and the odds ratio between its uppermost and lowermost category, derived from multilevel logistic models, is used as a measure of socioeconomic inequalities. Control variables include mother's and father's education, community socioeconomic status (SES) designed to represent the broad socio-economic ecology of the neighborhoods in which families live, and relevant mother- and child-level covariates.

Results

Across countries in SSA, though socioeconomic inequalities in stunting do exist in both urban and rural areas, they are significantly larger in urban areas. Intra-urban differences in child malnutrition are larger than overall urban-rural differentials in child malnutrition, and there seem to be no visible relationships between within-urban inequities in child health on the one hand, and urban population growth, urban malnutrition, or overall rural-urban differentials in malnutrition, on the other. Finally, maternal and father's education, community SES and other measurable covariates at the mother and child levels only explain a slight part of the within-urban differences in child malnutrition.

Conclusion

The urban advantage in health masks enormous disparities between the poor and the non-poor in urban areas of SSA. Specific policies geared at preferentially improving the health and nutrition of the urban poor should be implemented, so that while targeting the best attainable average level of health, reducing gaps between population groups is also on target. To successfully monitor the gaps between urban poor and non-poor, existing data collection programs such as the DHS and other nationally representative surveys should be re-designed to capture the changing patterns of the spatial distribution of population.
Intra-thoracic desmoid tumour in a patient with a previous aortocoronary bypass
Authors: Borzellino Giuseppe , Minicozzi Anna Maria , Giovinazzo Francesco , Faggian Giuseppe , Iuzzolino Paolo , Cordiano Claudio
Published: July 2006

Background

Intra-thoracic desmoid tumours with mediastinal invasion are very rare. Although rare they have to be taken into account in the differential diagnosis of a thoracic mass and therapeutic options have to be weighted since surgical treatment may require wide excision.

Case presentation

A 48-year-old male diabetic, dyslipidaemic, former heavy smoker with psychiatric illness was operated by sternotomy for a triple aorto-coronary bypass 4 years before, presented with complains of recent onset such as constant and oppressive chest pain. At surgery a mass extending from the aortic arch into the entire anterior mediastinum and to most of the right pleural cavity was found. The mass was separated from sternal periosteum and vessels of aorto-coronary by pass were isolated starting from the aortic arch up to the pericardium. The histological examination revealed aggressive fibromatosis.

Conclusion

Although technically demanding, radical surgical excision is actually the most indicated therapeutic approach for intra-thoracic desmoid tumours.
Institutions and disciplinary fortunes: two moments in the history of UK geography in the 1960s I: geography in the ‘plateglass universities’
Authors: Johnston Ron
Published: July 2006

Geography grew rapidly within British universities during the 1950s and 1960s. At the beginning of the latter decade, however, the discipline was excluded from most of the new universities established to meet expanding student demand. This first essay in a pair looks at why such an ostensibly successful discipline was not incorporated in the plans for those new institutions, focusing on the external view of geography at the time and on its lack of effective champions in the highest ‘corridors of power’, notably its learned societies.
Endpoints in vaccine trials
Authors: Hudgens Michael G , Gilbert Peter B , Self Steven G
Published: July 2006

In this paper we discuss statistical considerations regarding endpoints in preventive vaccine trials. Brief discussion is given to preclinical, Phase I, and Phase II trials, with the bulk of attention paid to endpoint choice and analysis in Phase III efficacy trials. In addition to traditional efficacy measures of vaccine effects for immunized individuals, consideration is given to waning, strain specific efficacy, correlates of protective immunity, postinfection endpoints, and cluster randomized trials.
Regulating Bone Growth and Development with Bone Morphogenetic Proteins
Authors: LEBOY PHOEBE S.
Published: July 2006

Abstract:  There are many gene products reported to promote osteoblast differentiation and thus increase bone formation, but only the transcription factor Runx2 and members of the bone morphogenetic protein (BMP) family of growth/differentiation factors have been shown to be absolute requirements for osteogenesis. Mice lacking the transcription factor Runx2 (also known as cbfa1) develop no bone. Similarly, osteoblast differentiation and bone formation is blocked when BMP signaling is suppressed by overexpression of noggin, a selective BMP antagonist. It is therefore not unexpected that several different mechanisms have evolved to regulate the effects of BMP‐induced signaling. In this session we focus on the multiple ways in which cells can modulate BMP‐induced osteogenesis and mechanisms by which BMP signaling can lead to transcriptional control of gene expression.
BMP and BMP Inhibitors in Bone
Authors: ROSEN VICKI
Published: July 2006

Abstract:  Bone morphogenetic proteins (BMPs) are signaling molecules that act locally on target cells to affect cell survival, proliferation, and differentiation. While first identified as bone‐inducing agents, BMPs are now known to affect the formation and function of many organ systems. Here we focus only on the roles of BMPs in the skeleton. In the developing mouse embryo, BMPs direct skeletal patterning, chondrogenesis, and bone formation. In postnatal animals, BMPs are potent bone regeneration factors, affecting both the amount of new bone formed and the rate at which bone healing occurs. The amount of BMP available for signaling is tightly regulated in both the embryo and postnatally, and in the context of the skeleton, several structurally distinct BMP ligand antagonists have been shown to alter the ability of BMPs to bind to their receptors, blocking BMP activity in physiologically important circumstances. For example, noggin knockout mice display cartilage hyperplasia during skeletal development that results in the loss of joint formation (too much BMP activity), while mice that overexpress noggin in skeletal cells display severe osteopenia and bone fragility (too little BMP activity). Sclerostin, chordin, CTGF, follistatin, and gremlin are additional BMP antagonists that may act in the skeleton to regulate BMP availability. Another class of BMP inhibitors are the proteins that bind to BMP receptors but have no inherent signaling function and thus act as BMP receptor antagonists. To date, inhibin and BMP‐3 have been identified as BMP receptor antagonists that can block BMP signaling in bone. Identification of BMP antagonists allows us to investigate their role in diseases that affect skeletal function, such as osteopenia and nonunion fracture, and may provide a novel therapeutic intervention point for treatment.
Dysregulation of the BMP‐4 Signaling Pathway in Fibrodysplasia Ossificans Progressiva
Authors: KAPLAN FREDERICK S. , FIORI JENNIFER , DE LA PEÑA LOURDES SERRANO , AHN JAIMO , BILLINGS PAUL C. , SHORE EILEEN M.
Published: July 2006

Abstract:  Identification of gene mutations in Mendelian disorders is often determined by linkage analysis and positional cloning, an approach that is difficult for fibrodysplasia ossificans progressiva (FOP) due to a low reproductive fitness that results in a small number of multigenerational families showing inheritance of the disease. Altered signaling pathways can be investigated as a complementary method to identify the consequences of the mutated gene responsible for FOP and to identify potential therapeutic targets. Candidate signaling pathways for FOP are those that malfunctioning could account for the malformation of the great toes during embryonic development and could explain the postnatal progressive heterotopic endochondral ossification. Signaling pathways that fit these criteria are the BMP signaling pathway and its interacting pathways. A large body of data suggest that the BMP‐4 signaling pathway is dysregulated in FOP.
COX‐2 has a Critical Role During Incorporation of Structural Bone Allografts
Authors: O'KEEFE REGIS J. , TIYAPATANAPUTI PRAROP , XIE CHAO , LI TIAN FANG , CLARK CHRIS , ZUSCIK MICHEAL J. , CHEN DI , DRISSI HICHAM , SCHWARZ EDWARD , ZHANG XINPING
Published: July 2006

Abstract:  Nonsteroidal anti‐inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX) activity, reduced pain and are commonly used in patients with skeletal injury. In this article we will also present data to show that selective COX‐2 inhibitor delays allograft healing and incorporation. In contrast, local delivery of prostaglandin E2 (PGE2) enhanced bone formation at cortical bone graft junction. A 4‐mm mid‐diaphyseal segmental femoral defect was created and then repaired by frozen bone allograft of the same size. A 22‐gauge metal pin was placed in the intramedullary cavity to stabilize the bone graft. Healing was evaluated weekly by X ray and by a semiquantitative histomorphometric analysis at 5 weeks postsurgery. Celecoxib (25 mg/kg/day) and Ketorolac (4 mg/kg/day) were administered daily for 2 weeks or 5 weeks. PGE2 was infused locally at a dose of 800 nmol/kg per day via osmotic minipump for 4 weeks. Inhibition of cyclooxygenase by daily administration of the Celecoxib or Ketorolac for 5 weeks reduced new bone ingrowth by about 60% (P < 0.05). The percentage of bony bridging in both drug‐treated groups was significantly decreased at 5 weeks. Temporal administration of Celecoxib for 2 weeks also significantly reduced bone formation by 45% and withdrawal of the Celecoxib only led to slight recovery of bone formation at the graft side. In contrast to the inhibitory effects of NSAIDS, PGE2 infusion at the cortical bone junction increased bone formation by about twofold. These results demonstrated that COX‐2 is essential for bone allograft incorporation. Furthermore, our data support the notion that COX‐2‐dependent PGE2 produced at the early stage of bone healing is prerequisite for efficient skeletal repair.
Canonical Wnt Signaling in Osteoblasts Is Required for Osteoclast Differentiation
Authors: GLASS DONALD A. , KARSENTY GERARD
Published: July 2006

Abstract:  Inactivation of Lrp5, a gene encoding a likely Wnt co‐receptor, results in low bone mass (osteopenia) by decreasing bone formation, suggesting that Wnt signaling in osteoblasts regulates bone formation. Here we show that Tcf1 and Tcf4 are expressed in osteoblasts during development and after birth; stabilization of β‐catenin, an essential component of canonical Wnt signaling, in differentiated osteoblasts results in high bone mass while its deletion from differentiated osteoblasts leads to osteopenia. Histological analysis showed that these mutations affect bone resorption. Cellular and molecular studies showed that β‐catenin together with TCF proteins regulates in osteoblasts the expression of Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that, in differentiated osteoblasts, β‐catenin and presumably Wnt signaling are negative regulators of osteoclast differentiation; thus they broaden our knowledge about functions that Wnt proteins may have at various stages of skeletogenesis.
Osteoclasts and Integrins
Authors: TEITELBAUM STEVEN L.
Published: July 2006

Abstract:  The osteoclast is the unique bone resorptive cell that accomplishes its mission by forming an isolated acidified microenvironment between itself and the bone surface. Creation of this compartment is the first step in bone degradation and establishes that an intimate physical relationship must exist between the osteoclast and bone. Thus, identification of the mechanisms by which the osteoclast attaches to bone is essential to understanding how the cell degrades skeletal tissue. Our studies have investigated whether absence of the αvβ3 integrin modifies the ability of c‐Fms to induce Rho GTPases, and the implications for formation of the osteoclast cytoskeleton.
The Regulation of Cathepsin K Gene Expression
Authors: TROEN BRUCE R.
Published: July 2006

Abstract: Cathepsin K is essential for normal bone resorption. Osteoclasts synthesize and secrete cathepsin Kinto the extracellular compartment at the attachment site between osteoclasts and the bone surface, wherein the organic matrix is subsequently degraded by cathepsin K. RANKL, NFAT, Mitf, and various components of AP‐1 enhance osteoclast formation and bone resorption, whereas IFN‐γ, calcitonin, estradiol, and calcium inhibit it. These agents appear to act correspondingly to alter cathepsin K mRNA and protein expression in order to stimulate and suppress the osteoclast's resorbing potential. RANKL signaling via the calcineurin‐calcium‐NFAT signaling cascade plays a significant role in the regulation of cathepsin K expression. Activation via p38 and the micropthalmia transcription factor also enhances cathepsin K expression. Future studies will be needed to elucidate the relative roles of various signaling pathways at different stages of osteoclast formation and activation and to determine whether genetically disrupting these pathways can modulate bone resorption with or without impeding other osteoclast functions.
New Insights into the Mechanisms Involved in the Pleiotropic Actions of 1,25Dihydroxyvitamin D3
Authors: CHRISTAKOS SYLVIA , DHAWAN PUNEET , SHEN QI , PENG XIAORONG , BENN BRYAN , ZHONG YAN
Published: July 2006

Abstract:  Vitamin D functions to regulate calcium homeostasis in intestine, kidney, and bone. Vitamin D deficiency during bone development causes rickets and in adults vitamin D deficiency, which has been shown to be common in the elderly population, can cause secondary hyperparathyroidism that can result in osteomalacia and increased risk of fracture. Recent evidence has suggested that vitamin D can have numerous other physiological functions including protection against certain autoimmune diseases, such as diabetes and multiple sclerosis and inhibition of proliferation of a number of malignant cells including breast and prostate cancer cells. Exactly how vitamin D affects numerous different systems is a subject of continuing investigation. This article will review new developments related to the function and regulation of vitamin D target proteins in classic vitamin D target tissues that have provided novel insight into the mechanism of vitamin D action.
Bone Strength: Current Concepts
Authors: TURNER CHARLES H.
Published: July 2006

Abstract:  Bones serve several mechanical functions, including acoustic amplification in the middle ear, shielding vital organs from trauma, and serving as levers for muscles to contract against. Bone is a multiphase material made up of a tough collagenous matrix intermingled with rigid mineral crystals. The mineral gives bone its stiffness. Without sufficient mineralization, bones will plastically deform under load. Collagen provides toughness to bone making it less brittle so that it better resists fracture. Bone adapts to mechanical stresses largely by changing its size and shape, which are major determinants of its resistance to fracture. Tissue is added in regions of high mechanical stress providing an efficient means for improving bone strength. Experiments have shown that small additions of bone mineral density (BMD) (5–8%) caused by mechanical loading can improve bone strength by over 60% and extend bone fatigue life by 100‐fold. Consequently, it is clear that bone tissue possesses a mechanosensing apparatus that directs osteogenesis to where it is most needed for improving bone strength. The biological processes involved in bone mechanotransduction are poorly understood and further investigation of the molecular mechanisms involved might uncover drug targets for osteoporosis. Several pathways are emerging from current research, including membrane ion channels, ATP signaling, second messengers, such as prostaglandins and nitric oxide, insulin‐like growth factors, and Wnt signaling.
Novel Targets and Therapeutics for Bone Loss
Authors: MARGOLIS RONALD N. , WIMALAWANSA SUNIL J.
Published: July 2006

Abstract:  Advances in the treatment of osteoporosis over the past decade have resulted in the generation of novel therapeutic agents aimed at providing both anticatabolic and anabolic effects in bone. In‐depth understanding of the biology of key factors regulating bone metabolism has begun to reveal new approaches to treating this costly and debilitating disease. During the next decade we will observe the development and evolution of several new classes of therapeutic targets and agents to combat this disease.
Interactive Effect of Interleukin‐6 and Prostaglandin E2 on Osteoclastogenesis via the OPG/RANKL/RANK System
Authors: LIU XIN‐HUA , KIRSCHENBAUM ALEXANDER , YAO SHEN , LEVINE ALICE C.
Published: July 2006

Abstract:  The OPG/RANKL/RANK system regulates osteoclastogenesis. Both cyclooxygenase‐2 (COX‐2)/prostaglandin E2 (PGE2) and interleukin‐6 (IL‐6) are reported to induce osteoclast differentiation. The mechanisms underlying these signaling pathways on the OPG/RANKL/RANK system are not fully understood. We herein demonstrate that COX‐2 and PGE2 stimulated osteoclastogenesis through inhibition of OPG secretion, stimulation of RANKL production by osteoblasts, and upregulation of RANK expression in osteoclasts. PGE2 also stimulated IL‐6 production, and IL‐6, in turn, increased PGE2 secretion, COX‐2, and EP4/EP2 expression in bone cells. These findings provide evidence of interactive effect of PGE2 and IL‐6 signaling pathways in osteoclastogenesis via effect on the OPG/RANKL/RANK system.
The Role of OPG/TRAIL Complex in Multiple Myeloma
Authors: BRUNETTI GIACOMINA , COLUCCI SILVIA , RIZZI RITA , MORI GIORGIO , COLAIANNI GRAZIANA , ORANGER ANGELA , ZALLONE ALBERTA , LISO VINCENZO , GRANO MARIA
Published: July 2006

Abstract:  Multiple myeloma (MM) is often associated with an increased osteoclast (OC) activity. Using an in vitro osteoclastogenesis model consisting of MM unstimulated and unfractionated peripheral blood mononuclear cells (PBMCs), we showed that T cells support OC formation and survival. Differently, in T cell‐depleted MM PBMC cultures, exogenous macrophage‐colony stimulating factor (M‐CSF) and receptor activated of nuclear factor‐κB ligand (RANKL) were necessary for osteoclastogenesis. We found RANKL, OPG, and TRAIL overexpression by fresh MM T cells. Despite high osteoprotegerin (OPG) levels, the persistence of osteoclastogenesis can be related to the formation of the OPG/TRAIL complex. Our results highlight that MM T cells support OC formation and survival, possibly involving OPG/TRAIL interaction.
IL‐7 Drives T Cell‐Mediated Bone Loss Following Ovariectomy
Authors: ROBBIE‐RYAN MICHAELA , PACIFICI ROBERTO , WEITZMANN M. NEALE
Published: July 2006

Abstract:  Ovariectomy‐induced bone loss stems in large measure from a realignment of adaptive immune responses leading to the activation and expansion of tumor necrosis factor (TNF)‐producing T cells. The mechanisms driving this T cell expansion are complex but we have recently reported that the pro‐osteoclastogenic cytokine interleukin (IL)‐7 plays a critical role in this process. The mechanisms of IL‐7 action are intricate and poorly defined. We present herein an overview of our current understanding of IL‐7 action on bone turnover and the role of IL‐7 in ovariectomy‐induced bone loss.