bluuebunny/crossref_metadata_2025 huggingface dataset:
Building Network Visualization Tools to Facilitate Metacognition in Complex Analysis
Authors: Mirel Barbara
Published: May 2011

If whole communities of domain analysts are to be able to use interactive network visualization tools productively and efficiently, tool design needs to adequately support the metacognition implicit in complex visual analytic tasks. Metacognition for such exploratory network-mediated tasks applies across disciplines. This essay presents metacognitive demands inherent in complex tasks aimed at uncovering relevant relationships for hypothesizing purposes and proposes network visualization tool designs that can support these metacognitive demands.
Model Ideas: From Stem Cell Simulation to Floating Art Work
Authors: Prophet Jane
Published: May 2011

This paper discusses the role of models in the development of an interactive artwork made as the result of interdisciplinary collaboration. A variety of different types of model were used, each with different functions and status to the team.
Net-Working with Maciunas
Authors: Schmidt-Burkhardt Astrit
Published: May 2011

The history of networking in art took on a new quality in the 1960s with George Maciunas. His sophisticated Fluxus diagrams link together the most heterogeneous knowledge cultures, artistic trends and artists. Later, in the 1980s, when the ascendancy of the computer launched the concept of the network it became clear that the social network had been one of the chief characteristics of Fluxus. In fact, Maciunas built up an international, but selective network of contacts, which he then subjected to the explosive potential of his pictorial representations.
Narcotic of the Narrative
Authors: Shelley Ward
Published: May 2011

Artist Ward Shelley works with charts and diagrams. In this article he describes his relationship to the work of Alfred Barr and to Barr's use of narrative structures to claim cultural authority for modern art.
A Unified View of Models
Authors: Arata Luis O.
Published: May 2011

This paper proposes a definition of models based on function, yielding a unified view of modeling as an art at work in any discipline.
A Taste for the Beautiful
Authors: Taylor Hollis
Published: May 2011

Bowerbirds are named for the structures they build, paint, and decorate. This photo essay documents the efforts of three species of Australian bowerbirds. The influence of sexual selection is pertinent, as the female bowerbird performs her concomitant function as art critic.
Serious Play as a Practice of Paradox
Authors: Statler Matt , Heracleous Loizos , Jacobs Claus D.
Published: May 2011

A recent stream of organizational research has used the term serious play to describe situations in which people engage in playful behaviors deliberately with the intention to achieve serious, work-related objectives. In this article, the authors reflect on the ambiguity of this term, and reframe serious play as a practice characterized by the paradox of intentionality (when actors engage deliberately in a fun, intrinsically motivating activity as a means to achieve a serious, extrinsically motivated work objective). This reframing not only extends the explanatory power of the concept of serious play but also helps bridge the concerns of scholars and practitioners: first, by enabling us to understand a variety of activities in organizations as serious play, which can help practitioners address specific organizational challenges; second, by recognizing the potential for emergent serious play, and the creation of the conditions to foster this emergence; third, by pointing toward specific, individual or group-level outcomes associated with the practice; and finally, by uncovering its ethical dimensions and encouraging the understanding of the role of serious play on ethical decision making.
Inmate Custody Levels and Prison Rule Violations
Authors: Worrall John L. , Morris Robert G.
Published: May 2011

Researchers have recently combined individual-level data with institutional measures to detect prison-level correlates of inmate misconduct. Although this body of literature has yielded insights into how the prison environment contributes to misconduct, we argue that it has ignored an important level of analysis, namely the custody level. As some inmates are placed in more restrictive confinement than others, custody levels may absorb some of the variation in individual-level and/or prison-level correlates of misconduct. Accordingly, we analyzed data from over 70,000 inmates who were housed in Texas prisons during 2008 and found that custody levels were strongly and positively associated with misconduct, even (a) after accounting for the endogeneity of custody levels and (b) once inmate- and prison-level measures were included. We draw on labeling theory in our efforts to explain the relationship between custody levels and misconduct.
Location of Multiple-Server Common Service Centers or Facilities, for Minimizing General Congestion and Travel Cost Functions
Authors: Marianov Vladimir , Serra Daniel
Published: May 2011

The authors propose a model for locating a fixed number of multiple-server service centers or facilities that may become congested. Customers arriving at these centers must wait in line until served. The locations of the facilities and the allocations of customers to them are chosen by the planner, so to minimize both travel costs and system-wide congestion (or queuing) at centers. All the customers arriving at the facilities must be served, up to a certain maximum line length. The travel cost in which customers incur is a function of the length of the trip to the facility, while the congestion cost at a facility is a general function of the number of customers waiting on line or being served at the facility. The resulting model is a nonlinear p-median formulation. A solution method for this nonlinear model is proposed, and computational experience is presented.
Differing Effects of Representative Bureaucracy in Charter Schools and Traditional Public Schools
Authors: Roch Christine H. , Pitts David W.
Published: May 2011

The authors examine the influence of teacher and administrator representation by race and ethnicity on disciplinary tools and standardized test scores within traditional public elementary schools and charter schools. The authors argue that school officials within charter schools will be less likely to consider race and ethnicity when making schooling decisions because of their attention to the culture and norms within charter schools. As a result, the authors expect that the translation from passive to active representation will be more difficult in charter schools than in traditional elementary schools. Using data from Georgia, the authors analyze this question empirically and find a statistically significant influence of representation among teachers on disciplinary tools and test scores and a more limited influence of administrative representation on standardized tests. Findings also support the central research question of this study, that is, whether the effects of racial and ethnic representation appear more limited among charter schools than traditional public schools.
Chicken Soup Really Is Good for the Soul
Authors: Troisi Jordan D. , Gabriel Shira
Published: May 2011

Theories of social surrogacy and embodied cognition assume that cognitive associations with nonhuman stimuli can be affectively charged. In the current research, we examined whether the “comfort” of comfort foods comes from affective associations with relationships. Two experiments support the hypotheses that comfort foods are associated with relationships and alleviate loneliness. Experiment 1 found that the consumption of comfort foods automatically activates relationship-related concepts. Experiment 2 found that comfort foods buffer against belongingness threats in people who already have positive associations with relationships (i.e., are secure in attachment style). Implications for social surrogacy, need to belong, embodied cognition, and eating behavior are discussed.
Relevance of IgVH Gene Somatic Hypermutation and Interphase Cytogenetics in Lymphomatous Presentation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Authors: Yeung Cecilia C. S. , Powers Michelle L. E. , Dung Nguyen Tu , Kreisel Friederike , Frater John L. , Zehnbauer Barbara A. , Burack Richard , Hassan Anjum
Published: May 2011

Background. Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are regarded as the same entity, with SLL restricted to tissue cases featuring no leukemic phase. In this study, the authors evaluate a group of SLL cases for cytogenetic abnormalities and IgVH gene mutational status to illicit differences between CLL and SLL. Design. IgVH gene polymerase chain reaction amplification and subsequent sequencing were preformed on formalin-fixed, paraffin-embedded archival tissue of 44 patients (SLL n = 34 or CLL n = 10). Cytogenetic data, CD38, and ZAP-70 expression were also evaluated for these cases. Results. The data indicate that 9/34 (26%) SLL cases have somatic hypermutation >2%, which is less than the CLL group where 40% were mutated (4/10). Cytogenetic abnormalities were seen in 58% of the SLL cases with many showing abnormalities associated with favorable to intermediate prognosis. Conclusion. The authors’ attempt to compare CLL with SLL with regards to cytogenetic and IgVH mutational status shows no statistically significant difference.
Can Adult Neural Stem Cells Create New Brains? Plasticity in the Adult Mammalian Neurogenic Niches
Authors: Kazanis Ilias
Published: May 2011

Since the first experimental reports showing the persistence of neurogenic activity in the adult mammalian brain, this field of neurosciences has expanded significantly. It is now widely accepted that neural stem and precursor cells survive during adulthood and are able to respond to various endogenous and exogenous cues by altering their proliferation and differentiation activity. Nevertheless, the pathway to therapeutic applications still seems to be long. This review attempts to summarize and revisit the available data regarding the plasticity potential of adult neural stem cells and of their normal microenvironment, the neurogenic niche. Recent data have demonstrated that adult neural stem cells retain a high level of pluripotency and that adult neurogenic systems can switch the balance between neurogenesis and gliogenesis and can generate a range of cell types with an efficiency that was not initially expected. Moreover, adult neural stem and precursor cells seem to be able to self-regulate their interaction with the microenvironment and even to contribute to its synthesis, altogether revealing a high level of plasticity potential. The next important step will be to elucidate the factors that limit this plasticity in vivo, and such a restrictive role for the microenvironment is discussed in more details.
Dopaminergic Neurotransmission in the Human Brain
Authors: Ko Ji Hyun , Strafella Antonio P.
Published: May 2011

Dopamine plays an important role in several brain functions and is involved in the pathogenesis of several psychiatric and neurological disorders. Neuroimaging techniques such as positron emission tomography allow us to quantify dopaminergic activity in the living human brain. Combining these with brain stimulation techniques offers us the unique opportunity to tackle questions regarding region-specific neurochemical activity. Such studies may aid clinicians and scientists to disentangle neural circuitries within the human brain and thereby help them to understand the underlying mechanisms of a given function in relation to brain diseases. Furthermore, it may also aid the development of alternative treatment approaches for various neurological and psychiatric conditions.
Comparative Effects of Nesiritide and Nitroglycerin on Renal Function, and Incidence of Renal Injury by Traditional and RIFLE Criteria in Acute Heart Failure
Authors: Ng Tien M. H. , Ackerbauer Kimberly A. , Hyderi Alifiya F. , Hshieh Shenche , Elkayam Uri
Published: May 2011

Background: Acute renal insufficiency is associated with poorer outcomes in heart failure. Data regarding the renal effects of vasodilatory therapy in acute heart failure are inconclusive. Hypothesis: Nesiritide and nitroglycerin are associated with differing effects on the incidence of acute renal injury and glomerular filtration rate changes. Methods: A retrospective cohort study of patients hospitalized with acute congestive heart failure who received intravenous nesiritide or nitroglycerin for ≥6 hours. Acute kidney injury was assessed by risk, injury, failure, loss, and end stage (RIFLE) classification (creatinine/GFR criteria) and by traditional acute rise in creatinine of 0.3 mg/dL or 25%. Secondary endpoints included change in estimated glomerular filtration rate, serum creatinine, serum blood urea nitrogen, blood pressure, and urine output. Results: A total of one hundred and thirty-one patients (age 57 ± 12 years, 67% male, left ventricular ejection fraction 38 ± 35%, 30% ischemic) received nesiritide (N = 37) or nitroglycerin (N = 94). Diuretic regimen and doses were similar in both the groups. Mean duration of therapy was not different (nesiritide 38.6 ± 35.7 h vs nitroglycerin 30.7 ± 22.6 h, P = .13). No differences were detected in incidence of renal injury using either criteria (RIFLE: nesiritide 19% vs nitroglycerin 22%, P = .88; traditional: 22% vs 34%, P = .16); however, glomerular filtration rate declined (−1 ± 18 mL/min vs −9 ± 21 mL/min, P = .03) and blood urea nitrogen increased (−0.2 ± 9.9 mg/dL vs 4.2 ± 9.1 mg/dL, P = .02) to a greater degree with nitroglycerin. Nesiritide was associated with lower hourly blood pressures and a higher incidence of systolic blood pressure <80 mm Hg. Conclusion: The incidence of renal injury was not different between nesiritide- and nitroglycerin-treated patients with acute heart failure; however, nitroglycerin was associated with a decline in glomerular filtration rate and increase in blood urea nitrogen despite higher baseline and on treatment blood pressures.
Consumer Trust in Sources of Physician Quality Information
Authors: Alexander Jeffrey A. , Hearld Larry R. , Hasnain-Wynia Romana , Christianson Jon B. , Martsolf Grant R.
Published: May 2011

Trust in the source of information about physician quality is likely to be an important factor in how consumers use that information in encounters with their doctor or in decisions about choice of provider. In this article, the authors use survey data from a nationally representative sample of 8,140 individuals with chronic illness to examine variation in consumer trust in different sources of physician quality information and how market segmentation factors explain such variation. The authors find that consumers place greater trust in physicians and hospitals relative to institutional sources and personal sources. The level of trust, however, varies considerably across consumers as a function of demographic, socioeconomic, behavioral/lifestyle factors but is not related to measures of context. These results suggest that the sources of public reports comparing physician quality may be a barrier to the use of quality data by consumers in the ways envisioned by supporters of greater quality transparency.
Access to Care Provided by Better Safety Net Systems for the Uninsured: Measuring and Conceptualizing Adequacy
Authors: Hall Mark A.
Published: May 2011

This descriptive study assesses the access to care provided by five model and diverse safety net programs that enroll uninsured adults in a coordinated system offering primary care, hospital care, prescription drugs, and most specialist services. Physician use by safety net program members was similar to insured groups. However, there was less use of hospitals in the two programs that relied on uncompensated charity care. Considering access measures commonly used in population-based surveys, the uninsured in these five communities fared no better than uninsured elsewhere. However, respondents may consider enrollment in a well-structured safety net program to be equivalent to insurance. If so, population surveys may be least accurate in identifying uninsured people in the very communities that have the best safety net programs. On balance the five safety net systems profiled here meet the needs of low-income uninsured residents at a level that is roughly similar to that for people with insurance.
General Practitioners and Clinical Practice Guidelines: A Reexamination
Authors: Clerc Isabelle , Ventelou Bruno , Guerville Marc-André , Paraponaris Alain , Verger Pierre
Published: May 2011

General practitioners’ (GPs’) use of clinical practice guidelines (CPGs) may be influenced by various contextual and attitudinal factors. This study examines general attitudes toward CPGs to establish profiles according to these attitudes and to determine if these profiles are associated with awareness and with use of CPGs in daily practice. The authors conducted a cross-sectional telephone survey of 1,759 French GPs and measured (a) their general attitudes toward CPGs and (b) their awareness and use in daily practice of CPGs for six specific health problems. A bivariate probit model was used with sample selection to analyze the links between GPs’ general attitudes and CPG awareness/use. The authors found three GP profiles according to their opinions toward CPGs and a positive association between these profiles and CPG awareness but not use. It is important to build awareness of CPGs before GPs develop negative attitudes toward them.
Access to and Use of Asthma Health Services Among Latino Children
Authors: Jandasek Barbara , Ortega Alexander N. , McQuaid Elizabeth L. , Koinis-Mitchell Daphne , Fritz Gregory K. , Kopel Sheryl J. , Seifer Ronald , Klein Robert B. , Canino Glorisa
Published: May 2011

This study determines asthma-related health care access and utilization patterns for Latino children of Puerto Rican and Dominican origin residing in Rhode Island (RI) and Latino children residing in Puerto Rico (Island). Data included 804 families of children with persistent asthma recruited from clinics. Island children were less likely to receive regular asthma care and care from a consistent provider and more likely to have been to the emergency department and hospitalized for asthma than RI children. Island children were 2.33 times more likely to have used the emergency department for asthma compared with RI non-Latino White (NLW) children. Latino children residing in both Island and RI were less likely to have used specialty care and more likely to have had a physician visit for asthma in the past year than RI NLW children. The differences might reflect the effects of the different delivery systems on pediatric health care utilization and asthma management.
Psychopathy Moderates the Relationship Between Time in Treatment and Levels of Empathy in Incarcerated Male Sexual Offenders
Authors: Roche Michael J. , Shoss Naomi E. , Pincus Aaron L. , Ménard Kim S.
Published: May 2011

This study examined whether psychopathy moderated the relationship between time in treatment and forms of empathy in a sample of incarcerated male sexual offenders ( N = 58). Empathy was assessed as a general personality trait as well as in attitudes toward specific victim groups (children, women).The three empathy measures were submitted to principal components analysis with oblique rotation, revealing a 3-component solution: general empathy, hostility toward women, and empathy for children. Hierarchical linear regression analyses demonstrated that level of psychopathy significantly moderated the effects of time in treatment on levels of general and victim-specific empathy, such that offenders with higher levels of psychopathy did not exhibit greater empathy with longer reported time in treatment. In contrast, offenders with lower levels of psychopathy exhibited greater empathy with longer time in treatment. Implications for treatment planning for sexual offenders are discussed.
Dynamic Risk Assessment in Sexual Offenders Using STABLE-2000 and the STABLE-2007
Authors: Eher Reinhard , Matthes Anna , Schilling Frank , Haubner-MacLean Tanja , Rettenberger Martin
Published: May 2011

The predictive accuracy of STABLE-2000 and STABLE-2007 was examined within a prospective research design in a German-speaking sample of 263 adult male prison-released sexual offenders followed up for an average of 6.4 years. The STABLE-2007 was significantly related to all outcomes (AUC = 0.67-0.71), whereas the STABLE-2000 demonstrated only weak predictive accuracy for sexual reoffense (AUC = 0.62). Supporting the results of the construction sample, the STABLE-2007 incrementally added to the predictive accuracy of the STATIC-99 for violent and general reoffense (conviction and incarceration). Moreover, the STABLE-2007 total scores and the nominal risk/need categories made significant incremental contributions over the SORAG for predicting sexual reoffense.
Navigating the Gender Box: Locating Masculinity in the Introduction to Women and Gender Studies Course
Authors: Gaffney Karen , Manno Andrew J.
Published: May 2011

This essay reflects our collaboration on integrating the topic of masculinities into the Introduction to Women and Gender Studies course that we helped design as part of our Option in Women and Gender Studies at Raritan Valley Community College in central New Jersey. This essay argues that the integration of masculinity is essential to learning the social construction of gender and applying that lens. We designed the course to position what we call the ‘‘gender box’’ front and center (borrowing from the concepts Jackson Katz describes in his film Tough Guise). We also created a Social Action Assignment to allow students to plan and carry out a specific change in relation to gender. This essay charts our successes and observations in these areas, but it also explores challenges we continue to face, specifically the persistent lack of male students in the Intro course.
Men Learning Feminism: Protecting Privileges Through Discourses of Resistance
Authors: Pleasants Robert K.
Published: May 2011

This qualitative study examines how men respond to learning feminism in the context of college women’s studies courses. Specifically, it categorizes and describes forms of resistance to feminism that men enact through discourses that serve to reinforce and reproduce male privileges despite their stated willingness to learn feminism and position themselves as allies. This study is based on data collected from in-depth interviews with eight men taking women’s studies courses at a large Southeastern university. Discourses used by participants are discussed as three larger appeals: to self, to progress, and to authority. After a description of the discourses within each appeal, interconnections among discourses are made to examine how men avoid reflectively questioning their male privilege. In conclusion, the author discusses implications for a feminist pedagogy that helps male students consciously, personally, and actively engage with feminism.
Girl parts: The female body, subjectivity and technology in posthuman young adult fiction
Authors: Flanagan Victoria
Published: May 2011

Futuristic fantasy fiction that is produced for female adolescent readers offers a vision of the relationship between the female body, feminine subjectivity and technology that is both unique and ideologically complex because of the way in which it simultaneously interrogates and adheres to liberal humanist conceptualisations of the subject. This article examines three contemporary works of young adult fiction — Uglies by Scott Westerfeld (2005), The Adoration of Jenna Fox by Mary E. Pearson (2008) and ‘Anda’s Game’ by Cory Doctorow (2008) — in light of Donna Haraway’s emancipatory vision of the cyborg, investigating how such narratives construct the ideological relationship between technology and feminine subjectivity.
A defence of the category ‘women’
Authors: Gunnarsson Lena
Published: May 2011

Against influential strands of feminist theory, I argue that there is nothing essentialist or homogenising about the category ‘women’. I show that both intersectional claims that it is impossible to separate out the ‘woman part’ of women, and deconstructionist contentions that the category ‘women’ is a fiction, rest on untenable meta-theoretical assumptions. I posit that a more fruitful way of approaching this disputed category is to treat it as an abstraction. Drawing on the philosophical framework of critical realism I elucidate the nature of the vital and inevitable process of abstraction, as a means of finding a way out of the theoretical and methodological impasse that the ‘ban’ on the category ‘women’ has caused. Contrary to many contemporary feminist theorists, I contend that, although the category ‘women’ does not reflect the whole reality of concrete and particular women, it nevertheless refers to something real, namely the structural position as woman.
Adolescent Immigrant Education: It Is About More Than Learning English
Authors: Bennett Jo , Jaradat Maram
Published: May 2011

In this case study, you are the associate superintendent and chief academic officer (CAO) of a large school district in the southwest. The case involves the complex issue of how to serve the burgeoning adolescent immigrant population in your school district. The study considers how a school that is situated in the heart of a Hispanic/Latino community can address the academic needs of adolescent newcomer immigrants, both collectively and individually, by making decisions informed by instructional experts. The institutional practices and policies of your school are steeped in memory-laden ways of behaving that have constrained its ability to always be responsive to the school community. You have been working for 4 years with a 2-year International Academy for high school students who are new to the United States and perform lower than the third-grade level on a placement test when they begin as students in the ninth grade. As you work with the school, issues about how decisions are made in the district and at schools are rising to the surface. You have just received a phone call from the principal at the Academy. Teachers in the English department (English as a second language, reading, and composition) have walked out and are threatening to stay away for the rest of the week if some agreement about how to address the language issues at the Academy is not reached.
Female Forces: Beauty, Brains, and a Badge
Authors: Rabe-Hemp Cara E.
Published: May 2011

As a lens through which gender is negotiated and reproduced, this study examines Female Forces, a reality television show, which follows women police in the highly contested task of crime fighting. Results suggest that the media depictions of women police reify the stereotypes that women police are caretakers and nurturers, rather than crime fighters. This is accomplished through an overemphasis on femininity, domestication, and beauty in the officers’ behaviors and narratives. The implications for women police, citizens, and the administrators who hire them are critical as our notions of what female police are and should be are represented, digested, and re-created through television.
How Do the Sexual Behaviors of Foreign-Born Hispanic Men Who Have Sex With Men Differ by Relationship Status?
Authors: De Santis Joseph
Published: May 2011

High-risk sexual behaviors may result in acquisition of sexually transmitted infections including HIV. Hispanic men who have sex with men (MSM) experience a disproportionate incidence of these infections. Various risk factors, cultural aspects, and relationship factors may influence the sexual behaviors of this subgroup of MSM. The purpose of this study was to describe the sexual behaviors of a sample of foreign-born Hispanic MSM and to compare these sexual behaviors in terms of condom usage, risky sexual behaviors, avoidance of body fluids, and sexual negotiation when stratified by relationship status. Using a cross-sectional, descriptive research design, a convenience sample of 135 foreign-born Hispanic MSM, the majority of whom were Cubans, was recruited and surveyed from the South Florida area. The majority of participants reported engaging in the high-risk sexual behaviors of sex without condoms, substance abuse before or during sex, anal sex, contact with body fluids, and did not negotiate safer sex behaviors. Differences in sexual behaviors when compared by relationship status were found only in terms of certain risky sexual behaviors but not in terms of condom usage, contact with body fluids, or sexual negotiation. Despite participation in a number of high-risk activities and finding few differences among those men in relationships and those not in primary relationships, factors that promote or inhibit participation in high-risk sexual behaviors among Hispanic MSM in various types of relationships need further exploration.
A ‘system of light before being a figure of stone’: The phantasmagoric prison
Authors: Fiddler Michael
Published: May 2011

This article explores the uncanny interplay between folk and official readings of Victorian prison architecture. From building designs to cinematic depictions, the visual underpins any understanding of the prison. Using Bakhtin’s notion of heteroglossia, it will be shown how the visual elements of prison buildings, both physical and cinematic, obscure a ‘programmatic organisation of space’. As such, the prison is akin to a ‘phantasmagoria’. Both have visual elements that embrace and encourage an imaginative response, but that also mask a rational core. The term ‘Gothic(k)’ is developed here to describe those elements of the prison that constitute its ‘place-myth’. The prison no longer requires a physical apparatus to project its message or consolidate this place-myth. By drawing upon the Gothic(k) readings of the prison and the analogy of the phantasmagoria, we see how the prison has been fully rendered as a ‘system of light’.
Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice
Authors: Meiler Steffen E. , Wade Marlene , Kutlar Ferdane , Yerigenahally Shobha D. , Xue Yongjun , Moutouh-de Parseval Laure A. , Corral Laura G. , Swerdlow Paul S. , Kutlar Abdullah
Published: May 2011

Pharmacologic induction of fetal hemoglobin (HbF) expression is an effective treatment strategy for sickle cell disease (SCD) and β-thalassemia. Pomalidomide is a potent structural analog of thalidomide and member of a new class of immunomodulatory drugs. Recent reports demonstrated that pomalidomide reduced or eliminated transfusion requirements in certain hematologic malignancies and induced HbF ex vivo in CD34+ progenitor cells from healthy and SCD donors. We investigated the effects of pomalidomide on erythropoiesis and hemoglobin synthesis in a transgenic mouse model of SCD. We found that 8 weeks of treatment with pomalidomide induced modest increases of HbF with similar efficacy as hydroxyurea. However, in stark contrast to hydroxyurea's myelosuppressive effects, pomalidomide augmented erythropoiesis and preserved bone marrow function. Surprisingly, combinatory therapy with both drugs failed to mitigate hydroxyurea's myelotoxic effects and caused loss of HbF induction. These findings support further evaluation of pomalidomide as a novel therapy for SCD.
DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway
Authors: Lambert Alexandra A. , Barabé Frédéric , Gilbert Caroline , Tremblay Michel J.
Published: May 2011

Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor expressed at high levels on dendritic cells (DCs). This surface molecule acts as an attachment factor for HIV-1 on DCs and contributes to trans- and cis-infection pathways. Moreover, DICR is induced by HIV-1 in CD4+ T cells and promotes virus replication in this cell type. Nothing is known hitherto about the DCIR-dependent signaling, which is induced following HIV-1 ligation. First, specific pharmacologic inhibitors were tested on HIV-1 binding/entry and, second, specific antisense oligonucleotides targeted, more specifically kinases and phosphatases, were used. Our results show that SHP-1, SHP-2, Syk, and Src kinases (ie, Src, Fyn, and Hck) as well as PKC-α and MAP kinases (ie, Erk1/2 and p38) are all involved in the DCIR-mediated signal transduction pathway triggered by HIV-1. By mutagenesis and through the use of intracellular phosphorylated peptides, we show as well a pivotal role for the tyrosine and threonine residues of the DCIR immunoreceptor tyrosine-based inhibitory motif (ITIM). Our data suggest for the first time an involvement of ITIM domain in HIV-1–mediated signaling events and a relationship between phosphorylation events and DCIR function with respect to HIV-1 biology.
A study of toxicity and differential gene expression in murine liver following exposure to anti-malarial drugs: amodiaquine and sulphadoxine-pyrimethamine
Authors: Mishra Shrawan Kumar , Singh Prabhat , Rath Srikanta Kumar
Published: May 2011

Background

Amodiaquine (AQ) along with sulphadoxine-pyrimethamine (SP) offers effective and cheaper treatment against chloroquine-resistant falciparum malaria in many parts of sub-Saharan Africa. Considering the previous history of hepatitis, agranulocytosis and neutrocytopenia associated with AQ monotherapy, it becomes imperative to study the toxicity of co-administration of AQ and SP. In this study, toxicity and resulting global differential gene expression was analyzed following exposure to these drugs in experimental Swiss mice.

Methods

The conventional markers of toxicity in serum, oxidative stress parameters in tissue homogenates, histology of liver and alterations in global transcriptomic expression were evaluated to study the toxic effects of AQ and SP in isolation and in combination.

Results

The combination therapy of AQ and SP results in more pronounced hepatotoxicity as revealed by elevated level of serum ALT, AST with respect to their individual drug exposure regimen. Furthermore, alterations in the activity of major antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase), indicating the development of oxidative stress, was more significant in AQ+SP combination therapy. cDNA microarray results too showed considerably more perturbed gene expression following combination therapy of AQ and SP as compared to their individual drug treatment. Moreover, a set of genes were identified whose expression pattern can be further investigated for identifying a good biomarker for potential anti-malarial hepatotoxicity.

Conclusion

These observations clearly indicate AQ+SP combination therapy is hepatotoxic in experimental Swiss mice. Microarray results provide a considerable number of potential biomarkers of anti-malarial drug toxicity. These findings hence will be useful for future drug toxicity studies, albeit implications of this study in clinical conditions need to be monitored with cautions.
The emergence of insecticide resistance in central Mozambique and potential threat to the successful indoor residual spraying malaria control programme
Authors: Abilio Ana P , Kleinschmidt Immo , Rehman Andrea M , Cuamba Nelson , Ramdeen Varsha , Mthembu David S , Coetzer Sarel , Maharaj Rajendra , Wilding Craig S , Steven Andrew , Coleman Marlize , Hemingway Janet , Coleman Michael
Published: May 2011

Background

Malaria vector control by indoor residual spraying was reinitiated in 2006 with DDT in Zambézia province, Mozambique. In 2007, these efforts were strengthened by the President's Malaria Initiative. This manuscript reports on the monitoring and evaluation of this programme as carried out by the Malaria Decision Support Project.

Methods

Mosquitoes were captured daily through a series of 114 window exit traps located at 19 sentinel sites, identified to species and analysed for sporozoites. Anopheles mosquitoes were collected resting indoors and tested for insecticide resistance following the standard WHO protocol. Annual cross sectional household parasite surveys were carried out to monitor the impact of the control programme on prevalence of Plasmodium falciparum in children aged 1 to 15 years.

Results

A total of 3,769 and 2,853 Anopheles gambiae s.l. and Anopheles funestus, respectively, were captured from window exit traps throughout the period. In 2010 resistance to the pyrethroids lambda-cyhalothrin and permethrin and the carbamate, bendiocarb was detected in An. funestus. In 2006, the sporozoite rate in An. gambiae s.s. was 4% and this reduced to 1% over 4 rounds of spraying. The sporozoite rate for An. funestus was also reduced from 2% to 0 by 2008. Of the 437 Anopheles arabiensis identified, none were infectious. Overall prevalence of P. falciparum in the sentinel sites fell from 60% to 32% between October 2006 and October 2008.

Conclusion

Both An. gambiae s.s. and An. funestus were controlled effectively with the DDT-based IRS programme in Zambézia, reducing disease transmission and burden. However, the discovery of pyrethroid resistance in the province and Mozambique's policy change away from DDT to pyrethroids for IRS threatens the gains made here.
Epigenetic markers for early detection of nasopharyngeal carcinoma in a high risk population
Authors: Hutajulu Susanna H , Indrasari Sagung R , Indrawati Luh PL , Harijadi Ahmad , Duin Sylvia , Haryana Sofia M , Steenbergen Renske DM , Greijer Astrid E , Middeldorp Jaap M
Published: May 2011

Background

Undifferentiated nasopharyngeal carcinoma (NPC) is strongly related to Epstein-Barr virus (EBV) infection, allowing aberrant antibodies against EBV and viral DNA load as screening tools in high risk populations. Methylation analysis in the promoter of tumor suppressor genes (TSGs) may serve as a complementary marker for identifying early cases. This study determined methylation status of multiple TSGs and evaluated whether it may improve early detection.

Methods

Nasopharyngeal brushings were taken from 53 NPC patients, 22 high risk subjects and 25 healthy EBV carriers. Corresponding NPC paraffin tissue was included. DNA was bisulfite-modified preceding analysis by methylation-specific PCR (MSP). Ten TSGs were studied.

Results

NPC paraffin and brushing DNA revealed an 81.8% concordance so that MSP analysis was done using either one of both specimens. NPC samples showed methylation for individual TSGs (DAPK1 79.2%, CDH13 77.4%, DLC1 76.9%, RASSF1A 75.5%, CADM1 69.8%, p16 66.0%, WIF1 61.2%, CHFR 58.5%, RIZ1 56.6% and RASSF2A 29.2%). High risk individuals, having elevated EBV IgA and viral load, showed high frequency of methylation of CDH13, DAPK1, DLC1 and CADM1, but low frequency of methylation of p16 and WIF1 and undetectable methylation of RASSF1A, CHFR, RIZ1 and RASSF2A. Healthy subjects showed similar patterns as high risk individuals. A combination of RASSF1A and p16 gave good discrimination between NPC and non-NPC, but best results were combined analysis of five methylation markers (RASSF1A, p16, WIF1, CHFR and RIZ1) with detection rate of 98%.

Conclusion

Multiple marker MSP is proposed as a complementary test for NPC risk assessment in combination with EBV-based markers.
Tetherin inhibits prototypic foamy virus release
Authors: Xu Fengwen , Tan Juan , Liu Ruikang , Xu Dan , Li Yue , Geng Yunqi , Liang Chen , Qiao Wentao
Published: May 2011

Background

Tetherin (also known as BST-2, CD317, and HM1.24) is an interferon- induced protein that blocks the release of a variety of enveloped viruses, such as retroviruses, filoviruses and herpesviruses. However, the relationship between tetherin and foamy viruses has not been clearly demonstrated.

Results

In this study, we found that tetherin of human, simian, bovine or canine origin inhibits the production of infectious prototypic foamy virus (PFV). The inhibition of PFV by human tetherin is counteracted by human immunodeficiency virus type 1 (HIV-1) Vpu. Furthermore, we generated human tetherin transmembrane domain deletion mutant (delTM), glycosyl phosphatidylinositol (GPI) anchor deletion mutant (delGPI), and dimerization and glycosylation deficient mutants. Compared with wild type tetherin, the delTM and delGPI mutants only moderately inhibited PFV production. In contrast, the dimerization and glycosylation deficient mutants inhibit PFV production as efficiently as the wild type tetherin.

Conclusions

These results demonstrate that tetherin inhibits the release and infectivity of PFV, and this inhibition is antagonized by HIV-1 Vpu. Both the transmembrane domain and the GPI anchor of tetherin are important for the inhibition of PFV, whereas the dimerization and the glycosylation of tetherin are dispensable.
Dynamic distribution and tissue tropism of classical swine fever virus in experimentally infected pigs
Authors: Liu Jun , Fan Xue-Zheng , Wang Qin , Xu Lu , Zhao Qi-Zu , Huang Wei , Zhou Yuan-Cheng , Tang Bo , Chen Lei , Zou Xing-Qi , Sha Sha , Zhu Yuan-Yuan
Published: May 2011

Background

Classical swine fever (CSF), caused by the Classical swine fever virus (CSFV), is an Office International des Epizooties (OIE) notifiable disease. However, we are far from fully understand the distribution, tissue tropism, pathogenesis, replication and excretion of CSFV in pigs. In this report, we investigated the dynamic distribution and tissue tropism of the virus in internal organs of the experimentally infected pigs using real-time RT-PCR and immunohistochemistry (IHC).

Results

A relative quantification real-time PCR was established and used to detect the virus load in internal organs of the experimentally infected pigs. The study revealed that the virus was detected in all 21 of the internal organs and blood collected from pigs at day 1 to day 8 post infections, and had an increasing virus load from day 1 to day 8 post infections. However, there was irregular distribution virus load in most internal organs over the first 2 days post infection. Blood, lymphoid tissue, pancreas and ileum usually contain the highest viral loads, while heart, duodenum and brain show relatively low viral loads.

Conclusions

All the data suggest that CSFV had an increasing virus load from day 1 to day 8 post infections in experimentally infected pigs detected by real-time RT-PCR, which was in consistent with the result of the IHC staining. The data also show that CSFV was likely to reproduce in blood, lymphoid tissue, pancreas and the ileum, while unlikely to replicate in the heart, duodenum and brain. The results provide a foundation for further clarification of the pathogenic mechanism of CSFV in internal organs, and indicate that blood, lymphoid tissue, pancreas and ileum may be preferred sites of acute infection.
The potential for bi-lateral agreements in medical tourism: A qualitative study of stakeholder perspectives from the UK and India
Authors: Martínez Álvarez Melisa , Chanda Rupa , Smith Richard D
Published: May 2011

Background

Globalisation has prompted countries to evaluate their position on trade in health services. However, this is often done from a multi-lateral, rather than a regional or bi-lateral perspective. In a previous review, we concluded that most of the issues raised could be better addressed from a bi-lateral relationship. We report here the results of a qualitative exercise to assess stakeholders' perceptions on the prospects for such a bi-lateral system, and its ability to address concerns associated with medical tourism.

Methods

30 semi-structured interviews were carried out with stakeholders, 20 in India and 10 in the UK, to assess their views on the potential offered by a bi-lateral relationship on medical tourism between both countries. Issues discussed include data availability, origin of medical tourists, quality and continuity of care, regulation and litigation, barriers to medical tourism, policy changes needed, and prospects for such a bi-lateral relationship.

Results

The majority of stakeholders were concerned about the quality of health services patients would receive abroad, regulation and litigation procedures, lack of continuity of care, and the effect of such trade on the healthcare available to the local population in India. However, when considering trade from a bi-lateral point of view, there was disagreement on how these issues would apply. There was further disagreement on the importance of the Diaspora and the validity of the UK's 'rule' that patients should not fly more than three hours to obtain care. Although the opinion on the prospects for an India-UK bi-lateral relationship was varied, there was no consensus on what policy changes would be needed for such a relationship to take place.

Conclusions

Whilst the literature review previously carried out suggested that a bi-lateral relationship would be best-placed to address the concerns regarding medical tourism, there was scepticism from the analysis provided in this paper based on the over-riding feeling that the political 'cost' involved was likely to be the major impediment. This makes the need for better evidence even more acute, as much of the current policy process could well be based on entrenched ideological positions, rather than secure evidence of impact.
Vitamin D Receptor Protein Expression in Tumor Tissue and Prostate Cancer Progression
Authors: Hendrickson Whitney K. , Flavin Richard , Kasperzyk Julie L. , Fiorentino Michelangelo , Fang Fang , Lis Rosina , Fiore Christopher , Penney Kathryn L. , Ma Jing , Kantoff Philip W. , Stampfer Meir J. , Loda Massimo , Mucci Lorelei A. , Giovannucci Edward
Published: May 2011

Purpose

Data suggest that circulating 25-hydroxyvitamin D [25(OH)D] interacts with the vitamin D receptor (VDR) to decrease proliferation and increase apoptosis for some malignancies, although evidence for prostate cancer is less clear. How VDR expression in tumor tissue may influence prostate cancer progression has not been evaluated in large studies.

Patients and Methods

We examined protein expression of VDR in tumor tissue among 841 patients with prostate cancer in relation to risk of lethal prostate cancer within two prospective cohorts, the Physicians' Health Study and Health Professionals Follow-Up Study. We also examined the association of VDR expression with prediagnostic circulating 25(OH)D and 1,25-dihydroxyvitamin D levels and with two VDR single nucleotide polymorphisms, FokI and BsmI.

Results

Men whose tumors had high VDR expression had significantly lower prostate-specific antigen (PSA) at diagnosis (P for trend < .001), lower Gleason score (P for trend < .001), and less advanced tumor stage (P for trend < .001) and were more likely to have tumors harboring the TMPRSS2:ERG fusion (P for trend = .009). Compared with the lowest quartile, men whose tumors had the highest VDR expression had significantly reduced risk of lethal prostate cancer (hazard ratio [HR], 0.17; 95% CI, 0.07 to 0.41). This association was only slightly attenuated after adjustment for Gleason score and PSA at diagnosis (HR, 0.33; 95% CI, 0.13 to 0.83) or, additionally, for tumor stage (HR, 0.37; 95% CI, 0.14 to 0.94). Neither prediagnostic plasma vitamin D levels nor VDR polymorphisms were associated with VDR expression.

Conclusion

High VDR expression in prostate tumors is associated with a reduced risk of lethal cancer, suggesting a role of the vitamin D pathway in prostate cancer progression.