bluuebunny/crossref_metadata_2025 huggingface dataset:
Late Pulmonary, Cardiovascular, and Renal Complications after Hematopoietic Stem Cell Transplantation and Recommended Screening Practices
Authors: Tichelli André , Rovó Alicia , Gratwohl Alois
Published: December 2008

Non-malignant late effects after hematopoietic stem cell transplantation (HSCT) are heterogeneous in nature and intensity. The type and severity of the late complications depend on the type of transplantation and the conditioning regimen applied. Based on the most recent knowledge, we discuss three typical non-malignant complications in long-term survivors after HSCT, namely pulmonary, cardiovascular and renal complications. These complications illustrate perfectly the great diversity in respect of frequency, time of appearance, risk factors, and outcome. Respiratory tract complications are frequent, appear usually within the first two years, are closely related to chronic graft-versus-host disease (GVHD) and are often of poor prognosis. Cardiac and cardiovascular complications are mainly related to cardiotoxic chemotherapy and total body irradiation, and to the increase of cardiovascular risk factors. They appear very late after HSCT, with a low magnitude of risk during the first decade. However, their incidence might increase significantly with longer follow-up. The chronic kidney diseases are usually asymptomatic until end stage disease, occur within the first decade after HSCT, and are mainly related with the use of nephrotoxic drugs such as calcineurin inhibitors. We will discuss the practical screening recommendations that could assist practitioner in the follow-up of long-term survivors after HSCT.
The Regulation of Hepcidin and Its Effects on Systemic and Cellular Iron Metabolism
Authors: Fleming Mark D.
Published: December 2008

Systemic iron homeostasis depends on the regulated expression of hepcidin, a peptide hormone that negatively regulates iron egress from intestinal cells and macrophages by altering the expression of the cellular iron exporter ferroportin. In doing so, hepcidin can control both the total body iron by modulating intestinal iron absorption as well as promote iron available for erythropoiesis by affecting the efficiency with which macrophages recycle iron from effete red blood cells. This review focuses on the systemic and cellular physiology of hepcidin regulation in relation to iron stores, erythropoiesis, inflammation, and hypoxia and how hepcidin regulation and dysregulation contributes to normal iron homeostasis and iron metabolism disorders.
Gene Replacement Therapy for Sickle Cell Disease and Other Blood Disorders
Authors: Townes Tim M.
Published: December 2008

Previous studies have demonstrated that sickle cell disease (SCD) can be corrected in mouse models by transduction of hematopoietic stem cells with lentiviral vectors containing anti-sickling globin genes followed by transplantation of these cells into syngeneic recipients. Although self-inactivating (SIN) lentiviral vectors with or without insulator elements should provide a safe and effective treatment in humans, some concerns about insertional mutagenesis persist. An ideal correction would involve replacement of the sickle globin gene (βS) with a normal copy of the gene (βA). We recently derived embryonic stem (ES) cells from a novel knockin mouse model of SCD and tested a protocol for correcting the sickle mutation by homologous recombination. Animals derived after gene replacement produced high levels of normal human hemoglobin (HbA), and the pathology associated with SCD was corrected. These experiments provided a foundation for similar studies in which our group collaborated with Rudolf Jaenisch’s laboratory to correct SCD by gene replacement in iPS (induced pluripotent stem) cells derived by direct reprogramming of sickle skin fibroblasts. Corrected iPS cells were differentiated into hematopoeitic progenitors that were transplanted into irradiated sickle recipients. The transplanted animals produced high levels of normal human HbA, and the pathology of SCD was corrected. These proof-of-principle studies provide a foundation for the development of gene replacement therapy for human patients with SCD and other blood disorders.
Which Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Should Be Treated with Eculizumab?
Authors: Haspel Richard L. , Hillmen Peter
Published: December 2008

A 45-year-old woman presents for evaluation as a result of persistent anemia. Ultimately, she is diagnosed with hemolytic anemia ascribed to paroxysmal nocturnal hemoglobinuria. She is otherwise well and has an otherwise normal complete blood cell count. She requires transfusion about once every 6 weeks for symptomatic anemia. She wonders whether she would benefit from eculizumab.
Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia When a Matched Related Donor Is Not Available
Authors: Appelbaum Frederick R.
Published: December 2008

Although for many patients with acute myeloid leukemia (AML) allogeneic hematopoietic cell transplantation (HCT) from a matched related donor provides the best, and sometimes the sole chance for cure, only about 30% of individuals have HLA-matched family members. Fortunately, recent advances on a number of fronts have expanded the acceptable donor pool. With the use of high-resolution typing, HCT outcomes using unrelated donors matched at HLA-A, -B, -C and -DRB1 give results very similar to those expected with matched related donors. A single mismatch, as determined either by low- or high-resolution testing, results in modestly worse outcomes, with mismatches at B or C better tolerated than mismatches at A or DRB1. Initial results of umbilical cord blood transplantation for adults showed a clear association of cell dose and outcome, limiting the procedure to a minority of adults where cord bloods with at least 2.5 or 3 × 107 total nucleated cells/kg could be found. More recently, the use of double cord transplants has shown considerable promise, lowering the risk of graft rejection and possibly the risk of relapse as well. Haploidentical transplantation using T-cell–replete marrow and post-transplant high-dose cyclophosphamide, or T-cell–depleted peripheral blood and marrow containing high doses of CD34+ cells is under investigation. Together, these various approaches are broadening the transplant options for patients with AML.
MDS: A Stem Cell Disorder—But What Exactly Is Wrong with the Primitive Hematopoietic Cells in This Disease?
Authors: Nimer Stephen D.
Published: December 2008

Despite the various abnormalities identified in the immune system or the bone marrow microenvironment in patients with myelodysplastic syndrome (MDS), most of the investigation of this disorder has centered on the hematopoietic stem/progenitor compartment. It is generally written that MDS is a stem cell disorder, and there is certainly evidence supporting this view. However, whether it occurs in a cell with only myeloid multipotentiality (i.e., that involves megakaryocytic, erythroid and granulocytic/monocytic lineages) or occurs in a true stem cell is open to debate. The absence of an assay for human stem cells necessitates the use of surrogate markers for such cells, such as gene expression profiles, or the identification of specific genetic or epigenetic abnormalities that are found in multiple lineages. Clearly, the common cytogenetic and genetic abnormalities found in MDS are most indicative of a clonal myeloid disease similar to AML, rather than a lymphoid disease, and the often tri-lineage ineffective hematopoiesis and dysplasia are generally not found within the lymphoid compartment. Recent studies, using modern molecular detection techniques, have identified new recurring molecular lesions in these disorders but have not really unraveled its pathogenesis.
Molecular Profiling in CLL
Authors: Gribben John G.
Published: December 2008

Chronic lymphocytic leukemia (CLL) has an extremely heterogeneous clinical course, with some patients requiring immediate therapy and others living without need for treatment for decades. There has been considerable interest in the underlying molecular mechanisms of this heterogeneity to understand not only the expected clinical course for individual patients but also the underlying pathogenesis of this disease. A number of clinical parameters have been identified that are predictive of the clinical course. More recently, a number of molecular biomarkers, most notably cytogenetics by fluorescent in situ hybridization (FISH), immunoglobulin heavy chain (IgVH) mutational status and expression of ZAP70, have been identified and verified as also providing prognostic information. The current challenge is to understand how we should use this new information in clinical practice and whether we should alter treatment based upon the detection of “high-risk” features. Over the past decade there has been considerable progress in development of more effective treatments for CLL, but current consensus is that treatment of CLL should be based upon the treatment of symptomatic disease. Specific treatment decisions based upon the detection of “high-risk” features remains a question for clinical trials, which will address the potential value of early treatment for specific groups of patients and whether all patients with CLL should receive a standard treatment or whether treatment should be modified in different risk groups.
Epigenetic Modulation and Other Options to Improve Outcome of Stem Cell Transplantation in MDS
Authors: Kröger Nicolaus
Published: December 2008

Allogeneic stem cell transplantation can cure patients with myelodysplastic syndromes. However, more than 50% of the patients who underwent allogeneic stem cell transplantation have failed to benefit from this treatment approach either due to treatment-related mortality or to relapse. The introduction of toxicity or dose-reduced conditioning has significantly reduced the treatment-related mortality but did not affect the risk of relapse. New effective drugs, such as hypomethylating agents, histone-deacetylase inhibitors or lenalidomide, can be used alone or in combination to improve the pretransplant remission status before allogeneic stem cell transplantation or after transplantation to prevent relapse as maintenance or consolidation therapy. This review will focus on these new possibilities and give some perspectives as to how the results of allogeneic stem cell transplantation can be further improved
New Advances in the Pathogenesis and Therapy of Essential Thrombocythemia
Authors: Levine Ross L. , Heaney Mark
Published: December 2008

Essential thrombocythemia (ET) is a hematopoietic disorder that manifests clinically as thrombocytosis, and patients with ET are at increased risk for developing thrombosis, myelofibrosis, and transformation to acute myeloid leukemia. Although ET was recognized as a distinct clinical syndrome more than 6 decades ago and was classified as a myeloproliferative neoplasm (MPN) by William Dameshek in 1951, the molecular pathogenesis of ET remained unknown until 2005, when activating mutations in the JAK2 tyrosine kinase (JAK2V617F) were identified in a significant proportion of patients with ET, polycythemia vera (PV) and primary myelofibrosis (PMF). In addition, subsequent studies have identified gain-of-function mutations in the thrombopoietin receptor (MPL) in a subset of patients with JAK2V617F-negative ET, suggesting that JAK2 activation by distinct mechanisms contributes to the pathogenesis of ET. Despite these important observations, important questions remain regarding the role of JAK2/MPL mutations in ET pathogenesis, the etiology of JAK2/MPL negative ET, the factors that distinguish ET from other MPNs with the JAK2V617F mutation, and the role of JAK2-targeted therapies for the treatment of these MPNs.
Plasma brain natriuretic peptide as a surrogate marker for cardioembolic stroke
Authors: Yukiiri Kazushi , Hosomi Naohisa , Naya Takayuki , Takahashi Tsutomu , Ohkita Hiroyuki , Mukai Mao , Masugata Hisashi , Murao Koji , Ueno Masaki , Nakamura Takehiro , Dobashi Hiroaki , Miki Takanori , Kuroda Yasuhiro , Kohno Masakazu
Published: December 2008

Background

Cardioembolic stroke generally results in more severe disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic stroke from non-cardioembolic stroke (atherothrombotic stroke and lacunar stroke). In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic stroke or non-cardioembolic stroke, and assessed the prediction factors of plasma brain natriuretic peptide and whether we could differentiate between stroke subtypes on the basis of plasma brain natriuretic peptide concentrations in addition to patient's clinical variables.

Methods

Our patient cohort consisted of 131 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005 to December 31, 2007. The mean age of patients (43 females, 88 males) was 69.6 ± 10.1 years. Sixty-two patients had cardioembolic stroke; the remaining 69 patients had non-cardioembolic stroke (including atherothrombotic stroke, lacunar stroke, or the other). Clinical variables and the plasma brain natriuretic peptide were evaluated in all patients.

Results

Plasma brain natriuretic peptide was linearly associated with atrial fibrillation, heart failure, chronic renal failure, and left atrial diameter, independently (F4,126 = 27.6, p < 0.0001; adjusted R2 = 0.45). Furthermore, atrial fibrillation, mitral regurgitation, plasma brain natriuretic peptide (> 77 pg/ml), and left atrial diameter (> 36 mm) were statistically significant independent predictors of cardioembolic stroke in the multivariable setting (Χ2 = 127.5, p < 0.001).

Conclusion

It was suggested that cardioembolic stroke was strongly predicted with atrial fibrillation and plasma brain natriuretic peptide. Plasma brain natriuretic peptide can be a surrogate marker for cardioembolic stroke.
Biased selection of leading process branches mediates chemotaxis during tangential neuronal migration
Authors: Martini Francisco J. , Valiente Manuel , López Bendito Guillermina , Szabó Gábor , Moya Fernando , Valdeolmillos Miguel , Marín Oscar
Published: December 2008

Current models of chemotaxis during neuronal migration and axon guidance propose that directional sensing relies on growth cone dynamics. According to this view, migrating neurons and growing axons are guided to their correct targets by steering the growth cone in response to attractive and repulsive cues. Here, we have performed a detailed analysis of the dynamic behavior of individual neurons migrating tangentially in telencephalic slices using high-resolution time-lapse videomicroscopy. We found that cortical interneurons consistently display branched leading processes as part of their migratory cycle, a feature that seems to be common to many other populations of GABAergic neurons in the brain and spinal cord. Analysis of the migratory behavior of individual cells suggests that interneurons respond to chemoattractant signals by generating new leading process branches that are better aligned with the source of the gradient, and not by reorienting previously existing branches. Moreover, experimental evidence revealed that guidance cues influence the angle at which new branches emerge. This model is further supported by pharmacological experiments in which inhibition of branching blocked chemotaxis, suggesting that this process is an essential component of the mechanism controlling directional guidance. These results reveal a novel guidance mechanism during neuronal migration that might be extensively used in brain development.
Evidence for a composite anterior determinant in the hover flyEpisyrphus balteatus(Syrphidae), a cyclorrhaphan fly with an anterodorsal serosa anlage
Authors: Lemke Steffen , Schmidt-Ott Urs
Published: December 2008

Most insect embryos develop from a monolayer of cells around the yolk, but only part of this blastoderm forms the embryonic rudiment. Another part forms extra-embryonic serosa. Size and position of the serosa anlage vary between species, and previous work raises the issue of whether such differences co-evolve with the mechanisms that establish anteroposterior (AP) polarity of the embryo. AP polarity of the Drosophila embryo depends on bicoid, which is necessary and sufficient to determine the anterior body plan. Orthologs of bicoid have been identified in various cyclorrhaphan flies and their occurrence seems to correlate with a mid-dorsal serosa or amnioserosa anlage. Here, we introduce with Episyrphus balteatus (Syrphidae) a cyclorrhaphan model for embryonic AP axis specification that features an anterodorsal serosa anlage. Current phylogenies place Episyrphus within the clade that uses bicoid mRNA as anterior determinant, but no bicoid-like sequence could be identified in this species. Using RNA interference (RNAi) and ectopic mRNA injection, we obtained evidence that pattern formation along the entire AP axis of the Episyrphus embryo relies heavily on the precise regulation of caudal, and that anterior pattern formation in particular depends on two localized factors rather than one. Early zygotic activation of orthodenticle is separated from anterior repression of caudal, two distinct functions which in Drosophila are performed jointly by bicoid, whereas hunchback appears to be regulated by both factors. Furthermore, we found that overexpression of orthodenticle is sufficient to confine the serosa anlage of Episyrphus to dorsal blastoderm. We discuss our findings in a phylogenetic context and propose that Episyrphus employs a primitive cyclorrhaphan mechanism of AP axis specification.
On the Salience of Ethnic Conflict
Authors: Esteban Joan , Ray Debraj
Published: December 2008

A classical theme in social analysis views economic class divisions as the main cause of social conflict. Yet many, if not most of the conflicts we observe today appear to be ethnic in nature. It appears that the "vertical" nature of class divisions is often dominated by the "horizontal" antagonisms across groups delineated by noneconomic markers. This paper highlights the perverse synergy of economic inequality within ethnic groups, and its role in the salience of ethnic conflict. In a model of group formation which allows both class and ethnic groupings to emerge, we show that ethnic, as opposed to class, conflict may be focal, and precisely in the presence of economic inequality. (JEL D72, D74)
Words Alone are Certain Good(s): Philology and Greek Material Culture
Authors: Martin Richard P.
Published: December 2008

The relation between philology and the study of material culture within Classics has been long and complex. Where does it now stand? At the request of the editor of TAPA , in conjunction with the journal’s recent focus on material culture, the author attempts to sum up some major trends. After an overview of historical developments, this article investigates the current practices and positions of those who are trying to bridge the divide between the “dirt” and the “word.” A fourfold set of common methodological approaches is described, followed by a fourfold division of ways in which text and object might be seen as interacting.
Narratology and Linguistics: An Interdisciplinary Perspective on Homeric Speech Representation
Authors: Beck Deborah
Published: December 2008

This paper examines the different forms of speech representation in the Iliad and the Odyssey using both linguistics and narratological theory. Heretofore, narratologists working on Homeric poetry have paid little attention to non-direct modes of speech representation, which this paper argues can best be understood as complementary to direct speech with their own distinct functions in the overall structure of the poems. The linguistic speech act type of a given speech plays a prominent role in how that speech is represented. We understand both non-direct speech and direct speech more fully if we explain how these techniques work alongside one another. Moreover, we will see that the Iliad and the Odyssey share a broadly consistent approach to speech representation, but each poem uses the speech representational spectrum to depict different types of speech.
Placing Greco-Roman History in World Historical Context
Authors: Pollard Elizabeth Ann
Published: December 2008

Increased influence of world historical models for periodization, state content standards for history, and assessment instruments such as the AP and SAT II all demonstrate that Greco-Roman historians must become more involved in the pedagogy of world history and in the production of scholarship to inform that teaching. This article investigates several leading world historical periodization models, as well as the problematic translation of those models into content standards and standardized tests, in order to explore the problems and possibilities of how to place Greco-Roman history into world historical context in both teaching and scholarly publication.
Extravagant Postcolonialism: Ethics and Individualism in Anglophonic, Anglocentric Postcolonial Fiction; or, “What Was (This) Postcolonialism?”
Authors: May Brian
Published: December 2008

“Extravagant Postcolonialism” takes up the issue of postcolonial individualism, the larger claim being that postcolonial fiction by and large distinguishes the rare, imaginative, “extravagant” individual as uniquely capable of ethical apprehension and action. I begin by considering a question of postcolonial justice, the “economic” version of which postcolonial fiction tends to eschew as unethical. Having demonstrated how these fictions associate ethical intuition with something a little less business-like--what Gayatri Spivak calls, adapting Freud, “postcolonial nostalgia”--I go on (in the final section) to show how postcolonial nostalgia may be regarded as a fundamentally imaginative, private, and authoritative mode of consciousness. This last section of the essay also shows how nostalgia at times takes the form of a recognizably “modernist” epiphany. Postcolonialism of the extravagant variety, I conclude, has more in common with modernism than with the kind of avowedly transcendent contemporaneity that now goes by the name “postmodernism.”
Allegorical Agency and the Sins of Angels
Authors: Escobedo Andrew
Published: December 2008

This essay reevaluates the relationship between personification and agency—taking Milton’s Paradise Lost as a primary example—and in the process offer some insights into our conventional ideas about the agency of “literal” characters in narrative. Personifications exercise a volition radically divided between causality and freedom, I argue, whereas literal characters produce the impression of free agency not so much by resembling real people as by accepting a compromise with narrative determinism. This essay explores these issues first by examining a decidedly non-allegorical figure, Milton’s Satan, who in heaven makes the most perplexing choice in the history of literature, and then by looking at the appearance of the most peculiar character in the poem, Milton’s Sin.
A Portrait of the Artist as a Young Man and the “Individuating Rhythm” of Modernity
Authors: Boes Tobias
Published: December 2008

In this essay, I reexamine the relationship between Joyce’s novel and the Bildungsroman tradition and argue that the distinctive form of A Portrait is the result of Joyce’s attempts to adapt the genre to the demands of Irish modernity. Drawing in equal parts on the poetics of Mikhail Bakhtin and Henri Lefebvre’s sociological “rhythmanalysis,” I show how Stephen Dedalus’s peculiar developmental trajectory, caught between progressive and regressive elements, mirrors the situation of his country, which was similarly entangled in a web of contradictory conceptions of historical development.
The Primitive Mind of Silas Marner
Authors: Neill Anna
Published: December 2008

This essay investigates the peculiar phenomenon of catalepsy in the context of Eliot’s narrative realism. The primitive mental state depicted in Silas Marner and those reduced social forms that it engenders together obstruct the operation of sympathy—a key feature of Eliot’s organicist aesthetics. Catalepsy, with its sudden and inexplicable reduction of the organism to purely automatic functions, at once bars the narrator from the character’s consciousness and prevents an intuitive study of mind-world through the organs of sympathy that, in Eliot’s other novels, complements the scientific exploration of nature’s still unknown laws.
Improving Professional Judgments of Risk and Amenability in Juvenile Justice
Authors: Mulvey Edward P. , Iselin Anne-Marie R.
Published: December 2008

The dual requirement to ensure community safety and promote a youthful offender's positive development permeates policy and frames daily practice in juvenile justice. Balancing those two demands, explain Edward Mulvey and Anne-Marie Iselin, requires justice system professionals at all levels to make extremely difficult decisions about the likely risk and amenability to treatment of adolescent offenders. Mulvey and Iselin point out that although various forms of "structured" decision-making instruments are used widely in other fields, juvenile justice professionals today make limited use of these tools. Instead, they make decisions based mainly on their intuition about whether the adolescent before them is more likely to harm the community or to use justice system services to turn his life around. The reluctance of busy court professionals to use these structured decision-making tools, they say, arises partly from their heavy work load. But it also grows out of the ethos of the juvenile court itself. Restricting an adolescent's freedom or access to interventions based on a tallying of empirical data is antithetical to viewing each adolescent as a unique individual whose life chances may remain intact with developmentally appropriate intervention. Mulvey and Iselin recommend and examine three ways to integrate structured judgment approaches into the juvenile justice system that both capitalize on their strengths and support the court's attempts to provide fair, individualized justice. First, more reliance on actuarial methods at detention and intake would promote more efficient and equitable screening of cases for subsequent court involvement. Second, the use of structured decision making by probation officers could provide more consistent and valid guidance for the court when formulating dispositions. Finally, implementing structured data systems to chart the progress of adolescents in placement could allow judges to oversee service providers more effectively. The challenge for the juvenile system, say the authors, will be to harness the new capacities of the science of decision making and of computer technology to increase the efficiency of its limited resources for the benefit both of the community and of the adolescents in the system.
Juvenile Justice and Substance Use
Authors: Chassin Laurie
Published: December 2008

Laurie Chassin focuses on the elevated prevalence of substance use disorders among young offenders in the juvenile justice system and on efforts by the justice system to provide treatment for these disorders. She emphasizes the importance of diagnosing and treating these disorders, which are linked both with continued offending and with a broad range of negative effects, such as smoking, risky sexual behavior, violence, and poor educational, occupational, and psychological outcomes. The high rates of substance use problems among young offenders, says Chassin, suggest a large need for treatment. Although young offenders are usually screened for substance use disorders, Chassin notes the need to improve screening methods and to ensure that screening takes place early enough to allow youths to be diverted out of the justice system into community-based programs when appropriate. Cautioning that no single treatment approach has been proven most effective, Chassin describes current standards of "best practices" in treating substance use disorders, examines the extent to which they are implemented in the juvenile justice system, and describes some promising models of care. She highlights several treatment challenges, including the need for better methods of engaging adolescents and their families in treatment and the need to better address environmental risk factors, such as family substance use and deviant peer networks, and co-occurring conditions, such as learning disabilities and other mental health disorders. Chassin advocates policies that encourage wider use of empirically validated therapies and of documented best practices for treating substance use disorders. High relapse rates among youths successfully treated for substance use disorders also point to a greater need for aftercare services and for managing these disorders as chronic illnesses characterized by relapse and remission. A shortage of aftercare services and a lack of service coordination in the juvenile justice system, says Chassin, suggest the need to develop treatment models that integrate and coordinate multiple services for adolescent offenders, particularly community-based approaches, both during and after their justice system involvement.
Prevention and Intervention Programs for Juvenile Offenders
Authors: Greenwood Peter
Published: December 2008

Over the past decade researchers have identified intervention strategies and program models that reduce delinquency and promote pro-social development. Preventing delinquency, says Peter Greenwood, not only saves young lives from being wasted, but also prevents the onset of adult criminal careers and thus reduces the burden of crime on its victims and on society. It costs states billions of dollars a year to arrest, prosecute, incarcerate, and treat juvenile offenders. Investing in successful delinquency-prevention programs can save taxpayers seven to ten dollars for every dollar invested, primarily in the form of reduced spending on prisons. According to Greenwood, researchers have identified a dozen "proven" delinquency-prevention programs. Another twenty to thirty "promising" programs are still being tested. In his article, Greenwood reviews the methods used to identify the best programs, explains how program success is measured, provides an overview of programs that work, and offers guidance on how jurisdictions can shift toward more evidence-based practices The most successful programs are those that prevent youth from engaging in delinquent behaviors in the first place. Greenwood specifically cites home-visiting programs that target pregnant teens and their at-risk infants and preschool education for at-risk children that includes home visits or work with parents. Successful school-based programs can prevent drug use, delinquency, anti-social behavior, and early school drop-out. Greenwood also discusses community-based programs that can divert first-time offenders from further encounters with the justice system. The most successful community programs emphasize family interactions and provide skills to the adults who supervise and train the child. Progress in implementing effective programs, says Greenwood, is slow. Although more than ten years of solid evidence is now available on evidence-based programs, only about 5 percent of youth who should be eligible participate in these programs. A few states such as Florida, Pennsylvania, and Washington have begun implementing evidence-based programs. The challenge is to push these reforms into the mainstream of juvenile justice.
Back to the World
Authors: Bajac Vladislav
Published: December 2008

During the early 1990s, following the collapse of the Soviet Union, the six republics of the former Yugoslavia began to break apart, beginning with a declaration of independence by Slovenia in 1991. The declaration was challenged by the forces of the Yugoslav People's Army, directed from Belgrade, Serbia. Full-scale war spread to the other Yugoslav republics, and in 1999, nato forces intervened. A massive bombing campaign of Serbia and Kosovo lasted seventy-eight days, and included the targeting of Belgrade. At the time, public opinion in the West was inflamed against Serbia and the Serbian people in general, who were seen as supporting the policies of President Slobodan Milos.ević. u.s. President Bill Clinton defended the bombing, calling it necessary to stop the Serbs from committing genocide. Following the war, President Milos.ević was arrested, then charged by the u.n.'s International Criminal Tribunal for the former Yugoslavia with crimes against humanity; he died at The Hague while awaiting trial.—Editor
The Native Encounter with Christianity: Franciscans and Nahuas in Sixteenth-Century Mexico
Authors: Morales Francisco OFM
Published: December 2008

Among the nations of the New World, Mexico is probably the country in which the Franciscans worked most intensively. Having been the first missionaries to arrive in Mexico, they covered most of its territory and worked with numerous native groups: Nahuas, Otomies, Mazahuas, Huastecas, Totonacas, Tarascans, Mayas. Their intense missionary activity is evident in the many indigenous languages the Franciscans learned, the grammars and vocabularies they wrote, the numerous Biblical texts they translated, and the catechisms they wrote with ideographical techniques quite alien to the European mind. This activity left an indelible mark in Mexico, a mark still alive in popular traditions, monumental constructions, popular devotions, and folk art. Without a doubt, in spite of the continuous growth of the Spanish and Mestizo populations during colonial times, the favorite concern of Franciscan pastoral activity was the indigenous population. Thus, Franciscan schools and colleges, hospitals, and publications were addressed to it. For their part, the native population showed the same preference for the Franciscans. To the eyes of the civil and ecclesiastical authorities, Franciscans and natives appeared as an inseparable body, an association not always welcomed by the Spanish Crown. In fact, since the middle of the sixteenth century bishops and royal officials tried to separate them, assigning secular priests in the native towns and limiting the ecclesiastical authority of the friars.
Saving the Nation Through Exclusion: Alien Laws in the Early Republic in the United States and Mexico
Authors: Pani Erika
Published: December 2008

In 1798, the U.S. Congress enacted a series of laws that affected resident aliens by restricting their access to citizenship and making those deemed to be “dangerous to the peace and safety of the Unites States” subject to deportation at the will of the Executive. In 1827, the Mexican government enacted the first of three laws for the expulsion of Spaniards, which ordered the removal of those born on the Spanish peninsula. In both cases, these laws went against the premises for membership that the young nations had set after independence. In both cases, it was argued that such violent measures were necessary to save the nation. As such, they suggest that even though the modern nation is often described as a subjective community, linked by horizontal bonds of solidarity, few mechanisms are as effective in forging an “us” than the construction of a hostile “them.”
The Feast of Corpus Christi: Artisan Crafts and Skilled Trades in Eighteenth-Century Rio de Janeiro
Authors: Cruz Santos Beatriz Catão
Published: December 2008

In this text, motivated by the need to offer a different perspective to the representation of theSenado da Câmara(Municipal Council) in relation to the society that participated in Corpus Christi, I return to the study of the feast in the eighteenth century. The câmara was responsible for the spatial-temporal framework of the ritual in the diverse cities of Portuguese America, among other prerogatives and duties identified and analyzed by the historiography regarding this institution of the Ancien Regime. According to the câmara's minutes, the “Church, the Senate and the People (Povo)” would be present at the feast, thus establishing in the discourse a tripartite and corporative social order that does not identify the participants, whether individuals or the diverse “bodies” that comprised the Church or the people. And, of even greater importance, the câmara's discourse makes reference to the three bodies it claims to represent. However, it is known that if the camara symbolically evokes therespublica(commonwealth) through the organization and appearance at thisroyal feast, in political terms, the participation of elements that comprised the people in the Senado da Câmara, in other words, of the artisan crafts and skilled trades, was restricted to Bahia and Rio de Janeiro for a short period of time.
Spike-Rate Coding and Spike-Time Coding Are Affected Oppositely by Different Adaptation Mechanisms
Authors: Prescott Steven A. , Sejnowski Terrence J.
Published: December 2008

Spike-frequency adaptation causes reduced spiking during prolonged stimulation, but the full impact of adaptation on neural coding is far more complex, especially if one takes into account the diversity of biophysical mechanisms mediating adaptation and the different ways in which neural information can be encoded. Here, we show that adaptation has opposite effects depending on the neural coding strategy and the biophysical mechanism responsible for adaptation. Under noisy conditions, calcium-activated K+current (IAHP) improved efficient spike-rate coding at the expense of spike-time coding by regularizing the spike train elicited by slow or constant inputs; noise power was increased at high frequencies but reduced at low frequencies, consistent with noise shaping that improves coding of low- frequency signals. In contrast, voltage-activated M-type K+current (IM) improved spike-time coding at the expense of spike-rate coding by stopping the neuron from spiking repetitively to slow inputs so that it could generate isolated, well timed spikes in response to fast inputs. Using dynamical systems analysis, we demonstrate howIAHPminimizes perturbation of the interspike interval caused by high- frequency noise, whereasIMminimizes disruption of spike-timing accuracy caused by repetitive spiking. The dichotomous outcomes are related directly to the distinct activation requirements forIAHPandIM, which in turn dictate whether those currents mediate negative feedback onto spiking or membrane potential. Thus, based on their distinct activation properties,IAHPimplements noise shaping that improves spike-rate coding of low-frequency signals, whereasIMimplements high-pass filtering that improves spike-time coding of high- frequency signals.
Spine Neck Plasticity Controls Postsynaptic Calcium Signals through Electrical Compartmentalization
Authors: Grunditz Åsa , Holbro Niklaus , Tian Lei , Zuo Yi , Oertner Thomas G.
Published: December 2008

Dendritic spines have been proposed to function as electrical compartments for the active processing of local synaptic signals. However, estimates of the resistance between the spine head and the parent dendrite suggest that compartmentalization is not tight enough to electrically decouple the synapse. Here we show in acute hippocampal slices that spine compartmentalization is initially very weak, but increases dramatically upon postsynaptic depolarization. Using NMDA receptors as voltage sensors, we provide evidence that spine necks not only regulate diffusional coupling between spines and dendrites, but also control local depolarization of the spine head. In spines with high-resistance necks, presynaptic activity alone was sufficient to trigger calcium influx through NMDA receptors and R-type calcium channels. We conclude that calcium influx into spines, a key trigger for synaptic plasticity, is dynamically regulated by spine neck plasticity through a process of electrical compartmentalization.
Differential Recruitment of Anterior Intraparietal Sulcus and Superior Parietal Lobule during Visually Guided Grasping Revealed by Electrical Neuroimaging
Authors: Tunik Eugene , Ortigue Stephanie , Adamovich Serge V. , Grafton Scott T.
Published: December 2008

Dorsal parietal cortex is required for visually guided prehension. Transcranial magnetic stimulation to either the anterior intraparietal sulcus (aIPS) or superior parietal lobule (SPL) disrupts on-line adaptive adjustments of grasp when objects are perturbed. We used high-density electroencephalography during grasping to determine the relative timing of these two areas and to test whether the temporal contribution of each site would change when the task goal was perturbed. During object grasping with the right-hand, two distinct evoked responses were present over the 50–100 and 100–200 ms periods after movement onset. Distributed linear source estimation of these scalp potentials localized left lateralized sources, first in the aIPS and then the SPL. The duration of the response from the aIPS area was longer when there was an object perturbation. Initiation of a corrective movement coincided with activation in SPL. These data support a two-stage process: the integration of target goal and an emerging action plan within aIPS and subsequent on-line adjustments within SPL.
Neuroprotective Effects of Near-Infrared Light in anIn VivoModel of Mitochondrial Optic Neuropathy
Authors: Rojas Julio C. , Lee Jung , John Joseph M. , Gonzalez-Lima F.
Published: December 2008

Near-infrared light (NIL) promotes a wide range of biological effects including enhancement of energy production, gene expression and prevention of cell death. This is the first report of thein vivoneuroprotective effects of NIL against optic neuropathy induced by mitochondrial complex I inhibition. Subjects were pigmented rats that received single bilateral intravitreal doses of rotenone, a mitochondrial complex I inhibitor, or rotenone plus one of three different doses of NIL. Treatment effects were evaluated at behavioral, structural and neurochemical levels. Rotenone induced a decrease in visual function, as determined by changes in the dark-adapted illuminance sensitivity threshold, escape latency and rate of successful trials in a two-choice visual task, compared with vehicle-treated controls. Behavioral impairment correlated with a decrease in retinal and visual pathway metabolic activity, retinal nerve fiber layer thickness and ganglion cell layer cell density. These changes were prevented by NIL treatments in a dose-dependent manner. Whole-brain cytochrome oxidase and superoxide dismutase activities were also increased in NIL-treated subjects in a dose-dependent manner, suggesting anin vivotranscranial effect of NIL. In whole-brain membrane isolates, NIL prevented the rotenone-induced decrease in cell respiration. The results show that NIL treatment can effectively prevent the neurotoxic effects of rotenone and that it might be used in the treatment of neurodegenerative disorders associated with mitochondrial dysfunction.
Nrf2 Activation in Astrocytes Protects against Neurodegeneration in Mouse Models of Familial Amyotrophic Lateral Sclerosis
Authors: Vargas Marcelo R. , Johnson Delinda A. , Sirkis Daniel W. , Messing Albee , Johnson Jeffrey A.
Published: December 2008

Activation of the transcription factor Nrf2 in astrocytes coordinates the upregulation of antioxidant defenses and confers protection to neighboring neurons. Dominant mutations in Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons. Non-neuronal cells, including astrocytes, shape motor neuron survival in ALS and are a potential target to prevent motor neuron degeneration. The protective effect of Nrf2 activation in astrocytes has never been examined in a chronic model of neurodegeneration. We generated transgenic mice over-expressing Nrf2 selectively in astrocytes using the glial fibrillary acidic protein (GFAP) promoter. The toxicity of astrocytes expressing ALS-linked mutant hSOD1 to cocultured motor neurons was reversed by Nrf2 over-expression. Motor neuron protection depended on increased glutathione secretion from astrocytes. This protective effect was also observed by crossing the GFAP-Nrf2 mice with two ALS-mouse models. Over-expression of Nrf2 in astrocytes significantly delayed onset and extended survival. These findings demonstrate that Nrf2 activation in astrocytes is a viable therapeutic target to prevent chronic neurodegeneration.
The in vitro growth and maturation of follicles
Authors: Picton H M , Harris S E , Muruvi W , Chambers E L
Published: December 2008

The development of technologies to grow oocytes from the most abundant primordial follicles to maturity in vitro holds many attractions for clinical practice, animal production technology and research. The production of fertile oocytes and live offspring has been achieved in mice following the long-term culture of oocytes in primordial follicles from both fresh and cryopreserved ovarian tissue. In contrast, in non-rodent species advances in follicle culture are centred on the growth of isolated preantral follicles. As a functional unit, mammalian preantral follicles are well-suited to culture but primordial and primary follicles do not grow well after isolation from the ovarian stroma. The current challenges for follicle culture are numerous and include: optimisation of culture media and the tailoring of culture environments to match the physiological needs of the cell in vivo; the maintenance of cell–cell communication and signalling during culture; and the evaluation of the epigenetic status, genetic health and fertility of in vitro derived mature oocytes. In large animals and humans, the complete in vitro growth and maturation of oocytes is only likely to be achieved following the development of a multistage strategy that closely mimics the ovary in vivo. In this approach, primordial follicle growth will be initiated in situ by the culture of ovarian cortex. Isolated preantral follicles will then be grown to antral stages before steroidogenic function is induced in the somatic cells. Finally, cytoplasmic and nuclear maturation will be induced in the in vitro derived oocytes with the production of fertile metaphase II gametes.
Pain and opioids
Authors: Murányi Marianna , Radák Zsolt
Published: December 2008

A szövetkárosító hatású ingerek fájdalomérzetet váltanak ki, megvédve a szervezetet a káros behatásoktól, illetve felhívják a figyelmünket a szervezet kórfolyamataira. Fájdalomreceptorok (nociceptorok) a szervezetünkben mindenhol megtalálhatók. A fájdalom védekezőmechanizmusokat indít be, így vegetatív és motoros reflexválaszokat, illetve érzelmekkel, viselkedéssel kapcsolatos válaszokat vált ki. A krónikus fájdalom azonban gyakorlatilag haszontalan, kóros pszichés állapotokhoz vezethet. Fájdalomcsillapításra számos lehetőség van, beleértve nemszteroid gyulladásgátlókat, opioidokat, idegsebészeti beavatkozásokat, valamint noninvazív kezelésmódokat. Az opioidok centrális és periferiális farmakológiai hatásait elsősorban a központi idegrendszer és a gastrointestinalis rendszer opioidreceptorai közvetítik. A fájdalomcsillapítás a központi idegrendszer különböző szintjein jön létre, és két módon befolyásolhatja a fájdalomérzést: gátolja a fájdalom percepcióját, illetve megváltoztatja az érzelmi reakciókat. Opioidok használata indikált posztoperatív fájdalmakban, neuropathiás fájdalomban, illetve tumoros megbetegedésekben. Az opioidok használatakor azonban számolni kell a kellemetlen mellékhatásokkal is, így légzésbénító hatásával, valamint a kialakuló toleranciával és dependenciával, amely nem teszi az opioidokat optimális fájdalomcsillapítókká. Annak érdekében, hogy rendelkezésre álljon egy optimális opioid fájdalomcsillapító, a mai napig kutatások folynak mind magyar, mind külföldi laboratóriumokban. Továbbá az opioidoknak eufóriát okozó hatásuk miatt nagy az abúzuspotenciálja, ami sürgetővé teszi a gyógyszerfüggőség molekuláris mechanizmusának feltárását. Mindezek fényében nagy jelentősége van az opioidok kutatásának.