bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacogenomic Effects of Apolipoprotein E on Intracerebral Hemorrhage
Authors: James Michael L. , Sullivan Patrick M. , Lascola Christopher D. , Vitek Michael P. , Laskowitz Daniel T.
Published: December 2008

Background and Purpose—

The purpose of the study was to evaluate the effect of
APOE
genotype and the feasibility of administering an apolipoprotein E-mimetic therapeutic to modify outcomes in a murine model of intracerebral hemorrhage.

Methods—

Intracerebral hemorrhage was induced via stereotactic injection of 0.1 U Clostridial collagenase into the left basal ganglia of wild-type and apolipoprotein-E targeted-replacement mice, consisting of either homozygous 3/3 or 4/4 genotypes. Animals were randomized to receive either vehicle or apolipoprotein E-mimetic peptide. Outcomes included functional neurological tests (21-point neuroseverity score and Rotorod latency) over the initial 7 days after injury, radiographic and histological hemorrhage size at 3 and 7 days, brain water content for cerebral edema at 24 hours, and quantitative polymerase chain reaction for inflammatory markers at 6, 24, and 48 hours.

Results—

Apolipoprotein-E targeted-replacement mice consisting of homozygous 3/3 demonstrated superior neuroseverity scores and Rotorod latencies over the first 3 days after intracerebral hemorrhage, decreased cerebral edema at 24 hours, and reduced upregulation of IL-6 and endothelial nitric oxide synthase at 6 hours when compared to their apolipoprotein-E targeted-replacement mice consisting of homozygous 4/4 counterparts. After intravenous administration of 1 mg/kg apolipoprotein E-mimetic peptide, both wild-type and apolipoprotein-E targeted-replacement mice consisting of homozygous 4/4 exhibited improved functional outcomes over 7 days after intracerebral hemorrhage, less edema at 24 hours, and reduced upregulation of IL-6 and endothelial nitric oxide synthase when compared to mice that did not receive the peptide.

Conclusions—

Our data indicate that
APOE
genotype influences neurological outcome after intracerebral hemorrhage in a murine model. In particular
APOE4
is associated with poor functional outcome and increased cerebral edema. Additionally, this outcome can be modified by the addition of an apolipoprotein E mimetic-peptide, COG1410.
The Metabolic Syndrome Is Associated With a Higher Resistance to Intravenous Thrombolysis for Acute Ischemic Stroke in Women Than in Men
Authors: Arenillas Juan F. , Sandoval Patricio , Pérez de la Ossa Natalia , Millán Mónica , Guerrero Cristina , Escudero Domingo , Dorado Laura , López-Cancio Elena , Castillo José , Dávalos Antoni
Published: December 2008

Background and Purpose—

The metabolic syndrome (MetS) might confer a higher resistance to intravenous thrombolysis in acute middle cerebral artery (MCA) ischemic stroke. MetS increases the risk of stroke in women to a greater extent than in men. We aimed to investigate whether there might be sex differences in the impact of MetS on the response to intravenous thrombolysis for acute MCA ischemic stroke.

Methods—

We prospectively studied consecutive ischemic stroke patients, treated with intravenous tissue-type plasminogen activator according to SITS-MOST criteria, with an MCA occlusion on prebolus transcranial Doppler examination. Resistance to thrombolysis was defined as the absence of complete MCA recanalization 24 hours after tissue-type plasminogen activator infusion by transcranial Doppler criteria. MetS was diagnosed according to the criteria established by the American Heart Association/National Heart, Lung, and Blood Institute 2005 statement.

Results—

A total of 125 patients (75 men, 50 women; mean age, 67.6±11 years) were included. MetS was diagnosed in 76 (61%) patients. Resistance to clot lysis at 24 hours was observed in 53 (42%) patients. Two multivariate-adjusted, logistic-regression models identified that MetS was associated with a higher resistance to tissue-type plasminogen activator, independently of other significant baseline variables (odds ratio=9.8; 95% CI, 3.5 to 27.8;
P
=0.0001) and of the individual components of the MetS. The MetS was associated with a significantly higher odds of resistance to thrombolysis in women (odds ratio=17.5; 95% CI, 1.9 to 163.1) than in men (odds ratio=5.1; 95% CI, 1.6 to 15.6;
P
for interaction=0.0004).

Conclusions—

The effect of MetS on the resistance to intravenous thrombolysis for acute MCA ischemic stroke appears to be more pronounced in women than in men.
The Ontology of Public Space
Authors: Stivers Camilla
Published: December 2008

The “new governance” envisions a network of so-called actors—sometimes organizations, sometimes individuals—which collaborate with each other to accomplish policy goals. But the ontology of this model has been largely unexplored. When examined, its objectivist assumptions obscure network dynamics and render mysterious whatever collaboration manages to occur. These assumptions, it is argued, are not logically or empirically necessary. An alternative ontology, grounded in phenomenology, opens democratic vistas that comport as well or better with empirical reality and provide much stronger support for democratic governance.
Exploring Inmate Reentry in a Local Jail Setting
Authors: White Michael D. , Saunders Jessica , Fisher Christopher , Mellow Jeff
Published: December 2008

Although prisoner reentry has taken center stage in correctional research and policy discussions, there has been little emphasis on reentry among jail populations. This paper examines a jail-based reentry program in New York City that begins while individuals are incarcerated and includes 90 days of postrelease services. This article explores these assumptions through an evaluation of a jail-based reentry program in New York City that begins while individuals are incarcerated and includes 90 days of postrelease services. To determine program impact, the authors compare samples of participants with nonparticipants and program completers with noncompleters. The groups are matched using developmental trajectories derived from group-based trajectory modeling, in addition to propensity score matching. Findings show that participants perform no better than nonparticipants over a 1-year follow-up, but those who stay engaged for at least 90 days of postrelease services experience significantly fewer (and slower) returns to jail. The findings regarding program completion are tempered by several methodological concerns, however. The article concludes with a discussion of how the study may offer insights for program implementation and operation with this target population.
A Cross-Nations, Cross-Cultures, and Cross-Conditions Analysis on the Equivalence of the Balanced Inventory of Desirable Responding
Authors: Li Andrew , Reb Jochen
Published: December 2008

This article examines measurement equivalence of the Balanced Inventory of Desirable Responding (BIDR) across two nations (the United States and Singapore), two cultural values (horizontal individualism and horizontal collectivism) and two motivational conditions (standard and faking). One sample of undergraduate students from each country ( N Singapore = 158, N United States = 166) participated in this study, and a within-subject experimental design is used. Specifically, at Time 1, participants were simply asked to respond to the BIDR and the INDCOL (standard condition). At Time 2, the participants were instructed to engage in social desirability (faking condition). Multigroup confirmatory factor analyses are used to evaluate the equivalence of the BIDR. The authors found support for the equivalence of the BIDR across the two cultural values. However, there is weaker support for the equivalence of the BIDR across the two countries and the two motivational conditions. The implications of these findings are discussed.
Defining and Classifying Cancer Cachexia: A Proposal by the SCRINIO Working Group
Authors: Bozzetti Federico , Mariani Luigi
Published: December 2008

Background: Although cancer cachexia is widely diffuse in the cancer patient population, there is no objective definition and classification of this syndrome. The purpose of this study is to propose a simple and quick classification that relies on the severity of the body weight loss and presence/absence of symptoms that are associated with cancer cachexia. Methods: The authors used a database of an ongoing multicenter prospective investigation on the screening of the nutrition risk of 1307 cancer outpatients from different (mainly Italian) university or scientific institutes or hospitals. The database included demographic, oncologic, clinical, and nutrition data. The patients were divided into 4 classes based on combinations of body weight loss (<10%, precachexia; ≥10%, cachexia) and the presence/absence of at least 1 symptom of anorexia, fatigue, or early satiation. The authors verified statistically whether these 4 classes were associated with the distribution of main clinical, nutrition, and oncologic variables, after adjustment for treatment status, by using the Cochrane‐Mantel‐Hanszel test for count data and ANOVA for continuous data. Results: Moving from “asymptomatic precachexia” (class 1) to “symptomatic cachexia” (class 4), there were statistically significant trends (P < .0001) in the percentage of gastrointestinal vs nongastrointestinal tumors, severity of cancer stage, percentage of weight loss, number of symptoms per patient, Eastern Cooperative Oncology Group (ECOG) performance status, and nutritional risk score. Conclusions: The statistical analysis has validated the classification by identifying stages with different severity of cachexia. This classification could be adopted within a comprehensive oncologic approach to the weight‐losing patients, until more specific diagnostic techniques are available in clinical practice.
Father Involvement Ideals and the Union Transitions of Unmarried Parents
Authors: Hohmann-Marriott Bryndl E.
Published: December 2008

As more unmarried couples become parents, it is important to understand the dynamics that help these couples to maintain strong relationships. This article explores the association of the two partners' beliefs about father involvement with their likelihood of union dissolution and transition to marriage, using the first two waves of the Fragile Families survey ( n = 2,303). It finds that couples are more likely to end their union when partners do not believe that fathers' caregiving is very important and when the father participates less. Partners are less likely to marry if the mother does not believe that fathers' caregiving is very important. These effects are distinct from the quality of the couple's relationship and suggest that unmarried parents who value the father's role as a hands-on parent may be more motivated to build a stronger relationship.
Assessing the Anomalous Research on Hispanic Victimization
Authors: Brown Ben
Published: December 2008

This article provides an overview and critique of the research on Hispanic victimization. Analyses of data gathered prior to the mid- to late 1990s consistently show Hispanics were victimized at disproportionately high rates, but numerous recent studies indicate Hispanics were not victimized at disproportionately high rates. Given that research has consistently shown victimization rates are highest among the poor and that Hispanics are a disproportionately impoverished demographic, the findings that Hispanics were not victimized at disproportionately high rates are enigmatic. It is suggested that social changes in the United States—specifically, the increase in the portion of the Hispanic population composed of immigrants and the development of Latin American enclaves—have reduced the efficacy of conventional methodological tactics and that the recent findings on Hispanic victimization were affected by the inadequate representation of disadvantaged Hispanics (especially immigrants and migrants) in survey studies and the reluctance of Hispanic immigrants to report crimes to the police. Finally, it is argued that the practice of conducting analyses of ethnic variation in victimization wherein all non-Hispanics (Asians, Blacks, Native Americans, and Whites) are amalgamated into a single category and compared with Hispanics has generated misleading results.
Experiences of Sexual Coercion Among Adolescent Women
Authors: Wagman Jennifer , Baumgartner Joy Noel , Waszak Geary Cindy , Nakyanjo Neema , Ddaaki William George , Serwadda David , Gray Ron , Nalugoda Fred Kakaire , Wawer Maria J.
Published: December 2008

Limited data from low-income countries are available on the continuum of coercive experiences, the contexts in which they occur, and how adolescent women perceive and respond to coercion. This article presents results from focus group discussions and in-depth interviews with pregnant and never pregnant sexually active female adolescents, aged 15 to 17, residing in Rakai District, Uganda, to examine sexual coercion, its context, and the links between coercion and adolescent reproductive health outcomes, including early sexual debut and pregnancy. Informants described multiple forms of sexual coercion, including coerced or forced intercourse, unwanted sexual touching, verbal harassment, and transactional sex. Sexual coercion was perceived to be a normal part of intimate relationships; in particular, informants felt that a woman’s lack of decision-making authority, including choices on sexual encounters, was implicit to marriage. This information may help violence prevention programs develop a range of strategies for addressing sexual coercion among adolescents.
Deracialization and Latino Politics
Authors: Gonzalez Juenke Eric , Sampaio Anna Christina
Published: December 2008

Deracialization literature has a rich history, but it has generally focused on local-level black candidates in nonpartisan environments. This article extends the deracialization literature to a competitive statewide context and focuses on Latino candidates, offering a broader partisan environment where established deracialization theory and voter response are tested at the individual level. Both John Salazar’s and Ken Salazar’s successful 2004 campaigns for national office are explored using qualitative and quantitative data. The combined approaches yield evidence that Latinos in competitive partisan environments are influenced to deracialize their campaigns and that conservative non-Latino voters are positively and significantly influenced by these nonracial messages.
Changing Mass Attitudes and Democratic Deepening
Authors: Fails Matthew D. , Pierce Heather Nicole
Published: December 2008

A large literature evaluates the correlates of mass attitudes toward democracy because such attitudes are regarded as critical for the stability and depth of democratic regimes. This article uses cross-national public opinion surveys to conduct the first comprehensive test of this conventional wisdom. The authors examine whether aggregate levels of democratic legitimacy are related to the level, stability, and deepening of democracy and find no empirical support for these theoretical expectations. Rather, the authors find evidence that legitimacy attitudes are significantly shaped by the prior institutionalization of democracy, suggesting that the existing literature may have reversed the direction of the causal arrow.
Governors Turn Pro
Authors: Bowman Ann O'M. , Woods Neal D. , Stark Milton R.
Published: December 2008

This study examines the institutional development of governors’ offices. Pooled analyses from 1983 to 2004 indicate that government growth and workload foster institutionalization, as does rivalry with the legislature. Bargaining relationships with external actors appear to have more limited impact. The authors also find that the dispersion of authority within the executive branch plays a significant role in explaining the development of institutionalized staff structures. Overall, the results indicate that separation of powers between the executive and legislative branches affects gubernatorial institutionalization but that researchers should also consider the intercurrencies that exist within the executive branch.
From Consent to Advice and Consent
Authors: Hendershot Marcus E.
Published: December 2008

This study seeks to understand long-standing structural changes within the executive—Senate relationships that govern the judicial appointment process. Utilizing a new source of data that comprises district court appointments from 1901 through 2006, the analysis models the duration of selection and confirmation events to find evidence of interbranch constraint. Temporal variance and heteroskedasticity in these measures suggest that the last century of appointment activity can be divided into four distinct regimes that reflect a repeating cycle of executive independence and senatorial constraint, which in turn helps integrate existing accounts of change and conflict within the appointment process of federal judges.
A Duration Model for the Estimation of the Contracting Out of Urban Water Management in Southern Spain
Authors: González-Gómez Francisco , Guardiola Jorge
Published: December 2008

Research that tries to explain the decisions of local government in the contracting out of certain services frequently disregards the temporal dimension. In this article, the authors take time into account in the analysis, proposing a duration model as an alternative to discrete choice models. The objective is to analyze the explanatory factors in the contracting out of municipal services. This methodology is applied to the water services of 744 municipalities in southern Spain during the period from 1985 to 2006. From the results, the authors conclude that complexity in the environment, economies of scale, financial restrictions, and stability of the local government are determinants in the decision.
Dietary Considerations for the Prevention and Treatment of Obesity in Youth
Authors: Melanson Kathleen J.
Published: December 2008

The global rise of obesity in children has raised serious concern for their current and future health and well-being. The prevention and treatment of childhood and adolescent obesity must encompass all aspects of a child's life, including home, school, and other settings. A multidisciplinary approach is critical, including physical activity, behavioral factors, and proper dietary habits. Age-appropriate nutrition education and role modeling from adults in children's lives can be important in promoting lifelong healthy eating. Foods to emphasize include vegetables, fruits, whole grains, legumes, low-fat dairy products, and lean sources of protein. Foods and beverages with low nutrient density and high energy density should be consumed in moderation, within a child's discretionary calorie allowance. The overall diet must support proper growth, health, development, academic achievement, and well-being without supplying excess energy beyond needs.
B7-H4–deficient mice display augmented neutrophil-mediated innate immunity
Authors: Zhu Gefeng , Augustine Mathew M. , Azuma Takeshi , Luo Liqun , Yao Sheng , Anand Sudarshan , Rietz A. Cecilia , Huang Jiaqiang , Xu Haiying , Flies Andrew S. , Flies Sarah J. , Tamada Koji , Colonna Marco , van Deursen Jan M. A. , Chen Lieping
Published: December 2008

B7-H4 is an immunoglobulin superfamily molecule and shown to be inhibitory for T-cell responses. To explore physiologic roles of B7-H4, we created B7-H4–deficient (KO) mice by genetic targeting. B7-H4KO mice are healthy and their T- and B-cell responses to polyclonal antigens are in normal range. However, B7-H4KO mice are more resistant to infection by Listeria monocytogenes than their littermates. Within 3 days after infection, bacterial colonies in livers and spleens are significantly lower than the controls, suggesting a role of B7-H4 in enhancing innate immunity. Further studies demonstrate that neutrophils increase in peripheral organs of B7-H4KO mice more so than their littermates but their bactericidal functions remain unchanged. Augmented innate resistance is completely dependent on neutrophils, even in the absence of adaptive immunity. In vitro B7-H4 inhibits the growth of bone marrow–derived neutrophil progenitors, suggesting an inhibitory function of B7-H4 in neutrophil expansion. Our results identify B7-H4 as a negative regulator of the neutrophil response to infection and provide a new target for manipulation of innate immunity.
ATR-dependent phosphorylation of FANCA on serine 1449 after DNA damage is important for FA pathway function
Authors: Collins Natalie B. , Wilson James B. , Bush Thomas , Thomashevski Andrei , Roberts Kate J. , Jones Nigel J. , Kupfer Gary M.
Published: December 2008

Previous work has shown several proteins defective in Fanconi anemia (FA) are phosphorylated in a functionally critical manner. FANCA is phosphorylated after DNA damage and localized to chromatin, but the site and significance of this phosphorylation are unknown. Mass spectrometry of FANCA revealed one phosphopeptide, phosphorylated on serine 1449. Serine 1449 phosphorylation was induced after DNA damage but not during S phase, in contrast to other posttranslational modifications of FA proteins. Furthermore, the S1449A mutant failed to completely correct a variety of FA-associated phenotypes. The DNA damage response is coordinated by phosphorylation events initiated by apical kinases ATM (ataxia telangectasia mutated) and ATR (ATM and Rad3-related), and ATR is essential for proper FA pathway function. Serine 1449 is in a consensus ATM/ATR site, phosphorylation in vivo is dependent on ATR, and ATR phosphorylated FANCA on serine 1449 in vitro. Phosphorylation of FANCA on serine 1449 is a DNA damage–specific event that is downstream of ATR and is functionally important in the FA pathway.
Genetic deletion of JAM-C reveals a role in myeloid progenitor generation
Authors: Praetor Asja , McBride Jacqueline M. , Chiu Henry , Rangell Linda , Cabote Lorena , Lee Wyne P. , Cupp James , Danilenko Dimitry M. , Fong Sherman
Published: December 2008

Hematopoietic stem cells (HSCs) have the capacity to self-renew and continuously differentiate into all blood cell lineages throughout life. At each branching point during differentiation, interactions with the environment are key in the generation of daughter cells with distinct fates. Here, we examined the role of the cell adhesion molecule JAM-C, a protein known to mediate cellular polarity during spermatogenesis, in hematopoiesis. We show that murine JAM-C is highly expressed on HSCs in the bone marrow (BM). Expression correlates with self-renewal, the highest being on long-term repopulating HSCs, and decreases with differentiation, which is maintained longest among myeloid committed progenitors. Inclusion of JAM-C as a sole marker on lineage-negative BM cells yields HSC enrichments and long-term multilineage reconstitution when transferred to lethally irradiated mice. Analysis of Jam-C–deficient mice showed that two-thirds die within 48 hours after birth. In the surviving animals, loss of Jam-C leads to an increase in myeloid progenitors and granulocytes in the BM. Stem cells and myeloid cells from fetal liver are normal in number and homing to the BM. These results provide evidence that JAM-C defines HSCs in the BM and that JAM-C plays a role in controlling myeloid progenitor generation in the BM.
Hematopoietic defects in the Ts1Cje mouse model of Down syndrome
Authors: Carmichael Catherine L. , Majewski Ian J. , Alexander Warren S. , Metcalf Donald , Hilton Douglas J. , Hewitt Chelsee A. , Scott Hamish S.
Published: December 2008

Down syndrome (DS) persons are born with various hematopoietic abnormalities, ranging from relatively benign, such as neutrophilia and macrocytosis, to a more severe transient myeloproliferative disorder (TMD). In most cases, these abnormalities resolve in the first few months to years of life. However, sometimes the TMD represents a premalignant disease that develops into acute megakaryocytic leukemia (AMKL), usually in association with acquired GATA1 mutations. To gain insight into the mechanisms responsible for these abnormalities, we analyzed the hematopoietic development of the Ts1Cje mouse model of DS. Our analyses identified defects in mature blood cells, including macrocytosis and anemia, as well as abnormalities in fetal liver and bone marrow stem and progenitor cell function. Despite these defects, the Ts1Cje mice do not develop disease resembling either TMD or AMKL, and this was not altered by a loss of function allele of Gata1. Thus, loss of Gata1 and partial trisomy of chromosome 21 orthologs, when combined, do not appear to be sufficient to induce TMD or AMKL-like phenotypes in mice.
Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins
Authors: O'Connor Marie N. , Salles Isabelle I. , Cvejic Ana , Watkins Nicholas A. , Walker Adam , Garner Stephen F. , Jones Chris I. , Macaulay Iain C. , Steward Michael , Zwaginga Jaap-Jan , Bray Sarah L. , Dudbridge Frank , de Bono Bernard , Goodall Alison H. , Deckmyn Hans , Stemple Derek L. , Ouwehand Willem H.
Published: December 2008

In this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell, the megakaryocyte, together with nucleated blood cell elements, endothelial cells, and erythroblasts, identified novel platelet membrane proteins with hitherto unknown roles in thrombus formation. We determined the phenotype induced by antisense morpholino oligonucleotide (MO)–based knockdown of 5 of these genes in a laser-induced arterial thrombosis model. To validate the model, the genes for platelet glycoprotein (GP) IIb and the coagulation protein factor VIII were targeted. MO-injected fish showed normal thrombus initiation but severely impaired thrombus growth, consistent with the mouse knockout phenotypes, and concomitant knockdown of both resulted in spontaneous bleeding. Knockdown of 4 of the 5 novel platelet proteins altered arterial thrombosis, as demonstrated by modified kinetics of thrombus initiation and/or development. We identified a putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition of thrombus formation. We conclude that phenotypic analysis of MO-injected zebrafish is a fast and powerful method for initial screening of novel platelet proteins for function in thrombosis.
Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide
Authors: Karp Judith E. , Flatten Karen , Feldman Eric J. , Greer Jacqueline M. , Loegering David A. , Ricklis Rebecca M. , Morris Lawrence E. , Ritchie Ellen , Smith B. Douglas , Ironside Valerie , Talbott Timothy , Roboz Gail , Le Son B. , Meng Xue Wei , Schneider Paula A. , Dai Nga T. , Adjei Alex A. , Gore Steven D. , Levis Mark J. , Wright John J. , Garrett-Mayer Elizabeth , Kaufmann Scott H.
Published: December 2008

The farnesyltransferase inhibitor tipifarnib exhibits modest activity against acute myelogenous leukemia. To build on these results, we examined the effect of combining tipifarnib with other agents. Tipifarnib inhibited signaling downstream of the farnesylated small G protein Rheb and synergistically enhanced etoposide-induced antiproliferative effects in lymphohematopoietic cell lines and acute myelogenous leukemia isolates. We subsequently conducted a phase 1 trial of tipifarnib plus etoposide in adults over 70 years of age who were not candidates for conventional therapy. A total of 84 patients (median age, 77 years) received 224 cycles of oral tipifarnib (300-600 mg twice daily for 14 or 21 days) plus oral etoposide (100-200 mg daily on days 1-3 and 8-10). Dose-limiting toxicities occurred with 21-day tipifarnib. Complete remissions were achieved in 16 of 54 (30%) receiving 14-day tipifarnib versus 5 of 30 (17%) receiving 21-day tipifarnib. Complete remissions occurred in 50% of two 14-day tipifarnib cohorts: 3A (tipifarnib 600, etoposide 100) and 8A (tipifarnib 400, etoposide 200). In vivo, tipifarnib plus etoposide decreased ribosomal S6 protein phosphorylation and increased histone H2AX phosphorylation and apoptosis. Tipifarnib plus etoposide is a promising orally bioavailable regimen that warrants further evaluation in elderly adults who are not candidates for conventional induction chemotherapy. These clinical studies are registered at www.clinicaltrials.gov as #NCT00112853.
A randomized controlled trial comparing standard- and low-dose strategies for transfusion of platelets (SToP) to patients with thrombocytopenia
Authors: Heddle Nancy M. , Cook Richard J. , Tinmouth Alan , Kouroukis C. Tom , Hervig Tor , Klapper Ellen , Brandwein Joseph M. , Szczepiorkowski Zbigniew M. , AuBuchon James P. , Barty Rebecca L. , Lee Ker-Ai ,   for the SToP Study investigators of the BEST Collaborative
Published: December 2008

A noninferiority study was performed comparing low-dose and standard-dose prophylactic platelet transfusions. A double-blind randomized controlled trial (RCT) was performed in 6 sites in 3 countries. Thrombocytopenic adults requiring prophylactic platelet transfusion were randomly allocated to standard-dose (300-600 × 109 platelets/product) or low-dose (150- < 300 × 109 platelets/product) platelets. The primary outcome (World Health Organization [WHO] bleeding ≥ grade 2) was assessed daily through clinical examination, patient interview, and chart review. A WHO grade was assigned through adjudication. The Data Safety Monitoring Board stopped the study because the difference in the grade 4 bleeding reached the prespecified threshold of 5%. At this time, 129 patients had been randomized and 119 patients were included in the analysis (58 low dose; 61 standard dose). Three patients in the low-dose arm (5.2%) had grade 4 bleeds compared with none in the standard-dose arm. WHO bleeding grade 2 or higher was 49.2% (30/61) in the standard-dose arm and 51.7% (30/58) in the low-dose group (relative risk [RR], 1.052; 95% confidence interval [CI], 0.737-1.502). A higher rate of grade 4 bleeding in patients receiving low-dose prophylactic platelet transfusions resulted in this RCT being stopped. Whether this finding was due to chance or represents a real difference requires further investigation. These clinical studies are registered on http://www.clinicaltrials.gov as NCT00420914.
The impact of Fc engineering on an anti-CD19 antibody: increased Fcγ receptor affinity enhances B-cell clearing in nonhuman primates
Authors: Zalevsky Jonathan , Leung Irene W. L. , Karki Sher , Chu Seung Y. , Zhukovsky Eugene A. , Desjarlais John R. , Carmichael David F. , Lawrence Chris E.
Published: December 2008

CD19, a B cell–restricted receptor critical for B-cell development, is expressed in most B-cell malignancies. The Fc-engineered anti-CD19 antibody, XmAb5574, has enhanced Fcγ receptor (FcγR) binding affinity, leading to improved FcγR-dependent effector cell functions and antitumor activity in murine xenografts compared with the non–Fc-engineered anti-CD19 IgG1 analog. Here, we use XmAb5574 and anti-CD19 IgG1 to further dissect effector cell functions in an immune system closely homologous to that of humans, the cynomolgus monkey. XmAb5574 infusion caused an immediate and dose-related B-cell depletion in the blood (to <10% of baseline levels) concomitant with a sustained reduction of natural killer (NK) cells. NK cells had fully recovered by day 15, whereas B-cell recovery was underway by day 57. B cells in secondary lymphoid tissues were depleted (to 34%-61% of vehicle), with involuted germinal centers apparent in the spleen. Anti-CD19 IgG1 had comparable serum exposure to XmAb5574 but demonstrated no B-cell depletion and no sustained NK-cell reduction. Thus, increasing FcγR binding affinity dramatically increased B-cell clearing. We propose that effector cell functions, possibly those involving NK cells, mediate XmAb5574 potency in cynomolgus monkeys, and that enhancing these mechanisms should advance the treatment of B-cell malignancies in humans.
Cardiac tamponade, an unusual and fatal complication of esophagus dilatation for benign stenosis: a case report
Authors: Greven Wendela L , Kooij Nicole , Peters Herman M , Kardux Joost , Spronk Peter E
Published: December 2008

Introduction

We present a patient with a fatal late esophago-pericardial fistula three months after dilatation for benign oesophagus stenosis

Case presentation

A 71-year-old caucasian male with a known benign esophagus stenosis was referred to the ICU. On arrival an asystole developed which proved to be due to a large pericardial effusion. Pericardial fluids were drained, but the patients' condition worsened and he died due to multiple organ failure. Postmortum investigation revealed an esophago-pericardial fistula.

Conclusion

Causes of an acute tamponade should also be sought in semirecent events, such as manipulation to the oesophagus months before the acute critical illness.
Does mood really influence comparative optimism? Tracking an elusive effect
Authors: Drace Sasa , Desrichard Olivier , Shepperd James A. , Hoorens Vera
Published: December 2008

Methodological limitations call into question prior evidence that positive moods are associated with greater comparative optimism. Experiments 1–4 tested if mood affects comparative optimism using a mood manipulation that minimized experimenter demand. While the procedure was successful in inducing mood, we found no evidence for a mood effect on comparative optimism. The absence of a mood effect was not due to participants correcting their judgments in response to a presumed mood bias (Experiments 2, 3 and 4) or to participants proactively regulating their mood (Experiments 3 and 4). Experiment 5 compared the mood manipulation of Experiments 1–4 with an autobiographical recall procedure. Although the two methods were equally effective in inducing mood, only autobiographical recall influenced participants' comparative optimism. Study 6 provides preliminary evidence that experimenter demand may be responsible for the effects of autobiographical recall on comparative judgments.
The role of attributions in the process of overcoming shame: A qualitative analysis
Authors: Van Vliet K. Jessica
Published: December 2008

ObjectivesWhile attributions have been found to play an important role in the experience of shame, little is currently known about attributions that occur as part of shame reparation. This exploratory study investigated the attributions associated with recovery from shame, based on the perspectives of participants.

DesignGrounded theory was used in data collection and analysis. This approach has been used extensively for developing understandings of how people construct meaning, interpret events, and act on the basis of their beliefs and interpretations.

MethodsThe participants were nine women and four men between the ages of 24 and 70. Data came from interviews in which the participants recalled a distressing shame experience and described how they recovered. Emphasis was on the participants' subjective perspectives, meanings, and interpretations.

ResultsShame involved global and stable dispositional attributions where the entire self was regarded as flawed and unattractive, and participants perceived themselves as powerless to change an unwanted identity. Internal causal attributions and self‐blame were present in most but not all shame experiences. Recovery involved a movement towards specific and unstable attributions that enhanced self‐concept and maximized a sense of power and control over the future. Shared and external factors that contributed to the event were also identified.

ConclusionsWhen applied to psychotherapy for shame‐related distress, these findings point to the importance of exploring clients' attributions related to specific shame events and using interventions that promote attributional change. Directions for further research are discussed.
Exposure of the mouse perinatal testis to radiation leads to hypospermia at sexual maturity
Authors: Forand A , Messiaen S , Habert R , Bernardino-Sgherri J
Published: December 2008

The first round of mouse spermatogenesis begins from 3 to 4 days after birth through differentiation of gonocytes into spermatogonial-stem cells and type A spermatogonia. Consequently, this step of differentiation may determine generation of the original population of stem cells and the fertility potential of the adult mouse. We aimed to determine the effect of perinatal exposure to ionizing radiation on the testis at the end of the first wave of spermatogenesis and at sexual maturity. Our results show that, radiation sensitivity of the testis substantially decreases from late foetal life to the end of the first week after birth. In addition, partial or full recovery from radiation induced testicular weight loss occurred between the first round of spermatogenesis and sexual maturity, and this was associated with the stimulation of spermatogonial proliferation. Exposure of mice at 17.5 days after conception or at 1 day after birth to γ-rays decreased the sperm counts at sexual maturity, while exposure of 8 day-old mice had no effect. This suggests that irradiation of late foetal or early neonatal testes has a direct impact on the generation of the neonatal spermatogonial-stem cell pool.
Biotechnology as a useful tool for nutritional improvement of cereal-based materials enriched with polyunsaturated fatty acids and pigments
Authors: čertík M. , Adamechová Z. , Hanusová V. , Breierová E.
Published: December 2008

The fungi
Thamnidium elegans
, as a producer of γ-linolenic acid (GLA), and
Mortierella alpina
, as a producer of dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA) and eicosapentaenoic acid (EPA), and the yeasts
Rhodotorula glutinis
and
Sporobolomyces roseus
, as producers of ß-carotene, torulene and torularhodin, were tested for their ability to utilize cereal substrates during solid state fermentations (SSF). Depending on the strain and conditions, the cereal materials were effectively enriched with polyunsaturated fatty acids (PUFAs) or carotenoids. These naturally prepared bioproducts could find applications in food, feed, biomedical, pharmaceutical and veterinary fields.
Genetic modification of cereals in the Agricultural Research Institute of the Hungarian Academy of Sciences
Authors: Sági L. , Rakszegi M. , Spitkó T. , Mészáros K. , Németh-Kisgyörgy B. , Soltész A. , Szira F. , Ambrus H. , Mészáros A. , Galiba G. , Vágújfalvi A. , Barnabás B. , Marton L.
Published: December 2008

Research with transgenic plants in the Agricultural Research Institute of the Hungarian Academy of Sciences is primarily related to applications that are essential for the genetic improvement of cereals. The two main directions are connected to wheat and maize breeding and are focused on improving agronomic and nutritional traits. This paper highlights experiments in these areas, which are conducted in national as well as international collaborations. The transparency of this work is ensured by the dissemination of information about approved confined field tests to the public via the internet.
Effects of fore-crop fertilization on the yield and quality of kidney beans under vegetable crop rotation conditions
Authors: Mitova I. , Dimitrov I. , Atanasova E. , Stancheva I.
Published: December 2008

Kidney beans (
Phaseolus vulgaris
(L.) Savi.) ssp. Nanus cv. Lodi were grown as a mid-early second crop after lettuce on an alluvial meadow soil with pH(
H2O
) = 6.4 and a plant density of 22 plants per m
2
. The bean crop was grown without fertilization, but the lettuce crop was treated with mineral, organic or foliar fertilization. The application of different fertilizer sources to the fore-crop resulted in high yields of the subsequent bean crop, with good quality parameters and without polluting the arable soil layer with fertilizer residues. Foliar fertilization applied to the fore-crop resulted in a lower accumulation of nitrates in fresh beans in comparison with the other fertilizer sources. Organic fertilization supplied during the cultivation of the previous crop had a stronger effect than mineral fertilization on certain quality parameters of the kidney bean plants, such as dry matter, vitamin C content, and the accumulation of nitrates.
Gene effects and mean performance of nitrogen and phosphorus use in wheat after inoculation with arbuscular mycorrhiza fungi and Azotobacter chroococcum under low input conditions
Authors: Singh R. , Behl R. , Jain P. , Singh K. , Narula N.
Published: December 2008

The present investigation was conducted to study the impact of bio-inoculants under low input field conditions on the magnitude and direction of gene effects and the mean performance of nitrogen (N) and phosphorus (P) use in wheat. Three wheat cultivars suitable for different agro-ecological conditions, i.e. WH 147 (low mineral input), WH 533 (water deficit), Raj 3077 (high mineral input), and six generations (P1, P2, F1, F2, BC1and BC2) of three crosses, namely WH 147 × WH 533, WH 533 × Raj 3077 and WH 147 × Raj 3077, were evaluated in a randomized block design with three replications under low input field conditions (80 kg N + 40 kg P + 18 kg ZnSO4doses applied in each treatment) with three treatments, i.e. control, inoculation with arbuscular mycorrhiza fungi (AMF,Glomus fasciculatum) and dual inoculation with AMF andAzotobacter chroococcum(Azc). Bioinoculation with AMF and AMF+Azchad a positive impact on the mean performance of all the wheat crosses. The mean performance of AMF was maximum in the cross WH 147 × WH 533 for N and P response (%), N and P use index (%) and P content (ppm), whereas for N and P uptake it was maximum in the cross WH 147 × Raj 3077. The response and use index for N and P were better in the combined AMF+Azctreatment in all three crosses. The adequacy of the additive-dominance model for the phosphorus uptake (mg/plant) by all three crosses in all three treatments (i.e. control, AMF, AMF+Azc) suggested that additive (d) and dominance (h) gene effects mainly governed the inheritance of this trait. In all cases, digenic interactions were present, where the duplicate type of epistasis prevailed except for the P content in the control in the cross WH 147 × WH 533, where the complementary type of interaction was present. Pedigree selection in crosses WH 147 × WH 533 and WH 147 × Raj 3077 could be effective for breeding pure lines of wheat for sustainable agriculture (low input genotypes responsive to biofertilizers such as AMF andAzotobacter).
Evaluation of the re-use of treated wastewater for irrigation
Authors: Selim M.
Published: December 2008

Fresh water is considered one of the most important factors in expanding the cultivated area. In arid and semi-arid zones, water resources are scarce. Recently many scientists in different countries have concluded that the re-use of wastewater could help to solve water scarcity problems. An additional target is to protect the environment by reducing the pollution load with little or no risk to the plants, groundwater or human health. Therefore, the principal objective of the present study was to demonstrate the economic aspects of re-using secondary treated wastewater in irrigation, in order to make the best use of existing resources. Thus, field trials were established in a rotation of summer and winter crops during the 2000–2002 seasons to evaluate the effect of irrigation with secondary treated wastewater on the yield and quality of field crops compared with canal water. The present study discusses a part of this study, concerning the effect on the yield and quality of lentils and pearl millet. The experimental treatments for both crops were the same in both growing seasons, involving two water irrigation sources (secondary treated wastewater and canal water) and two fertilization treatments (application of recommended rates of chemical fertilizers and control without fertilizer application). The data demonstrated that crops irrigated with secondary treated wastewater performed equally well or significantly better than those irrigated with canal water. Heavy metal concentrations were very low, and had no influence on crop quality, determined as the chemical composition of lentil seeds and the dry forage yield of millet. Animal performance was also taken into consideration. The results indicated that the seed and biological yields of plants given wastewater in the absence of chemical fertilizers were nearly equal to those of plants given the recommended dose of chemical fertilizers, indicating that wastewater could provide an adequate amount of N, P and K to cover crop requirements at different growth stages.
Marker-assisted selection for the development of improved barley and wheat lines
Authors: Hudcovicová M. , Šudyová V. , Šliková S. , Gregová E. , Kraic J. , Ordon F. , Mihálik D. , Horevaj V. , Šramková Z.
Published: December 2008

Marker-assisted selection (MAS) is an efficient modern method for transferring alleles or specific chromosome segments including important agronomic traits into elite cultivars. This approach makes genotypic selection possible, whereby the selection process is more effective. The Research Institute of Plant Production Piešťany uses genetic markers linked to important traits in the following pre-breeding programmes: 1. development of winter barley lines resistant to BaYMV/BaMMV, 2. development of spring barley lines resistant to BYDV, 3. development of winter wheat lines resistant to leaf rust (gene pyramiding), 4. improvement of wheat quality by new combination(s) of known HMW-GS and/or by introduction of novel HMW-GS alleles. Several hundreds of genotypes are usually analysed for the presence or absence of linked molecular markers and selected for use in breeding programmes.
Application of molecular markers in parental selection in soybean
Authors: Sudaric A. , Vrataric M. , Rajcan I. , Duvnjak T. , Volenik M.
Published: December 2008

The rate of genetic gain in the quantity and quality of soybean grain depends considerably on the genetic diversity of the selected parental components. Genetic diversity assessment is a crucial aspect of breeding that maximizes genetic improvement. The objectives of this study were to evaluate the genetic diversity of the selected soybean germplasm using genetic markers, as well as to compare the effectiveness of breeding procedures with and without the use of genetic markers in parental selection. The genetic relationships within the selected soybean germplasm were estimated using 14 simple sequence repeats (SSRs). The agronomic performance (grain yield, protein and oil content in the grain) of the parental components and derived lines was determined in field trials. Based on SSR marker data and phenotypic data, an association was found between the agronomic performance of the derived lines and the genetic distance between the parental lines. Crosses between more diverse parents resulted in derived lines with greater values for grain yield and grain quality compared with the parents than crosses between similar parents. The results indicated the usefulness of genetic marker information in parental selection, contributing to breeding efficiency.