bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Intravascular Ultrasound Guidance on Long-Term Mortality in Stenting for Unprotected Left Main Coronary Artery Stenosis
Authors: Park Seung-Jung , Kim Young-Hak , Park Duk-Woo , Lee Seung-Whan , Kim Won-Jang , Suh Jon , Yun Sung-Cheol , Lee Cheol Whan , Hong Myeong-Ki , Lee Jae-Hwan , Park Seong-Wook
Published: April 2009

Background—

Although intravascular ultrasound (IVUS) guidance has been useful in stenting for unprotected left main coronary artery stenosis, its impact on long-term mortality is still unclear.

Methods and Results—

In the MAIN-COMPARE registry, patients with unprotected left main coronary artery stenosis in a hemodynamically stable condition underwent elective stenting under the guidance of IVUS (756 patients) or conventional angiography (219 patients). Patients with acute myocardial infarction were excluded. The 3-year outcomes between the 2 groups were primarily compared using propensity-score matching in the entire and separate populations according to stent type. In 201 matched pairs of the overall population, there was a tendency of lower risk of 3-year morality with IVUS guidance compared with angiography guidance (6.0% versus 13.6%, log-rank
P
=0.063; hazard ratio, 0.54; 95% CI, 0.28 to 1.03; Cox-model
P
=0.061). In particular, in 145 matched pairs of patients receiving drug-eluting stent, the 3-year incidence of mortality was lower with IVUS guidance as compared with angiography guidance (4.7% versus 16.0%, log-rank
P
=0.048; hazard ratio, 0.39; 95% CI, 0.15 to 1.02; Cox model
P
=0.055). In contrast, the use of IVUS guidance did not reduce the risk of mortality in 47 matched pairs of patients receiving bare-metal stent (8.6% versus 10.8%, log-rank
P
=0.35; hazard ratio, 0.59; 95% CI, 0.18 to 1.91; Cox model
P
=0.38). The risk of myocardial infarction or target vessel revascularization was not associated with the use of IVUS guidance.

Conclusions—

Elective stenting with IVUS guidance, especially in the placement of drug-eluting stent, may reduce the long-term mortality rate for unprotected left main coronary artery stenosis when compared with conventional angiography guidance.
Multipotent Progenitor Cells Are Present in Human Peripheral Blood
Authors: Cesselli Daniela , Beltrami Antonio Paolo , Rigo Silvia , Bergamin Natascha , D'Aurizio Federica , Verardo Roberto , Piazza Silvano , Klaric Enio , Fanin Renato , Toffoletto Barbara , Marzinotto Stefania , Mariuzzi Laura , Finato Nicoletta , Pandolfi Maura , Leri Annarosa , Schneider Claudio , Beltrami Carlo Alberto , Anversa Piero
Published: April 2009

To determine whether the peripheral blood in humans contains a population of multipotent progenitor cells (MPCs), products of leukapheresis were obtained from healthy donor volunteers following the administration of granulocyte colony-stimulating factor. Small clusters of adherent proliferating cells were collected, and these cells continued to divide up to 40 population doublings without reaching replicative senescence and growth arrest. MPCs were positive for the transcription factors Nanog, Oct3/4, Sox2, c-Myc, and Klf4 and expressed several antigens characteristic of mesenchymal stem cells. However, they were negative for markers of hematopoietic stem/progenitor cells and bone marrow cell lineages. MPCs had a cloning efficiency of ≈3%, and following their expansion, retained a highly immature phenotype. Under permissive culture conditions, MPCs differentiated into neurons, glial cells, hepatocytes, cardiomyocytes, endothelial cells, and osteoblasts. Moreover, the gene expression profile of MPCs partially overlapped with that of neural and embryonic stem cells, further demonstrating their primitive, uncommitted phenotype. Following subcutaneous transplantation in nonimmunosuppressed mice, MPCs migrated to distant organs and integrated structurally and functionally within the new tissue, acquiring the identity of resident parenchymal cells. In conclusion, undifferentiated cells with properties of embryonic stem cells can be isolated and expanded from human peripheral blood after granulocyte colony-stimulating factor administration. This cell pool may constitute a unique source of autologous cells with critical clinical import.
Severe Cerebral White Matter Hyperintensities Predict Severe Cognitive Decline in Patients With Cerebrovascular Disease History
Authors: Dufouil Carole , Godin Ophélia , Chalmers John , Coskun Oghuzan , MacMahon Stephen , Tzourio-Mazoyer Nathalie , Bousser Marie-Germaine , Anderson Craig , Mazoyer Bernard , Tzourio Christophe
Published: April 2009

Background and Purpose—

Cerebral white matter hyperintensities (WMHs) are believed to be the consequence of small vessel disease, and it is uncertain whether their extent predicts the risk of dementia in patients with vascular disease history.

Method—

Brain MRI was performed in 226 participants of the PROGRESS study. WMH severity was assessed using a visual rating scale. During follow-up, patients were classified for incident severe cognitive deterioration (including dementia) using standard criteria.

Results—

Over 4-year follow-up, the incidence of severe cognitive deterioration ranged from 1.1 to 9.1 per 100 person-years in patients with respectively no or severe WMHs at baseline. In multivariable analysis, incident severe cognitive deterioration was associated with baseline severe WMHs (odds ratio=7.7,
P
<0.005).

Conclusion—

Higher WMH load is a strong predictor of dementia and cognitive decline in patients with cerebrovascular disease history.
Ambivalent Commitments: Troubles of Morality, Religiosity and Aspiration among Young Egyptians
Authors: Schielke Samuli
Published: April 2009

In contrast to a line of studies that inquire how Muslims try to solve the problem of living piously in a society dominated by materialist tendencies and secular rationality, in this article I turn the question around and problematize the will to live piously and the focus on self-discipline. In everyday lives of young men from the Nile Delta region, the Islamic revivalist project of creating comprehensive moral and civic virtues uneasily coexists with other less total aims and ideals, notably community and family bonds, romantic love, success and self-realization. I attempt to take these contradictions seriously and dwell on the ways people live them and their attempts to make sense of their lives. In particular, I look at the ways people employ the normative registers of religion, love and aspiration in their lives, the promises each of these ideals entail and the options that are available should any of these promises fail.
Spiritual Warfare 101: Preparing the Student for Christian Battle
Authors: Stambach Amy
Published: April 2009

Taking its subtitle from a theological college course description, this paper examines the intersections of theological and anthropological ideas of culture, as seen through the eyes of Kenyan evangelists and American missionaries. One of the key concepts developed in the course, and in the broader program of this U.S.-funded nondenominational church in East Africa, is that understanding culture is key to learning and unlocking the spiritual 'personalities' (both godly and satanic) involved in spiritual warfare. Both Kenyans and Americans conceive of warfare as the struggle between secular and Christian worldviews and consider education to be one of the strongest weapons needed to win the battle. However, where U.S. teachers focus on animism and world-religious conflict as evidence of lingering immorality and ungodliness, Kenyans focus on American ethnocentrism and xenophobia as evidence of ongoing cultural misunderstandings and injustice. Analysis is based on examination of mission records and on field research conducted in Nairobi and western Kenya.
Context and Causal Mechanisms in Political Analysis
Authors: Falleti Tulia G. , Lynch Julia F.
Published: April 2009

Political scientists largely agree that causal mechanisms are crucial to understanding causation. Recent advances in qualitative and quantitative methodology suggest that causal explanations must be contextually bounded. Yet the relationship between context and mechanisms and this relationship's importance for causation are not well understood. This study defines causal mechanisms as portable concepts that explain how and why a hypothesized cause, in a given context, contributes to a particular outcome. In turn, it defines context as the relevant aspects of a setting in which an array of initial conditions leads to an outcome of a defined scope and meaning via causal mechanisms. Drawing from these definitions is the argument that credible causal explanation can occur if and only if researchers are attentive to the interaction between causal mechanisms and context, regardless of whether the methods employed are small-sample, formal, statistical, or interpretive.
Sibling Relationships and Adolescents' Mental Health
Authors: Vogt Yuan Anastasia S.
Published: April 2009

Although sibling structure influences some aspects of adolescents' well-being, including deviance and educational achievement, little research has explored the association between sibling structure and adolescents' mental health. This study explores how sibling structure (the number of siblings, full versus step- or half-siblings, the relative age of siblings, and the gender composition of siblings) influences adolescents' mental health and whether sibling relationship quality mediates or interacts with sibling structure. Using data from the 1995 National Longitudinal Study of Adolescent Health, the author performs multilevel modeling to control for siblings' sharing a joint family context. Results indicate that sibling structure has few associations with mental health and sibling relationship quality generally does not mediate (or suppress) these associations. However, sibling structure moderates the association between sibling relationship quality and adolescents' mental health. Thus, sibling structure and relationship quality appear to be interconnected in their influence on adolescents' mental health.
The Ecological Impacts of Large-Scale Agrofuel Monoculture Production Systems in the Americas
Authors: Altieri Miguel A.
Published: April 2009

This article examines the expansion of agrofuels in the Americas and the ecological impacts associated with the technologies used in the production of large-scale monocultures of corn and soybeans. In addition to deforestation and displacement of lands devoted to food crops due to expansion of agrofuels, the massive use of transgenic crops and agrochemical inputs, mainly fertilizers and herbicides used in the production of agrofuels, pose grave environmental problems.
Putting Patients First
Authors: Chance Zoë , Deshpandé Rohit
Published: April 2009

It is more than mere coincidence that the highest rates of HIV occur in the world’s poorest countries. Of the over forty million people currently living with HIV, 95 percent are in the developing world. The first part of this article explores the economics of HIV and treatment from a social marketing perspective. The second part of the article uses three specific case histories of successful social marketing organizations in Africa, Asia, and South America to inductively generate a consumer (patient)-centric marketing model. The focal organizations are unique in that they all identify patient needs first, then work backwards to develop economically viable solutions. Their solutions are not without flaws, and the future of these programs remains uncertain, but the authors hope that illuminating specific cases within the consumer-centric marketing paradigm will shed light on ways in which other organizations may be able to serve the poor profitably.
Hetero-Romantic Love and Heterosexiness in Children's G-Rated Films
Authors: Martin Karin A. , Kazyak Emily
Published: April 2009

In this article, the authors examine accounts of heterosexuality in media for children. The authors analyze all the G-rated films grossing $100 million dollars or more between 1990 and 2005 and find two main accounts of heterosexuality. First, heterosexuality is constructed through hetero-romantic love relationships as exceptional, powerful, magical, and transformative. Second, heterosexuality outside of relationships is constructed through portrayals of men gazing desirously at women's bodies. Both of these findings have implications for our understanding of heteronormativity. The first is seemingly at odds with theories that claim that heterosexuality's mundane, assumed, everyday ordinariness lends heteronormativity its power. In fact, the authors suggest heterosexual exceptionalism may extend the pervasiveness of heterosexuality and serve as a means of inviting investment in it. The second offers ways to begin to think about how heteronormativity is gendered and racialized.
Supporting Systematic Reviews Using Text Mining
Authors: Ananiadou Sophia , Rea Brian , Okazaki Naoaki , Procter Rob , Thomas James
Published: April 2009

In this article, we describe how we are using text mining solutions to enhance the production of systematic reviews. The aims of this collaborative project are the development of a text mining framework to support systematic reviews and the provision of a service exemplar serving as a test bed for deriving requirements for the development of more generally applicable text mining tools and services.
Part 1—Factors Associated with School Nurse Ratios: An Analysis of State Data
Authors: Maughan Erin
Published: April 2009

Despite the recognized importance of school nurses, the ratios of nurse to pupil are insufficient in many states across the country. The purpose of this study was to describe school nurse-to-pupil ratios by state and to statistically identify factors that may influence these ratios. Funding per pupil unit in general and support services and laws mandating school nurse ratios were some of the factors found to be associated with school ratios. Although the study has significant limitations, this is the first study of its kind to examine factors associated with ratios using secondary databases that are state-specific. Data such as this provide a context for studying those factors potentially influencing ratios. Further studies are needed to explore the numerous potential determinants described in the literature. Once key factors are identified, school nurses can effectively focus their efforts to lower school nurse-pupil ratios.
The long-term cost of multiple sclerosis in France and potential changes with disease-modifying interventions
Authors: Kobelt G , Texier-Richard B , Lindgren P
Published: April 2009

Objective

To evaluate the long-term costs and quality of life (QoL) with and without disease-modifying treatments (DMTs) of patients with multiple sclerosis (MS).

Methods

Data on resource consumption, productivity losses, QoL (utility), and fatigue were collected from 1355 patients registered with a patient association and descriptive analyses was performed.

A Markov model was developed to estimate costs and utility over 20 years using the survey data. Disease progression without DMTs was taken from an epidemiological cohort in France (EDMUS cohort, LYON). Progression under DMTs was estimated from the Stockholm MS registry. Results are presented as cost per quality-adjusted life-years (QALYs), from the societal perspective, in EUR2007, discounted at 3%.

Results

Mean Expanded Disability Status Scale (EDSS) was 4.4 and mean total annual costs per patient were EUR44,400, of which 47% were productivity losses and 11% informal care. Public payers cover an estimated 48% of costs. Mean utility was 0.52, and the loss compared with the normal population was estimated at 0.28. Costs and utility ranged from EUR16,000 and 0.79 at EDSS 1 to EUR76,000 and 0.11 at EDSS 8–9.

Over 20 years, costs were estimated at EUR429,000 and QALYs at 8.96 for patients without DMTs and at EUR433,207 and 9.24 QALYs if all patients were starting treated with DMTs at EDSS 1–3.

Conclusion

Although the data for this analysis come from different sources, the results indicate that the cost increase with DMTs is moderate.
Digital cameras and domestic photography: communication, agency and structure
Authors: Cobley Paul , Haeffner Nick
Published: April 2009

This article seeks to open up debate on the nature of communication in digital domestic photography. The discussion locates itself between the putative poles of `digital democracy' and `digital literacy', questioning the communicative co-ordinates of the snapshot and identifying the `idiomatic genres' in which it takes place. The authors argue that digital cameras enable domestic photographers to take `good' or professional-looking photographs and make certain capacities of professional cameras available for consumer use. Conversely, however, they argue that the question of critical understanding of the politics of representation in domestic camera use remains, since technical proficiency is not necessarily always accompanied by analysis. One reason suggested for this is that, frequently, the uses of photography are insufficiently analysed. The article therefore criticizes the idea that (domestic) photography can be understood in terms of `language' without paying due attention to the use of photography to capture the nonverbal.
Differential discourses: the contribution of visual analysis to defining scientific literacy in the early years classroom
Authors: Britsch Susan
Published: April 2009

This article presents a kindergarten science inquiry as an exemplar for the purpose of suggesting an analytic graphic that is visually inclusive of the multimodal resources brought to bear by children and teachers engaged in classroom interaction. The central aim is the visual representation of the analysis so that the analysis itself becomes visual communication, a means of generating knowledge about multimodal discourse. This makes the discourse structure much more accessible to viewers than a verbal transcript. Findings demonstrate that the children and teacher carried out activity that reflected generally mismatched classroom discourses. The children engaged in the science processes of observation, interpretation, and design of the investigation while the teacher focused on the social process of classroom management. Visual communication is central in helping researchers and teachers to visually associate the elements and structure of interactions so that teaching response can be designed.
Growing and gaining through caring for a loved one with dementia
Authors: Netto Nicholas Raphael , Jenny Goh Yen Ni , Philip Yap Lin Kiat
Published: April 2009

Aim: To investigate the gains experienced by family caregivers of persons with dementia.

Methods: Twelve respondents were recruited using purposive sampling from three institutions around Singapore. A qualitative design, guided by the grounded theory approach, was adopted and involved semi-structured, in-depth, face-to-face interviews. The interviews were recorded, transcribed and analyzed using open, axial and selective coding.

Results: All caregivers interviewed reported having gained from caregiving. The most common gain was that of `personal growth' which comprised being more patient/understanding, becoming stronger/more resilient, having increased self-awareness and being more knowledgeable. Another theme that emerged was `gains in relationships' whereby caregivers experienced an improvement in their relationship with the care recipient, with others in the family or in their ability to interact with other older persons. The third gain experienced was that of `higher-level gains' which encompassed gains in spirituality, deepened relations with God, and a more enlightened perspective in life.

Discussion: This research supports a shift from the conventional focus on burdens to a more holistic approach that considers how caregivers can grow and emerge stronger from the caregiving experience. This has implications in the design and delivery of services as utilizing these gains as a coping resource may enable better support for caregivers. It is pertinent that professionals supporting caregivers internalize the perspective of gains so that it becomes a natural way of seeing their clients and in the process help caregivers find meaning and enrichment in their caregiving journey.
Factors Influencing Attitudes to Violence Against Women
Authors: Flood Michael , Pease Bob
Published: April 2009

Attitudes toward men's violence against women shape both the perpetration of violence against women and responses to this violence by the victim and others around her. For these reasons, attitudes are the target of violence-prevention campaigns. To improve understanding of the determinants of violence against women and to aid the development of violence-prevention efforts, this article reviews the factors that shape attitudes toward violence against women. It offers a framework with which to comprehend the complex array of influences on attitudes toward violent behavior perpetrated by men against women. Two clusters of factors, associated with gender and culture, have an influence at multiple levels of the social order on attitudes regarding violence. Further factors operate at individual, organizational, communal, or societal levels in particular, although their influence may overlap across multiple levels. This article concludes with recommendations regarding efforts to improve attitudes toward violence against women.
A Multicenter, Open-Label, 24-Week Follow-Up Study for Efficacy on Cognitive Function of Donepezil in Binswanger-Type Subcortical Vascular Dementia
Authors: Jay Cheol Kwon  , Eung Gyu Kim  , Jae Woo Kim  , Oh Dae Kwon  , Bong Goo Yoo  , Hyon Ah Yi  , Nack Cheon Choi  , Seon Young Ahn  , Byung Hwa Lee  , Myong Jin Kang  , Dae Seob Choi  ,   BKVD Study Group
Published: April 2009

Objectives: To evaluate the efficacy and tolerability of donepezil in patients with Binswanger type subcortical vascular dementia. Methods: Patients (n = 34, mean age = 71.8 + 7.12) with Binswanger type subcortical vascular dementia from 8 multicenter, according to clinical and neuroradiological working criteria, were selected to receive donepezil 5 mg/day (n = 2) or donepezil 10 mg/day (n = 32, after 5 mg/day) for 24 weeks. Our primary endpoints were change from baseline to weeks 12 and 24 in the Seoul Neuropsychological Screening Battery-Dementia version (SNSB-D) and the Korean version of neuropsychiatric inventory (K-NPI). Results: A total of 24 patients received donepezil completed the study (mean age = 72.0 + 7.5 K-Mini-Mental State Examination [MMSE] = 21.0 + 5.1). After 12 weeks and 24 weeks, patients showed improvements in cognitive function on the SNSB-D compared baseline of 16.29 points at 12 weeks (P < .05) and 12.44 points at 24 weeks (P < .05). Significant improvements were shown in only memory domain, immediate verbal recall and delayed recall tests. Subgroup with better cognitive function (SNSB-D > 100) were more effective in frontal and memory domains than the other subgroup (SNSB-D < 100). Withdrawal rates due to adverse events were very low (4.16%). Conclusions: Donepezil-treated patients with Binswanger type subcortical vascular dementia demonstrated significant improvement in cognition compared with baseline, and donepezil was well tolerated.
Perspectives of Senior-Level Executives on Effective Followership and Leadership
Authors: Agho Augustine O.
Published: April 2009

Using a three-page questionnaire administered to a sample of 302 senior-level executives, this study examined the perceptions of executives on the distinguishing characteristics of effective leaders and followers. Most of the characteristics associated with effective leaders were perceived to be different from those associated with effective followers. A significant number of the respondents agreed that (a) leadership and followership are interrelated roles; (b) leadership and followership skills have to be learned; (c) effective leaders and effective followers can influence work performance, quality of work output, satisfaction and morale, and cohesiveness of work groups; and (d) researchers have not devoted enough attention to the study of followership.
Physical Activity, Blood Lipids, and Lipoproteins
Authors: Mestek Michael L.
Published: April 2009

Dyslipidemia is a major modifiable cardiovascular disease (CVD) risk factor. While pharmacological treatment has been a focal point of dyslipidemia management for several years, increasing physical activity is a safe, cost-effective treatment option that should also be recommended by health care practitioners. Moderate aerobic exercise consistently increases high-density lipoprotein cholesterol (HDL-C) and reduces triglycerides (TG), independent of changes in body weight. However, reductions in total and low-density lipoprotein cholesterol are reported less often following aerobic exercise. Therefore, clinicians should understand that aerobic exercise is not likely to be an effective treatment option for their management. Recent empirical evidence also indicates that aerobic exercise may be of benefit for treating emerging lipid and lipoprotein risk factors such as lipoprotein particle size and number and triglyceride-rich lipoproteins. Further work is needed to clarify the impact of aerobic exercise on apolipoproteins. Based on current evidence, prescribing aerobic exercise as a means of increasing HDL-C and lowering TG is usually an efficacious strategy for treating these aspects of dyslipidemia. These effects are likely to be accompanied by changes in emerging lipid and lipoprotein risk factors.
Profound Intrauterine Growth Restriction (IUGR) Due to Donohue Syndrome: the Story of One Family
Authors: Alsammoua Samawal , McPherson Roisin , Robins James
Published: April 2009

We describe the obstetric care delivered to a woman over the course of three pregnancies during which time she and her partner were diagnosed as carriers of a rare autosomal recessive disorder: Donohue syndrome. She went on to deliver two affected children and one child who was unaffected. The first baby was growth restricted in utero and had many classical clinical and biochemical features of the syndrome. This infant died at the age of five months. The mother declined prenatal testing in her subsequent pregnancies. Fortunately, she was to deliver a healthy baby in her second pregnancy. However, her third pregnancy was again complicated by severe intrauterine growth restriction. She was delivered of the second affected baby who again demonstrated many of the features and abnormalities associated with Donohue syndrome. This baby died at thirteen months of age. The process leading to the diagnosis, the ultrasound growth charts related to affected and unaffected fetuses and the implications for subsequent management are described.
Effect of heat treatment on microstructure and transparent conducting properties of sol-gel ZnO/Al thin films
Authors: Chen J. L. , Chen D. , Chen Z. H.
Published: April 2009

Transparent and conducting Al doped ZnO (AZO) thin films with c axis preferred orientation were prepared on glass substrates via the sol-gel route. The physical and chemical changes of the precursors during thermal treatment were systematically investigated by differential scanning calorimeter and thermogravimetric analysis and the crystallinity of AZO films was characterised by X-ray diffraction. The surface morphology evolution of the films post-heated at 420, 450, 530 and 550°C respectively was observed by SEM. Results reveal that the crystallising process of ZnO/Al comprises two stages: the primary nucleation and growth occurs at 318°C and the continuous crystallisation at 488°C. The optimised preheating and post-heating temperatures are determined at 420 and 530°C respectively. The annealing treatment in vacuum can contribute considerably to the electrical conductivity. The film post-heated at 530°C shows a homogenous dense microstructure and exhibits the minimum sheet resistance of 140 Ω/sq. The visible optical transmittance of all films is more than 90%.
Hot deformation behaviour of thixocast Al–Si–Mg alloy during compression at elevated temperatures
Authors: Haghshenas M. , Zarei-Hanzaki A. , Sayed A.
Published: April 2009

In the present study, the flow behaviour and constitutive equation of a Thixocast A356 Al alloy has been studied using the hot compression test at 450, 500 and 540°C under the strain rates of 0·0001, 0·0005, 0·001 and 0·01 s−1. The compression flow curves exhibited an initial sharp increase with strain followed by a moderate work hardening behaviour. The maximum stress was decreased as the strain rate reduced and the temperature increased. At the lowest examined temperature (450°C) and the highest applied strain rate (0·01 s−1), a flow softening behaviour was observed. This was attributed to the morphological changes of the present precipitates.
Temperature cycling and the rate of the bainite transformation
Authors: Hasan H. S. , Peet M. , Bhadeshia H. K. D. H. , Wood S. , Booth E.
Published: April 2009

The possibility that the thermal cycling of supercooled austenite, within the bainite transformation range, accelerates the kinetics of decomposition, is investigated both by analysing previous work and by conducting a series of new experiments. The cyclic variations in temperature do not seem to anomalously affect the rate of transformation.
IL-7 adjuvant treatment enhances long-term tumor antigen-specific CD8+ T-cell responses after immunization with recombinant lentivector
Authors: Colombetti Sara , Lévy Frédéric , Chapatte Laurence
Published: April 2009

Immunization with recombinant lentivector elicits higher frequencies of tumor antigen-specific memory CD8+ T cells than peptide-based vaccines. This finding correlates with our observation that, upon recombinant lentivector immunization, a higher fraction of antigen-specific effector CD8+ T cells does not down-regulate the expression of the survival/memory marker interleukin-7 receptor α chain (IL-7Rα). Here we show that, surprisingly, higher expression of IL-7Rα on recombinant lentivector-induced effector CD8+ T cells does not result in the up-regulation of survival molecules, such as Bcl-2. We thus hypothesized that physiologic levels of IL-7 might be limiting in vivo for delivering survival signals to the expanding population of effector cells. To test this hypothesis, we administered recombinant IL-7 during the effector phase of the response. We observed an up-regulation of Bcl-2 and a strong expansion of antigen-specific effector CD8+ T cells, and of naive CD8+ T cells. Strikingly, IL-7 treatment elicited also a significant increase in the number of antigen-specific memory CD8+ T cells in recombinant lentivector-immunized mice, but not in peptide-immunized mice. Altogether, these data show that IL-7 adjuvant treatment can enhance long-term antigen-specific CD8+ T-cell responses. However, its efficacy depends on the expression of IL-7Rα at the surface of effector CD8+ T cells.
The histone deacetylase inhibitors LAQ824 and LBH589 do not require death receptor signaling or a functional apoptosome to mediate tumor cell death or therapeutic efficacy
Authors: Ellis Leigh , Bots Michael , Lindemann Ralph K. , Bolden Jessica E. , Newbold Andrea , Cluse Leonie A. , Scott Clare L. , Strasser Andreas , Atadja Peter , Lowe Scott W. , Johnstone Ricky W.
Published: April 2009

LAQ824 and LBH589 (panobinostat) are histone deacetylase inhibitors (HDACi) developed as cancer therapeutics and we have used the Eμ-myc lymphoma model to identify the molecular events required for their antitumor effects. Induction of tumor cell death was necessary for these agents to mediate therapeutic responses in vivo and both HDACi engaged the intrinsic apoptotic cascade that did not require p53. Death receptor pathway blockade had no effect on the therapeutic activities of LAQ824 and LBH589; however, overexpression of Bcl-2 or Bcl-XL protected lymphoma cells from HDACi-induced killing and suppressed their therapeutic activities. Deletion of Apaf-1 or Caspase-9 delayed HDACi-induced lymphoma killing in vitro and in vivo, associated with suppression of many biochemical indicators of apoptosis, but did not provide long-term resistance to these agents and failed to inhibit their therapeutic activities. Eμ-myc lymphomas lacking a functional apoptosome displayed morphologic and biochemical features of autophagy after treatment with LAQ824 and LBH589, indicating that, in the absence of a complete intrinsic apoptosis pathway involving apoptosome formation, these HDACi can still mediate a therapeutic response. Our data indicate that damage to the mitochondria is the key event necessary for LAQ824 and LBH589 to mediate tumor cell death and a robust therapeutic response.
Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases
Authors: Del Giudice Ilaria , Chiaretti Sabina , Tavolaro Simona , De Propris Maria Stefania , Maggio Roberta , Mancini Francesca , Peragine Nadia , Santangelo Simona , Marinelli Marilisa , Mauro Francesca Romana , Guarini Anna , Foà Robin
Published: April 2009

In chronic lymphocytic leukemia (CLL), spontaneous regressions are an exceptional phenomenon, whose biologic features are unknown. We describe 9 CLL patients who underwent a spontaneous clinical regression over an 11-year follow-up, despite a residual neoplastic clone detected by flow cytometry. CD38 and ZAP-70 were negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes, mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with the usage of VH3-30 gene in 2. The light chain variable region genes were mutated in 6 of 8 cases, with the use of Vκ4-1 gene in 3. Microarray analysis of CLL cells showed a distinctive genomic profile with an overrepresentation of BCR-related and ribosomal genes, regulators of signal transduction and transcription. The number of activated T lymphocytes expressing IFN-γ, TNF-α, and IL-4 was similar between CLL in spontaneous regression and healthy persons. In conclusion, spontaneous clinical regressions can occur in CLL despite the persistence of the neoplastic clone, and the biologic features include negative CD38 and ZAP-70, mutated VH3-30 and Vκ4-1 genes. The peculiar gene profile suggests that BCR signaling may play an important role in this scenario as the most significant feature of the leukemic clone in regression.
On the edge of Bantu expansions: mtDNA, Y chromosome and lactase persistence genetic variation in southwestern Angola
Authors: Coelho Margarida , Sequeira Fernando , Luiselli Donata , Beleza Sandra , Rocha Jorge
Published: April 2009

Background

Current information about the expansion of Bantu-speaking peoples is hampered by the scarcity of genetic data from well identified populations from southern Africa. Here, we fill an important gap in the analysis of the western edge of the Bantu migrations by studying for the first time the patterns of Y-chromosome, mtDNA and lactase persistence genetic variation in four representative groups living around the Namib Desert in southwestern Angola (Ovimbundu, Ganguela, Nyaneka-Nkumbi and Kuvale). We assessed the differentiation between these populations and their levels of admixture with Khoe-San groups, and examined their relationship with other sub-Saharan populations. We further combined our dataset with previously published data on Y-chromosome and mtDNA variation to explore a general isolation with migration model and infer the demographic parameters underlying current genetic diversity in Bantu populations.

Results

Correspondence analysis, lineage sharing patterns and admixture estimates indicate that the gene pool from southwestern Angola is predominantly derived from West-Central Africa. The pastoralist Herero-speaking Kuvale people were additionally characterized by relatively high frequencies of Y-chromosome (12%) and mtDNA (22%) Khoe-San lineages, as well as by the presence of the -14010C lactase persistence mutation (6%), which likely originated in non-Bantu pastoralists from East Africa. Inferred demographic parameters show that both male and female populations underwent significant size growth after the split between the western and eastern branches of Bantu expansions occurring 4000 years ago. However, males had lower population sizes and migration rates than females throughout the Bantu dispersals.

Conclusion

Genetic variation in southwestern Angola essentially results from the encounter of an offshoot of West-Central Africa with autochthonous Khoisan-speaking peoples from the south. Interactions between the Bantus and the Khoe-San likely involved cattle herders from the two groups sharing common aspects of their social organization. The presence of the -14010C mutation in southwestern Angola provides a link between the East and Southwest African pastoral scenes that might have been established indirectly, through migrations of Khoe herders across southern Africa. Differences in patterns of mtDNA and Y-chromosome intrapopulation diversity and interpopulation differentiation may be explained by contrasting demographic histories underlying the current female and male genetic variation.
Bos taurus genome assembly
Authors: Liu Yue , Qin Xiang , Song Xing-Zhi Henry , Jiang Huaiyang , Shen Yufeng , Durbin K James , Lien Sigbjørn , Kent Matthew Peter , Sodeland Marte , Ren Yanru , Zhang Lan , Sodergren Erica , Havlak Paul , Worley Kim C , Weinstock George M , Gibbs Richard A
Published: April 2009

Background

We present here the assembly of the bovine genome. The assembly method combines the BAC plus WGS local assembly used for the rat and sea urchin with the whole genome shotgun (WGS) only assembly used for many other animal genomes including the rhesus macaque.

Results

The assembly process consisted of multiple phases: First, BACs were assembled with BAC generated sequence, then subsequently in combination with the individual overlapping WGS reads. Different assembly parameters were tested to separately optimize the performance for each BAC assembly of the BAC and WGS reads. In parallel, a second assembly was produced using only the WGS sequences and a global whole genome assembly method. The two assemblies were combined to create a more complete genome representation that retained the high quality BAC-based local assembly information, but with gaps between BACs filled in with the WGS-only assembly. Finally, the entire assembly was placed on chromosomes using the available map information.

Over 90% of the assembly is now placed on chromosomes. The estimated genome size is 2.87 Gb which represents a high degree of completeness, with 95% of the available EST sequences found in assembled contigs. The quality of the assembly was evaluated by comparison to 73 finished BACs, where the draft assembly covers between 92.5 and 100% (average 98.5%) of the finished BACs. The assembly contigs and scaffolds align linearly to the finished BACs, suggesting that misassemblies are rare. Genotyping and genetic mapping of 17,482 SNPs revealed that more than 99.2% were correctly positioned within the Btau_4.0 assembly, confirming the accuracy of the assembly.

Conclusion

The biological analysis of this bovine genome assembly is being published, and the sequence data is available to support future bovine research.
Functional genomics of HMGN3a and SMARCAL1 in early mammalian embryogenesis
Authors: Uzun Alper , Rodriguez-Osorio Nelida , Kaya Abdullah , Wang Hongfeng , Parrish John J , Ilyin Valentin A , Memili Erdogan
Published: April 2009

Background

Embryonic genome activation (EGA) is a critical event for the preimplantation embryo, which is manifested by changes in chromatin structure, transcriptional machinery, expression of embryonic genes, and degradation of maternal transcripts. The objectives of this study were to determine transcript abundance of HMGN3a and SMARCAL1 in mature bovine oocytes and early bovine embryos, to perform comparative functional genomics analysis of these genes across mammals.

Results

New annotations of both HMGN3a and SMARCAL1 were submitted to the Bovine Genome Annotation Submission Database at BovineGenome.org. Careful analysis of the bovine SMARCAL1 consensus gene set for this protein (GLEAN_20241) showed that the NCBI protein contains sequencing errors, and that the actual bovine protein has a high degree of homology to the human protein. Our results showed that there was a high degree of structural conservation of HMGN3a and SMARCAL1 in the mammalian species studied. HMGN3a transcripts were present at similar levels in bovine matured oocytes and 2–4-cell embryos but at higher levels in 8–16-cell embryos, morulae and blastocysts. On the other hand, transcript levels of SMARCAL1 decreased throughout preimplantation development.

Conclusion

The high levels of structural conservation of these proteins highlight the importance of chromatin remodeling in the regulation of gene expression, particularly during early mammalian embryonic development. The greater similarities of human and bovine HMGN3a and SMARCAL1 proteins may suggest the cow as a valuable model to study chromatin remodeling at the onset of mammalian development. Understanding the roles of chromatin remodeling proteins during embryonic development emphasizes the importance of epigenetics and could shed light on the underlying mechanisms of early mammalian development.
Capecitabine plus Irinotecan (XELIRI regimen) compared to 5-FU/LV plus Irinotecan (FOLFIRI regimen) as neoadjuvant treatment for patients with unresectable liver-only metastases of metastatic colorectal cancer: a randomised prospective phase II trial
Authors: Skof Erik , Rebersek Martina , Hlebanja Zvezdana , Ocvirk Janja
Published: April 2009

Background

Phase II studies have shown that the combination of capecitabine and irinotecan (the XELIRI regimen) is active in metastatic colorectal cancer (MCRC). There are, however, no data about the use of the XELIRI regimen in the neoadjuvant treatment.

Methods

Patients with unresectable liver-only metastases of MCRC with ≤ 75 years of age were randomised to either the XELIRI (irinotecan 250 mg/m2 given on day one and capecitabine 1000 mg/m2 twice daily from day 2–15, every 21 days) or the FOLFIRI arm (irinotecan 180 mg/m2, 5-FU 400 mg/m2, LV 200 mg/m2, 5-FU 2400 mg/m2 (46-h infusion) – all given on day one, every 14 days). Primary end points were objective response rate (ORR) and rate of radical (R0) surgical resection. Secondary end points were progression-free survival (PFS), overall survival (OS) and safety.

Results

Altogether 87 patients were enrolled (41 pts in the XELIRI and 46 pts in the FOLFIRI arm). The median age was 63 years (63 years in the XELIRI and 62 years in the FOLFIRI arm) (p = 0.33). ORR was 49% in the XELIRI and 48% in the FOLFIRI arm (p = 0.76). The rate of radical R0 resection was 24% in both arms of patients. At the end of treatment, 37% of patients in the XELIRI and 26% of patients in the FOLFIRI arm were without evidence of the disease (CR+R0 resection) (p = 0.56). There were no statistical differences in grade 3 or 4 adverse events between both arms: diarrhoea 7% vs. 6%, neutropenia 5% vs. 13%, ischemic stroke 0 vs. 2%, acute coronary syndrome 2% vs. 4%, respectively. At the median follow up of 17 (range 1–39) months, the median PFS was 10.3 months in the XELIRI and 9.3 months in the FOLFIRI arm (p = 0.78), the median OS was 30.7 months in the XELIRI arm and 16.6 months in the FOLFIRI arm (p = 0.16).

Conclusion

The XELIRI regimen showed similar ORR as the FOLFIRI regimen in the neoadjuvant treatment of patients with MCRC. In addition, the XELIRI regimen showed similar PFS and OS with acceptable toxicity compared to the FOLFIRI regimen.

Trial Registration

Current Controlled Trials ISRCTN19912492
Resource heterogeneity and foraging behaviour of cattle across spatial scales
Authors: Utsumi Santiago A , Cangiano Carlos A , Galli Julio R , McEachern Mary B , Demment Montague W , Laca Emilio A
Published: April 2009

Background

Understanding the mechanisms that influence grazing selectivity in patchy environments is vital to promote sustainable production and conservation of cultivated and natural grasslands. To better understand how patch size and spatial dynamics influence selectivity in cattle, we examined grazing selectivity under 9 different treatments by offering alfalfa and fescue in patches of 3 sizes spaced with 1, 4, and 8 m between patches along an alley. We hypothesized that (1) selectivity is driven by preference for the forage species that maximizes forage intake over feeding scales ranging from single bites to patches along grazing paths, (2) that increasing patch size enhances selectivity for the preferred species, and that (3) increasing distances between patches restricts selectivity because of the aggregation of scale-specific behaviours across foraging scales.

Results

Cows preferred and selected alfalfa, the species that yielded greater short-term intake rates (P < 0.0001) and greater daily intake potential. Selectivity was not affected by patch arrangement, but it was scale dependent. Selectivity tended to emerge at the scale of feeding stations and became strongly significant at the bite scale, because of differences in bite mass between plant species. Greater distance between patches resulted in longer patch residence time and faster speed of travel but lower overall intake rate, consistent with maximization of intake rate. Larger patches resulted in greater residence time and higher intake rate.

Conclusion

We conclude that patch size and spacing affect components of intake rate and, to a lesser extent, the selectivity of livestock at lower hierarchies of the grazing process, particularly by enticing livestock to make more even use of the available species as patches are spaced further apart. Thus, modifications in the spatial pattern of plant patches along with reductions in the temporal and spatial allocation of grazing may offer opportunities to improve uniformity of grazing by livestock and help sustain biodiversity and stability of plant communities.
Assessing the molecular divergence between Anopheles (Kerteszia) cruzii populations from Brazil using the timeless gene: further evidence of a species complex
Authors: Rona Luísa DP , Carvalho-Pinto Carlos J , Gentile Carla , Grisard Edmundo C , Peixoto Alexandre A
Published: April 2009

Background

Anopheles(Kerteszia) cruziiwas the most important vector of human malaria in southern Brazil between 1930–1960. Nowadays it is still considered an importantPlasmodiumspp. vector in southern and south-eastern Brazil, incriminated for oligosymptomatic malaria. Previous studies based on the analysis ofXchromosome banding patterns and inversion frequencies inAn. cruziipopulations from these areas have suggested the occurrence of three sibling species. In contrast, two genetically distinct groups amongAn. cruziipopulations from south/south-east and north-east Brazil have been revealed by isoenzyme analysis. Therefore,An. cruziiremains unclear.

Methods

In this study, a partial sequence of thetimelessgene (~400 bp), a locus involved in the control of circadian rhythms, was used as a molecular marker to assess the genetic differentiation betweenAn. cruziipopulations from six geographically distinct areas of Brazil.

Results

Thetimelessgene revealed thatAn. cruziifrom Itaparica Island, Bahia State (north-east Brazil), constitutes a highly differentiated group compared with the other five populations from south and south-east Brazil. In addition, significant genetic differences were also observed among some of the latter populations.

Conclusion

Analysis of the genetic differentiation in thetimelessgene amongAn. cruziipopulations from different areas of Brazil indicated that this malaria vector is a complex of at least two cryptic species. The data also suggest that further work might support the occurrence of other siblings within this complex in Brazil.