bluuebunny/crossref_metadata_2025 huggingface dataset:
Middle School Teams Increasing Access to General Education for Students With Significant Disabilities
Authors: Matzen Katherine , Ryndak Diane , Nakao Taketo
Published: January 2009

The experiences of three students with significant disabilities and their educational teams were studied during these students’ first year of receiving general education services. Interviews were conducted with general educators, special educators, and parents to identify issues encountered during the year. Also, classroom observations were conducted throughout the year in both self-contained and general education settings for each student, and time sampling data were collected on instruction, downtime, and problem behavior. Results indicated that the education teams encountered several issues related to providing general education access for students with significant disabilities relating to two primary areas: (a) philosophical differences about the purpose of providing access to general education for students with significant disabilities, and (b) efforts to collaboratively team and meet the educational needs of the students with significant disabilities. Observational results indicated that the students received more instruction, experienced less downtime, and engaged in fewer problem behaviors in general education settings.
Nursing Care for Adaptation
Authors: Moreno María Elisa , Durán María Mercedes , Hernandez Ángela
Published: January 2009

The Roy adaptation model has been adopted as the frame of reference for the nursing curriculum at the Universidad de La Sabana School of Nursing in Colombia. The purpose of this paper is to discuss, through an example, the application process of the Roy model, the reflection that has been developed to study in great depth its central concepts and scientific and philosophic principles, and to explain the concept of nursing care for adaptation as a fundamental aspect for its application. Likewise, the process generated from the model's application in teaching and practice are presented.
A Phenomenological Study on the Experience of North Korean Refugees
Authors: Hyun Kyoung Kim  , Ok Ja Lee
Published: January 2009

The purpose of this phenomenological study was to explore the experience of North Korean refugees living in South Korea. From the analysis of the participants' comments, six essences were identified: entrance to a new world after struggling for survival, unexpected shock and chaos, reconsidering the reasons for leaving North Korea, recovery from trauma, rebuilding meaning, and posttraumatic growth.
Consciousness, Intentionality, and Community
Authors: Zahourek Rothlyn P. , Larkin Dorothy M.
Published: January 2009

Consciousness and intentionality often have been related and studied together. These concepts also are readily viewed and understood for practice, research, and education in a unitary paradigm. How these ideas relate to community is less known. Considering the expansion of our capacity for communication through the World Wide Web and other technologic advances and appreciating recent research on the nonlocal character of intentionality and consciousness, it is more apparent how concepts of community can be seen in the same unitary context. The authors address these issues and review relevant nursing research.
An Exploration of the Perception of Time From the Perspective of the Science of Unitary Human Beings
Authors: Ring Marcia E.
Published: January 2009

What is time? The science of unitary human beings describes pandimensional reality as a domain without spatial or temporal attributes. As part of this pandimensional reality, unitary human beings experience time as passing, and involving the past, present, and future. The theory of accelerating evolution describes changes in human and environmental energy fields that are always accelerating and are manifested as differences in the experience of time as being slow, fast, and still. Time, be it measured or experienced, has no meaning in and of itself, but can only be understood in terms of the ever-evolving life process.
On the Use of Hidden Markov Modeling and Time-frequency Features for Damage Classification in Composite Structures
Authors: Wenfan Zhou  , Kovvali Narayan , Reynolds Whitney , Papandreou-Suppappola Antonia , Chattopadhyay Aditi , Cochran Douglas
Published: January 2009

A novel approach based on hidden Markov models (HMMs) is proposed for damage classification in composite structures. Time-frequency damage features are first extracted from the measured signals using the matching pursuit decomposition algorithm. The features are then incorporated as observation sequences to be modeled statistically by the HMMs. Once built, the HMMs are integrated very efficiently into a Bayesian framework for the classification of structural damage. Both discrete and continuous observation density HMMs are considered; continuous HMMs are shown to yield better accuracy, but at the cost of added computational complexity. A decision fusion procedure is employed to combine the local classification results at each sensor, significantly enhancing the overall classification performance. The utility of the proposed technique is demonstrated by its application to the classification of delamination damage, impact damage, and progressive tensile damage in laminated composites.
Values in Authentic Action
Authors: Sosik John J. , Jung Dongil , Dinger Sandi L.
Published: January 2009

This study examined whether managers' values intensities and self-concept salience influence their altruistic leadership behavior and performance. Hypotheses derived from the goal hierarchy model of personality and the positive psychology literatures were tested using multisource data. Two hundred and eighteen managers reported their self-transcendence and self-enhancement values intensity and hoped-for and feared possible selves. Nine-hundred and thirty-five subordinates rated their manager's altruistic behavior and 218 superiors provided ratings of managerial performance. Results of partial least squares analysis indicated that managers' collective self salience partially mediated the relationships between self-transcendence and self-enhancement values intensity and altruistic behavior. Subordinates' ratings of managers' altruistic behavior predicted superiors' ratings of managerial performance. Managers' self-monitoring moderated the relationships between self-construals, altruistic behavior, and performance.
Leader—Member Exchange as a Moderator of the Relationship Between Work Group Diversity and Team Performance
Authors: Stewart Marcus M. , Johnson Olenda E.
Published: January 2009

This study tests a moderator of the association between diversity and work group performance: leader—member exchange (LMX). The authors theorized performance effects associated with the differentiation and aggregate level of the dyadic LMX relationships in work groups and that the nature of these LMX effects would vary qualitatively as a function of work group diversity. The model was tested with a U.S. military operational simulation, including 224 high-ranking officers in 65 temporary work groups. Results indicate that LMX interacted with work group gender diversity, such that in more gender diverse groups LMX differentiation was positively associated with work group performance when aggregate LMX was high (above the median); among less gender diverse groups, LMX differentiation was not associated with performance when aggregate LMX was high, consistent with prior research. No effects of gender diversity were found among work groups reporting low aggregate LMX or with regard to group member functional background diversity.
Parent Agreement on Ratings of Children’s Attention Deficit/Hyperactivity Disorder and Broadband Externalizing Behaviors
Authors: Langberg Joshua M. , Epstein Jeffery N. , Simon John O. , Loren Richard E. A. , Arnold L. Eugene , Hechtman Lily , Hinshaw Stephen P. , Hoza Betsy , Jensen Peter S. , Pelham William E. , Swanson James M. , Wigal Timothy
Published: January 2009

Mothers and fathers often disagree in their ratings of child behavior, as evidenced clinically and as supported by a substantial literature examining parental agreement on broadband rating scales. The present study examined mother—father agreement on Diagnostic and Statistical Manual—based symptom-specific ratings of Attention-Deficit/Hyperactivity Disorder (ADHD), as compared to agreement on broadband ratings of externalizing behavior. Based on mother and father ratings of 324 children who participated in the Multimodal Treatment Study of Children with ADHD (MTA), parental agreement was computed and patterns of disagreement examined. Mother—father ratings were significantly correlated; however, a clear pattern of higher ratings by mothers was present. Agreement on attention-deficit/hyperactivity disorder symptom-specific ratings was significantly lower than that for broadband externalizing behaviors and oppositional defiant disorder symptoms. Of several moderator variables tested, parental stress was the only one that predicted the discrepancy in ratings. Disagreement between parents is clinically significant and may pose complications to the diagnostic process.
Social Capital and Health Care Access
Authors: Pitkin Derose Kathryn , Varda Danielle M.
Published: January 2009

There is a growing interest in community-level characteristics such as social capital and its relationship to health care access. To assess the rigor with which this construct has been empirically applied in research on health care access, a systematic review was conducted. A total of 2,396 abstracts were reviewed, and 21 met the criteria of examining some measure of social capital and its effects on health care access. The review found a lack of congruence in how social capital was measured and interpreted and a general inconsistency in findings, which made it difficult to draw firm conclusions about the effects of social capital on health care access. Insights from the social network literature can help improve the conceptual and measurement problems. Future work should distinguish among bonding, bridging, and linking social capital and their sources and benefits, and examine whether three dimensions of social capital actually exist: cognitive, behavioral, and structural.
Technical Assistance as a Prevention Capacity-Building Tool: A Demonstration Using the Getting To Outcomes® Framework
Authors: Hunter Sarah B. , Chinman Matthew , Ebener Patricia , Imm Pam , Wandersman Abraham , Ryan Gery W.
Published: January 2009

Demands on community-based prevention programs for performance accountability and positive outcomes are ever increasing in the face of constrained resources. Relatively little is known about how technical assistance (TA) should be structured to benefit community-based organizations and to lead to better outcomes. In this study, data from multiple sources were used to describe an effective TA model designed to improve the capacity of community-based organizations to plan, implement, and evaluate prevention programming. This article is the first of its kind to provide detailed analyses of the TA delivered to community-based organizations to build substance abuse prevention capacity. The results of this study describe the range of TA services provided and the importance of two-way communication between the TA provider and recipient. TA recipients reported high satisfaction and an improved understanding of targeted TA activities. However, achieving these benefits requires significant program staff time, and not all skills were successfully transferred. Results from this study suggest how TA may be structured to be effective in supporting quality prevention programming in community settings.
`Hath charms to soothe . . .'
Authors: Allen Rory , Hill Elizabeth , Heaton Pam
Published: January 2009

Semi-structured interviews were conducted with 12 high-functioning adults on the autism spectrum, in order to examine the nature of their personal experiences of music. Consistent with the literature on typically developing people's engagement with music, the analysis showed that most participants exploit music for a wide range of purposes in the cognitive, emotional and social domains, including mood management, personal development and social inclusion. However, in contrast to typically developing people, the ASD group's descriptions of mood states reflected a greater reliance on internally focused (arousal) rather than externally focused (emotive) language.
Electrodermal reactivity to emotion processing in adults with autistic spectrum disorders
Authors: Hubert B.E. , Wicker B. , Monfardini E. , Deruelle C.
Published: January 2009

Although alterations of emotion processing are recognized as a core component of autism, the level at which alterations occur is still debated. Discrepant results suggest that overt assessment of emotion processing is not appropriate. In this study, skin conductance response (SCR) was used to examine covert emotional processes. Both behavioural responses and SCRs of 16 adults with an autistic spectrum disorder (ASD) were compared to those of 16 typical matched adults. Participants had to judge emotional facial expressions, the age of faces or the direction of a moving object. Although behavioural performance was similar in the two populations, individuals with an ASD exhibited lower SCRs than controls in the emotional judgement task. This suggests that such individuals may rely on different strategies due to altered autonomic processing. Furthermore, failure to produce normal physiological reactions to emotional faces may be related to social impairments in individuals with an ASD.
Similarities and differences between children and adolescents with autism spectrum disorder and those with obsessive compulsive disorder
Authors: Zandt Fiona , Prior Margot , Kyrios Michael
Published: January 2009

In order to examine hypothesized underlying neurocognitive processes in repetitive behaviour, children and adolescents (7—16 years) with autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) were compared on a range of executive function (EF) measures. Performance on neuropsychological tests assessing executive functioning showed a trend for children with ASD to perform poorly on tasks requiring generation of multiple responses, while children with OCD tended to demonstrate impairments on a task requiring inhibition. Parental ratings on a questionnaire measure of EF indicated impairments in both groups relative to controls. Relationships between questionnaire and performance measures of EF were generally weak. There was some limited support for a relationship between EF and repetitive behaviour, but effects tended to be small and variable across groups and measures.
Playing with principles in an era of securitized aid
Authors: Shannon Róisín
Published: January 2009

The international community's response to reconstructing Afghanistan, following the US-led regime change invasion post-11 September 2001 (9/11), brought actors such as the military and private corporations more fully into the humanitarian sphere. As a result, the Non-Governmental Organizations (NGOs), traditionally charged with taking humanitarian action, face a number of challenges and dilemmas. Their legitimacy and their ability to act impartially, be perceived as neutral and to maintain their independence have become increasingly constrained. How the NGOs adapt when their humanitarian space is constrained affects who, where and what aid gets delivered and on what principles. However, little is known about the dynamics of humanitarian space or how the NGOs have adapted in practice. Filling the gap in empirical knowledge might enable the NGOs to deal better with the constrained environments they are likely to encounter as the ‘war on terror’ continues to unfold. This research, based on field work in Afghanistan during mid-2006, suggests the politicization, developmentalization and securitization of aid, often referred to as ‘new humanitarianism’, has triumphed in the post-9/11 environment. The role of the NGOs as neutral actors has been seriously undermined, not least by the NGOs themselves. Having legitimized regime change intervention, they find themselves prevented from negotiating their space with any group not approved by the architects of the new political dispensation. As the country slips towards a serious humanitarian crisis, there may be no way back from their lost neutrality. The best use that can be made of these findings is to identify what the Afghanistan experience can teach NGOs for operating under constrained humanitarianism.
Social capital formation and local capture in decentralization
Authors: Abe Akiko
Published: January 2009

This article traces the roots of social capital formation in Zambézia, Mozambique, using data from the fieldwork and introducing the analytical framework of social knowledge, and examines the issues of decentralization in societies with low stocks of social capital. The case of Zambézia suggests that traditions of collective action for common goods and good local leadership can be a key to enhance stocks of social capital. To overcome inequality and the so-called local capture problems in societies with low stocks of social capital, alternative communication methods, public-civil society partnership and more intensified allocation of researchers in the field are recommended.
Space odyssey: towards a social semiotic model of three-dimensional space
Authors: Stenglin Maree Kristen
Published: January 2009

The aim of this article is to articulate a set of principles that can be applied to both the analysis and design of three-dimensional spaces. To achieve this aim, the article discusses the way three-dimensional spaces can be organized as a semiotic resource — a mode, which, like other modes, is multifunctional. The discussion begins by introducing a powerful social semiotic tool, Halliday's metafunctional theory (1978), which has previously been used to theorize numerous semiotic resources in western cultures: language, visual images, speech, music, sound and movement. It then `opens up' a grammar of three-dimensional space using Halliday's notion of three communicative functions. The research presented in this article is illustrated with a museum example, the Hyde Park Barracks Museum, Sydney. However, it is equally relevant to natural spaces as well as built spaces across a broad range of other fields: homes, schools, workplaces, retail sites, hospitals and virtual spaces.
Persistence of self in individuals with Alzheimer's disease
Authors: Fazio Sam , Mitchell David B.
Published: January 2009

The persistence of self in individuals with probable Alzheimer's disease was investigated via language and visual self-recognition. Seventy-eight adults (ages 66—103) participated: 26 with mild cognitive impairments, 26 with moderate cognitive impairments, and 26 without impairment. Although frequency of language usage (during an interview) declined across impairment levels, there were no significant differences in either rates or proportions of pronoun and attribute usage. When asked to identify themselves in photographs taken with an instant camera, cognitively impaired individuals — in spite of forgetting the photographic session only minutes earlier — exhibited unimpaired self-recognition, a dissociation consistent with a preserved self. Taken together, these findings indicate a persistence of self in individuals with dementia, and have implications for how Alzheimer's is characterized and experienced, and how individuals are cared for.
African American caregivers
Authors: Hughes Travonia , Tyler Kenneth , Danner Deborah , Carter Adah
Published: January 2009

Despite the significance of an early diagnosis of Alzheimer's disease (AD), African Americans are diagnosed in later stages of the disease and present with greater cognitive impairment at the time of diagnosis when compared to Euro-Americans. To this end, there exists a paucity of research on diagnostic pathways among African Americans with dementia. More specifically, few studies have explored help-seeking pathways from the initial manifestation of symptoms until an actual diagnosis of Alzheimer's disease was received from the perspective of African American caregivers. Thus, the present study examined the retrospective experiences of 17 African American caregivers who were given a diagnosis of Alzheimer's disease for a family member with dementia. Participants completed face-to-face semi-structured interviews. Study findings revealed a complex interplay between the patient with dementia, entities that comprise their social support network, and clinicians.
Caring for individuals with end-stage dementia at the end of life
Authors: Sanders Sara , Swails Peggy
Published: January 2009

Little is known about the beliefs and practices of social workers who work with individuals with end-stage dementia. With more individuals reaching the end stages of the disease, it is crucial to determine how professionals view their work with end-stage dementia patients and their caregivers. During this ethnographic study, the beliefs and practices about dementia care of 13 hospice social workers from the United States were documented for 10 months through interviews, in-field observations, and chart reviews. It was determined that although hospice social workers use a wealth of practice skills with individuals with end-stage dementia and their caregivers and strive to enhance the personhood of the patients, they also possess a neutral to negative view of practice with this population and see their role as limited and ambiguous compared to how they view their work with cognitively intact patients. This study has implications for how hospice social workers and other healthcare professionals provide end-of-life care for patients and families who are dealing with dementia and the types of training that should be implemented in hospice agencies to strengthen end-stage dementia care.
Inhibitive Effect of Artemether on Tumor Growth and Angiogenesis in the Rat C6 Orthotopic Brain Gliomas Model
Authors: Wu Zhi-ping , Gao Cheng-wei , Wu Yong-gui , Zhu Qi-shun , Yan Chen  , Xin Liu  , Chuen Liu
Published: January 2009

To explore the inhibitive effect of artemether on glioma growth and angiogenesis in brain tumor bearing SD rat. MTT assay was used to evaluate the inhibitory effect of artemether treatment on C6 glioma cells. Forty SD rats which were subcutaneous planted with SD rat C6 glioma cell to establish SD rat orthotopic glioma model were divided resourcefully into 5 groups. each group was 8 rats. Length-path (a mm) and short-path (b mm) of tumor each rat was measured. Tumor volume was calculated using the following formula: V (mm3) = a2b_/6. Microvessel density (MVD) in different therapy groups was significantly lower than that in normal saline control group and brain glioma volume in different therapy groups was significantly smaller than that in normal saline control group. There were remarkably inhibitory effects of artmeter on brain glioma growth and angiogenesis in SD rats and the mechanism that artemether inhibited brain glioma growth might be penetrating the blood-brain barrier and inhibiting angiogenesis.
Endovascular Treatment of Carotid Stump Syndrome
Authors: Carrafiello Gianpaolo , DeLodovici Maria Luisa , Piffaretti Gabriele , Castelli Patrizio
Published: January 2009

We present the case of a carotid stump syndrome in a 72-year-old woman with a 3-day history of recurrent transient ischemic attacks. Computed tomographic angiography showed the occlusion of the ipsilateral internal carotid artery, and the presence of an internal stump with ophtalmic reverse flow, confirming the suspect of a stump syndrome. The patient underwent stent-graft exclusion of the carotid stump; she was last seen 12 months after the procedure when she remained totally asymptomatic.
Treating Bulimia Nervosa With a Stratified-Care Approach
Authors: Golan Moria , Heyman Noa , Enten Roni
Published: January 2009

This study examines the long-term outcome of a stratified-care regimen for patients with bulimia nervosa. Each patient admitted to the program is stratified by severity of illness, comorbidity, and level of functioning in the community and offered a personalized program from 2 to 16 hours per week. Of 398 candidates for treatment in the community-based eating disorder treatment facilities, 257 were admitted and 141 were interviewed and served as controls. Symptoms and global outcome were assessed using the 17-item Outcome Scale devised by Eckert et al. Of the admitted patients, 24% dropped out after less than 2 months, 91% of those treated for at least 2 months achieved improvement of symptoms and general functioning, 62% were fully recovered, 22% were nearly recovered, 7% were symptomatic but less than at baseline, and 9% experienced no remission. At the 5-year follow-up from termination, 77% of treated patients were fully recovered, 3% were nearly recovered, 16% felt remission but still were symptomatic, and 4% were in poor condition. The above services address the needs of patients based on course of illness and level of functioning, allowing them to stay in the community and avoid hospitalization while discouraging enrollment in unsuccessful therapy and minimalist programs.
Cystic Fibrosis, Cystic Fibrosis—Related Diabetes, and Adolescence A Case Study
Authors: Casey Susan C.
Published: January 2009

This is a case study depicting the complications of managing cystic fibrosis and cystic fibrosis—related diabetes with the challenges of biological family dysfunction. It illustrates the variability of severity within the diagnosis of cystic fibrosis, as well as the fact that, despite multiple challenges, this adolescent is able to maintain a normal nutritional status and progress to better self-management.
Antigen-loaded exosomes alone induce Th1-type memory through a B cell–dependent mechanism
Authors: Qazi Khaleda Rahman , Gehrmann Ulf , Domange Jordö Emilie , Karlsson Mikael C. I. , Gabrielsson Susanne
Published: January 2009

Exosomes are nanovesicles harboring proteins important for antigen presentation. We compared the potency of differently loaded exosomes, directly loaded with OVA323-339 peptide (Pep-Exo) or exosomes from OVA-pulsed DCs (OVA-Exo), for their ability to induce specific T-cell proliferation in vitro and in vivo. Both Pep-Exo and OVA-Exo elicited specific transgenic T-cell proliferation in vitro, with the Pep-Exo being more efficient. In contrast, only OVA-Exo induced specific T-cell responses in vivo highlighting the importance of indirect loading strategies in clinical applications. Coadministration of whole OVA overcame the unresponsiveness with Pep-Exo but still elicited a lower response compared with OVA-Exo. In parallel, we found that OVA-Exo not only augmented the specific T-cell response but also gave a Th1-type shift and an antibody response even in the absence of whole OVA. We detected IgG2a and interferon-γ production from splenocytes showing the capability of exosomes to provide antigen for B-cell activation. Furthermore, we found that B cells are needed for exosomal T-cell stimulation because Bruton tyrosine kinase–deficient mice showed abrogated B- and T-cell responses after OVA-Exo immunization. These findings reveal that exosomes are potent immune regulators and are relevant for the design of vaccine adjuvants and therapeutic intervention strategies to modulate immune responses.
FAS-L, IL-10, and double-negative CD4−CD8− TCR α/β+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function
Authors: Magerus-Chatinet Aude , Stolzenberg Marie-Claude , Loffredo Maria S. , Neven Bénédicte , Schaffner Catherine , Ducrot Nicolas , Arkwright Peter D. , Bader-Meunier Brigitte , Barbot José , Blanche Stéphane , Casanova Jean-Laurent , Debré Marianne , Ferster Alina , Fieschi Claire , Florkin Benoit , Galambrun Claire , Hermine Olivier , Lambotte Olivier , Solary Eric , Thomas Caroline , Le Deist Francoise , Picard Capucine , Fischer Alain , Rieux-Laucat Frédéric
Published: January 2009

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRαβ+ CD4−CD8− T cells (DNT cells), and autoimmunity. Previously, DNT cell detection and a functional defect of T cells in a FAS-induced apoptosis test in vitro had been used for ALPS diagnosis. However, a functional defect can also be detected in mutation-positive relatives (MPRs) who remain free of any ALPS-related disease. In contrast, lymphocytes from patients carrying a somatic mutation of FAS exhibit normal sensitivity to FAS-induced apoptosis in vitro. We assessed the soluble FAS-L concentration in the plasma of ALPS patients carrying FAS mutations. Overall, we showed that determination of the FAS-L represents, together with the IL-10 concentration and the DNT cell percentage, a reliable tool for the diagnosis of ALPS.
Human plasmacytoid dendritic cells are unresponsive to bacterial stimulation and require a novel type of cooperation with myeloid dendritic cells for maturation
Authors: Piccioli Diego , Sammicheli Chiara , Tavarini Simona , Nuti Sandra , Frigimelica Elisabetta , Manetti Andrea G.O. , Nuccitelli Annalisa , Aprea Susanna , Valentini Sara , Borgogni Erica , Wack Andreas , Valiante Nicholas M.
Published: January 2009

Dendritic cell (DC) populations play unique and essential roles in the detection of pathogens, but information on how different DC types work together is limited. In this study, 2 major DC populations of human blood, myeloid (mDCs) and plasmacytoid (pDCs), were cultured alone or together in the presence of pathogens or their products. We show that pDCs do not respond to whole bacteria when cultured alone, but mature in the presence of mDCs. Using purified stimuli, we dissect this cross-talk and demonstrate that mDCs and pDCs activate each other in response to specific induction of only one of the cell types. When stimuli for one or both populations are limited, they synergize to reach optimal activation. The cross-talk is limited to enhanced antigen presentation by the nonresponsive population with no detectable changes in the quantity and range of cytokines produced. We propose that each population can be a follower or leader in immune responses against pathogen infections, depending on their ability to respond to infectious agents. In addition, our results indicate that pDCs play a secondary role to induce immunity against human bacterial infections, which has implications for more efficient targeting of DC populations with improved vaccines and therapeutics.
Zyxin is a novel interacting partner for SIRT1
Authors: Fujita Yuki , Yamaguchi Atsushi , Hata Katsuhiko , Endo Mitsuharu , Yamaguchi Naoto , Yamashita Toshihide
Published: January 2009

Background

SIRT1 is a mammalian homologue of NAD+-dependent deacetylase sirtuin family. It regulates longevity in several model organisms and is involved with cell survival, differentiation, metabolism among other processes in mammalian cells. SIRT1 modulates functions of various key targets via deacetylation. Recent studies have revealed SIRT1 protects neurons from axonal degeneration or neurodegeneration. Further, SIRT1 null mice exhibit growth retardation and developmental defects, suggesting its critical roles in neurons and development.

Results

To identify novel binding partners for SIRT1 in the central nervous system, we performed yeast two-hybrid screening on human fetal brain cDNA library and found that zyxin is a possible binding partner. SIRT1 and zyxin transcript were both preferentially expressed in developmental mouse brain. Zyxin accumulates in the nucleus where it is co-localized with SIRT1 after treatment with leptomycin B in COS-7 cells. Furthermore, SIRT1 deacetylates zyxin, suggesting SIRT1 could interact with nuclear-accumulated zyxin and modulate its function through deacetylation.

Conclusion

Zyxin could be a novel interacting partner of SIRT1. Zyxin is an adaptor protein at focal adhesion plaque, regulating cytoskeletal dynamics and signal transduction to convey signal from the ECM (extracellular matrix) to the nucleus. Our results raise the possibility that SIRT1 regulates signal transmission from ECM to the nucleus by modulating the functions of zyxin via deacetylation.
Differential selection on gene translation efficiency between the filamentous fungus Ashbya gossypii and yeasts
Authors: Jiang Huifeng , Zhang Yue , Sun Jun , Wang Wen , Gu Zhenglong
Published: January 2009

Background

The filamentous fungus Ashbya gossypii grows into a multicellular mycelium that is distinct from the unicellular morphology of its closely related yeast species. It has been proposed that genes important for cell cycle regulation play central roles for such phenotypic differences. Because A. gossypii shares an almost identical set of cell cycle genes with the typical yeast Saccharomyces cerevisiae, the differences might occur at the level of orthologous gene regulation. Codon usage patterns were compared to identify orthologous genes with different gene regulation between A. gossypii and nine closely related yeast species.

Results

Here we identified 3,151 orthologous genes between A. gossypii and nine yeast species. Two groups of genes with significant differences in codon usage (gene translation efficiency) were identified between A. gossypii and yeasts. 333 genes (Group I) and 552 genes (Group II) have significantly higher translation efficiency in A. gossypii and yeasts, respectively. Functional enrichment and pathway analysis show that Group I genes are significantly enriched with cell cycle functions whereas Group II genes are biased toward metabolic functions.

Conclusion

Because translation efficiency of a gene is closely related to its functional importance, the observed functional distributions of orthologous genes with different translation efficiency might account for phenotypic differentiation between A. gossypii and yeast species. The results shed light on the mechanisms for pseudohyphal growth in pathogenic yeast species.
Microvolt T-wave alternans as a predictor of mortality and severe arrhythmias in patients with left-ventricular dysfunction: a systematic review and meta-analysis
Authors: van der Avoort Charlotte J , Filion Kristian B , Dendukuri Nandini , Brophy James M
Published: January 2009

Background

Studies have demonstrated that the use of implantable cardioverter defibrillators (ICDs) is effective for the primary prevention of arrhythmic events but due to imposing costs, there remains a need to identify which patients will derive the greatest benefit. Microvolt T-wave alternans (MTWA) has been proposed to assist in this stratification.

Methods

We systematically searched the literature using MEDLINE, EMBASE, Current Contents, the Cochrane Library, INAHTA, and the Web of Science to identify all primary prevention randomized controlled trials and prospective cohort studies with at least 12 months of follow-up examining MTWA as a predictor of mortality and severe arrhythmic events in patients with severe left-ventricular dysfunction. The search was limited to full-text English publications between January 1990 and May 2007. The primary outcome was a composite of mortality and severe arrhythmias. Data were synthesized using Bayesian hierarchical models.

Results

We identified no trials and 8 published cohort studies involving a total of 1,946 patients, including 332 positive, 656 negative, 84 indeterminate, and 874 non-negative (which includes both positive and indeterminate tests) MTWA test results. The risk of mortality or severe arrhythmic events was higher in patients with a positive MTWA compared to a negative test (RR = 2.7, 95% credible interval (CrI) = 1.4, 6.1). Similar results were obtained when comparing non-negative MTWA to a negative test.

Conclusion

A positive MTWA test predicts mortality or severe arrhythmic events in a population of individuals with severe left ventricular dysfunction. However, the wide credible interval suggests the clinical utility of this test remains incompletely defined, ranging from very modest to substantial. Additional high quality studies are required to better refine the role of MTWA in the decision making process for ICD implantation.
Epithelial ovarian cancer relapsing as isolated lymph node disease: natural history and clinical outcome
Authors: Legge Francesco , Petrillo Marco , Adamo Vincenzo , Pisconti Salvatore , Scambia Giovanni , Ferrandina Gabriella
Published: January 2009

Background

Several evidences suggested that ovarian cancer (OC) patients showing isolated lymph node recurrence (ILNR) have an indolent evolution. The aim of the study was to retrospectively review ILNR observed in our Institution over the past 11 years in order to investigate: the pattern of disease progression after the first diagnosis of ILNR, and their clinical outcome.

Methods

Between September 1995 and September 2006, 523 epithelial OC were diagnosed in our centers, and 301 of these relapsed. Cases with a diagnosis of ILNR, and at least 12 months of follow up after the diagnosis of ILNR were included. Post-relapse survival (PRS) was recorded from the date of the diagnosis of ILNR to the date of death or date last seen. Survival probabilities were estimated according to the method of Kaplan and Meier and compared by the log rank test. Cox's regression model with stepwise variable selection was used to analyse the role of clinico-pathological parameters as prognostic factors for PRS.

Results

Thirty-two cases were identified as ILNR (10.6% of the recurrences, and 6.1% of the OC population). Most of the patients continued to exhibit the same pattern of progression during follow up, with 75% of the patients free from peritoneal disease after 2 years from the diagnosis of ILNR. Median Post-Relapse Survival (PRS) was 37 months, and median Overall Survival (OS) was 109 months, with all patients surviving more than 2 years after the initial diagnosis. In multivariate analysis only Platinum-Free Interval (PFI) retained a prognostic role for PRS (p value = 0.033).

Conclusion

ILNR represents a less aggressive pattern of OC relapse which keeps progressing in the lymph nodes in a relatively high percentage of cases. On the other hand, the occurrence of peritoneal spreading after ILNR is associated with a rapidly fatal outcome.
Summary of the primer on tumor immunology and the biological therapy of cancer
Authors: Li Yufeng , Liu Shujuan , Margolin Kim , Hwu Patrick
Published: January 2009

The International Society for Biological Therapy of Cancer (iSBTc) is one of the "premier destinations for interaction and innovation in the cancer biologics community". It provides a primer course each year during the annual meeting to address the most important areas of tumor immunology and immunotherapy. The course has been given by prominent investigators in the area of interest, covering the core principles of cancer immunology and immunotherapy. The target audience for this program includes investigators from academic, regulatory, and biopharmaceutical venues. The program goal is to enable the attendees to learn the current status and the most recent advances in biologic therapies, and to leverage this knowledge towards the improvement of cancer therapy. The 2008 immunologic primer course was held on October 30 at the 23rd Annual meeting of iSBTc in San Diego, CA. Nine internationally renowned investigators gave excellent presentations on different topics. The topics covered in this primer included: (1) cytokines in cancer immunology; (2) anti-angiogenic therapy; (3) end stage: immune killing of tumors; (4) blocking T cell checkpoints; (5) approach to identification and therapeutic exploitation of tumor antigens; (6) T regulatory cells; (7) adoptive T cell therapy; (8) immune monitoring of cancer immunotherapy; and (9) immune adjuvants. We summarized the topics in this primer for public education. The related topic slides and schedule can be accessed online http://www.isbtc.org/meetings/am08/primer08.
Determination of patient-specific internal gross tumor volumes for lung cancer using four-dimensional computed tomography
Authors: Ezhil Muthuveni , Vedam Sastry , Balter Peter , Choi Bum , Mirkovic Dragan , Starkschall George , Chang Joe Y
Published: January 2009

Background

To determine the optimal approach to delineating patient-specific internal gross target volumes (IGTV) from four-dimensional (4-D) computed tomography (CT) image data sets used in the planning of radiation treatment for lung cancers.

Methods

We analyzed 4D-CT image data sets of 27 consecutive patients with non-small-cell lung cancer (stage I: 17, stage III: 10). The IGTV, defined to be the envelope of respiratory motion of the gross tumor volume in each 4D-CT data set was delineated manually using four techniques: (1) combining the gross tumor volume (GTV) contours from ten respiratory phases (IGTVAllPhases); (2) combining the GTV contours from two extreme respiratory phases (0% and 50%) (IGTV2Phases); (3) defining the GTV contour using the maximum intensity projection (MIP) (IGTVMIP); and (4) defining the GTV contour using the MIP with modification based on visual verification of contours in individual respiratory phase (IGTVMIP-Modified). Using the IGTVAllPhases as the optimum IGTV, we compared volumes, matching indices, and extent of target missing using the IGTVs based on the other three approaches.

Results

The IGTVMIP and IGTV2Phases were significantly smaller than the IGTVAllPhases (p < 0.006 for stage I and p < 0.002 for stage III). However, the values of the IGTVMIP-Modified were close to those determined from IGTVAllPhases (p = 0.08). IGTVMIP-Modified also matched the best with IGTVAllPhases.

Conclusion

IGTVMIP and IGTV2Phases underestimate IGTVs. IGTVMIP-Modified is recommended to improve IGTV delineation in lung cancer.
Independent component analysis of Alzheimer's DNA microarray gene expression data
Authors: Kong Wei , Mou Xiaoyang , Liu Qingzhong , Chen Zhongxue , Vanderburg Charles R , Rogers Jack T , Huang Xudong
Published: January 2009

Background

Gene microarray technology is an effective tool to investigate the simultaneous activity of multiple cellular pathways from hundreds to thousands of genes. However, because data in the colossal amounts generated by DNA microarray technology are usually complex, noisy, high-dimensional, and often hindered by low statistical power, their exploitation is difficult. To overcome these problems, two kinds of unsupervised analysis methods for microarray data: principal component analysis (PCA) and independent component analysis (ICA) have been developed to accomplish the task. PCA projects the data into a new space spanned by the principal components that are mutually orthonormal to each other. The constraint of mutual orthogonality and second-order statistics technique within PCA algorithms, however, may not be applied to the biological systems studied. Extracting and characterizing the most informative features of the biological signals, however, require higher-order statistics.

Results

ICA is one of the unsupervised algorithms that can extract higher-order statistical structures from data and has been applied to DNA microarray gene expression data analysis. We performed FastICA method on DNA microarray gene expression data from Alzheimer's disease (AD) hippocampal tissue samples and consequential gene clustering. Experimental results showed that the ICA method can improve the clustering results of AD samples and identify significant genes. More than 50 significant genes with high expression levels in severe AD were extracted, representing immunity-related protein, metal-related protein, membrane protein, lipoprotein, neuropeptide, cytoskeleton protein, cellular binding protein, and ribosomal protein. Within the aforementioned categories, our method also found 37 significant genes with low expression levels. Moreover, it is worth noting that some oncogenes and phosphorylation-related proteins are expressed in low levels. In comparison to the PCA and support vector machine recursive feature elimination (SVM-RFE) methods, which are widely used in microarray data analysis, ICA can identify more AD-related genes. Furthermore, we have validated and identified many genes that are associated with AD pathogenesis.

Conclusion

We demonstrated that ICA exploits higher-order statistics to identify gene expression profiles as linear combinations of elementary expression patterns that lead to the construction of potential AD-related pathogenic pathways. Our computing results also validated that the ICA model outperformed PCA and the SVM-RFE method. This report shows that ICA as a microarray data analysis tool can help us to elucidate the molecular taxonomy of AD and other multifactorial and polygenic complex diseases.
Use of anabolic-androgenic steroids masking the diagnosis of pleural tuberculosis: a case report
Authors: de Larrea Carlos Fernández , Duplat Aglae , Rivera-Olivero Ismar , de Waard Jacobus H
Published: January 2009

Introduction

Tuberculous pleural effusions are not always easy to diagnose but the presence of a lymphocyte-rich exudate associated with an increased adenosine deaminase level and a positive skin test result are highly sensitive diagnostic signs.

Case presentation

We report a case of pleural tuberculosis in a 31-year-old white male patient from Caracas, Venezuela who was negative for human immunodeficiency virus and presented 2 weeks after injecting the anabolic-androgenic steroid nandrolone decanoate, in whom all the tests for tuberculosis were initially negative; an eosinophilic pleural effusion with a low adenosine deaminase level, a negative tuberculin skin test and negative for acid-fast bacilli staining and culture of the pleural fluid. After excluding other causes of eosinophilic pleural effusion malignant pleural effusion was suspected. The patient did not return until 4 months later. The second thoracentesis obtained a pleural fluid suggestive for tuberculosis, with a predominance of lymphocytes, an elevated adenosine deaminase level (51 U/l) and a positive tuberculin skin test. Culture of pleural fragments confirmed pleural tuberculosis.

Conclusion

This case suggests that the use of an anabolic-androgenic steroid masks the definitive diagnosis of pleural tuberculosis by changing the key diagnostic parameters of the pleural fluid, a finding not previously reported. Available evidence of the effects of anabolic steroids on the immune system also suggests that patients using anabolic-androgenic steroids might be susceptible to developing tuberculosis in either reactivating a latent infection or facilitating development of the disease after a recent infection.
Drebrin A regulates dendritic spine plasticity and synaptic function in mature cultured hippocampal neurons
Authors: Ivanov Anton , Esclapez Monique , Pellegrino Christophe , Shirao Tomoaki , Ferhat Lotfi
Published: January 2009

Drebrin A, one of the most abundant neuron-specific F-actin-binding proteins, is found exclusively in dendrites and is particularly concentrated in dendritic spines receiving excitatory inputs. We investigated the role of drebrin A in synaptic transmission and found that overexpression of drebrin A augmented the glutamatergic synaptic transmission, probably through an increase of active synaptic site density. Interestingly, overexpression of drebrin A also affected the frequency, amplitude and kinetics of miniature inhibitory postsynaptic currents (mIPSCs), despite the fact that GABAergic synapse density and transmission efficacy were not modified. Downregulation of drebrin A led to a decrease of both glutamatergic and GABAergic synaptic activity. In heterologous cells, drebrin A reorganized and stabilized F-actin and these effects were mediated by its actin-binding domain. Thus, drebrin A might regulate dendritic spine morphology via regulation of actin cytoskeleton remodeling and dynamics. Our data demonstrate for the first time that drebrin A modulates glutamatergic and GABAergic synaptic activities.