bluuebunny/crossref_metadata_2025 huggingface dataset:
Damage Detection for Composite Laminate Plates with A Distributed Hybrid PZT/FBG Sensor Network
Authors: Zhanjun Wu  , Qing Xinlin P. , Chang Fu-Kuo
Published: March 2009

Debond detection is a critical technique to ensure composite structural safety. Although there are many novel sensors being developed in recent years, piezoelectric transducers (PZT) and fiber Bragg grating (FBG) sensors have been shown as ideal sensors for monitoring structural health. To utilize their merits and overcome their drawbacks a hybrid PZT/FBG system has been developed to detect damage in composite laminate plates. The hybrid diagnostic system combines piezoelectric actuators which input a controlled excitation to the structure and fiber optic sensors which capture the corresponding structural response. Tests have been carried out to demonstrate the feasibility of detecting simulated damage monitoring on an aluminum plate and debond damage on composite plates using the suggested hybrid system. Test results show that the system is capable of detecting damage in both aluminum and composite plates. The major advantage of this system lies in actuator/ sensor decoupling, because they use different mechanisms for signal transmission. It may also offer long distance signal transmission because it utilizes fiber optics to transfer sensor signals to its interrogation system. The potential to sense acoustic stress waves and absolute quasi-static strains with large amount of sensors engraved along a single optical fiber may also increase the practibility of using a PZT/FBG hybrid system.
Guided-wave Health Monitoring of Aircraft Composite Panels under Changing Temperature
Authors: Salamone Salvatore , Bartoli Ivan , Lanza Di Scalea Francesco , Coccia Stefano
Published: March 2009

This study deals with the health monitoring of fiber-reinforced composite panels using ultrasonic guided waves and flexible piezocomposite transducer patches in a changing temperature environment corresponding to normal aircraft operations (—40°C to +60°C). The wave propagation problem is first studied analytically by a model that accounts for temperature effects on the transducer piezo-mechanical properties, the transducer-panel interaction, and the panel wave dispersion properties. Experiments are also conducted on a Carbon-fiber Reinforced Plastic (CFRP) [0/±45/0]S laminate subjected to the —40°C to +60°C temperature excursion. Both model and experiment indicate substantial changes in the detected guided wave amplitude solely due to the temperature excursion. The second part of the study presents an application to bond defect detection in a simulated CFRP skin-to-spar joint of Unmanned Aerial Vehicle wings. It is shown that a statistical outlier analysis based on multiple guided-wave amplitude features and on a baseline partition is effective in detecting bond defects (poorly cured adhesive and two sizes of disbonds) despite the —40°C to +60°C temperature change. The results encourage the development of a continuous health monitoring system for composite aircraft wings during their normal operations.
Explicit Reasoning, Confirmation Bias, and Illusory Transactive Memory
Authors: Tschan Franziska , Semmer Norbert K. , Gurtner Andrea , Bizzari Lara , Spychiger Martin , Breuer Marc , Marsch Stephan U.
Published: March 2009

Teamwork is important in medicine, and this includes team-based diagnoses. The influence of communication on diagnostic accuracy in an ambiguous situation was investigated in an emergency medical simulation. The situation was ambiguous in that some of the patient's symptoms suggested a wrong diagnosis. Of 20 groups of physicians, 6 diagnosed the patient, 8 diagnosed with help, and 6 missed the diagnosis. Based on models of decision making, we hypothesized that accurate diagnosis is more likely if groups (a) consider more information, (b) display more explicit reasoning, and (c) talk to the room. The latter two hypotheses were supported. Additional analyses revealed that physicians often failed to report pivotal information after reading in the patient chart. This behavior suggested to the group that the chart contained no critical information. Corresponding to a transactive memory process, this process results in what we call illusory transactive memory. The plausible but incorrect diagnosis implied that the two lungs should sound differently. Despite objectively identical sounds, some physicians did hear a difference, indicating confirmation bias. Training physicians in explicit reasoning could enhance diagnostic accuracy.
Analysis of Cross-Sectional Univariate Measurements for Family Dyads Using Linear Mixed Modeling
Authors: Knafl George J. , Dixon Jane K. , O'Malley Jean P. , Grey Margaret , Deatrick Janet A. , Gallo Agatha M. , Knafl Kathleen A.
Published: March 2009

Outcome measurements from members of the same family are likely correlated. Such intrafamilial correlation (IFC) is an important dimension of the family as a unit but is not always accounted for in analyses of family data. This article demonstrates the use of linear mixed modeling to account for IFC in the important special case of univariate measurements for family dyads collected at a single point in time. Example analyses of data from partnered parents having a child with a chronic condition on their child's adaptation to the condition and on the family's general functioning and management of the condition are provided. Analyses of this kind are reasonably straightforward to generate with popular statistical tools. Thus, it is recommended that IFC be reported as standard practice reflecting the fact that a family dyad is more than just the aggregate of two individuals. Moreover, not accounting for IFC can affect the conclusions.
Advocating for a Parent with Dementia in a Long-term Care Facility
Authors: Legault Alain , Ducharme Francine
Published: March 2009

Daughter caregivers of elders with dementia become their parents' advocates over time. This role takes on even greater importance when one or both parents are placed in a long-term care facility. This article presents the results of a qualitative study aimed at explaining how this advocacy role evolves following institutionalization. In-depth interviews were conducted with daughters ( N = 14) of an institutionalized parent with dementia and selected using a theoretical sampling procedure. Data analysis using grounded theory revealed three interrelated processes that explain role transformation of the daughters: integration in the care setting, evaluation of quality of care, and development of trust. Implications for involving daughters as care partners in long-term care settings are offered.
Common Insights, Differing Methodologies
Authors: Evans Mike , Hole Rachelle , Berg Lawrence D. , Hutchinson Peter , Sookraj Dixon
Published: March 2009

In this article, we discuss three broad research approaches: indigenous methodologies, participatory action research, and White studies. We suggest that a fusion of these three approaches can be useful, especially in terms of collaborative work with indigenous communities. More specifically, we argue that using indigenous methodologies and participatory action research, but refocusing the object of inquiry directly and specifically on the institutions and structures that indigenous peoples face, can be a particularly effective way of transforming indigenous peoples from the objects of inquiry to its authors. A case study focused on the development of appropriate research methods for a collaborative project with the urban aboriginal communities of the Okanagan Valley in British Columbia, Canada, provides an illustration of the methodological fusion we propose.
Beyond the `Sexualization of Culture' Thesis: An Intersectional Analysis of `Sixpacks',`Midriffs' and `Hot Lesbians' in Advertising
Authors: Gill Rosalind
Published: March 2009

This article argues that the notion of the `sexualization of culture' is too general to be a useful conceptual tool. The article has two main objectives. First, it seeks to interrogate the notion of `sexualization' as a way of understanding the proliferation of sexually explicit imagery within contemporary advertising. Rather than taking up a position `for' or `against' `sexualization' (in the familiar way), it seeks to open up the notion in order to explore the diverse practices that are commonly grouped together under this heading. Using advertising as an example, it argues that `sexualization' is far from being a singular or homogenous process, that different people are `sexualized' in different ways and with different meanings — and indeed that many remain excluded from what has been called the `democratization of desire' operating in visual culture. Secondly, the article develops a feminist intersectional analysis to critically read some of the different ways in which advertising might be said to be sexualized. It looks at three different and contrasting, but easily recognizable `figures' within contemporary advertising: the good-looking male `sixpack', the sexually agentic heterosexual `midriff' and the `hot lesbian', usually intertwined with her beautiful double or Other. The aim is to highlight the point that sexualization does not operate outside of processes of gendering, radicalization and classing, and works within a visual economy that remains profoundly ageist and heteronormative. The article argues that an attention to differences is crucial to understanding the phenomena, practices and scopic regimes that are often lumped together under the heading `equalization of culture'.
`Hot Lesbians': Young People's Talk About Representations of Lesbianism
Authors: Jackson Sue , Gilbertson Tamsyn
Published: March 2009

Media representation of heterosexual alternatives is particularly salient for young people negotiating sexuality, more so for those with limited access to other cultural resources to inform their homosexual understandings. With the centrality of media as resource in mind, we present in this article findings from our focus group research with 25 high school students aged 16—18 in which we invited them to discuss representations of homosexuality in the media. Our analyses, which focus here on lesbian sexuality, used a thematic discursive approach. We found constructions of lesbianism as `heteroflexible', `hot' and experimental to be common patterns in participants' talk, whereas notions of lesbian desire were largely silenced. While most of the talk drew on heteronormativity, we found small pockets of its deconstruction in mobilization of alternative discourses and rejection of sexual categories.
The value of authenticity in residential tourism
Authors: Mantecón Alejandro , Huete Raquel
Published: March 2009

This article argues that the main social agents involved in the residential tourism sector do not perceive the `search for authenticity' as a tourist need that demands their attention and promotion. Authenticity has not been identified as a key factor in attracting tourists. Authenticity could have an important influence on the behaviour of people who choose the Costa Blanca in the Province of Alicante, Spain, as the area in which to buy a second/holidays home. Results obtained from qualitative research, including 37 in-depth interviews, are presented here in order to examine how the local stakeholders perceive the role played by authenticity in attracting visitors to Alicante. In the light of the findings discussed, we try to understand the meaning and the possibilities given to the `authentic' tourist experiences on offer within the context of the residential tourism system of the Spanish Mediterranean coast.
An ecological perspective on the socially embedded nature of reading and writing
Authors: Pantaleo Sylvia
Published: March 2009

This article examines the writing of three Grade 3 students and discusses how these girls drew upon their symbolic tools, specifically those developed as a result of their experiences with particular kinds of texts. The students were participants in a multifaceted study that explored Grades 3 and 4 students' understandings of and responses to picturebooks with interactive devices. The research also examined how the children used their knowledge of the interactive devices to create their own print texts. The discussion of the three students' writing is framed by a sociocultural theory of writing, focusing specifically on the connections between the reading and the writing completed by the children. However, an ecological perspective on their writing also requires a discussion of the classroom context to understand the children's compositions.
Bilingualism and phonological segmentation of speech: The case of English-French pre-schoolers
Authors: Laurent Angélique , Martinot Clara
Published: March 2009

From studies of bilingual education practices, some authors have suggested that bilingualism, in a favourable environment, facilitates development of metaphonological abilities. In a monolingual context, these abilities develop in interaction with literacy. The objective of the present study is to determine if bilingual children have some metaphonological knowledge before learning to read. In other terms, does bilingualism improve metaphonological abilities? To answer this question, 50 prereaders were tested: 30 of them were monolingual French speakers; 20 were bilingual English-French speakers from a traditional French school. To test phonological abilities, two tasks were set: a free phonological segmentation task and a phonemic deletion task. Bilingual prereaders did not show better performance at the tasks but did show a different way of segmenting items. The results are discussed in the framework of phonological development theories and bilingual education.
Offender-based Restorative Justice and Poetry: Reparation or Wishful Thinking?
Authors: Farrier Alan , Froggett Lynn , Poursanidou Dina
Published: March 2009

Increasingly, arts-based interventions are being implemented as a means of engaging young offenders, resulting in a public debate over the value of such projects. Whilst there is evidence that many Youth Offending Teams (YOTs) throughout England and Wales endorse such approaches, the processes by which they may benefit young people and have the potential to change attitudes to offending remain under-theorized. In this article we examine a YOT-related creative writing project that embraces an offender-based restorative justice model that depends on a reparative mind-set. We argue that such arts-based projects are complex and potentially far-reaching in their effects.
Immigrant children from Latin America at Japanese schools
Authors: Castro-Vázquez Genaro
Published: March 2009

An ethnographic study conducted between 2003 and 2006 followed three children from Latin America attending three different public Japanese primary schools. The investigation concerned a Japanese-language tutoring programme for foreign children, which was evaluated by participant observation and a set of in-depth interviews with officials, school principals and teachers. The programme appeared to be ineffective because of the influence of a strong assimilation policy, homogenous and standard teaching, and ethnic and gender assumptions at the schools.
The Meaning of Working: A Perspective From Practice
Authors: Flesher Jeff
Published: March 2009

The problem and the solution. This concluding article presents a praxis-based reflection on the applied role of work meaning, its academic research, and the articles presented in this issue. Focusing on issues of convergence and divergence of meaning and the organizational leadership challenges in a global economic and business environment, the article addresses meaning of working issues in human resource development (HRD) and talent management practice. It further explains the role of meaning of working as an important component of professional development in HRD and identifies areas for further research and scholarship.
Work Values and Business Ethics in Korea
Authors: Cho Eunsang
Published: March 2009

The problem and the solution. To contribute to the discussion on the meaning of work in Korea, this article starts by reporting findings from a review of Korean literature.The article further presents findings from a survey of both managerial and union members on the perceived importance of core values in the workplace. Among four people-centered core values, human-centered management/human resource development and knowledge sharing were the values preferred by the managerial group. Managers placed more importance on accountability values, among which obedience to the law was significantly emphasized by the managers.With respect to the social responsibility values, the managerial group scored higher for the value of social responsibility, faithful tax payment, and transparency of information disclosure with no significant difference.As to the leadership values, the managerial group's scores were higher for flexibility and capacity for change management, vision formation, and implementation capacity.The article closes with a discussion of the findings, limitations of this research, recommendations for further research, and the practical implications.
Split-Belt Treadmill Adaptation Transfers to Overground Walking in Persons Poststroke
Authors: Reisman Darcy S. , Wityk Robert , Silver Kenneth , Bastian Amy J.
Published: March 2009

Background and Objective. Following stroke, subjects retain the ability to adapt interlimb symmetry on the split-belt treadmill. Critical to advancing our understanding of locomotor adaptation and its usefulness in rehabilitation is discerning whether adaptive effects observed on a treadmill transfer to walking over ground. We examined whether aftereffects following split-belt treadmill adaptation transfer to overground walking in healthy persons and those poststroke. Methods. Eleven poststroke and 11 age-matched and gender-matched healthy subjects walked over ground before and after walking on a split-belt treadmill. Adaptation and aftereffects in step length and double support time were calculated. Results. Both groups demonstrated partial transfer of the aftereffects observed on the treadmill ( P < .001) to overground walking ( P < .05), but the transfer was more robust in the subjects poststroke ( P < .05). The subjects with baseline asymmetry after stroke improved in asymmetry of step length and double limb support ( P = .06). Conclusions. The partial transfer of aftereffects to overground walking suggests that some shared neural circuits that control locomotion for different environmental contexts are adapted during split-belt treadmill walking. The larger adaptation transfer from the treadmill to overground walking in the stroke survivors may be due to difficulty adjusting their walking pattern to changing environmental demands. Such difficulties with context switching have been considered detrimental to function poststroke. However, we propose that the persistence of improved symmetry when changing context to overground walking could be used to advantage in poststroke rehabilitation.
Calcineurin inactivation leads to decreased responsiveness to LPS in macrophages and dendritic cells and protects against LPS-induced toxicity in vivo
Authors: Jennings Charay , Kusler Brenda , Jones Patricia P.
Published: March 2009

Microbial components such as lipopolysaccharide (LPS) bind to Toll-like receptors (TLRs) and activate innate and inflammatory responses. Responses to LPS and other microbial components are limited by the activation of negative feedback mechanisms that reduce responsiveness to subsequent LPS exposure, often termed LPS tolerance. Our laboratory has previously shown that calcineurin, a phosphatase known for its activation of T cells via NFAT, negatively regulates the TLR pathway in macrophages; consequently, calcineurin inhibitors (FK506 and cyclosporin A) mimic TLR ligands in activating the TLR pathway, NF-KB, and associated innate and inflammatory responses. This study investigated the physiological consequences of calcineurin inactivation for LPS-induced inflammatory responses in vitro and in vivo using two models: calcineurin inhibition by FK506 (tacrolimus) and myeloid cell-specific calcineurin deletion. Activation of dendritic cells and macrophages with FK506 in vitro was shown to induce a state of reduced responsiveness to LPS (i.e. a form of LPS tolerance). Similarly, macrophages from FK506-treated mice or from mice in which the calcineurin B1 (CnB1) subunit was conditionally knocked out in myeloid cells were found to have diminished LPS-induced inflammatory responses. In addition, mice with CnB1-deficient myeloid cells and mice undergoing FK506 treatment showed improved survival and recovery when challenged with high doses of systemic LPS compared to controls. These results demonstrate that inactivation of calcineurin in macrophages and other myeloid cells by inhibition or deletion can induce a form of LPS tolerance and protect the host from LPS toxicity in vivo.
Cetuximab-mediated cellular cytotoxicity is inhibited by HLA-E membrane expression in colon cancer cells
Authors: Levy Estrella Mariel , Sycz Gabriela , Arriaga Juan Martin , Barrio María Marcela , von Euw Erika María , Morales Sergio Bayo , González Mariana , Mordoh José , Bianchini Michele
Published: March 2009

Cetuximab, an anti-epidermal growth factor receptor monoclonal antibody, has been shown to increase the median survival of colorectal cancer patients. We previously reported that the expression of HLA-E is significantly increased in primary human colorectal cancer, perhaps contributing to tumour escape from immune surveillance. To establish if HLA-E could be a factor that renders colorectal cancer cells less susceptible to antibody-dependent cellular cytotoxicity (ADCC), in the present study we analysed Cetuximab-mediated cytotoxicity against several colorectal cancer cell lines expressing, or not, HLA-E at the cell surface. We first observed that colorectal cancer cells treated with Cetuximab were killed more efficiently by ADCC. Interestingly, treatment of target cells with recombinant human-β2-microglobulin inhibits Cetuximab-mediated ADCC through HLA-E membrane stabilization. The specific immunosuppressive role of HLA-E was confirmed using an anti-NKG2A monoclonal antibody, that restored the ability of immune cells to kill their target. This result demonstrates that HLA-E at the cell surface can reliably suppress the ADCC effect. On the other hand, Cetuximab induced a direct growth inhibition but only at high concentrations; furthermore, the CDC effect was quite moderate, and we failed to observe a pro-apoptotic effect. Taking into account that our findings suggest that ADCC activity is the main anti-tumour effect observed at clinically achievable concentrations of Cetuximab at the tumour site, we suggest that determination of HLA-E in colorectal cancer could be relevant to predict success of Cetuximab treatment.
Evolution of MIR168 paralogs in Brassicaceae
Authors: Gazzani Silvia , Li Mingai , Maistri Silvia , Scarponi Eliana , Graziola Michele , Barbaro Enrico , Wunder Jörg , Furini Antonella , Saedler Heinz , Varotto Claudio
Published: March 2009

Background

In plants, expression of ARGONAUTE1 (AGO1), the catalytic subunit of the RNA-Induced Silencing Complex responsible for post-transcriptional gene silencing, is controlled through a feedback loop involving the miR168 microRNA. This complex auto-regulatory loop, composed of miR168-guided AGO1-catalyzed cleavage of AGO1 mRNA and AGO1-mediated stabilization of miR168, was shown to ensure the maintenance of AGO1 homeostasis that is pivotal for the correct functioning of the miRNA pathway.

Results

We applied different approaches to studying the genomic organization and the structural and functional evolution of MIR168 homologs in Brassicaeae. A whole genome comparison of Arabidopsis and poplar, phylogenetic footprinting and phylogenetic reconstruction were used to date the duplication events originating MIR168 homologs in these genomes. While orthology was lacking between Arabidopsis and poplar MIR168 genes, we successfully isolated orthologs of both loci present in Arabidopsis (MIR168a and MIR168b) from all the Brassicaceae species analyzed, including the basal species Aethionema grandiflora, thus indicating that (1) independent duplication events took place in Arabidopsis and poplar lineages and (2) the origin of MIR168 paralogs predates both the Brassicaceae radiation and the Arabidopsis alpha polyploidization. Different phylogenetic footprints, corresponding to known functionally relevant regions (transcription starting site and double-stranded structures responsible for microRNA biogenesis and function) or for which functions could be proposed, were found to be highly conserved among MIR168 homologs. Comparative predictions of the identified microRNAs also indicate extreme conservation of secondary structure and thermodynamic stability.

Conclusion

We used a comparative phylogenetic footprinting approach to identify the structural and functional constraints that shaped MIR168 evolution in Brassicaceae. Although their duplication happened at least 40 million years ago, we found evidence that both MIR168 paralogs have been maintained throughout the evolution of Brassicaceae, most likely functionally as indicated by the extremely high conservation of functionally relevant regions, predicted secondary structure and thermodynamic profile. Interestingly, the expression patterns observed in Arabidopsis indicate that MIR168b underwent partial subfunctionalization as determined by the experimental characterization of its expression pattern provided in this study. We found further evolutionary evidence that pre-miR168 lower stem (the RNA-duplex structure adjacent to the miR-miR* stem) is significantly longer than animal lower stems and probably plays a relevant role in multi-step miR168 biogenesis.
Comparative transcriptomic characterization of aluminum, sodium chloride, cadmium and copper rhizotoxicities in Arabidopsis thaliana
Authors: Zhao Cheng-Ri , Ikka Takashi , Sawaki Yoshiharu , Kobayashi Yuriko , Suzuki Yuji , Hibino Takashi , Sato Shigeru , Sakurai Nozomu , Shibata Daisuke , Koyama Hiroyuki
Published: March 2009

Background

Rhizotoxic ions in problem soils inhibit nutrient and water acquisition by roots, which in turn leads to reduced crop yields. Previous studies on the effects of rhizotoxic ions on root growth and physiological functions suggested that some mechanisms were common to all rhizotoxins, while others were more specific. To understand this complex system, we performed comparative transcriptomic analysis with various rhizotoxic ions, followed by bioinformatics analysis, in the model plant Arabidopsis thaliana.

Results

Roots of Arabidopsis were treated with the major rhizotoxic stressors, aluminum (Al) ions, cadmium (Cd) ions, copper (Cu) ions and sodium (NaCl) chloride, and the gene expression responses were analyzed by DNA array technology. The top 2.5% of genes whose expression was most increased by each stressor were compared with identify common and specific gene expression responses induced by these stressors. A number of genes encoding glutathione-S-transferases, peroxidases, Ca-binding proteins and a trehalose-synthesizing enzyme were induced by all stressors. In contrast, gene ontological categorization identified sets of genes uniquely induced by each stressor, with distinct patterns of biological processes and molecular function. These contained known resistance genes for each stressor, such as AtALMT1 (encoding Al-activated malate transporter) in the Al-specific group and DREB (encoding dehydration responsive element binding protein) in the NaCl-specific group. These gene groups are likely to reflect the common and differential cellular responses and the induction of defense systems in response to each ion. We also identified co-expressed gene groups specific to rhizotoxic ions, which might aid further detailed investigation of the response mechanisms.

Conclusion

In order to understand the complex responses of roots to rhizotoxic ions, we performed comparative transcriptomic analysis followed by bioinformatics characterization. Our analyses revealed that both general and specific genes were induced in Arabidopsis roots exposed to various rhizotoxic ions. Several defense systems, such as the production of reactive oxygen species and disturbance of Ca homeostasis, were triggered by all stressors, while specific defense genes were also induced by individual stressors. Similar studies in different plant species could help to clarify the resistance mechanisms at the molecular level to provide information that can be utilized for marker-assisted selection.
Plant origin and ploidy influence gene expression and life cycle characteristics in an invasive weed
Authors: Broz Amanda K , Manter Daniel K , Bowman Gillianne , Müller-Schärer Heinz , Vivanco Jorge M
Published: March 2009

Background

Ecological, evolutionary and physiological studies have thus far provided an incomplete picture of why some plants become invasive; therefore we used genomic resources to complement and advance this field. In order to gain insight into the invasive mechanism of Centaurea stoebe we compared plants of three geo-cytotypes, native Eurasian diploids, native Eurasian tetraploids and introduced North American tetraploids, grown in a common greenhouse environment. We monitored plant performance characteristics and life cycle habits and characterized the expression of genes related to constitutive defense and genome stability using quantitative PCR.

Results

Plant origin and ploidy were found to have a significant effect on both life cycle characteristics and gene expression, highlighting the importance of comparing appropriate taxonomic groups in studies of native and introduced plant species. We found that introduced populations of C. stoebe exhibit reduced expression of transcripts related to constitutive defense relative to their native tetraploid counterparts, as might be expected based on ideas of enemy release and rapid evolution. Measurements of several vegetative traits were similar for all geo-cytotypes; however, fecundity of tetraploids was significantly greater than diploids, due in part to their polycarpic nature. A simulation of seed production over time predicts that introduced tetraploids have the highest fecundity of the three geo-cytotypes.

Conclusion

Our results suggest that characterizing gene expression in an invasive species using populations from both its native and introduced range can provide insight into the biology of plant invasion that can complement traditional measurements of plant performance. In addition, these results highlight the importance of using appropriate taxonomic units in ecological genomics investigations.
Diabetic cardiomyopathy: effects of fenofibrate and metformin in an experimental model – the Zucker diabetic rat
Authors: Forcheron Fabien , Basset Alexandra , Abdallah Pauline , Del Carmine Peggy , Gadot Nicolas , Beylot Michel
Published: March 2009

Background

Diabetic cardiomyopathy (DCM) contributes to cardiac failure in diabetic patients. It is characterized by excessive lipids accumulation, with increased triacylglycerol (TAG) stores, and fibrosis in left ventricle (LV). The mechanisms responsible are incompletely known and no specific treatment is presently defined. We evaluated the possible usefulness of two molecules promoting lipid oxidation, fenofibrate and metformin, in an experimental model of DCM, the Zucker diabetic rat (ZDF).

Methods

ZDF and controls (C) rats were studied at 7, 14 and 21 weeks. After an initial study at 7 weeks, ZDF rats received no treatment, metformin or fenofibrate until final studies (at 14 or 21 weeks). C rats received no treatment. Each study comprised measurements of metabolic parameters (plasma glucose, TAG, insulin levels) and sampling of heart for histology and measurements of TAG content and relevant mRNA concentration.

Results

ZDF rats were insulin-resistant at 7 weeks, type 2 diabetic at 14 weeks and diabetic with insulin deficiency at 21 weeks. Their plasma TAG levels were increased. ZDF rats had at 7 weeks an increased LV TAG content with some fibrosis. LV TAG content increased in untreated ZDF rats at 14 and 21 weeks and was always higher than in C. Fibrosis increased also moderately in untreated ZDF rats. Metformin and fenofibrate decreased plasma TAG concentrations. LV TAG content was decreased by metformin (14 and 21 weeks) and by fenofibrate (14 weeks). Fibrosis was reduced by fenofibrate only and was increased by metformin. Among the mRNA measured, fenofibrate increased Acyl-CoA Oxidase mRNA level, metformin decreased Acyl-CoA Synthase and increased AdipoR1 and pro-inflammatory mRNA levels.

Conclusion

Fenofibrate had favourable actions on DCM. Metformin had beneficial effect on TAG content but not on fibrosis. PPARα agonists could be useful for the prevention and treatment of DCM.
Microbial factories for recombinant pharmaceuticals
Authors: Ferrer-Miralles Neus , Domingo-Espín Joan , Corchero José Luis , Vázquez Esther , Villaverde Antonio
Published: March 2009

Most of the hosts used to produce the 151 recombinant pharmaceuticals so far approved for human use by the Food and Drug Administration (FDA) and/or by the European Medicines Agency (EMEA) are microbial cells, either bacteria or yeast. This fact indicates that despite the diverse bottlenecks and obstacles that microbial systems pose to the efficient production of functional mammalian proteins, namely lack or unconventional post-translational modifications, proteolytic instability, poor solubility and activation of cell stress responses, among others, they represent convenient and powerful tools for recombinant protein production. The entering into the market of a progressively increasing number of protein drugs produced in non-microbial systems has not impaired the development of products obtained in microbial cells, proving the robustness of the microbial set of cellular systems (so far Escherichia coli and Saccharomyces cerevisae) developed for protein drug production. We summarize here the nature, properties and applications of all those pharmaceuticals and the relevant features of the current and potential producing hosts, in a comparative way.
Reduction in corpora lutea number in obese melanocortin-4-receptor-deficient mice
Authors: Sandrock Mara , Schulz Angela , Merkwitz Claudia , Schöneberg Torsten , Spanel-Borowski Katharina , Ricken Albert
Published: March 2009

Obese melanocortin-4-receptor-deficient (MC4R-/-) male mice are reported to have erectile dysfunction, while homozygous MC4R-/- female mice are apparently fertile. A recently established obese mouse strain, carrying an inactivating mutation in the MC4R gene, revealed difficulties in breeding for the homozygous female mice. This prompted us to determine the presence of follicles and corpora lutea (CL) in ovaries of MC4R-/- mice aged 3–6 months in comparison to wild type (MC4R+/+) littermates. Serial sections of formaldehyde-fixed ovaries of mice with vaginal signs of estrus and metestrus were assessed for the number of healthy and regressing follicles and CL. The number of CL, as an estimate for the ovulation rate, decreased to zero during aging in MC4R-/- mice. The number of small- (diameter 100–200 micrometer) and large-sized follicles namely antral follicles (diameter >200 micrometer) were slightly increased in MC4R-/- compared to MC4R+/+ mice. Greater differences were found in very large to cystic follicles, which were more numerous in MC4R-/- mice. The number of regressing antral follicles was higher in the MC4R-/- group compared to the MC4R+/+ group. This was associated with a wide range in the number of collapsed zonae pellucidae as the last remnants of regressed follicles. A conspicuous hypertrophy of the interstitial cells was noted in 6-month-old MC4R-/- mice. In conclusion, cystic follicles and the reduction in CL number point to a decreased ovulation rate in obese MC4R-/- mice.
Identifying disease-specific genes based on their topological significance in protein networks
Authors: Dezső Zoltán , Nikolsky Yuri , Nikolskaya Tatiana , Miller Jeremy , Cherba David , Webb Craig , Bugrim Andrej
Published: March 2009

Background

The identification of key target nodes within complex molecular networks remains a common objective in scientific research. The results of pathway analyses are usually sets of fairly complex networks or functional processes that are deemed relevant to the condition represented by the molecular profile. To be useful in a research or clinical laboratory, the results need to be translated to the level of testable hypotheses about individual genes and proteins within the condition of interest.

Results

In this paper we describe novel computational methodology capable of predicting key regulatory genes and proteins in disease- and condition-specific biological networks. The algorithm builds shortest path network connecting condition-specific genes (e.g. differentially expressed genes) using global database of protein interactions from MetaCore. We evaluate the number of all paths traversing each node in the shortest path network in relation to the total number of paths going via the same node in the global network. Using these numbers and the relative size of the initial data set, we determine the statistical significance of the network connectivity provided through each node. We applied this method to gene expression data from psoriasis patients and identified many confirmed biological targets of psoriasis and suggested several new targets. Using predicted regulatory nodes we were able to reconstruct disease pathways that are in excellent agreement with the current knowledge on the pathogenesis of psoriasis.

Conclusion

The systematic and automated approach described in this paper is readily applicable to uncovering high-quality therapeutic targets, and holds great promise for developing network-based combinational treatment strategies for a wide range of diseases.
The clinical effectiveness of different parenting programmes for children with conduct problems: a systematic review of randomised controlled trials
Authors: Dretzke Janine , Davenport Clare , Frew Emma , Barlow Jane , Stewart-Brown Sarah , Bayliss Sue , Taylor Rod S , Sandercock Josie , Hyde Chris
Published: March 2009

Background

Conduct problems are common, disabling and costly. The prognosis for children with conduct problems is poor, with outcomes in adulthood including criminal behaviour, alcoholism, drug abuse, domestic violence, child abuse and a range of psychiatric disorders.

There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems in a number of countries over the past 10 years. Existing reviews of parent training have methodological limitations such as inclusion of non-randomised studies, the absence of investigation for heterogeneity prior to meta-analysis or failure to report confidence intervals.

The objective of the current study was to systematically review randomised controlled trials of parenting programmes for the treatment of children with conduct problems.

Methods

Standard systematic review methods were followed including duplicate inclusion decisions, data extraction and quality assessment. Twenty electronic databases from the fields of medicine, psychology, social science and education were comprehensively searched for RCTs and systematic reviews to February 2006.

Inclusion criteria were: randomised controlled trial; of structured, repeatable parenting programmes; for parents/carers of children up to the age of 18 with a conduct problem; and at least one measure of child behaviour. Meta-analysis and qualitative synthesis were used to summarise included studies.

Results

57 RCTs were included. Studies were small with an average group size of 21. Meta-analyses using both parent (SMD -0.67; 95% CI: -0.91, -0.42) and independent (SMD -0.44; 95% CI: -0.66, -0.23) reports of outcome showed significant differences favouring the intervention group. There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes.

Conclusion

Parenting programmes are an effective treatment for children with conduct problems. The relative effectiveness of different parenting programmes requires further research.
Impact of intraoperative lung-protective interventions in patients undergoing lung cancer surgery
Authors: Licker Marc , Diaper John , Villiger Yann , Spiliopoulos Anastase , Licker Virginie , Robert John , Tschopp Jean-Marie
Published: March 2009

Introduction

In lung cancer surgery, large tidal volume and elevated inspiratory pressure are known risk factors of acute lung (ALI). Mechanical ventilation with low tidal volume has been shown to attenuate lung injuries in critically ill patients. In the current study, we assessed the impact of a protective lung ventilation (PLV) protocol in patients undergoing lung cancer resection.

Methods

We performed a secondary analysis of an observational cohort. Demographic, surgical, clinical and outcome data were prospectively collected over a 10-year period. The PLV protocol consisted of small tidal volume, limiting maximal pressure ventilation and adding end-expiratory positive pressure along with recruitment maneuvers. Multivariate analysis with logistic regression was performed and data were compared before and after implementation of the PLV protocol: from 1998 to 2003 (historical group, n = 533) and from 2003 to 2008 (protocol group, n = 558).

Results

Baseline patient characteristics were similar in the two cohorts, except for a higher cardiovascular risk profile in the intervention group. During one-lung ventilation, protocol-managed patients had lower tidal volume (5.3 ± 1.1 vs. 7.1 ± 1.2 ml/kg in historical controls, P = 0.013) and higher dynamic compliance (45 ± 8 vs. 32 ± 7 ml/cmH2O, P = 0.011). After implementing PLV, there was a decreased incidence of acute lung injury (from 3.7% to 0.9%, P < 0.01) and atelectasis (from 8.8 to 5.0, P = 0.018), fewer admissions to the intensive care unit (from 9.4% vs. 2.5%, P < 0.001) and shorter hospital stay (from 14.5 ± 3.3 vs. 11.8 ± 4.1, P < 0.01). When adjusted for baseline characteristics, implementation of the open-lung protocol was associated with a reduced risk of acute lung injury (adjusted odds ratio of 0.34 with 95% confidence interval of 0.23 to 0.75; P = 0.002).

Conclusions

Implementing an intraoperative PLV protocol in patients undergoing lung cancer resection was associated with improved postoperative respiratory outcomes as evidence by significantly reduced incidences of acute lung injury and atelectasis along with reduced utilization of intensive care unit resources.
Prospective Study of Factors Predicting Adherence to Medical Advice in Men With Testicular Cancer
Authors: Moynihan Clare , Norman Andy R. , Barbachano Yolanda , Burchell Louise , Huddart Robert , Dearnaley David P. , Horwich Alan
Published: March 2009

Purpose

To identify predictive factors of adherence to medical advice, specifically the likelihood of attendance to a recommended follow-up regimen in patients with newly diagnosed testicular cancer.

Patients and Methods

This was a prospective study measuring initially not only aspects of the doctor–patient interview, but also a range of demographic, psychological, social, and medical factors, and then recording attendance behavior on follow-up. All 209 new patients with testicular cancer referred between June 1992 and May 1995 were approached, and 184 men consented and completed questionnaires. The nonadherence end point (nonattender) was two failures to attend an outpatient appointment at least 1 month apart, despite a written reminder.

Results

Thirty-two participants (17%) were classified as nonattenders. No significant differences were found between attenders and nonattenders in the majority of psychosocial and medical variables that might have predicted nonadherence to medical advice. There was a highly significant association between nonattendance and a patient's perception of an unsatisfactory affective relationship with his clinician (P = .005; hazard ratio, 3.1; 95% CI, 1.4 to 6.6).

Conclusion

Patients who perceived an unsatisfactory affective relationship with their clinician that included an inability to trust the clinician and a perception that they were not being treated as “a person” were subsequently more likely to disregard medical advice regarding follow-up. Attention to the ways young men may wish to communicate with their clinicians is important, bearing in mind that they may not necessarily adhere to stereotypical images of masculine self-dependence.
Lack of Comprehension of Common Prostate Cancer Terms in an Underserved Population
Authors: Kilbridge Kerry L. , Fraser Gertrude , Krahn Murray , Nelson Elizabeth M. , Conaway Mark , Bashore Randall , Wolf Andrew , Barry Michael J. , Gong Debra A. , Nease Robert F. , Connors Alfred F.
Published: March 2009

Purpose

To assess the comprehension of common medical terms used in prostate cancer in patient education materials to obtain informed consent, and to measure outcomes after prostate cancer treatment. We address this issue among underserved, African-American men because of the increased cancer incidence and mortality observed in this population.

Patients and Methods

We reviewed patient education materials and prostate-specific quality-of-life instruments to identify technical terms describing sexual, urinary, and bowel function. Understanding of these terms was assessed in face-to-face interviews of 105, mostly African-American men, age ≥ 40, from two low-income clinics. Comprehension was evaluated using semiqualitative methods coded by two independent investigators. Demographics were collected and literacy was measured.

Results

Fewer than 50% of patients understood the terms “erection” or “impotent.” Only 5% of patients understood the term “incontinence” and 25% understood the term “bowel habits.” More patients recognized word roots than related terms or compound words (eg, “rectum” v “rectal urgency,” “intercourse” v “vaginal intercourse”). Comprehension of terms from all domains was statistically significantly correlated with reading level (P < .001). Median literacy level was fourth to sixth grade. Prostate cancer knowledge was poor. Many patients had difficulty locating key anatomic structures.

Conclusion

Limited comprehension of prostate cancer terms and low literacy create barriers to obtaining informed consent for treatment and to measuring prostate cancer outcomes accurately in our study population. In addition, the level of prostate cancer knowledge was poor. These results highlight the need for prostate cancer education efforts and outcomes measurements that consider literacy and use nonmedical language.