bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconsideration on the use of elastic models to predict the instantaneous load response of the knee joint
Authors: Li L P , Gu K B
Published: July 2011

Fluid pressurization in articular cartilages and menisci plays an important role in the mechanical function of the knee joint. However, fluid pressure has not been incorporated in previous finite element modelling of the knee, instead elastic models of the knee are widely used. It is believed that an elastic model can be used to predict the instantaneous load response of the knee as long as large effective moduli for the cartilaginous tissues are used. In the present study, the instantaneous response of the knee was obtained from a proposed model including fluid pressure and fibril reinforcement in the cartilaginous tissues. The results were then compared with those obtained from an elastic model using the effective modulus method. It was found that the deformations and contact pressures predicted by the two models were substantially different. An unconfined compression of a tissue disc was used to help understand the issue. It was clear that a full equivalence between the instantaneous and elastic responses could not be established even for this simple case. A partial equivalence in stress could be conditionally established for a given unconfined compression, but it was not valid for a different magnitude of compression. The instantaneous deformation of the intact tissues in the joint was even more difficult to determine using the effective modulus method. The results thus obtained were further compromised because of the uncertainty over the choice of effective modulus. The tissue non-linearity was one of the factors that made it difficult to establish the equivalence in stress. The pressurized tissue behaved differently from a solid material when non-linear fibril reinforcement was presented. The direct prediction of the instantaneous response using the proposed poromechanical model had the advantage of determining the fluid pressure and incompressible deformation.
Studies of the flow of air in a mixed-flow pump using numerical simulations
Authors: Fernández J , Marcos A , Barrio R , Blanco E , Parrondo J
Published: July 2011

This article presents an investigation of the three-dimensional (3D) turbulent flow through the impeller passages and surroundings of a mixed-flow pump. Rotating passages of turbomachinery contain some very interesting and complex fluid flow phenomena. The model tested has five impeller blades mounted on a conical hub and nine stator blades in a diffuser which brings the diagonally outward flow back to the axial direction. Numerical calculations of the unsteady flow were carried out with the code Fluent, using air as the working fluid. Three models have been applied for turbulence closure: standard k-epsilon, renormalization group k-epsilon, and Reynolds stress model, using conventional wall functions near solid surfaces. For this transient 3D computation, the numerical grid has been decomposed into eight separate regions in order to process these in a parallel cluster of desktop computers. The results obtained show entirely reasonable correlations with previously published experimental data, as detailed in the performance curve comparisons and also in the numerical and experimental flow fields. These outcomes confirm that such a complex transient phenomenon may be reasonably captured by means of a commercial computational fluid dynamics code.
Using Storytelling to Elicit Design Guidance for Medical Devices
Authors: Gausepohl Kim , Winchester Woodrow W. , Arthur James D. , Smith-Jackson Tonya
Published: July 2011

Medical device designers must understand the complex context of use within a health care environment to ensure product usability. Designers must overcome domain-specific obstacles during usability research, such as patient privacy standards, which prevent designers from observing practitioners in context. In this project, we investigated storytelling as an alternative elicitation method for medical device requirements when direct observations are limited or not possible. While gathering requirements for an infusion pump, we compared the types of information elicited by focus groups, interviews, and storytelling sessions. Several advantages and implications for the use of storytelling in usability research are discussed.
“We Knew Her . . .” Murder in a Small Town: A Hybrid Work in Three Voices
Authors: Reilly Rosemary C.
Published: July 2011

This hybrid work blends three voices: a mother and daughter who were deeply impacted by the murder of the daughter’s best friend; my methodological notes from a research study examining the influence of violent trauma on communities; and my emotional memory gathered as I listened and relistened to the digital interview. Drawing on the forms of creative nonfiction and poetic transcription, this piece attempts to communicate the depth of grief, loss, and disconnection that the murder of this young girl created for individuals and the community and the challenge of conducting trauma research.
Echocardiography in the Intensive Care Unit
Authors: Field Larry C. , Guldan George J. , Finley Alan C.
Published: July 2011

As ultrasound technology improves and ultrasound availability increases, echocardiography utilization is growing within intensive care units. Although not replacing the often-needed comprehensive echocardiographic evaluation, limited bedside echocardiography promises to provide intensivists with enhanced diagnostic ability and improved hemodynamic understanding of individual patients. Routine and emergency echocardiography within the intensive care unit focuses on identifying and optimizing medically treatable conditions in a timely manner. Methods for such goal-directed assessments are presented.
Ethical subjectivity and politics in organizations: A case of health care tendering
Authors: McMurray Robert , Pullen Alison , Rhodes Carl
Published: July 2011

This paper examines the relationship between ethics and politics in organizations with a specific focus on ethical subjectivity—that is, how people at work constitute themselves as subjects in relation to both their conduct and their sense of ethical responsibility to others. To investigate this we consider those ethics that were politically mobilized when five clinical partners tendered to buy out the medical practice in which they worked. We provide a detailed reading of a letter of complaint written by one of the partners and sent to their employer—a letter we consider to be a deliberate, political, ethically motivated and overt act of resistance. Drawing on the ethical philosophy of Emmanuel Levinas we argue that the practice of ethics is characterized by a tension where ethical commitments and realpolitik come crashing together. The implication we draw from this is that in organizations the ethical subject is always a political subject; the one who takes action in response to the call of the ethical demand. It is answering the call to political action by the ethical subject—a subject prepared to act in response to the experience of injustice while not resting easy on their own ethical righteousness—that provides an affirmative possibility for researching and theorizing ethics within a critical framework.
Blogging as a journalistic practice: A model linking perception, motivation, and behavior
Authors: Gil de Zúñiga Homero , Lewis Seth C , Willard Amber , Valenzuela Sebastian , Jae Kook Lee  , Baresch Brian
Published: July 2011

As blogs have become a fixture in today’s media environment, growing in number and influence in political communication and (mass) media discourse, research on the subject has proliferated, often emphasizing the high-profile conflicts and controversies at the intersection of blogging and journalism. Less examined, however, is the psychology of everyday citizen bloggers in this context. In studying a randomized sample of US bloggers, we attempt to puzzle out these questions: to what extent do bloggers (1) perceive their work as a form of journalism, and how might such a perception influence (2) their motivations for posting and (3) the topics around which they blog? Most critically, (4) this article constructs a model by which all these antecedents predict whether bloggers behave like professional journalists. Results indicate that bloggers who see their work as a form of journalism are more inclined to inform and influence readers, write about public affairs, and behave as a more traditional journalist.
‘Any one of these boat people could be a terrorist for all we know!’ Media representations and public perceptions of ‘boat people’ arrivals in Australia
Authors: McKay Fiona H , Thomas Samantha L , Warwick Blood R.
Published: July 2011

In April 2009 a boat (named the ‘SIEV 36’ by the Australian Navy) carrying 49 asylum seekers exploded off the north coast of Australia. Media and public debate about Australia’s responsibility to individuals seeking asylum by boat was instantaneous. This paper investigates the media representation of the ‘SIEV 36’ incident and the public responses to media reports through online news fora. We examined three key questions: 1) Does the media reporting refer back to and support previous policies of the Howard Government? 2) Does the press and public discourse portray asylum arrivals by boat as a risk to Australian society? 3) Are journalists following and applying industry guidelines about the reporting of asylum seeker issues? Our results show that while there is an attempt to provide a balanced account of the issue, there is variation in the degree to which different types of reports follow industry guidelines about the reporting of issues relating to asylum seekers and the use of ‘appropriate’ language.
Accomplishing parental engagement in child protection practice?
Authors: Broadhurst Karen , Holt Kim , Doherty Paula
Published: July 2011

The topic of parental engagement in the context of child protection is of significant international interest, given much documented problems of achieving effective ‘partnerships’ where professional agencies raise serious concerns about children. This article reports the findings of a qualitative study of interaction between professionals and parents in the quasi-judicial setting of pre-proceedings meetings in England. Recent legislative changes in England and Wales have aimed to improve the prospects for effective partnership work with parents through a revised pre-proceedings process. Through detailed examination of parent-professional interaction using methods of applied discourse studies, the study highlights the constraints that institutional requirements create in terms of the differential rights and obligations of parents and professionals. Inevitably, that talk is asymmetrically organized in favour of the local authority, leads to resistance on the part of parents. The study highlights problems of engaging parents who display both active and passive forms of resistance, as they seek to challenge or reject organizational goals. The study concludes with broader observations about the likely limits of legislative efforts that seek to ‘re-order’ the complex relationships between parents and professionals in child protection work.
Patent protection in the marine industry: international legal framework and strategic options
Authors: Mikalsen R , Harlfinger P , Roskilly A P
Published: July 2011

Legal protection of intellectual property is becoming increasingly important for developers of new technology, and the highly international marine industry faces some particular challenges in obtaining effective worldwide protection of innovation. Written for engineering professionals and managers in the marine industry, this paper takes a practical look at the international legal framework for patent protection of maritime inventions. A brief introduction to patents is first provided, summarizing important aspects of the patent system. The highly important exception from infringement for ships in international traffic is then reviewed and its practical implications discussed. Finally, some potential strategies for patent protection of maritime inventions in light of the current statutory framework and legal precedent are presented.
The “Second” Season
Authors: Longley Neil , Lacey Nelson J.
Published: July 2011

Most research on competitive balance (CB) in North American sport leagues examines regular-season outcomes only, and does not analyze the potential impacts of postseason playoff tournaments. This article finds that playoffs do matter in a CB sense, in that they can substantially reconfigure regular-season outcomes. More importantly, they may reconfigure outcomes in a way that is not neutral with respect to payroll. The article finds, for example, that in the NHL over the 1994-2004 time period, team success in the playoffs was much less dependent on payroll than it was during the regular-season. The article also analyzes the differential impacts of the specific type of playoff tournament employed, and finds that the choice of playoff “pooling” structures directly impacts the probability of “upsets” occurring in the playoffs.
The Culture of the Condemned: Pastoral Execution and Life on Death Row in the 1930s
Authors: Blue Ethan
Published: July 2011

Between 1830 and 1930, the removal of legal and extralegal executions from public view in the United States bolstered the law’s efficiency while expanding its reach. Scholars have focused on external political effects, largely ignoring the lives of the condemned in the modern killing states. As they were withdrawn ever further behind prison walls, the condemned rearticulated the meanings of their deaths, which would to exceed, to whatever extent possible, new biopolitical regimes. An examination of inmate culture reveals death row as a site of subtle, supple struggle between the modern state and those it would kill.
Timely Deaths: Medicalizing the Deaths of Aboriginal People in Police Custody
Authors: Razack Sherene H.
Published: July 2011

This article is part of a larger study of inquests into the deaths of Aboriginal people in custody. I suggest that the Aboriginal body is considered to be one that is already dead, and thus a body on whom a full measure of care would be wasted. The inquest becomes a place where this ‘‘truth’’ is established. I explore how the deaths of Aboriginal people in police custody have been persistently “medicalized” – that is, attributed to the medical condition of alcoholism, with the inevitable consequence that they cannot be connected to the violence of an ongoing colonialism. Aboriginal death becomes a timely rather than untimely death, the only thing we can expect from a disappearing race.
Exportability of Films in a Globalizing Market: The Intersection of Nation and Genre
Authors: Barthel-Bouchier Diane
Published: July 2011

While the dominance of the Hollywood major studios in the global film market is a well-known fact, less is known about the patterns of exportability by film genre and by nation. Here I present data pertaining to cross-national comparisons between France and the United States, as well as relevant global market figures for US films by genre. The findings challenge the assumption that specific genres, notably comedy, do not export. Rather, it appears that most US comedies that are successful in the States, like most other genres of US films, do and are exported. The case for France, however, appears quite different, insofar as the top films, which were overwhelmingly also comedies, did not export. Exports in the French case were more characteristic of niche marketing: namely quality nature films that could be easily translated, and films that fit specific cultural expectations ( Barnier and Moine, 2002 ; Frodon, 1998 ). This research also suggests that the traditional confrontation of theoretical approaches (cultural imperialist, cultural studies, and the economic approach) fits neither the current situation of a globalizing industry nor the cultural complexity of many films, but that a more nuanced approach should focus on strategies available to different players and relationships formed among producers and between producers and specific markets.
Observation of craters formed by single pulse discharge by stacking cross sectional shapes: comparison of craters in liquid and air
Authors: Yoshida M , Hanaoka D , Flynn B , McGeough J A
Published: July 2011

This paper describes the results of comparing craters formed by single pulse discharge in liquid and in air at comparatively short pulse durations. Investigations were conducted by stacking cross-sectional shapes that the authors developed to clarify the volumes of resolidified metal and molten metal at the crater. In liquid, most of the resolidified layer remained at the bottom of the crater or in its vicinity. In air, the resolidified layer existed only at the downstream side of the high-speed gas flow. The removal ratio was found to be minus in liquid as most of the molten material remained on the crater. In air, more than 70 per cent of the molten material was removed at pulse durations above 2.5 µs. Thermal analysis results indicate that about 26 per cent of the discharge energy was used for melting the workpiece regardless of the pulse duration in liquid. In air, the discharge energy was found to decrease with longer pulse durations (i.e. from 20 to 10 per cent for 2.5 to 2.8 µs) due to the decrease in the heat flux in the workpiece as a result of the arc column being moved at high speed by the high-speed gas flow in the discharge gap.
Geography’s medieval history
Authors: Lilley Keith D
Published: July 2011

This paper examines the marginal place of ‘medieval geography’ in contemporary geographical scholarship. Over the past two decades, geographers' studies of the subject’s historiography have tended to focus mainly on ‘modern’ and ‘early-modern’ rather than medieval geographies. This contrasts with the early 20th century when ‘medieval geography’ was seen by geographers to be part of the discipline’s long history. Set within the context of current discussion on writing geography’s histories, the paper examines how geographers, and latterly historians, have sought to characterize and represent medieval geographies. This reveals that the subject of geography in the Middle Ages shared in the same fluidities and ambivalences that characterize geography today. The paper thus helps to challenge orthodox views of geography’s history, and argues that the connections and continuities that have shaped geography for over two millennia cautions us against taking a compartmentalized approach to historiographies of geography.
Muddling the history of geography
Authors: Geary Patrick
Published: July 2011

The argument put forward by Keith Lilley (2011) foreshadows similar debates in other disciplines concerning the history of science and the place of history in disciplines. Geography, he contends, loses twice over from failing to fully study and integrate medieval geography into the history of the discipline, first in reducing geography's ‘territory' by cutting geography off from an important part of its past, and second by reinforcing what he considers a dubious assertion, namely that geography's history began only with the early modern period. Geography remains a contested enterprise, a muddled enterprise and, as Lilley and other scholars working on geography that took place before the discipline emerged continue to show, our understanding of its history is all the richer for its being muddled.
A comprehensive functional characterization of BRCA2 variants associated with Fanconi anemia using mouse ES cell–based assay
Authors: Biswas Kajal , Das Ranabir , Alter Blanche P. , Kuznetsov Sergey G. , Stauffer Stacey , North Susan L. , Burkett Sandra , Brody Lawrence C. , Meyer Stefan , Byrd R. Andrew , Sharan Shyam K.
Published: July 2011

Biallelic mutations in the human breast cancer susceptibility gene, BRCA2, are associated with Fanconi anemia, implying that some persons who inherit 2 deleterious variants of BRCA2 are able to survive even though it is well established that BRCA2 is indispensable for viability in mice. One such variant, IVS7 + 2T > G, results in premature protein truncation because of skipping of exon 7. Surprisingly, the persons who are either IVS7 + 2T > G homozygous or compound heterozygous are born alive but die of malignancy associated with Fanconi anemia. Using a mouse embryonic stem cell–based functional assay, we found that the IVS7 + 2T > G allele produces an alternatively spliced transcript lacking exons 4-7, encoding an in-frame BRCA2 protein with an internal deletion of 105 amino acids (BRCA2Δ105). We demonstrate that BRCA2Δ105 is proficient in homologous recombination-mediated DNA repair as measured by different functional assays. Evaluation of this transcript in normal and leukemia cells suggests that BRCA2Δ105 may contribute to the viability of persons inheriting this mutation. In this study, we have also characterized 5 other BRCA2 variants and found 3 of these (p.L2510P, p.R2336H, and p.W2626C) to be deleterious and 2 (p.I2490T and p.K2729N) probably neutral. Such studies are important to understand the functional significance of unclassified BRCA2 variants.
Characterization of immunologic properties of a second HLA-A2 epitope from a granule protease in CML patients and HLA-A2 transgenic mice
Authors: Lacey Simon F. , La Rosa Corinna , Kaltcheva Teodora , Srivastava Tumul , Seidel Aprille , Zhou Wendi , Rawal Ravindra , Hagen Katharine , Krishnan Aparna , Longmate Jeff , Andersson Helen A. , St. John Lisa , Bhatia Ravi , Pullarkat Vinod , Forman Stephen J. , Cooper Laurence J. N. , Molldrem Jeffrey , Diamond Don J.
Published: July 2011

The serine proteases, neutrophil elastase (HNE) and proteinase 3 (PR3), are aberrantly expressed in human myeloid leukemias. T-cell responses to these proteins have been correlated with remission in patients with chronic myeloid leukemia (CML). Human PR3/HNE-specific CD8+ T cells predominantly recognize a nonameric HLA-A2–restricted T-cell epitope called PR1 which is conserved in both Ags. However, CML patients have CD8+ T cells in peripheral blood recognizing an additional HLA-A2 epitope termed PR2. To assess immunologic properties of these Ags, novel recombinant vaccinia viruses (rVV) expressing PR3 and HNE were evaluated in HLA-A2 transgenic (Tg) mice (HHDII). Immunization of HHDII mice with rVV-PR3 elicited a robust PR3-specific CD8+ T-cell response dominated by recognition of PR2, with minimal recognition of the PR1 epitope. This result was unexpected, because the PR2 peptide has been reported to bind poorly to HLA. To account for these findings, we proposed that HHDII mice negatively selected PR1-specific T cells because of the presence of this epitope within murine PR3 and HNE, leading to immunodominance of PR2-specific responses. PR2-specific splenocytes are cytotoxic to targets expressing naturally processed PR3, though PR1-specific splenocytes are not. We conclude that PR2 represents a functional T-cell epitope recognized in mice and human leukemia patients. These studies are registered at www.clinicaltrials.gov as NCT00716911.
Effect of an ambulatory diagnostic and treatment programme in patients with sleep apnoea
Authors: Andreu A.L. , Chiner E. , Sancho-Chust J.N. , Pastor E. , Llombart M. , Gomez-Merino E. , Senent C. , Barbé F.
Published: July 2011

The aim of this study to evaluate the efficacy of a home-based programme on clinical response, continuous positive airway pressure (CPAP) compliance and cost in a population of high pre-test probability of suffering obstructive sleep apnoea syndrome (OSAS).

Patients were randomised into the following three groups. Group A: home respiratory polygraphy (RP) and home follow-up; group B: hospital polysomnography and hospital follow-up; and group C: home RP and hospital follow-up. Evaluation during 6 months included Epworth Sleepiness Scale (ESS), Functional Outcomes Sleep Questionnaire (FOSQ), and daily activity and symptom questionnaires. Compliance was assessed by memory cards (group A) and using an hourly counter (groups B and C).

66 patients were included (22 per branch), 83% were males, aged mean±sd52±10 yrs, body mass index 34±7kg·m−2, apnoea/hypopnoea index 43±20 h−1, CPAP pressure 8±2 cmH2O, with no between-group differences. Clinical response showed an ESS of mean±sd15±3 to 6±4, a FOSQ of 16±3 to 18±2, symptoms of 43±7 to 25±7, and activity of 37±11 to 25±8. At the end of the study, compliance was: group A 73%, group B 68% and group C 57%. The cost per patient was: group A €590±43, group B €894±11 and group C €644±93 (p<0.001).

In conclusion, patients with a high initial probability of having OSAS can be diagnosed and treated in a home setting, with a high level of CPAP compliance and lower cost than using either a hospital-based approach or home RP/hospital follow-up.
RNA is favourable for analysingEGFRmutations in malignant pleural effusion of lung cancer
Authors: Tsai T-H. , Su K-Y. , Wu S-G. , Chang Y-L. , Luo S-C. , Jan I-S. , Yu C-J. , Yu S-L. , Shih J-Y. , Yang P-C.
Published: July 2011

Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation ofEGFRstatus in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive forEGFRmutation detection.

To test whetherEGFRanalysis from RNA is less prone to interference from nontumour cells that have no or lowerEGFRexpression, we compared three methods (sequencing from cell-derived RNAversussequencing and mass-spectrometric analysis from genomic DNA), in parallel, forEGFRmutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs).

Among these MPE samples,EGFRmutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3versus44.7 and 46.7%; for L858R or exon 19 deletions, 61.3versus41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance,EGFRsequencing from RNA provided satisfactory detection of T790M (54.2%).

These results demonstrated thatEGFRsequencing using RNA as template greatly improves sensitivity forEGFRmutation detection from samples of MPE, highlighting RNA as the favourable source for analysingEGFRmutations from heterogeneous MPE specimens in NSCLC.
Lack of an exaggerated inflammatory response on virus infection in cystic fibrosis
Authors: Kieninger E. , Vareille M. , Kopf B.S. , Blank F. , Alves M.P. , Gisler F.M. , Latzin P. , Casaulta C. , Geiser T. , Johnston S.L. , Edwards M.R. , Regamey N.
Published: July 2011

Respiratory virus infections play an important role in cystic fibrosis (CF) exacerbations, but underlying pathophysiological mechanisms are poorly understood. We aimed to assess whether an exaggerated inflammatory response of the airway epithelium on virus infection could explain the increased susceptibility of CF patients towards respiratory viruses.

We used primary bronchial and nasal epithelial cells obtained from 24 healthy control subjects and 18 CF patients. IL-6, IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, RANTES/CCL5 and GRO-α/CXCL1 levels in supernatants and mRNA expression in cell lysates were measured before and after infection with rhinoviruses (RV-16 and RV-1B) and RSV. Cytotoxicity was assessed by lactate dehydrogenate assay and flow cytometry.

All viruses induced strong cytokine release in both control and CF cells. The inflammatory response on virus infection was heterogeneous and depended on cell type and virus used, but was not increased in CF compared with control cells. On the contrary, there was a marked trend towards lower cytokine production associated with increased cell death in CF cells.

An exaggerated inflammatory response to virus infection in bronchial epithelial cells does not explain the increased respiratory morbidity after virus infection in CF patients.
Determinants of success
Authors: Garrod R. , Malerba M. , Crisafulli E.
Published: July 2011

In chronic obstructive pulmonary disease (COPD) patients, pulmonary rehabilitation is a nonpharmacological intervention aimed at improving physical exercise tolerance, dyspnoea and perceived quality of life. However, identifying predictors of clinical response and which patients achieve benefit remains a difficult question to answer with no conclusive data available.

Baseline characteristics of COPD patients, such as degree of breathlessness, body weight and arterial partial pressure of oxygen, generally appear to be too direct to have a correlation with improvement of post-rehabilitation outcomes. Furthermore, some additional benefits of patients treated with rehabilitation are simply not detected by usual measures (social interaction, sleep quality and confidence).

Although there are some data suggesting that some medical conditions frequently associated with COPD (osteoporosis, metabolic syndrome and heart diseases) may negatively influence rehabilitation outcomes, at present the evidence is contradictory.
IκBα glutathionylation and reduced histone H3 phosphorylation inhibit eotaxin and RANTES
Authors: Seidel P. , Roth M. , Ge Q. , Merfort I. , S’ng C.T. , Ammit A.J.
Published: July 2011

Airway smooth muscle cells (ASMCs) secrete eotaxin and RANTES (regulated on activation, normal T-cell expressed and secreted) in response to tumour necrosis factor (TNF)-α, which is inhibited by the nuclear factor (NF)-κB inhibitor dimethylfumarate (DMF). NF-κB/IκB (inhibitor of NF-κB) glutathionylation and changes in chromatin remodelling can inhibit NF-κB activity. In this study, we determined whether NF-κB/IκB glutathionylation and reduced histone H3 phosphorylation might underlie the inhibitory effect of DMF on NF-κB activity, and eotaxin and RANTES secretion.

Primary human ASMCs were treated with DMF, diamide and/or glutathione (GSH) ethylester (OEt) prior to TNF-α stimulation and were subsequently analysed by ELISA, electrophoretic mobility shift assay, immunofluorescence, co-immunoprecipitation or immunoblotting.

DMF reduced intracellular GSH and induced IκBα glutathionylation (IκBα-SSG), which inhibited IκBα degradation, NF-κB p65 nuclear entry and NF-κB/DNA binding. In addition, DMF inhibited the phosphorylation of histone H3, which was possibly mediated by the inhibitory effect of DMF on mitogen- and stress-activated protein kinase (MSK)-1. However, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase MAPK and MAPK phosphatase-1, upstream of MSK-1, were not inhibited by DMF. Importantly, DMF-mediated effects on NF-κB, histone H3, eotaxin and RANTES were reversed by addition of GSH-OEt.

Our data suggest that DMF inhibits NF-κB-dependent eotaxin and RANTES secretion by reduction of GSH with subsequent induction of IκBα-SSG and inhibition of histone H3 phosphorylation. Our findings offer new potential drug targets to reduce airway inflammation in asthma.
The burden of TB–HIV in the EU: how much do we know? A survey of surveillance practices and results
Authors: Kruijshaar M.E. , Pimpin L. , Abubakar I. , Rice B. , Delpech V. , Drumright L.N. , Hollo V. , Huitric E. , van de Laar M. , Amato-Gauci A. , Manissero D. , Ködmön C.
Published: July 2011

Information on the burden of tuberculosis (TB)–HIV co-infection is critical for the planning and evaluation of TB–HIV control and treatment strategies. This study assessed current practices in countries of the European Union (EU) and European Economic Area (EEA) for monitoring HIV co-infection in TB surveillance systems, countries’ current co-infection burden and associated clinical practice.

An online survey was distributed to all national TB surveillance nominated European Centre for Disease Prevention and Control contact points in the EU/EEA.

We received 25 responses from 30 countries (83% response rate). Patients’ HIV status was collected in 18 out of the 25 TB surveillance systems, usuallyviaclinician reporting (16 out of 18 surveillance systems). Although most countries recommended routine testing of TB patients for HIV, the proportion actually tested varied from 5% to 90%. The burden of HIV co-infection was found to be elevated in countries with higher levels of HIV testing and higher prevalence of HIV.

We suggest that TB–HIV co-infection be monitored in all EU/EEA countries to facilitate the planning and evaluation of TB–HIV control strategies. Strengthening collaboration between TB and HIV clinicians and surveillance departments, and consideration of patient confidentiality restraints would be advantageous. The level of HIV testing in TB patients is low despite national recommendations and testing should be further promoted and monitored.
All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved interactions with Vangl, Dvl, and serine/threonine kinases
Authors: Kivimäe Saul , Yang Xiao Yong , Cheyette Benjamin NR
Published: July 2011

Background

The Dact family of scaffold proteins was discovered by virtue of binding to Dvl proteins central to Wnt and Planar Cell Polarity (PCP) signaling. Subsequently Dact proteins have been linked to a growing list of potential partners implicated in β-catenin-dependent and β-catenin-independent forms of Wnt and other signaling. To clarify conserved and non-conserved roles for this protein family, we systematically compared molecular interactions of all three murine Dact paralogs by co-immunoprecipitation of proteins recombinantly expressed in cultured human embryonic kidney cells.

Results

Every Dact paralog readily formed complexes with the Vangl, Dvl, and CK1δ/ε proteins of species ranging from fruit flies to humans, as well as with PKA and PKC. Dact proteins also formed complexes with themselves and with each other; their conserved N-terminal leucine-zipper domains, which have no known binding partners, were necessary and sufficient for this interaction, suggesting that it reflects leucine-zipper-mediated homo- and hetero-dimerization. We also found weaker, though conserved, interactions of all three Dact paralogs with the catenin superfamily member p120ctn. Complex formation with other previously proposed partners including most other catenins, GSK3, LEF/TCF, HDAC1, and TGFβ receptors was paralog-specific, comparatively weak, and/or more sensitive to empirical conditions.

Conclusions

Combined with published functional evidence from targeted knock-out mice, these data support a conserved role for Dact proteins in kinase-regulated biochemistry involving Vangl and Dvl. This strongly suggests that a principal role for all Dact family members is in the PCP pathway or a molecularly related signaling cascade in vertebrates.
Effect of hosts on competition among clones and evidence of differential selection between pathogenic and saprophytic phases in experimental populations of the wheat pathogen Phaeosphaeria nodorum
Authors: Sommerhalder Rubik J , McDonald Bruce A , Mascher Fabio , Zhan Jiasui
Published: July 2011

Background

Monoculture, multi-cropping and wider use of highly resistant cultivars have been proposed as mechanisms to explain the elevated rate of evolution of plant pathogens in agricultural ecosystems. We used a mark-release-recapture experiment with the wheat pathogen Phaeosphaeria nodorum to evaluate the impact of two of these mechanisms on the evolution of a pathogen population. Nine P. nodorum isolates marked with ten microsatellite markers and one minisatellite were released onto five replicated host populations to initiate epidemics of Stagonospora nodorum leaf blotch. The experiment was carried out over two consecutive host growing seasons and two pathogen collections were made during each season.

Results

A total of 637 pathogen isolates matching the marked inoculants were recovered from inoculated plots over two years. Genetic diversity in the host populations affected the evolution of the corresponding P. nodorum populations. In the cultivar mixture the relative frequencies of inoculants did not change over the course of the experiment and the pathogen exhibited a low variation in selection coefficients.

Conclusions

Our results support the hypothesis that increasing genetic heterogeneity in host populations may retard the rate of evolution in associated pathogen populations. Our experiment also provides indirect evidence of fitness costs associated with host specialization in P. nodorum as indicated by differential selection during the pathogenic and saprophytic phases.
The replication origin of a repABC plasmid
Authors: Cervantes-Rivera Ramón , Pedraza-López Francisco , Pérez-Segura Gabriela , Cevallos Miguel A
Published: July 2011

Background

repABC operons are present on large, low copy-number plasmids and on some secondary chromosomes in at least 19 α-proteobacterial genera, and are responsible for the replication and segregation properties of these replicons. These operons consist, with some variations, of three genes: repA, repB, and repC. RepA and RepB are involved in plasmid partitioning and in the negative regulation of their own transcription, and RepC is the limiting factor for replication. An antisense RNA encoded between the repB-repC genes modulates repC expression.

Results

To identify the minimal region of the Rhizobium etli p42d plasmid that is capable of autonomous replication, we amplified different regions of the repABC operon using PCR and cloned the regions into a suicide vector. The resulting vectors were then introduced into R. etli strains that did or did not contain p42d. The minimal replicon consisted of a repC open reading frame under the control of a constitutive promoter with a Shine-Dalgarno sequence that we designed. A sequence analysis of repC revealed the presence of a large A+T-rich region but no iterons or DnaA boxes. Silent mutations that modified the A+T content of this region eliminated the replication capability of the plasmid. The minimal replicon could not be introduced into R. etli strain containing p42d, but similar constructs that carried repC from Sinorhizobium meliloti pSymA or the linear chromosome of Agrobacterium tumefaciens replicated in the presence or absence of p42d, indicating that RepC is an incompatibility factor. A hybrid gene construct expressing a RepC protein with the first 362 amino acid residues from p42d RepC and the last 39 amino acid residues of RepC from SymA was able to replicate in the presence of p42d.

Conclusions

RepC is the only element encoded in the repABC operon of the R. etli p42d plasmid that is necessary and sufficient for plasmid replication and is probably the initiator protein. The oriV of this plasmid resides within the repC gene and is located close to or inside of a large A+T region. RepC can act as an incompatibility factor, and the last 39 amino acid residues of the carboxy-terminal region of this protein are involved in promoting this phenotype.
Blunting type 1 insulin-like growth factor receptor expression exacerbates neuronal apoptosis following hypoxic/ischemic injury
Authors: Liu Wen , D'Ercole Joseph A , Ye Ping
Published: July 2011

Background

Abundant experimental data have implicated an important role for insulin-like growth factor (IGF) in protecting neuronal cells from injury, including hypoxia/ischemia (H/I) injury, a major cause of neuron death. While the specific interaction of IGFs with neuronal or glial type 1 IGF receptors (IGF1R) has been shown to be essential to IGF actions during development, the same has not been directly demonstrated following H/I injury. To directly examine the role of neuronal IGF1R following H/I injury, we utilized conditional mutant nes-igf1r

-/Wt
mice and determined the impact of IGF1R haplodeficiency specifically in nestin-expressing neuronal precursors and their progeny on H/I-induced neuronal damage and apoptosis in hippocampus.

Results

H/I induced significant damage to the cerebral hemisphere and hippocampus ipsilateral to the ligated right common carotid artery both in control and nes-igf1r

-/Wt
mice at postnatal day 10. Blunting IGF1R expression, however, markedly exacerbated H/I-induced damage and appeared to increase mortality. In the ipsilateral hemisphere and hippocampus, nes-igf1r

-/Wt
mice had infarct areas double the size of those in controls. The size of the ipsilateral hemisphere and hippocampus in nes-igf1r

-/Wt
mice were 15% to 17% larger than those in controls, reflecting more severe edema. Consistent with its effects on infarct area, IGF1R haplodeficiency causes a greater decrease in neurons in the ipsilateral hippocampus of nes-igf1r

-/Wt
mice. The reduction in neurons was largely due to increases in neuronal apoptosis. Judged by pyknotic nuclei, TUNEL and caspase-3 labeling, nes-igf1r

-/Wt
mice had significantly more apoptotic cells than that in controls after injury. To determine possible mechanisms of IGF1R actions, the mRNA expression of the pro-survival proteins IAP-1 and XIAP was determined. Compared to controls, the abundance of cIAP-1 and XIAP mRNA was markedly suppressed in mice with blunted IGF1R or IGF-I expression, while was increased in the brain of IGF-I overexpressing transgenic mice.

Conclusion

IGF1R in neuronal cells is critically important for their survival following H/I injury, and IGF-upregulated expression of neuronal cIAP-1 and XIAP likely in part contributes to IGF-IGF1R protection against neuronal apoptosis following H/I injury.
Effectiveness of a short-course in improving knowledge and skills on evidence-based practice
Authors: Argimon-Pallàs Josep M , Flores-Mateo Gemma , Jiménez-Villa Josep , Pujol-Ribera Enriqueta
Published: July 2011

Background

To assess the effectiveness (change in knowledge and skills measured by the Fresno test) of a short course in Evidence Based Practice (EBP) carried out in a group of family medicine residents

Methods

Before-after study. Participants' were 152 Family Medicine residents in their second year of the training programme. Settings were Primary Care Teaching Units in Catalonia. Intervention was comprised of a four half-day training course designed to develop the knowledge and skills required to practice evidence-based care. The main outcome measure was change in EBP knowledge and skills, measured using the Spanish version of the Fresno test (score range, 0-212)

Results

The mean difference between pre-test and post-test was 47.7, a statistically significant result with 95% CI of 42.8-52.5 (p < 0.0001). An important improvement was observed in the questions related to calculations such as sensitivity, specificity, the absolute risk reduction or the number needed to treat. A more modest increase was found in the residents' knowledge and skills in finding the best clinical evidence, and appraising the validity and applicability of an article. Finally, a weak and non-statistically significant improvement was found in formulating a clinical question.

Conclusions

The study provides evidence for responsiveness to changes in knowledge and skills in EBP after an educational intervention.
Genome Wide Association Study to predict severe asthma exacerbations in children using random forests classifiers
Authors: Xu Mousheng , Tantisira Kelan G , Wu Ann , Litonjua Augusto A , Chu Jen-hwa , Himes Blanca E , Damask Amy , Weiss Scott T
Published: July 2011

Background

Personalized health-care promises tailored health-care solutions to individual patients based on their genetic background and/or environmental exposure history. To date, disease prediction has been based on a few environmental factors and/or single nucleotide polymorphisms (SNPs), while complex diseases are usually affected by many genetic and environmental factors with each factor contributing a small portion to the outcome. We hypothesized that the use of random forests classifiers to select SNPs would result in an improved predictive model of asthma exacerbations. We tested this hypothesis in a population of childhood asthmatics.

Methods

In this study, using emergency room visits or hospitalizations as the definition of a severe asthma exacerbation, we first identified a list of top Genome Wide Association Study (GWAS) SNPs ranked by Random Forests (RF) importance score for the CAMP (Childhood Asthma Management Program) population of 127 exacerbation cases and 290 non-exacerbation controls. We predict severe asthma exacerbations using the top 10 to 320 SNPs together with age, sex, pre-bronchodilator FEV1 percentage predicted, and treatment group.

Results

Testing in an independent set of the CAMP population shows that severe asthma exacerbations can be predicted with an Area Under the Curve (AUC) = 0.66 with 160-320 SNPs in comparison to an AUC score of 0.57 with 10 SNPs. Using the clinical traits alone yielded AUC score of 0.54, suggesting the phenotype is affected by genetic as well as environmental factors.

Conclusions

Our study shows that a random forests algorithm can effectively extract and use the information contained in a small number of samples. Random forests, and other machine learning tools, can be used with GWAS studies to integrate large numbers of predictors simultaneously.
Trends in colorectal cancer incidence: a period and birth-cohort analysis in a well-defined French population
Authors: Chauvenet Marion , Cottet Vanessa , Lepage Côme , Jooste Valérie , Faivre Jean , Bouvier Anne-Marie
Published: July 2011

Background

France stands among high-risk areas for colorectal cancer. Different trends in CRC incidence are reported around the world. The aim of this study was to provide temporal trends in CRC incidence over a 30-year period in a French well-defined population.

Methods

Between 1976 and 2005, 17,028 new cases were registered by the Burgundy digestive cancer registry. The mean variations in age-standardized incidence rates were estimated using a Poisson regression adjusted for age for each gender and location. The cumulative risk by birth cohort of developing a cancer over the age range 0-74 years was estimated using an age-cohort model.

Results

Incidence rates for right and left colon cancers increased more rapidly in males (respectively +11.7% and +10.3% on average by 5-year period) than in females (respectively +5.9% and +6.1%). It remained stable for sigmoid cancers in males (-0.1%) and decreased in females (-5.2%). It also decreased for rectal cancers both in males (-2.7%) and in females (-2.0%). The cumulative risk increased from 3.9% for males born around 1900 to 4.9% for those born around 1930 and then slightly decreased (4.5% among those born around 1950). It remained at the same level for females born around 1900 (2.7%) as for those born around 1930 (2.7%) and then slightly increased (2.9%) for those born around 1950. For right colon cancers, the cumulative risk increased strikingly in successive birth cohorts from 0.53% to 1.2% in males and 0.55% to 0.77% in females. The corresponding cumulative risks for the left colon were 0.24% and 0.42% in males and 0.14% and 0.29% in females. For sigmoid cancer, they decreased from 1.59% to 1.08% in males, and 0.88% to 0.80% in females.

Conclusion

Temporal variations in incidence rates of colorectal cancers differed according to subsite, suggesting different aetiological factors and implications for diagnosis and screening strategies. Total colonoscopy must be the preferred strategy in high-risk groups or after a positive faecal occult blood test.