bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating Health State Utility Values for Joint Health Conditions
Authors: Ara Roberta , Wailoo Allan J.
Published: August 2012

Background. Analysts frequently estimate the health state utility values (HSUVs) for joint health conditions (JHCs) using data from cohorts with single health conditions. The methods can produce very different results, and there is currently no consensus on the most appropriate technique. Objective. To conduct a detailed critical review of existing empirical literature to gain an understanding of the reasons for differences in results and identify where uncertainty remains that may be addressed by further research. Results. Of the 11 studies identified, 10 assessed the additive method, 10 the multiplicative method, 7 the minimum method, and 3 the combination model. Two studies evaluated just 1 of the techniques, whereas the others compared results generated using 2 or more. The range of actual HSUVs can influence general findings, and methods are sometimes compared using descriptive statistics that may not be appropriate for assessing predictive ability. None of the methods gave consistently accurate results across the full range of possible HSUVs, and the values assigned to normal health influence the accuracy of the methods. Conclusions. Within the limitations of the current evidence base, we would advocate the multiplicative method, conditional on adjustment for baseline utility, as the preferred technique to estimate HSUVs for JHCs when using mean values obtained from cohorts with single conditions. We would recommend that a range of sensitivity analyses be performed to explore the effect on results when using the estimated HSUVs in economic models. Although the linear models appeared to give more accurate results in the studies we reviewed, these models require validating in external data before they can be recommended.
The Reliability of Arthroscopic Classification of Acetabular Rim Labrochondral Disease
Authors: Nepple Jeffrey J. , Larson Christopher M. , Smith Matthew V. , Kim Young-Jo , Zaltz Ira , Sierra Rafael J. , Clohisy John C.
Published: August 2012

Background:

The results of surgical treatment for femoroacetabular impingement have been increasingly reported, and more advanced intra-articular disease has been identified as an important predictive factor of outcome. Yet, the reliability of arthroscopic hip disease classification has not been well defined.

Purpose/Hypothesis:

To determine the intraobserver and interobserver reliability of the Beck classification of labral and articular cartilage disease (anterior-superior acetabular rim) encountered in hip arthroscopy. Secondly, we identified the sources of poor reliability that may be improved with future disease classification schemes. Our hypothesis was that the Beck classification of labral and chondral lesions would demonstrate substantial reliability, while the differentiation of early forms of disease would be a common source of disagreement.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Four experienced hip arthroscopists reviewed standardized arthroscopic videos of 40 cases. Arthroscopic findings at the anterior-superior acetabular rim were classified using the Beck classification of labral and articular cartilage disease. Repeat classification of videos was performed at least 2 weeks later. The reliability of arthroscopic classification was defined using the average weighted Cohen κ values and agreement rates.

Results:

Arthroscopic classification of labral disease using the Beck classification demonstrated moderate to substantial interobserver reliability (average κ = .62; range, .48-.78) and an overall agreement rate of 81.7%. Intraobserver reliability showed a similar level of reliability (average κ = .65; agreement rate, 80.6%). The differentiation between labral degeneration and labral detachment was a common source of disagreement. Similarly, the Beck classification of articular cartilage disease had moderate to substantial interobserver reliability (average κ = .65; range, .49-.78) and overall agreement rate of 57.5%. Intraobserver reliability showed a slightly better level of reliability (average κ = .80; agreement rate, 77.5%). The differentiation between articular cartilage malacia and debonding was a common source of disagreement.

Conclusion:

The arthroscopic classification of acetabular rim disease with the Beck classification has substantial interobserver reliability. This level of reliability is similar to previously reported arthroscopic disease classifications in the knee and shoulder and seems appropriate for future outcome reporting. Future classifications that eliminate common sources of disagreement may further improve the reliability.
Children’s Perceptions of Their ADHD Symptoms
Authors: Wiener Judith , Malone Molly , Varma Angela , Markel Clarisa , Biondic Daniella , Tannock Rosemary , Humphries Tom
Published: August 2012

This study investigated the perceptions of children with Attention-Deficit/Hyperactivity Disorder (ADHD) of their ADHD symptoms in terms of the positive illusory bias (PIB), their attributions for their problem behaviors, and their beliefs about whether their problem behaviors and disorder are stigmatizing. Participants were 152 9- to 14-year-old children (86 ADHD). Children with ADHD demonstrated a PIB for their ADHD symptoms; the discrepancy between their self-reports and parent reports was greater than for children without ADHD. They also viewed their self-identified most problematic behavior as more uncontrollable and stigmatizing (i.e., bothersome to others, leading to differential treatment, and embarrassing) than comparison children. Their perception that their problem behaviors and their disorder were stigmatizing was negatively associated with behavioral self-concept and self-esteem. These results suggest that school psychologists should interpret the self-reports of problem behaviors of children with ADHD with caution while being aware of the vulnerability of these children to feelings of stigma.
Nation, Neighbourhood and Region: India’s Emergence as an Asia Power
Authors: Gordon Sandy
Published: August 2012

Analysis of rising powers needs to be conducted not just in terms of their overall capabilities but also of their geopolitical circumstances—where they are placed in respect of domestic polity, their neighbourhoods, their regions and the globe. As a rising power, India is particularly closely embedded in its South Asian neighbourhood by tightly enmeshed domestic and neighbourhood dissonances. These are in turn deeply affected by global conditions, especially the rise of China and globalisation of a militant version of Islam. This article analyses India’s ‘strategies’ in dealing with its circumstances and concludes that, at least for the present, India has delayed the process of ardent military modernisation in favour of balanced development in an attempt to achieve greater domestic harmony and reduce vulnerability to destabilising cross-border influences. Strategies in South Asia are, however, less well developed and require greater attention.
The Quadrilateral Initiative: An Evaluation
Authors: Sharma Ashok
Published: August 2012

Asia’s emergence as the world’s fastest-growing region, with rising military expenditures and a substantial restructuring of power, has given rise to new strategic alliances and coalitions between the region’s major players. The quadrilateral initiative, a grouping of the United States (US), Japan, Australia and India, emerged after tsunami cooperation in 2004 between these four countries and was later advocated by the Japanese Premier. Strategically designed to balance power and tackle issues like transnational security, terrorism and sea piracy in the Asia-Pacific region, the Quad was put on the backburner following Beijing’s protests that it had been specifically designed to encircle it. Nevertheless, India’s strategic ties with the US, Australia and Japan are growing and the US links with Japan and Australia have been strengthened in the Trilateral Security Dialogue. The article examines the factors that justify the existence of the Quad and asserts that the possibility of strategic partnership among these four maritime democracies remains alive.
Nuclear Weapon Programmes of India and Pakistan: A Comparative Assessment
Authors: Dhanda Suresh
Published: August 2012

After the 1998 tests, both India and Pakistan possess nuclear weapons, weapon usable material and significant civilian and military nuclear infrastructure. Both are seriously engaged in revising their plans and refining their weapons and delivery systems. They are spending enormous sums on the production, deployment, targeting, defence, supervision and control of their nuclear weapons and delivery systems, as well as on the infrastructure that would generate the fissile material, warheads, aircraft, missiles and command and control systems necessary for their nuclear programmes. But they observe utmost secrecy in all these matters. Hence, it is very difficult to comparatively assess their nuclear programmes. Much of the available literature is speculative and unreliable, and requires careful examination. The article compares the two nuclear programmes in terms of their respective nuclearisation routes, motivations, weapons capabilities, inventories, nuclear doctrines, command and control and delivery systems.
Internal Security Crises in Punjab, Kashmir and Jaffna: The Power of Moderation
Authors: Ahmed Ali
Published: August 2012

The article argues that the militarised nature of India’s initial reaction to an internal security crisis contributes to deterioration in the situation. The resulting full-blown insurgency, usually complicated by proxy war, takes several years to wind down due to the political prong of strategy not keeping pace with the military prong. This is to the detriment of the legitimacy of the state and exacts a high human price. Learning lessons from India’s initial reaction to insurgency outbreak therefore helps to highlight the importance of prevention and possibilities in non-militarised alternatives. The article considers the initial phases of three of India’s major counter-insurgency engagements—Punjab, Kashmir and in Tamil areas of Sri Lanka—to arrive at the conclusion that moderation in facing crisis prevents conflict outbreak.
Renewable Energies: Challenges and Benefits
Authors: Pflüger Antonio
Published: August 2012

Energy efficiency and energy conservation are the cornerstones of win-win strategies for reducing emissions while fostering economic development. Renewable energies can technically contribute to practically all sectors of energy demand, that is, fuel for transportation, electricity, low temperature heat for space heating and hot water and, to a limited degree, to high temperature process heat. However, costs and variability are the two major security concerns regarding renewable energies. An improvement of energy security by using renewable energies is possible but it causes additional costs. However, a sufficiently widespread variety of energy sources implies the acceptance of a certain spread of costs in any case. This means that efforts to improve energy security do not come for free. More secure energy systems require higher costs and thus, higher energy prices.
Environmental Challenges for Maldives
Authors: Karthikheyan T.C.
Published: August 2012

This article looks into the environmental challenges that Maldives, an island country in the South Asian region, is facing. It studies all possible sources of environmental challenges with inherent vulnerabilities of the country in terms of its geographic and environmental conditions, and analyses important contributing factors such as global warming, sea level rise, tourism and environmental degradation and, more importantly, the 2004 tsunami. The article particularly examines the effects of global warming on Maldives on the basis of the Intergovernmental Panel on Climate Change’s (IPCC) report on climate change. The impact of the tsunami and its repercussions on the Maldives’s ecological fragility are also discussed. Towards the conclusion, this article focuses on the need of the Maldivian government to formulate appropriate policies and also, at the same time, the difficulties in realising those policies.
Effect of Intensive Hand Washing Education on Hand Washing Behaviors in Thai Households with an Influenza-Positive Child in Urban Thailand
Authors: Kaewchana Suchada , Simmerman Mark , Somrongthong Ratana , Suntarattiwong Piyarat , Lertmaharit Somrat , Chotipitayasunondh Tawee
Published: August 2012

This study assessed the effect of intensive education on self-reported frequency of hand washing (FHW), measured quality of hand washing (QHW), and measured scores of knowledge, attitude, and practice (KAP) after 7 days and 90 days home-based intensive education of participants (aged >7 years) in households with a influenza-positive child. The authors provided intensive hand washing education using interactive participation including individual training, self-monitoring diary, provision of soap, and so on. There were significant improvements on FHW and QHW on day 7, control group (n1 = 135) reported 3.9 hand washing episodes/day, whereas the intervention group (n2 = 140) reported 5.7 episodes/day; control group (n1 = 164) obtained a 3.2 measured quality score, whereas the intervention group (n2 = 166) obtained a score of 6.4. Pre-education and 90 days post-education, FHW significantly improved by 2 episodes/day and QHW increased by 3 scores/episode. Knowledge of influenza and hand washing following coughing/sneezing showed significant improvement, but attitude modification toward severity of influenza requires a more intensified and longer intervention.
Soundwalks, Community, and the Secondary General Classroom
Authors: Jaworski Nick
Published: August 2012

This column presents an outline for the secondary general classroom. The project, called a “soundwalk,” requires students to use music, sounds, and technology to create immersive, cinematic audio tours of their school and community. The author argues that the soundwalk is a perfect opportunity for students within secondary general music courses to be creative in new ways and to share their work with peers, parents, and other community members. The process for creating a soundwalk is outlined and a resources section includes links to examples and further reading.
Primary Care Physicians’ Prevention Counseling With Patients With Multiple Morbidity
Authors: Bardach Shoshana H. , Schoenberg Nancy E.
Published: August 2012

The prevalence of multiple health conditions, or multiple morbidity (MM), is increasing. Providing medical care for adults with MM presents challenges, including balancing disease management with prevention. We conducted in-depth semistructured interviews with 12 primary care physicians to explore their perspectives on prevention counseling among patients with MM. Participants described the complex relationship between disease management and prevention, highlighted the importance of patient motivation, and discussed various strategies to promote receptivity to prevention recommendations. The perceived potential benefits of prevention recommendations encouraged physicians to persist with such counseling, despite challenges presented by visit time constraints, reimbursement procedures, and concerns over futility. Physicians recommended the development of alternate care delivery and reimbursement models to overcome challenges of the existing health care system and to meet the prevention needs of patients with MM. We explore the implications of these findings for maximizing the health and quality of life of adults with MM.
Waiting for the Barbarians: disciplinary devices on Metro de Santiago
Authors: Ureta Sebastian
Published: August 2012

Bodies are currently recognized as central to organizations. However, until now certain kinds of bodies have remained largely outside the concerns of organization studies, especially the ones of the human beings who use the products/services provided by organizations. Using a conceptual framework that mixes elements of Foucault’s developments on discipline and science and technology studies, this article attempts to contribute to filling this void by proposing to see the management of these bodies as a matter of performing disciplinary devices, understanding them as sociotechnical devices designed with the explicit aim of disciplining users’ bodies in accordance with certain predetermined programs or plans. In order to explore the empirical validity of this conceptualization, the article will study the performance of disciplinary devices by Metro de Santiago, Santiago de Chile’s underground railway, during preparations for a substantive increase in the number of daily users. Making a historical genealogy based on interviews with involved actors and document analysis, the article demonstrates disciplinary devices as always existing in a double way: as inscriptions of future users that the involved actors develop during the design phase and as incorporations when human beings have to start behaving in certain ways to deal with the organization. In the daily management of such disciplinary devices, never absent of conflict and resistances, lies a central way in which organizations exerts power over human bodies.
Corporate social responsibility and the parameters of dialogue with vulnerable others
Authors: Mayes Robyn , Pini Barbara , McDonald Paula
Published: August 2012

This article presents a case study of corporate dialogue with vulnerable others. Dialogue with marginalized external groups is increasingly presented in the business literature as the key to making corporate social responsibility possible in particular through corporate learning. Corporate public communications at the same time promote community engagement as a core aspect of corporate social responsibility. This article examines the possibilities for and conditions underpinning corporate dialogue with marginalized stakeholders as occurred around the unexpected and sudden closure in January 2009 of the AU$2.2 billion BHP Billiton Ravensthorpe Nickel mine in rural Western Australia. In doing so we draw on John Roberts’ notion of dialogue with vulnerable others, and apply a discourse analysis approach to data spanning corporate public communications and interviews with residents affected by the decision to close the mine. In presenting this case study we contribute to the as yet limited organizational research concerned directly with marginalized stakeholders and argue that corporate social responsibility discourse and vulnerable other dialogue not only affirms the primacy of business interests but also co-opts vulnerable others in the pursuit of these interests. In conclusion we consider case study implications for critical understandings of corporate dialogue with vulnerable others.
Finding out what’s happened: Two procedures for opening emergency calls
Authors: Cromdal Jakob , Landqvist Håkan , Persson-Thunqvist Daniel , Osvaldsson Karin
Published: August 2012

This article examines two corpora of telephone calls to the Swedish emergency services SOS-Alarm. The focus of analysis is on the procedural consequentiality of the routine opening by the operator. In the first corpus, the summons are answered by identification of the service via the emergency number. In the second corpus, the protocol has been altered, such that the opening entails the emergency number combined with a standard query concerning the nature of the incident. Through sequential and categorial analysis of the two collections, we highlight the distinct trajectories of action ensuing from the two opening protocols. The stand-alone emergency number opening typically results in callers asking for a specific service. In contrast, opening turns that end with a direct query about the incident tend to solicit brief descriptions of the trouble. We discuss the benefits of the latter procedure in terms of topical progression and institutional relevance, proposing that the work of emergency assistance agencies worldwide might consider implementing opening routines with a similar design.
The use of interactional metadiscourse in job postings
Authors: Fu Xiaoli
Published: August 2012

Interactional metadiscourse resources in various contexts have gained increasing attention recently. However, little work has ever been done in investigating the use of interactional metadiscourse in job postings. Based on Hyland’s (2005a, 2005b) model, I propose the taxonomy of interactional metadiscourse which consists of two broad categories: stance features and engagement features, and seven sub-categories: hedges, boosters, attitude markers, self-mentions, reader-inclusive pronouns, questions and directives. Drawing on a detailed analysis of 220 job postings totaling about 77,100 words, together with 30 informants’ feedback of the attitude toward the use of interactional metadiscourse, the article explores the ways in which the writer interacts with the reader via interactional metadiscourse in this genre. The study has yielded some interesting results: in job postings, the occurrences of stance markers and engagement markers are close in frequency; within the genre, two sub-corpora of job postings (one is oriented to college students and the other is not) have demonstrated remarkable differences in terms of interactional metadiscourse use. Moreover, a distinction is made between macro-interactional metadiscourse and micro-interactional metadiscourse, which is useful in evaluating the interactionality of the text.
Subgroup Analysis of US and Non-US Patients in a Global Study of High-Dose Donepezil (23 mg) in Moderate and Severe Alzheimer’s Disease
Authors: Salloway Stephen , Mintzer Jacobo , Cummings Jeffrey L. , Geldmacher David , Sun Yijun , Yardley Jane , Mackell Joan
Published: August 2012

To better understand responses in the large number of US-based patients included in a global trial of donepezil 23 mg/d versus 10 mg/d for moderate-to-severe Alzheimer’s disease (AD), post hoc exploratory analyses were performed to assess the efficacy and safety in US and non-US (rest of the world [RoW]) patient subgroups. In both subgroups, donepezil 23 mg/d was associated with significantly greater cognitive benefits than donepezil 10 mg/d. Significant global function benefits of donepezil 23 mg/d over 10 mg/d were also observed in the US subgroup only. Compared with RoW patients, US patients had relatively more severe AD, had been treated with donepezil 10 mg/d for longer periods prior to the start of the study, and a higher proportion took concomitant memantine. In both subgroups, donepezil had acceptable tolerability; overall incidence of treatment-emergent adverse events was higher in patients receiving donepezil 23 mg/d compared with donepezil 10 mg/d.
Contribution of Brain Imaging to the Understanding Of Gait Disorders in Alzheimer’s Disease
Authors: Annweiler Cédric , Beauchet Olivier , Celle Sébastien , Roche Frédéric , Annweiler Thierry , Allali Gilles , Bartha Robert , Montero-Odasso Manuel
Published: August 2012

Although gait disorders are common in Alzheimer’s disease (AD), determining which brain structures and related lesions are specifically involved is a goal yet to be reached. Our objective was to systematically review all published data that examined associations between gait disorders and brain imaging in AD. Of 486 selected studies, 4 observational studies met the selection criteria. The number of participants ranged from 2 to 61 community dwellers (29%-100% female) with prodromal or dementia-stage AD. Quantitative gait disorders (ie, slower gait velocity explained by shorter stride length) were associated with white matter lesions, mainly in the medial frontal lobes and basal ganglia. The nigrostriatal dopamine system was unaffected. Qualitative gait disorders (ie, higher stride length variability) correlated with lower hippocampal volume and function. Gait disorders in AD could be explained by a high burden of age-related subcortical hyperintensities on the frontal–subcortical circuits (nonspecific) together with hippocampal atrophy and hypometabolism (specific).
New technique of self-refilling friction stir welding to repair keyhole
Authors: Zhou L , Liu D , Nakata K , Tsumura T , Fujii H , Ikeuchi K , Michishita Y , Fujiya Y , Morimoto M
Published: August 2012

A new technique of self-refilling friction stir welding (SRFSW) relying on non-consumable joining tool has been developed to repair the keyhole left at the end of 316L stainless steel friction stir welding/friction stir processing (FSW/FSP) seam. The conventional FSW process was transformed by adopting a series of non-consumable tools with gradual change in geometry to create a solid state refilled joint step by step. Using the combined plastic deformation and flow of the material around the keyhole, the SRFSW process is able to repair the keyhole with both metallurgical and mechanical bonding characteristics, and the FSW/FSP seam can be achieved without keyhole or other obvious macro defects. Microstructural observation results showed that the grains in the refilled zone were significantly refined by the tool. Tensile test results showed the refilled joint fractured at the base metal side, and the relative tensile strength and elongation are 112 and 82% of the base metal respectively. Moreover, no sigma phase but few Cr carbides were found in the refilled zone, which would not result in obvious corrosion resistance degradation of 316L stainless steel.
Fluvastatin inhibits FLT3 glycosylation in human and murine cells and prolongs survival of mice with FLT3/ITD leukemia
Authors: Williams Allen B. , Li Li , Nguyen Bao , Brown Patrick , Levis Mark , Small Donald
Published: August 2012

FLT3 is frequently mutated in acute myeloid leukemia (AML), but resistance has limited the benefit of tyrosine kinase inhibitors (TKI). We demonstrate that statins can impair FLT3 glycosylation, thus leading to loss of surface expression and induction of cell death, as well as mitigation of TKI resistance. Immunofluorescence microscopy confirms a reduction in surface localization and an increase in intracellular FLT3/internal tandem duplication (ITD) accumulation. This aberrant localization was associated with increased STAT5 activation but inhibition of both MAPK and AKT phosphorylation. Growth inhibition studies indicate that FLT3/ITD-expressing cells were killed with an IC50 within a range of 0.2-2μM fluvastatin. Several mechanisms of resistance could be circumvented by fluvastatin treatment. An increase in the IC50 for inhibition of phosphorylated FLT3/ITD by lestaurtinib caused by exogenous FLT3 ligand, resistance to sorafenib caused by the D835Y or FLT3/ITD N676K mutations, and activation of the IL-3 compensatory pathway were all negated by fluvastatin treatment. Finally, fluvastatin treatment in vivo reduced engraftment of BaF3 FLT3/ITD cells in Balb/c mice. These results demonstrate that statins, a class of drugs already approved by the US Food and Drug Administration, might be repurposed for the management of FLT3 mutant acute myeloid leukemia cases either alone or in conjunction with FLT3 TKI.
Biphenotypic B-lymphoid/myeloid cells expressing low levels of Pax5: potential targets of BAL development
Authors: Simmons Szandor , Knoll Marko , Drewell Christopher , Wolf Ingrid , Mollenkopf Hans-Joachim , Bouquet Corinne , Melchers Fritz
Published: August 2012

The expression of Pax5 commits common lymphoid progenitor cells to B-lymphoid lineage differentiation. Little is known of possible variations in the levels of Pax5 expression and their influences on hematopoietic development. We have developed a retroviral transduction system that allows for the study of possible intermediate stages of this commitment by controlling the levels of Pax5 expressed in Pax5-deficient progenitors in vitro and in vivo. Retroviral transduction of Pax5-deficient pro-/pre-B cell lines with a doxycycline-inducible (TetON) form of the human Pax5 (huPax5) gene yielded cell clones that could be induced to different levels of huPax5 expression. Clones inducible to high levels developed B220+/CD19+/IgM+ B cells, while clones with low levels differentiated to B220+/CD19−/CD11b+/Gr-1− B-lymphoid/myeloid biphenotypic cells in vitro and in vivo. Microarray analyses of genes expressed at these lower levels of huPax5 identified C/ebpα, C/ebpδ, Pu.1, Csf1r, Csf2r, and Gata-3 as myeloid-related genes selectively expressed in the pro-/pre-B cells that can develop under myeloid/lymphoid conditions to biphenotypic cells. Therefore, reduced expression of huPax5 during the induction of early lymphoid progenitors to B-lineage–committed cells can fix this cellular development at a stage that has previously been seen during embryonic development and in acute lymphoblastic lymphoma–like biphenotypic acute leukemias.
Mechanism of platelet dense granule biogenesis: study of cargo transport and function of Rab32 and Rab38 in a model system
Authors: Ambrosio Andrea L. , Boyle Judith A. , Di Pietro Santiago M.
Published: August 2012

Dense granules are important in platelet aggregation to form a hemostatic plug as evidenced by the increased bleeding time in mice and humans with dense granule deficiency. Dense granules also are targeted by antiplatelet agents because of their role in thrombus formation. Therefore, the molecular understanding of the dense granule and its biogenesis is of vital importance. In this work, we establish a human megakaryocytic cell line (MEG-01) as a model system for the study of dense granule biogenesis using a variety of cell biology and biochemical approaches. Using this model system, we determine the late endocytic origin of these organelles by colocalization of the internalized fluid phase marker dextran with both mepacrine and transmembrane dense granule proteins. By mistargeting of mutant dense granule proteins, we demonstrate that sorting signals recognized by adaptor protein-3 are necessary for normal transport to dense granules. Furthermore, we show that tissue-specific Rab32 and Rab38 are crucial for the fusion of vesicles containing dense granule cargo with the maturing organelle. This work sheds light on the biogenesis of dense granules at the molecular level and opens the possibility of using this powerful model system for the investigation of new components of the biogenesis machinery.
Dissection of two soybean QTL conferring partial resistance to Phytophthora sojae through sequence and gene expression analysis
Authors: Wang Hehe , Wijeratne Asela , Wijeratne Saranga , Lee Sungwoo , Taylor Christopher G , St Martin Steven K , McHale Leah , Dorrance Anne E
Published: August 2012

Background

Phytophthora sojae is the primary pathogen of soybeans that are grown on poorly drained soils. Race-specific resistance to P. sojae in soybean is gene-for-gene, although in many areas of the US and worldwide there are populations that have adapted to the most commonly deployed resistance to P. sojae ( Rps) genes. Hence, this system has received increased attention towards identifying mechanisms and molecular markers associated with partial resistance to this pathogen. Several quantitative trait loci (QTL) have been identified in the soybean cultivar ‘Conrad’ that contributes to the expression of partial resistance to multiple P. sojae isolates.

Results

In this study, two of the Conrad QTL on chromosome 19 were dissected through sequence and expression analysis of genes in both resistant (Conrad) and susceptible (‘Sloan’) genotypes. There were 1025 single nucleotide polymorphisms (SNPs) in 87 of 153 genes sequenced from Conrad and Sloan. There were 304 SNPs in 54 genes sequenced from Conrad compared to those from both Sloan and Williams 82, of which 11 genes had SNPs unique to Conrad. Eleven of 19 genes in these regions analyzed with qRT-PCR had significant differences in fold change of transcript abundance in response to infection with P. sojae in lines with QTL haplotype from the resistant parent compared to those with the susceptible parent haplotype. From these, 8 of the 11 genes had SNPs in the upstream, untranslated region, exon, intron, and/or downstream region. These 11 candidate genes encode proteins potentially involved in signal transduction, hormone-mediated pathways, plant cell structural modification, ubiquitination, and basal resistance.

Conclusions

These findings may indicate a complex defense network with multiple mechanisms underlying these two soybean QTL conferring resistance to P. sojae. SNP markers derived from these candidate genes can contribute to fine mapping of QTL and marker assisted breeding for resistance to P. sojae.
Identification and analysis of pig chimeric mRNAs using RNA sequencing data
Authors: Ma Lei , Yang Shulin , Zhao Weiming , Tang Zhonglin , Zhang Tingting , Li Kui
Published: August 2012

Background

Gene fusion is ubiquitous over the course of evolution. It is expected to increase the diversity and complexity of transcriptomes and proteomes through chimeric sequence segments or altered regulation. However, chimeric mRNAs in pigs remain unclear. Here we identified some chimeric mRNAs in pigs and analyzed the expression of them across individuals and breeds using RNA-sequencing data.

Results

The present study identified 669 putative chimeric mRNAs in pigs, of which 251 chimeric candidates were detected in a set of RNA-sequencing data. The 618 candidates had clear trans-splicing sites, 537 of which obeyed the canonical GU-AG splice rule. Only two putative pig chimera variants whose fusion junction was overlapped with that of a known human chimeric mRNA were found. A set of unique chimeric events were considered middle variances in the expression across individuals and breeds, and revealed non-significant variance between sexes. Furthermore, the genomic region of the 5′ partner gene shares a similar DNA sequence with that of the 3′ partner gene for 458 putative chimeric mRNAs. The 81 of those shared DNA sequences significantly matched the known DNA-binding motifs in the JASPAR CORE database. Four DNA motifs shared in parental genomic regions had significant similarity with known human CTCF binding sites.

Conclusions

The present study provided detailed information on some pig chimeric mRNAs. We proposed a model that trans-acting factors, such as CTCF, induced the spatial organisation of parental genes to the same transcriptional factory so that parental genes were coordinatively transcribed to give birth to chimeric mRNAs.
Analysis of a comprehensive dataset of diversity generating retroelements generated by the program DiGReF
Authors: Schillinger Thomas , Lisfi Mohamed , Chi Jingyun , Cullum John , Zingler Nora
Published: August 2012

Background

Diversity Generating Retroelements (DGRs) are genetic cassettes that can introduce tremendous diversity into a short, defined region of the genome. They achieve hypermutation through replacement of the variable region with a strongly mutated cDNA copy generated by the element-encoded reverse transcriptase. In contrast to “selfish” retroelements such as group II introns and retrotransposons, DGRs impart an advantage to their host by increasing its adaptive potential. DGRs were discovered in a bacteriophage, but since then additional examples have been identified in some bacterial genomes.

Results

Here we present the program DiGReF that allowed us to comprehensively screen available databases for DGRs. We identified 155 DGRs which are found in all major classes of bacteria, though exhibiting sporadic distribution across species. Phylogenetic analysis and sequence comparison showed that DGRs move between genomes by associating with various mobile elements such as phages, transposons and plasmids. The DGR cassettes exhibit high flexibility in the arrangement of their components and easily acquire additional paralogous target genes. Surprisingly, the genomic data alone provide new insights into the molecular mechanism of DGRs. Most notably, our data suggest that the template RNA is transcribed separately from the rest of the element.

Conclusions

DiGReF is a valuable tool to detect DGRs in genome data. Its output allows comprehensive analysis of various aspects of DGR biology, thus deepening our understanding of the role DGRs play in prokaryotic genome plasticity, from the global down to the molecular level.
Autophagy and apoptosis-related genes in chronic liver disease and hepatocellular carcinoma
Authors: Kotsafti Andromachi , Farinati Fabio , Cardin Romilda , Cillo Umberto , Nitti Donato , Bortolami Marina
Published: August 2012

Background

Dysregulation of autophagy is important in the pathogenesis of many diseases, including cancer. Several aspects of the biological role of autophagy are however still unclear and the relationship between apoptosis and autophagy, particularly in the liver has yet to be thoroughly explored. In this study we evaluated the expression of Beclin 1 (one of the main autophagocytic agents, which bridges autophagy, apoptosis and both differentiation), and both pro- (Bad, Bax) and anti-apoptotic (Bcl-2, Bcl-xL) factors in liver samples from patients with different stages of liver disease.

Methods

The study concerned 93 patients from 49 cases of chronic hepatitis (CH) (30 HCV and 19 HBV-related), 13 of cirrhosis (CIRR) (10 HCV and 3 HBV-related), 21 of hepatocellular carcinoma (both HCC and peritumoral tissues [PHCC]), and 10 controls (CONTR). Real-time PCR and Western blotting were used to measure mRNA and protein expression levels.

Results

Beclin 1 mRNA levels were lower in HCC than in CH (P = 0.010) or CIRR (P = 0.011), and so were the Bcl-xL transcripts (P < 0.0001). Bad mRNA levels were higher in CH and CIRR than in CONTR, while Bax transcripts were increased in all tissues (P = 0.036). PHCC expressed the highest Bcl-2 mRNA levels. HBV-related CH tissues showed significantly higher Bcl-xL and Bad mRNA levels than HCV-related CH (P = 0.003 and P = 0.016, respectively).

Conclusions

High Beclin 1, Bcl-xL and Bad levels in CH and CIRR tissues suggest an interaction between autophagy and apoptosis in the early and intermediate stages of viral hepatitis. In HCC these processes seem to be downregulated, probably enabling the survival and growth of neoplastic hepatocytes.
Actinobaculum schaalii an emerging pediatric pathogen?
Authors: Zimmermann Petra , Berlinger Livia , Liniger Benjamin , Grunt Sebastian , Agyeman Philipp , Ritz Nicole
Published: August 2012

Background

Actinobaculum schaalii was first described as a causative agent for human infection in 1997. Since then it has mainly been reported causing urinary tract infections (UTI) in elderly individuals with underlying urological diseases. Isolation and identification is challenging and often needs molecular techniques. A. schaalii is increasingly reported as a cause of infection in humans, however data in children is very limited.

Case presentation

We present the case of an 8-month-old Caucasian boy suffering from myelomeningocele and neurogenic bladder who presented with a UTI. An ultrasound of the urinary tract was unremarkable. Urinalysis and microscopy showed an elevated leukocyte esterase test, pyuria and a high number of bacteria. Empiric treatment with oral co-trimoxazole was started.

Growth of small colonies of Gram-positive rods was observed after 48 h. Sequencing of the 16S rRNA gene confirmed an A. schaalii infection 9 days later. Treatment was changed to oral amoxicillin for 14 days. On follow-up urinalysis was normal and urine cultures were negative.

Conclusions

A.schaalii is an emerging pathogen in adults and children. Colonization and subsequent infection seem to be influenced by the age of the patient. In young children with high suspicion of UTI who use diapers or in children who have known abnormalities of their urogenital tract, infection with A. schaalii should be considered and empiric antimicrobial therapy chosen accordingly.
Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone
Authors: van Oosterwijk Jolieke G , de Jong Danielle , van Ruler Maayke AJH , Hogendoorn Pancras CW , Dijkstra PD Sander , van Rijswijk Carla SP , Machado Isidro , Llombart-Bosch Antonio , Szuhai Karoly , Bovée Judith VMG
Published: August 2012

Background

Chondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce.

Methods

We developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential.

Results

We show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type.

Conclusions

Based on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies.
Pain and stress assessment after retinopathy of prematurity screening examination: Indirect ophthalmoscopy versus digital retinal imaging
Authors: Moral-Pumarega M Teresa , Caserío-Carbonero Sonia , De-La-Cruz-Bértolo Javier , Tejada-Palacios Pilar , Lora-Pablos David , Pallás-Alonso Carmen R
Published: August 2012

Background

Increasingly, neonatal clinics seek to minimize painful experiences and stress for premature infants. Fundoscopy performed with a binocular indirect ophthalmoscope is the reference examination technique for screening of retinopathy of prematurity (ROP), and it is associated with pain and stress. Wide-field digital retinal imaging is a recent technique that should be evaluated for minimizing infant pain and stress.

Methods

The purpose of the study was to assess and compare the impact of using a binocular indirect ophthalmoscope (BIO), or wide-field digital retinal imaging (WFDRI) on pain and stress in infants undergoing ROP screening examination. This was a comparative evaluation study of two screening procedures. Ophthalmologic examinations (N = 70) were performed on 24 infants with both BIO and WFDRI. Pain assessments were performed with two specific neonatal scales (Crying, requires oxygen, increased vital signs, expression and sleeplessness, CRIES and, Premature infant pain profile, PIPP) just prior to the examination, and 30 seconds, 1 hour, and 24 hours later after ending the examination.

Results

Changes over time were significantly different between BIO and WFDRI with both scales (PIPP score, p = .007, and CRIES score, p = .001). Median PIPP score (interquartile interval) at baseline was 4 (3–5). At 30 seconds the score was 8 (6–9) for BIO and 6 (5–7) for WFDRI, respectively. The increase in PIPP score between baseline and 30 seconds was significantly lower with WFDRI (p = .006). The median increase in CRIES score from baseline to 30 seconds was 1 point lower for WFDRI than for BIO (p < .001). No significant difference in response remained at 1 hour or 24 hour assessments.

Conclusions

A transient short-term pain and stress response occurs with both BIO and WFDRI. Infants examined for screening of ROP with digital retinal imaging present less pain and stress at 30 seconds following completion of the exam when compared with binocular indirect ophthalmoscopy.
A first national survey of knowledge, attitudes and behaviours towards schizophrenia, bipolar disorders and autism in France
Authors: Durand-Zaleski Isabelle , Scott Jan , Rouillon Frédéric , Leboyer Marion
Published: August 2012

Background

In order to support evidence-based policies for reduction of stigma, a better understanding of its components: ignorance (knowledge), prejudice (attitude) and discrimination (behaviour) is necessary. This study explores public perceptions and quantifies stigma for three chronic mental disorders: autism, schizophrenia and bipolar disorders in France.

Methods

Survey of 1000 adults selected from an established market research panel. The 21-item questionnaire explored knowledge, attitudes and behaviours toward each disorder.

Results

Although 95% respondents recognized the names of each disorder fewer than 70% could report specific characteristics and only 33% considered that publically available information was adequate; most respondents identified the media as their main resource. Labeling of conditions in a negative way was frequent (61%) when referring to mental disorders in general, but fell significantly (18%) when linked to an individual with a disorder. Individuals with schizophrenia are assumed to be dangerous; 65% respondents would engage in social distancing from such an individual, versus 29% for bipolar disorders and 7% for autism (p < 0.001). In contrast to other disorders, discrimination against schizophrenia was only partly attenuated in those with familiarity with mental disorders (through personal or family illness).

Conclusion

This first population-based survey in France shows that attitudes towards bipolar disorders and autism are less prejudicial than towards schizophrenia. However, most public attitudes and behaviours towards different disorders appear to be based on assumptions rather than knowledge or evidence suggesting a generic information or anti-stigma programme is unlikely to be effective.