bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Primary Pelvic Organ Prolapse to Micturition and Defecation Symptoms
Authors: Groenendijk Annette G. , Birnie Erwin , Roovers Jan-Paul W. , Bonsel Gouke J.
Published: September 2011

Objective. To investigate the contribution of Pelvic Organ Prolapse (POP) to micturition and defecation symptoms.Method. Cross-sectional study including 64 women presenting with POP symptoms and 50 controls without POP complaints. Subjects were evaluated using POP-Quantification system, Urinary Distress Inventory, and Defecation Distress Inventory. The MOS SF-36 health survey and the Center for Epidemiological Studies Depression scale were used to measure self-perceived health status and depressive symptoms, respectively.Results. POP in terms of POP-Q had a moderate impact on the symptom observing vaginal protrusion (explained variance 0.31). It contributed modestly to obstructive voiding and overactive bladder symptoms (explained variance 0.09, resp., 0.14) but not to urinary incontinence. Constipation was more likely explained by clinical depression than by pelvic floor defects (explained variance 0.13, resp., 0.05).Conclusion. Stage of POP and specific prolapse symptoms are associated but such a strong association does not exist between POP and micturition or defecation symptoms.
Effect of ISPAD Anaerobic Digestion on Ammonia Volatilization from Soil Applied Swine Manure
Authors: King Susan , Schwalb Michael , Giard David , Whalen Joann , Barrington Suzelle
Published: September 2011

Swine manure subjected to in-storage psychrophilic anaerobic digestion (ISPAD) undergoes proteins degradation but limited NH3volatilization, producing an effluent rich in plant-available nitrogen. Accordingly, ISPAD effluent can offer a higher fertilizer value during land application, as compared to manure of similar age stored in an open tank. However, this additional nitrogen can also be lost by volatilization during land application. The objective of this study was therefore to measure NH3volatilization from both ISPAD and open tank swine manures when applied to 5 different soils, namely, washed sand, a Ste Rosalie clay, an Upland sandy loam, a St Bernard loam, and an Ormstown loam. This research was conducted using laboratory wind tunnels simulating land application. The five experimental soils offered similar pH values but different water holding capacity, cation exchange capacity, cation saturation, and organic matter. After 47 h of wind tunnel monitoring, the % of total available nitrogen (TAN orNH4 +and NH3) volatilized varied with both manure and soil type. For all soil types, the ISPAD manure consistently lost less NH3as compared to the open tank manure, averaging 53% less. Lower volatile solids content improving manure infiltration into the soil and a more complex ionic solution explain the effect of the ISPAD manure advantages. This was reinforced by the St Bernard sandy loam losing the same nitrogen mass for both manures, because of its higher pH and buffer pH coupled with an intermediate CEC resulting in more soil solution NH3. Within each manure type, % TAN volatilized was highest for washed sand and lowest for the clay soil. As a result, ISPAD manure can offer up to 21% more plant-available nitrogen fertilizer especially when the manure is not incorporated into the soil following its application.
Development of Novel Corrosion Techniques for a Green Environment
Authors: Ahmad Zaki , Patel Faheemuddin
Published: September 2011

The synergistic effect of air pollution, brown clouds and greenhouse gasses is deleterious to human health and industrial products. The use of toxic inhibitors, chemicals in water treatment plants, and anti-fouling agents in desalination plants has contributed to the greenhouse effect. Conventional anti-corrosion techniques such as paints, coatings, inhibitor treatments, and cathodic protection paid no regard to greenhouse effect. Work on eco-friendly anti-corrosion techniques is scanty and largely proprietary. The use of nano-TiO2particles introduced in alkyds and polyurethane-based coatings showed a higher corrosion resistance compared to conventional TiO2coatings with significant photocatalytic activity to kill bacteria. The use of UV radiations for photo-inhibition of stainless steel in chloride solution can replace toxic inhibitors. Corrosion inhibition has also been achieved by using natural materials such as polymers instead of toxic chemical inhibitors, without adverse environmental impact. TiO2films exposed to UV radiation have shown the capability to protect the steel without sacrificing the film. Self-healing materials with encapsulated nanoparticles in paints and coatings have shown to heal the defects caused by corrosion. These innovative techniques provide a direction to the corrosion scientists, engineers, and environmentalists who are concerned about the increasing contamination of the planet and maintaining a green environment.
Biomaterials to Enhance Stem Cell Function in the Heart
Authors: Segers Vincent F.M. , Lee Richard T.
Published: September 2011

Transplantation of stem cells into the heart can improve cardiac function after myocardial infarction and in chronic heart failure, but the extent of benefit and of reproducibility of this approach are insufficient. Survival of transplanted cells into myocardium is poor, and new strategies are needed to enhance stem cell differentiation and survival in vivo. In this review, we describe how biomaterials can enhance stem cell function in the heart. Biomaterials can mimic or include naturally occurring extracellular matrix and also instruct stem cell function in different ways. Biomaterials can promote angiogenesis, enhance engraftment and differentiation of stem cells, and accelerate electromechanical integration of transplanted stem cells. Biomaterials can also be used to deliver proteins, genes, or small RNAs together with stem cells. Furthermore, recent evidence indicates that the biophysical environment of stem cells is crucial for their proliferation and differentiation, as well as their electromechanical integration. Many approaches in regenerative medicine will likely ultimately require integration of molecularly designed biomaterials and stem cell biology to develop stable tissue regeneration.
Doctrine for Cybersecurity
Authors: Mulligan Deirdre K. , Schneider Fred B.
Published: September 2011

A succession of doctrines for enhancing cybersecurity has been advocated in the past, including prevention, risk management, and deterrence through accountability. None has proved effective. Proposals that are now being made view cybersecurity as a public good and adopt mechanisms inspired by those used for public health. This essay discusses the failings of previous doctrines and surveys the landscape of cybersecurity through the lens that a new doctrine, public cybersecurity, provides.
Moist Hadley Circulation: Possible Role of Wave–Convection Coupling in Aquaplanet Experiments
Authors: Horinouchi Takeshi
Published: September 2011

Aquaplanet simulations for a given sea surface temperature (SST) are conducted to elucidate possible roles of transient variability in the Hadley circulation and the intertropical convergence zone (ITCZ). Their roles are best illustrated with globally uniform SSTs. For such SSTs, an ITCZ and a Hadley circulation that are nearly equatorially symmetric emerge spontaneously. Their strength varies over a wide range from being faint to climatologically significant depending on a tunable parameter of the model’s cumulus parameterization. In some cases asymmetric Hadley circulations formed along with long-lived tropical cyclones.

The tunable parameter affects the transient variability of tropical precipitation. In the runs in which well-defined near-symmetric ITCZs formed, tropical precipitation exhibited clear signatures of convectively coupled equatorial waves. The waves can explain the concentration of precipitation to the equatorial region, which induces the Hadley circulation. Also, the meridional structures of simulated ITCZs are consistent with the distribution of convergence/divergence associated with dominant equatorial wave modes.

Even when the pole–equator temperature gradient is introduced, the dependence of the strength of the circulation to transient disturbances remains. Therefore, transient variability may have a broader impact on tropical climate and its numerical modeling than has been thought.

The reason that a wide variety of circulation is possible when the SST gradient is weak is because the distribution of latent heating can be interactively adjusted while a circulation is formed. Angular momentum budget does not provide an effective thermodynamic constraint, since baroclinic instability redistributes the angular momentum.
Dynamic Testing, Working Memory, and Reading Comprehension Growth in Children With Reading Disabilities
Authors: Lee Swanson H.
Published: September 2011

This longitudinal study assessed (a) whether performance changes in working memory (WM) as a function of dynamic testing were related to growth in reading comprehension and (b) whether WM performance among subgroups of children with reading disabilities (RD; children with RD only, children with both reading and arithmetic deficits, and low verbal IQ readers) varied as a function of dynamic testing. A battery of memory and reading measures was administered to 78 children (11.6 years) across three testing waves spaced 1 year apart. WM tasks were presented under initial and dynamic testing conditions (referred to as gain and maintenance testing). The important results were that (a) WM performance as a function of maintenance testing was a significant moderator of growth in reading comprehension and (b) WM performance of children with RD was statistically comparable within subgroups of RD but inferior to that of skilled readers across all testing conditions. The results support the notion that children’s WM performance under dynamic testing conditions was related to the rate of growth in reading comprehension but unrelated to subgroup differences in reading.
Clinical Pharmacology Basis of Deriving Dosing Recommendations for Dabigatran in Patients With Severe Renal Impairment
Authors: Hariharan Sudharshan , Madabushi Rajanikanth
Published: September 2011

The objective of this work was to derive a dosing regimen for dabigatran in patients with severe renal impairment by modeling and simulation. Data from a dedicated renal impairment study were used to model the pharmacokinetics of dabigatran in normal and renal‐impaired subjects. Model parameters were used to simulate the average concentration time‐course of dabigatran following various dosing regimens. Pharmacokinetics of dabigatran in normal and renal‐impaired subjects were best described by a 2‐compartment open model with first‐order absorption and elimination. Simulations were performed to select an appropriate regimen that reasonably matched the exposures on an average with those observed in subjects with moderate renal impairment who did not require a dose adjustment because of a favorable benefit‐risk. Dabigatran 150 mg given once daily resulted in 35% higher average Cmax,ss, whereas a 75 mg once daily regimen resulted in 42% lower average Cτ, relative to that observed with 150 mg administered twice daily in subjects with moderate renal impairment. A twice daily regimen of dabigatran 75 mg resulted in a reasonable matching of exposures and was selected as an appropriate dosing regimen in patients with severe renal impairment. This recommendation was incorporated in the dosing and recommendation section of dabigatran product insert.
Content analysis of School Psychology International, 1990–2011: An analysis of trends and compatibility with the NASP Practice Model
Authors: Little Steven G. , Akin-Little Angeleque , Lloyd Keryn
Published: September 2011

Formal analysis of research publications serves as one indicator of the current status of a profession or a journal. Content analyses provide both practitioners and academicians with information on the status of research in the profession. These types of analyses can also provide information on the concordance between published research and what professional organizations consider key areas of practice. The current study examined articles published in one journal, School Psychology International, for a 22-year period from 1990 through 2011 ( n = 671 articles). All articles were coded for demographics of the author, including country of origin and level of international content, and the content matching categories found in the NASP Model for Comprehensive and Integrated School Psychological Services. Results indicated that the journal is very much international with authors coming from 57 countries. With regard to gender, a trend was noticed for increased participation by women. Finally, the analysis of content found a pattern that was not highly consistent with the categories identified by NASP. Factors contributing to the lack of consistency between research and areas of practice are discussed.
Frogs and Ponds
Authors: Pierro Antonio , Presaghi Fabio , Higgins E. Tory , Klein Kristen M. , Kruglanski Arie W.
Published: September 2011

Regulatory mode is a psychological construct pertaining to the self-regulatory orientation of individuals or teams engaged in goal pursuit. Locomotion, the desire for continuous progress or movement in goal pursuit, and assessment, the desire to critically evaluate and compare goals and means, are orthogonal regulatory modes. However, they are also complementary, in that both locomotion and assessment are necessary for effectual goal pursuit. In the present research, the authors sought to demonstrate that multilevel regulatory mode complementarity can positively affect individual-level performance on goal-relevant tasks. The authors recruited 289 employees (177 men, 112 women) from preexisting work teams in workplace organizations in Italy and obtained (a) employees’ individual-level scores on the Regulatory Mode Scale and (b) supervisor ratings of each employee’s work performance. The results supported the multilevel complementarity hypothesis for regulatory mode. Limitations and recommendations for future research are discussed.
Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness
Authors: MacLean Katherine A , Johnson Matthew W , Griffiths Roland R
Published: September 2011

A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality – Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.
Sociodemographic Factors Associated With Self-Reported Exercise and Physical Activity Behaviors and Attitudes of South Australians
Authors: Thomas Susie , Halbert Julie , Mackintosh Shylie , Quinn Stephen , Crotty Maria
Published: September 2011

Objective: To determine self-reported physical activity barriers, behaviors, and beliefs about exercise of a representative sample and to identify associated sociodemographic factors. Method: Face-to-face interviews conducted between September and December 2008, using a random stratified sampling technique. Results: Barriers injury and illness were associated with being older, single, and not engaged in full-time work; lack of time was associated with being married, younger, female, and working full-time; and lack of motivation and cost were associated with being younger than 65 years. Advancing age was significantly associated ( p < .001) with reduced physical activity. Factors including age, education, marital status, and area of residence were all associated with preferences for environment to exercise in, while all age groups (74%) felt that walking was the most important type of exercise for older adults. Discussion Barriers to physical activity participation are multifaceted with different sociodemographic factors associated with different barriers. A better understanding of these factors may improve uptake of and adherence to exercise programs across the ages.
Self-Reported Vision Impairment and Its Contribution to Disability Among Older Adults
Authors: Steinman Bernard A. , Allen Susan M.
Published: September 2011

Objectives: To examine contributions of self-reported vision impairment to disability by persons 65 years and older. Method: We used data from the National Health and Nutrition Examination Survey (NHANES IV; 1999-2008; weighted N = 6,550). The four-staged Nagi model of the disability process, incorporating biomarkers, disease, and physical functioning, was used as a framework to guide variable selection. An unadjusted ordinal logistic regression model testing effects of vision on daily-life activities was compared with models that controlled covariates associated with each stage of the disability model. Results For older adults with vision impairments, effects of poor vision in predicting disability were substantially reduced or eliminated when other health covariates were controlled. Where significant effects of poor vision remained, the strongest effect was found for doing leisure activities at home ( OR = 5.29; 95% CI [3.14, 8.90]). Discussion: Results suggest the importance of considering multiple health factors when formulating comprehensive vision rehabilitation interventions.
With All My Relations: Counseling American Indians and Alaska Natives Within a Familial Context
Authors: Harper Faith G.
Published: September 2011

Statistics show that two thirds of American Indians and Alaska Natives (AIs/ANs) live outside of tribal areas, and 50% of those individuals who seek counseling services will not use tribal resources. There is a strong likelihood that counselors will have the opportunity to provide services to AI/AN clients. The review of the academic literature focused on counseling services for AIs/ANs revealed three primary themes. These themes include issues regarding cultural competency, awareness of different levels of acculturation, and the appropriateness of utilizing Eurocentric counseling theories with AIs/ANs. Perhaps more importantly, these themes often emerge within the context of family and tribal unity. These issues, as well as some general guidelines for counseling indigenous families, are addressed within this article.
Al Ellis: Up Close and Personal
Authors: Eckstein Daniel , Ellis Debbie Joffe
Published: September 2011

The purpose of the following article is to share some of the personal relationship comments and to provide a tribute to the significant 93 years that Albert Ellis lived and also make major contributions to the counseling profession.
Bullying as Intra-active Process in Neoliberal Universities
Authors: Zabrodska Katerina , Linnell Sheridan , Laws Cath , Davies Bronwyn
Published: September 2011

The reformed neoliberal universities, with their micromanagement of ever-increasing productivity, competitiveness, and individualization, have recently been described as unhealthy institutions, creating conditions that incite incivility, workplace bullying, and other forms of employee abuse. In this article, the authors employ collective biography as a form of “diffractive methodology” in order to provide new, theoretically driven insights into workplace bullying in neoliberal universities. Drawing on the concepts of intra-activity and performativity, the authors examine bullying in universities as an intra-active process that informs and is informed by the desire of an individual to be recognized and to perform as a viable academic subject—one who is professional, flexible, and accountable within a neoliberal environment.
Inward, Outward, Onward
Authors: Harris Genevieve
Published: September 2011

This article presents the connection of a personal dissertation process to the wider world of qualitative research. Using the concept of transitional space as a metaphor, the author chronicles her theoretical transition from critical race theory to poststructural theory to emerging questions about material feminism. This transition is mapped to three major qualitative research moments within the field: modernist, crisis of representation, and the future. Autoethnography and found text are used to present the micro- and macro-telling of the dissertation process. White racial identity development among Christian teacher educators at a religious university was the original dissertation focus. Ethical dilemmas that emerged during the data collection process, presenting the researcher with a theoretical crisis, needed to be addressed.
The African diasporic community in contemporary Ireland: Intersections of ascriptive and circumstantial identities
Authors: Ejorh Theophilus
Published: September 2011

African identity has remained a major subject of scholarly debate. Essentialist discourses promote the notion of a unified African identity, whereas historical and situational realities suggest the contrary. This article draws on empirical evidence from a recent doctoral research study to examine the dynamics of African identities in modern-day Ireland. It challenges the essentialist thesis of homogeneity, and argues instead that in the pragmatic context of migration Africans negotiate multidimensional identities and belongings, forced by compelling particularistic experiences and the need to adopt personal strategies for adaptation and inclusion. However, regardless of the tension between personal and collective identities and interests, prospects exist for fellowship within the African immigrant community, based on the sense of common migration from Africa and collective alienation in the host country. These shared characteristics ultimately become a necessary instrument for political and strategic effectiveness in building a viable African political community in Ireland.
‘Sod them, I'm English’: The changing status of the ‘majority’ English in post-devolution Britain
Authors: Skey Michael
Published: September 2011

As well as prompting an urgent reassessment of constitutional and legislative matters, processes of devolution have also contributed to a series of wide-ranging debates on identity in Britain. Yet, outside of survey data and a growing body of work looking to assess the status of minorities in Britain, relatively little has been heard from the wider population. This is particularly true for those who constitute the majority group within Britain, the English. In this paper, I want to offer a complementary perspective by using data from qualitative interviews to explore the ways in which members of the ‘ethnic majority’ in England discuss these issues. The findings suggest a tentative, but noticeable, shift towards an English identity, which is often defined as a necessary response to the increasing assertiveness of ‘other’ national groups within Britain.
‘Walking the line’: Southern Sudanese masculinities and reconciling one's past with the present
Authors: Marlowe Jay M.
Published: September 2011

This paper discusses an ethnographic engagement with Southern Sudanese men and their experiences of resettlement as refugees in Adelaide, Australia. They use the phrase ‘walking the line’ to convey the multiple challenges of reconciling one's past within thepresent contexts of life in a new host country. This geographic metaphor hints at the contested borderlands of masculinity, social relations and raising children that highlight the dynamic complexities related to gender and institutional power. The participant voices provide helpful perspectives on the endeavour of forging one's identity in forced migration and resettlement contexts.
The Diffusion of Innovation in Nursing Regulatory Policy
Authors: Torre Carolyn T. , Crowley Angela A.
Published: September 2011

Safe medication administration is an essential component of high-quality child care. Its achievement in New Jersey was impeded by a controversy over whether teaching child care providers medication administration involves registered nurses in the process of nursing delegation. Through the theoretical framework of the Diffusion of Innovation, this paper examines how the interpretation of regulatory policy related to nursing practice in New Jersey was adjusted by the Board of Nursing following a similar interpretation of regulatory policy by the Board of Nursing in Connecticut. This adjustment enabled New Jersey nurses to continue medication administration training for child care providers. National data supporting the need for training child care providers in medication administration is presented, the Diffusion of Innovation paradigm is described; the Connecticut case and the New Jersey dilemma are discussed; the diffusion process between the two states is analyzed and an assessment of the need for further change is made.
caCORRECT2: Improving the accuracy and reliability of microarray data in the presence of artifacts
Authors: Moffitt Richard A , Yin-Goen Qiqin , Stokes Todd H , Parry R Mitchell , Torrance James H , Phan John H , Young Andrew N , Wang May D
Published: September 2011

Background

In previous work, we reported the development of caCORRECT, a novel microarray quality control system built to identify and correct spatial artifacts commonly found on Affymetrix arrays. We have made recent improvements to caCORRECT, including the development of a model-based data-replacement strategy and integration with typical microarray workflows via caCORRECT's web portal and caBIG grid services. In this report, we demonstrate that caCORRECT improves the reproducibility and reliability of experimental results across several common Affymetrix microarray platforms. caCORRECT represents an advance over state-of-art quality control methods such as Harshlighting, and acts to improve gene expression calculation techniques such as PLIER, RMA and MAS5.0, because it incorporates spatial information into outlier detection as well as outlier information into probe normalization. The ability of caCORRECT to recover accurate gene expressions from low quality probe intensity data is assessed using a combination of real and synthetic artifacts with PCR follow-up confirmation and the affycomp spike in data. The caCORRECT tool can be accessed at the website: http://cacorrect.bme.gatech.edu.

Results

We demonstrate that (1) caCORRECT's artifact-aware normalization avoids the undesirable global data warping that happens when any damaged chips are processed without caCORRECT; (2) When used upstream of RMA, PLIER, or MAS5.0, the data imputation of caCORRECT generally improves the accuracy of microarray gene expression in the presence of artifacts more than using Harshlighting or not using any quality control; (3) Biomarkers selected from artifactual microarray data which have undergone the quality control procedures of caCORRECT are more likely to be reliable, as shown by both spike in and PCR validation experiments. Finally, we present a case study of the use of caCORRECT to reliably identify biomarkers for renal cell carcinoma, yielding two diagnostic biomarkers with potential clinical utility, PRKAB1 and NNMT.

Conclusions

caCORRECT is shown to improve the accuracy of gene expression, and the reproducibility of experimental results in clinical application. This study suggests that caCORRECT will be useful to clean up possible artifacts in new as well as archived microarray data.
Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling
Authors: Doggett Karen , Grusche Felix A , Richardson Helena E , Brumby Anthony M
Published: September 2011

Background

Epithelial neoplasias are associated with alterations in cell polarity and excessive cell proliferation, yet how these neoplastic properties are related to one another is still poorly understood. The study of Drosophila genes that function as neoplastic tumor suppressors by regulating both of these properties has significant potential to clarify this relationship.

Results

Here we show in Drosophila that loss of Scribbled (Scrib), a cell polarity regulator and neoplastic tumor suppressor, results in impaired Hippo pathway signaling in the epithelial tissues of both the eye and wing imaginal disc. scrib mutant tissue overgrowth, but not the loss of cell polarity, is dependent upon defective Hippo signaling and can be rescued by knockdown of either the TEAD/TEF family transcription factor Scalloped or the transcriptional coactivator Yorkie in the eye disc, or reducing levels of Yorkie in the wing disc. Furthermore, loss of Scrib sensitizes tissue to transformation by oncogenic Ras-Raf signaling, and Yorkie-Scalloped activity is required to promote this cooperative tumor overgrowth. The inhibition of Hippo signaling in scrib mutant eye disc clones is not dependent upon JNK activity, but can be significantly rescued by reducing aPKC kinase activity, and ectopic aPKC activity is sufficient to impair Hippo signaling in the eye disc, even when JNK signaling is blocked. In contrast, warts mutant overgrowth does not require aPKC activity. Moreover, reducing endogenous levels of aPKC or increasing Scrib or Lethal giant larvae levels does not promote increased Hippo signaling, suggesting that aPKC activity is not normally rate limiting for Hippo pathway activity. Epistasis experiments suggest that Hippo pathway inhibition in scrib mutants occurs, at least in part, downstream or in parallel to both the Expanded and Fat arms of Hippo pathway regulation.

Conclusions

Loss of Scrib promotes Yorkie/Scalloped-dependent epithelial tissue overgrowth, and this is also important for driving cooperative tumor overgrowth with oncogenic Ras-Raf signaling. Whether this is also the case in human cancers now warrants investigation since the cell polarity function of Scrib and its capacity to restrain oncogene-mediated transformation, as well as the tissue growth control function of the Hippo pathway, are conserved in mammals.
Differential roles of TGIF family genes in mammalian reproduction
Authors: Hu Yanqiu , Yu Hongshi , Shaw Geoff , Renfree Marilyn B , Pask Andrew J
Published: September 2011

Background

TG-interacting factors (TGIFs) belong to a family of TALE-homeodomain proteins including TGIF1, TGIF2 and TGIFLX/Y in human. Both TGIF1 and TGIF2 act as transcription factors repressing TGF-β signalling. Human TGIFLX and its orthologue, Tex1 in the mouse, are X-linked genes that are only expressed in the adult testis. TGIF2 arose from TGIF1 by duplication, whereas TGIFLX arose by retrotransposition to the X-chromosome. These genes have not been characterised in any non-eutherian mammals. We therefore studied the TGIF family in the tammar wallaby (a marsupial mammal) to investigate their roles in reproduction and how and when these genes may have evolved their functions and chromosomal locations.

Results

Both TGIF1 and TGIF2 were present in the tammar genome on autosomes but TGIFLX was absent. Tammar TGIF1 shared a similar expression pattern during embryogenesis, sexual differentiation and in adult tissues to that of TGIF1 in eutherian mammals, suggesting it has been functionally conserved. Tammar TGIF2 was ubiquitously expressed throughout early development as in the human and mouse, but in the adult, it was expressed only in the gonads and spleen, more like the expression pattern of human TGIFLX and mouse Tex1. Tammar TGIF2 mRNA was specifically detected in round and elongated spermatids. There was no mRNA detected in mature spermatozoa. TGIF2 protein was specifically located in the cytoplasm of spermatids, and in the residual body and the mid-piece of the mature sperm tail. These data suggest that tammar TGIF2 may participate in spermiogenesis, like TGIFLX does in eutherians. TGIF2 was detected for the first time in the ovary with mRNA produced in the granulosa and theca cells, suggesting it may also play a role in folliculogenesis.

Conclusions

The restricted and very similar expression of tammar TGIF2 to X-linked paralogues in eutherians suggests that the evolution of TGIF1, TGIF2 and TGIFLX in eutherians was accompanied by a change from ubiquitous to tissue-specific expression. The distribution and localization of TGIF2 in tammar adult gonads suggest that there has been an ultra-conserved function for the TGIF family in fertility and that TGIF2 already functioned in spermatogenesis and potentially folliculogenesis long before its retrotransposition to the X-chromosome of eutherian mammals. These results also provide further evidence that the eutherian X-chromosome has actively recruited sex and reproductive-related genes during mammalian evolution.
B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina
Authors: León de la Fuente Ricardo , Naesgaard Patrycja A , Nilsen Stein Tore , Woie Leik , Aarsland Torbjoern , Gallo Patricio , Grundt Heidi , Staines Harry , Nilsen Dennis WT
Published: September 2011

Background

Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS.

Methods

We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses.

Results

119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively.

The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients.

Conclusion

BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS.

Trial Registration

ClinicalTrials.gov Identifier:NCT01377402.
Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: Comparisons with the normal articular cartilage
Authors: Imabuchi Ryusei , Ohmiya Yoshihiro , Joon Kwon Hyuck , Onodera Shin , Kitamura Nobuto , Kurokawa Takayuki , Ping Gong Jian , Yasuda Kazunori
Published: September 2011

Background

We have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN) hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N, N'-Dimetyl acrylamide), at the bottom of the defect. The purpose of this study was to clarify gene expression profile of the regenerated tissue in comparison with that of the normal articular cartilage.

Methods

We created a cylindrical osteochondral defect in the rabbit femoral grooves. Then, we implanted the DN gel plug at the bottom of the defect. At 2 and 4 weeks after surgery, the regenerated tissue was analyzed using DNA microarray and immunohistochemical examinations.

Results

The gene expression profiles of the regenerated tissues were macroscopically similar to the normal cartilage, but showed some minor differences. The expression degree of COL2A1, COL1A2, COL10A1, DCN, FMOD, SPARC, FLOD2, CHAD, CTGF, and COMP genes was greater in the regenerated tissue than in the normal cartilage. The top 30 genes that expressed 5 times or more in the regenerated tissue as compared with the normal cartilage included type-2 collagen, type-10 collagen, FN, vimentin, COMP, EF1alpha, TFCP2, and GAPDH genes.

Conclusions

The tissue regenerated by using the DN gel was genetically similar but not completely identical to articular cartilage. The genetic data shown in this study are useful for future studies to identify specific genes involved in spontaneous cartilage regeneration.
EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment
Authors: Hu Yuanjie , Pioli Peter Dion , Siegel Eric , Zhang Qinghua , Nelson Jodi , Chaturbedi Abhishek , Mathews Marlon S , Ro Daniel I , Alkafeef Selma , Hsu Nelson , Hamamura Mark , Yu Liping , Hess Kenneth R , Tromberg Bruce J , Linskey Mark E , Zhou Yi-Hong
Published: September 2011

Purpose

There are conflicting reports regarding the function of EFEMP1 in different cancer types. In this study, we sought to evaluate the role of EFEMP1 in malignant glioma biology.

Experimental Design

Real-time qRT-PCR was used to quantify EFEMP1 expression in 95 glioblastoma multiforme (GBM). Human high-grade glioma cell lines and primary cultures were engineered to express ectopic EFEMP1, a small hairpin RNA of EFEMP1, or treated with exogenous recombinant EFEMP1 protein. Following treatment, growth was assayed both in vitro and in vivo (subcutaneous (s.c.) and intracranial (i.c.) xenograft model systems).

Results

Cox regression revealed that EFEMP1 is a favorable prognostic marker for patients with GBM. Over-expression of EFEMP1 eliminated tumor development and suppressed angiogenesis, cell proliferation, and VEGFA expression, while the converse was true with knock-down of endogenous EFEMP1 expression. The EFEMP1 suppression of tumor onset time was nearly restored by ectopic VEGFA expression; however, overall tumor growth rate remained suppressed. This suggested that inhibition of angiogenesis was only partly responsible for EFEMP1's impact on glioma development. In glioma cells that were treated by exogenous EFEMP1 protein or over-expressed endogenous EFEMP1, the EGFR level was reduced and AKT signaling activity attenuated. Mixing of EFEMP1 protein with cells prior to s.c. and i.c. implantations or injection of the protein around the established s.c. xenografts, both significantly suppressed tumorigenicity.

Conclusions

Overall, our data reveals that EEFEMP1 suppresses glioma growth in vivo, both by modulating the tumor extracellular microenvironment and by altering critical intracellular oncogenic signaling pathways.
A review of methods used in assessing non-serious adverse drug events in observational studies among type 2 diabetes mellitus patients
Authors: Hakobyan Liana , Haaijer-Ruskamp Flora M , de Zeeuw Dick , Dobre Daniela , Denig Petra
Published: September 2011

Clinical drug trials are often conducted in selective patient populations, with relatively small numbers of patients, and a short duration of follow-up. Observational studies are therefore important for collecting additional information on adverse drug events (ADEs). Currently, there is no guidance regarding the methodology for measuring ADEs in such studies. Our aim was to evaluate whether the methodology used to assess non-serious ADEs in observational studies is adequate for detecting these ADEs, and for addressing limitations from clinical trials in patients with type 2 diabetes mellitus. We systematically searched MEDLINE and EMBASE for observational studies reporting non-serious ADEs (1999-2008). Methods to assess ADEs were classified as: 1) medical record review; 2) surveillance by health care professionals (HCP); 3) patient survey; 4) administrative data; 5) laboratory/clinical values; 6) not specified. We compared the range of ADEs identified, number and selection of patients included, and duration of follow-up. Out of 10,125 publications, 68 studies met our inclusion criteria. The most common methods were based on laboratory/clinical values (n = 25) and medical record review (n = 18). Solicited surveillance by HCP (n = 17) revealed the largest diversity of ADEs. Patient surveys (n = 15) focused mostly on hypoglycaemia and gastrointestinal ADEs, laboratory values based studies on hepatic and metabolic ADEs, and administrative database studies (n = 5) on cardiovascular ADEs. Four studies presented ADEs that were identified with the use of more than one method. The patient population was restricted to a lower risk population in 19% of the studies. Less than one third of the studies exceeded pre-approval regulatory requirements for sample size and duration of follow-up. We conclude that the current assessment of ADEs is hampered by the choice of methods. Many observational studies rely on methods that are inadequate for identifying all possible ADEs. Patient-reported outcomes and combinations of methods are underutilized. Furthermore, while observational studies often include unselective patient populations, many do not adequately address other limitations of pre-approval trials. This implies that these studies will not provide sufficient information about ADEs to clinicians and patients. Better protocols are needed on how to assess adverse drug events not only in clinical trials but also in observational studies.
Identification of MACC1 as a novel prognostic marker in hepatocellular carcinoma
Authors: Qiu Jiliang , Huang Pinzhu , Liu Qian , Hong Jian , Li Binkui , Lu Canliang , Wang Li , Wang Jianping , Yuan Yunfei
Published: September 2011

Background

Metastasis-associated in colon cancer-1 (MACC1) is a newly identified gene that plays a role in colon cancer metastasis through upregulation of c-MET proto-oncogene (c-MET). However, the value of MACC1 as a potential biomarker for hepatocellular carcinoma (HCC) remains unknown.

Methods

MACC1 mRNA expression in 128 HCC tissues was examined by quantitative polymerase chain reaction. To show the potential correlation of MACC1 and c-MET, c-MET was also analysed.

Results

MACC1 was more highly expressed in HCC than in non-HCC tissues (P = 0.009). High MACC1 expression was significantly increased in cases with high alpha fetoprotein (AFP) (P = 0.025). A positive correlation was found between MACC1 and c-MET mRNAs (r = 0.235, P = 0.009). Both univariate and multivariate analyses revealed that MACC1 expression was associated with overall survival (OS) and disease-free survival (DFS). Moreover, stratified analysis showed that tumour-node-metastasis (TNM) stage I patients with high MACC1 levels had shorter OS and DFS than those with low MACC1.

Conclusions

MACC1 may identify low- and high-risk individuals with HCC and be a valuable indicator for stratifying the prognosis of TNM stage I patients. MACC1 may serve as a novel biomarker for HCC.
Strong convergence theorems for equilibrium problems and fixed point problems: A new iterative method, some comments and applications
Authors: He Zhenhua , Du Wei-Shih
Published: September 2011

In this paper, we introduce a new approach method to find a common element in the intersection of the set of the solutions of a finite family of equilibrium problems and the set of fixed points of a nonexpansive mapping in a real Hilbert space. Under appropriate conditions, some strong convergence theorems are established. The results obtained in this paper are new, and a few examples illustrating these results are given. Finally, we point out that some 'so-called' mixed equilibrium problems and generalized equilibrium problems in the literature are still usual equilibrium problems.

2010 Mathematics Subject Classification: 47H09; 47H10, 47J25.
Characterization of the axon initial segment (AIS) of motor neurons and identification of a para-AIS and a juxtapara-AIS, organized by protein 4.1B
Authors: Duflocq Amandine , Chareyre Fabrice , Giovannini Marco , Couraud François , Davenne Marc
Published: September 2011

Background

The axon initial segment (AIS) plays a crucial role: it is the site where neurons initiate their electrical outputs. Its composition in terms of voltage-gated sodium (Nav) and voltage-gated potassium (Kv) channels, as well as its length and localization determine the neuron's spiking properties. Some neurons are able to modulate their AIS length or distance from the soma in order to adapt their excitability properties to their activity level. It is therefore crucial to characterize all these parameters and determine where the myelin sheath begins in order to assess a neuron's excitability properties and ability to display such plasticity mechanisms. If the myelin sheath starts immediately after the AIS, another question then arises as to how would the axon be organized at its first myelin attachment site; since AISs are different from nodes of Ranvier, would this particular axonal region resemble a hemi-node of Ranvier?

Results

We have characterized the AIS of mouse somatic motor neurons. In addition to constant determinants of excitability properties, we found heterogeneities, in terms of AIS localization and Nav composition. We also identified in all α motor neurons a hemi-node-type organization, with a contactin-associated protein (Caspr)+ paranode-type, as well as a Caspr2+ and Kv1+ juxtaparanode-type compartment, referred to as a para-AIS and a juxtapara (JXP)-AIS, adjacent to the AIS, where the myelin sheath begins. We found that Kv1 channels appear in the AIS, para-AIS and JXP-AIS concomitantly with myelination and are progressively excluded from the para-AIS. Their expression in the AIS and JXP-AIS is independent from transient axonal glycoprotein-1 (TAG-1)/Caspr2, in contrast to juxtaparanodes, and independent from PSD-93. Data from mice lacking the cytoskeletal linker protein 4.1B show that this protein is necessary to form the Caspr+ para-AIS barrier, ensuring the compartmentalization of Kv1 channels and the segregation of the AIS, para-AIS and JXP-AIS.

Conclusions

α Motor neurons have heterogeneous AISs, which underlie different spiking properties. However, they all have a para-AIS and a JXP-AIS contiguous to their AIS, where the myelin sheath begins, which might limit some AIS plasticity. Protein 4.1B plays a key role in ensuring the proper molecular compartmentalization of this hemi-node-type region.