bluuebunny/crossref_metadata_2025 huggingface dataset:
The Value of Biomedical Research Training for Veterinary Anatomic and Clinical Pathologists
Authors: Sharkey L. C. , Simpson R. M. , Wellman M. L. , Craig L. E. , Birkebak T. A. , Kock N. D. , Miller M. A. , Harris R. K. , Munson L. ,   The ACVP Training Program Development Task Force
Published: October 2011

Veterinary pathologists traditionally have been actively engaged in research as principal investigators and as collaborators. Pathologists frequently obtain advanced training in research; however, it appears that in the last 10 years there has been a reversal of a previous trend toward increasing numbers of pathologists obtaining PhD degrees. This has arisen despite an established shortage of veterinarians engaged in research. This article evaluates the benefits of research training for individual pathologists, including a wide spectrum of professional opportunities and additional skill development beyond that usually provided by diagnostic pathology training alone. Various training models are discussed, including combined and sequential diagnostic residency and research degree training as well as the nondegree research fellowship programs more commonly pursued in human medicine. Best-practice recommendations for program infrastructure, mentorship, time management, and a team approach to research and research training are advocated to facilitate the development of successful programs and to encourage a continued emphasis on integrated training for pathologists as both clinical diagnosticians and experimentalists. This article is intended to help prospective and active pathology trainees, their mentors, and educational administrators optimize opportunities to ensure the future vitality of veterinary pathologists, and their contributions, in basic and applied research.
Reconceptualizing Capitalism
Authors: Das Raju J.
Published: October 2011

This paper analyzes the nature of capitalism by critically employing Marx’s comments in Capital on forms of subsumption of labor. It argues that to the extent that property owners employ wage laborers to produce for the market for a profit, they are capitalist, even if they may not reinvest their profit in technology. In this situation, wage-labor is formally subsumed under capital. The transition from this stage to real subsumption of labor, which signifies capitalist development with technological change, is not, however, automatic, as Marx tended to assume. It is mediated by class struggle, which occurs in the context of geographically varying factors, such as state interventions. Uneven development, seen as the uneven transition to real subsumption, is partly a product of place-specific outcomes of class struggle. The paper thus emphasizes the relation between class struggle and dynamics of capitalism including technological change. The conceptual arguments are illustrated with empirical evidence from India. The implications of the arguments for radical development theory and politics are also briefly explored.

JEL classification: P16, O53, O14, B24
Alliances as Contiguity in Spatial Models of Military Expenditures
Authors: Flores Alejandro Quiroz
Published: October 2011

What determines the level of a country’s military expenditures? Both history and theory indicate that military expenditures are strategic in nature—a country’s military expenditures depend on the military allocations of other countries. This article examines two potential sources of interdependence: geographic proximity and alliance membership. Estimation results from spatial autoregressive models show that a country’s military expenditures are positively correlated with those of its geographic neighbors. Since countries may respond positively to their neighbors’ military spending due to conflict or cooperation, the article uses alliance membership as an alternative measure of contiguity to discover potential cooperative relationships among geographic neighbors. Results indicate that a country’s military expenditures are positively correlated with the military spending of its alliance partners. This correlation is stronger between members of the same defensive alliance.
Militarized Compellent Threats, 1918–2001
Authors: Sechser Todd S.
Published: October 2011

The study of military coercion is a central topic in international relations, and in recent years research on coercive threats has yielded a long list of important theoretical innovations. In 1960, Thomas Schelling drew a distinction between threats meant to deter and those designed to compel, but empirical research about coercion has paid much more attention to deterrence than compellence. This is problematic because deterrence and compellence are thought to operate according to different dynamics. This article introduces the Militarized Compellent Threats dataset, which is designed specifically to help test hypotheses about the use and effectiveness of compellent threats in international politics. I describe the rationale behind the dataset, present coding procedures and basic descriptive statistics, and offer comparisons to several related datasets.
Using the Roy Adaptation Model to Develop an Antenatal Assessment Instrument
Authors: Lee Linda Yin King , Tsang Alan Yat Kwan , Wong Ka Fai , Lee Joseph Kok Long
Published: October 2011

The utility of a nursing model as a framework to understand and explain a health phenomenon is fundamental to guide nursing practice. In this article, the authors aim to provide an examination of the Roy adaptation model as a basis for the development of an instrument used for assessing the health needs of pregnant women. With the congruence between the concepts in the Roy adaptation model and antenatal practice, an antenatal assessment instrument is developed. The assessment areas focus on pregnant women’s behaviors in the four adaptation modes. The current experience is valuable for nurses who are involved in instrument development and midwifery practice.
Toward Development of a Middle-Range Theory of Psychological Adaptation in Death and Dying
Authors: Dobratz Marjorie C.
Published: October 2011

This paper presents a middle-range theory of psychological adaptation in death and dying that was abstracted from a series of quantitative and qualitative studies. The findings from these studies are described, a conceptual definition for end-of-life psychological adaptation is given, evidence is synthesized into a limited number of assumptions, testable hypotheses are derived, and the constructed middle-range theory is linked to the conceptual-theoretical framework of the Roy adaptation model.
Perspectives on Leadership
Authors: Ferguson-Paré Mary
Published: October 2011

Perspectives on leadership developed through a career as a nurse leader are shared, including the author’s guiding vision, a valuing of nursing as knowledge work, how to create a learning organization that supports professional practice, and other lessons learned through experience. Readers are urged to find the leadership voice within, be courageous, engage surrounding opportunities, and be guided by their vision of what nursing should be in the future.
What is Not Yet
Authors: Bunkers Sandra Schmidt
Published: October 2011

In this column, the author describes imaginative capacities that encourage imaginative thinking and creating anew. Concepts from the nursing theory of humanbecoming are presented to further explore the applicability of focusing on cultivating the imagination in nursing curricula. A nursing seminar is proposed, entitled What Is Not Yet, that could foster the creative potential of nurse leaders.
The Power of Theoretical Knowledge
Authors: Alligood Martha Raile
Published: October 2011

Nursing theoretical knowledge has demonstrated powerful contributions to education, research, administration and professional practice for guiding nursing thought and action. That knowledge has shifted the primary focus of the nurse from nursing functions to the person. Theoretical views of the person raise new questions, create new approaches and instruments for nursing research, and expand nursing scholarship throughout the world.
Phenomenon Development from Practice to Research
Authors: Pate Courtney M.
Published: October 2011

One of the most prudent and efficient ways of conquering the task of developing new knowledge, is the utilization of practice to find phenomena. The purpose of this column is to present the construction of a phenomenon to be utilized for future study and explication utilizing this format. New nursing knowledge was developed by constructing a practice situation, identifying a phenomenon of interest, grounding the phenomenon in the focus of the discipline, and defining concepts related to the phenomenon. Through this evolutionary process one is able to identify a phenomenon to focus on, apply it to a particular population, ground it in theory, and lastly develop it into the foundation of future research.
Assessing the sensitivity of methods for estimating principal causal effects
Authors: Stuart Elizabeth A , Jo Booil
Published: October 2011

The framework of principal stratification provides a way to think about treatment effects conditional on post-randomization variables, such as level of compliance. In particular, the complier average causal effect (CACE) – the effect of the treatment for those individuals who would comply with their treatment assignment under either treatment condition – is often of substantive interest. However, estimation of the CACE is not always straightforward, with a variety of estimation procedures and underlying assumptions, but little advice to help researchers select between methods. In this article, we discuss and examine two methods that rely on very different assumptions to estimate the CACE: a maximum likelihood (‘joint’) method that assumes the ‘exclusion restriction,’ (ER) and a propensity score-based method that relies on ‘principal ignorability.’ We detail the assumptions underlying each approach, and assess each methods' sensitivity to both its own assumptions and those of the other method using both simulated data and a motivating example. We find that the ER-based joint approach appears somewhat less sensitive to its assumptions, and that the performance of both methods is significantly improved when there are strong predictors of compliance. Interestingly, we also find that each method performs particularly well when the assumptions of the other approach are violated. These results highlight the importance of carefully selecting an estimation procedure whose assumptions are likely to be satisfied in practice and of having strong predictors of principal stratum membership.
Links Between Attention, Performance Pressure, and Movement in Skilled Motor Action
Authors: Gray Rob
Published: October 2011

The attentional focus adopted during the execution of a skilled motor action can have a profound effect on performance outcomes. Furthermore, it has been proposed that an “inward” shift in the focus of attention may be one of the primary causes of “choking under pressure.” But how does attention have its effect on performance? In particular, how does changing one’s focus of attention change movement during skill execution? Here, I highlight recent research reporting four different types of movement effects that have been linked to attention: movement variability, multi-joint coordination, movement economy, and motor-control strategy. Understanding the effects of attention and pressure at the level of kinematics/muscle activity is crucial for developing a comprehensive theoretical account of skilled motor action. It is also of great practical value as it identifies specific execution errors that can be addressed in practice.
Psychology of Science as a New Subdiscipline in Psychology
Authors: Feist Gregory J.
Published: October 2011

Scientific behavior, interest, talent, and achievement can be and have been investigated from each of the fundamental subdisciplines in psychology. Simply put, there is a psychology behind science. I review and summarize the major empirical findings from different subdisciplines—namely, cognitive, developmental, personality, social, and clinical. For the last 10 years, the discipline of the psychology of science has shown some real promise in becoming a new psychological subdiscipline in its own right. I review some of the evidence for such a claim.
The Risk of Polite Misunderstandings
Authors: Bonnefon Jean-François , Feeney Aidan , De Neys Wim
Published: October 2011

We review evidence showing that politeness taxes mental resources and creates confusion about what is truly meant during interactions. While this confusion can be useful in low-stakes situations, it can have negative, even dangerous consequences in high-stakes situations such as flying a plane in an emergency or helping a patient decide on a course of treatment. Unfortunately, high-stakes situations are especially conducive to politeness-based misunderstandings. Although policies that discourage politeness in high-stakes situations are undergoing empirical assessment, we suggest that research is needed on the nonverbal cues that help people disambiguate polite statements.
Treatment Fidelity of Motivational Interviewing Delivered by a School Nurse to Increase Girls' Physical Activity
Authors: Robbins Lorraine B. , Pfeiffer Karin A. , Maier Kimberly S. , LaDrig Stacey M. , Berg-Smith Steven Malcolm
Published: October 2011

Motivational interviewing, which involves the use of person-centered, directive counseling techniques, shows promise for changing adolescent behaviors. The purpose of this article was to describe the methodology and findings related to the treatment fidelity of three face-to-face motivational interviewing sessions involving middle school girls and a school nurse to help the girls increase their moderate-to-vigorous physical activity. The following four areas related to treatment fidelity were addressed: (a) study design, (b) training of interventionists, (c) intervention delivery, and (d) intervention receipt. Findings showed that 34 of 37 (91.9%) girls completed all three sessions. An initial motivational interviewing training workshop followed by evaluation of audiotaped sessions with constructive feedback can result in successful and consistent delivery by a school nurse.
Violentization Theory and Genocide
Authors: Winton Mark A.
Published: October 2011

The purpose of this article is to use Lonnie Athens’ violentization theory to explain the Bosnian and Rwandan genocides. These two case studies are used to compare and contrast how the brutalization, defiance, violent dominance engagements, and virulency stages emerged prior to and during the genocides. Using published texts such as interviews with perpetrators, human rights reports, and court transcripts, qualitative content analysis is employed to test the fit between violentization theory and the two case studies. The results demonstrate that violentization theory is consistent with the data and provides an explanation of how the genocides developed and were enacted. Similarities and differences between Rwanda and Bosnia are described to explain how the perpetrators went through the violentization process, and an additional stage is added to illustrate extreme violence. Suggestions for further research using this model are provided.
Collaboration Between Federal and Local Law Enforcement
Authors: Stewart Daniel M.
Published: October 2011

Collaboration between law enforcement agencies, at all levels of government, has been identified as a salient component of post–September 11 policing. This study surveys a representative sample of Texas police chiefs concerning their perceptions of the level of collaboration that is occurring between their respective departments and federal agencies. Results suggest that the majority of chiefs hold generally low perceptions of federal-local collaboration. Furthermore, regression analyses show that preparedness and departmental strategy perceptions are predictive of federal-local collaboration. Regarding structural factors, chiefs of large departments as well as university departments are more likely to report higher levels of collaboration with federal agencies. Policy implications and directions for future research are discussed.
Trajectories of care: Spouses coping with changes related to mild cognitive impairment
Authors: Roberto Karen A. , McCann Brandy Renee , Blieszner Rosemary
Published: October 2011

Mild cognitive impairment (MCI) refers to non-normative changes in memory and cognition. While researchers are beginning to address the social consequences of MCI, no investigations have tracked how married couples respond to MCI over time as symptoms stabilize or become more severe. Guided by life course and symbolic interactionist tenets, we examined how 40 older couples in the United States adjusted to daily life after one partner was diagnosed with MCI and how their marital roles and relationship changed over a three- to four-year period. Data were collected from 2004 through 2010. All couples experienced an initial period of transition in coping with MCI where they made adjustments in their daily lives and interactions. Following this adjustment period, four trajectories of care emerged depending on the extent of the older adult’s decline and the spouse’s response. We conclude that changes associated with MCI affect role identity and have consequences for spousal relationships.
Tracheal papillomatosis
Authors: Harris Kassem , Chalhoub Michel
Published: October 2011

Tracheal papillomatosis (TP) is a benign condition characterized by papillomatous growth of the bronchial epithelium that involves the trachea. This abnormal growth is a result of infection with human papilloma virus (HPV). Two subtypes of HPV were found in most cases of TP, HPV-6 and HPV-11. TP, presents in two forms, the juvenile onset (JO) or adult onset (AO). The clinical presentation is typically nonspecific and it ranges from mild symptoms like cough to life-threatening conditions like upper airway obstruction. Treatment depends on the location of the papillomas and age of the patient and the plan of therapy is usually made on an individual basis. Treatment can range from observation with symptomatic control to specific medical therapy and multiple surgeries in case of recurrence or progressively worsening disease. The recent invention of HPV vaccine is expected to be the first step in eradicating respiratory papillomatosis.
Relation Between CBM-R and CBM-mR Slopes
Authors: Yeo Seungsoo , Fearrington Jamie Y. , Christ Theodore J.
Published: October 2011

Oral reading tasks and Maze reading tasks are often used interchangeably to assess the level and rate of reading skill development. This study examined the concurrent validity of growth estimates derived from Curriculum-Based Measurement of Oral Reading (CBM-R) and Maze Reading (CBM-mR). Participants were 1,528 students from Grades 3 to 8. CBM-R and CBM-mR were administered in fall, winter, and spring. Results indicate that CBM-R growth estimates are not correlated with CBM-mR growth estimates as derived with bivariate latent growth modeling (BLGM). In addition, results indicate that CBM growth estimates do not contribute to predictions of student performance on statewide assessments. Implications for practice and future research are discussed.
Isolated Anterior Compartment Syndrome After a Bimalleolar-Equivalent Ankle Fracture in a Collegiate Football Player
Authors: Starr Adam M. , Swan Kenneth G. , Swan Kenneth G.
Published: October 2011

Compartment syndrome after an ankle fracture is an extremely rare and potentially devastating event. The authors report a case of an isolated anterior compartment syndrome in a college student athlete who suffered a bimalle olar ankle fracture dislocation. A review of the literature highlights the importance of vigilance when the sports medicine physician and the community orthopaedist are treating these seemingly basic orthopaedic injuries.
Static Balance in Patients With Patellofemoral Pain Syndrome
Authors: Citaker Seyit , Kaya Defne , Yuksel Inci , Yosmaoglu Baran , Nyland John , Atay Ozgur Ahmet , Doral Mahmut Nedim
Published: October 2011

Background: The relationship between one-leg static standing balance (OLSSB) and patellofemoral pain syndrome (PFPS) is unknown.

Hypothesis: OLSSB decreases in patients with PFPS.

Design: Prospective case series.

Methods: Fifty-two women with unilateral PFPS were enrolled in this study. OLSSB was evaluated with a stabilometer. Q angle was measured with a lengthened-arm universal goniometer. Lower extremity alignment was analyzed with full-length standing anteroposterior teleroentgenograms. Quadriceps and hamstring strength was measured on an isokinetic dynamometer.

Results: There were significant differences in OLSSB, Q angle, and strength of quadriceps and hamstring between the symptomatic and asymptomatic sides. There was a correlation between the strength of the quadriceps and hamstring and OLSSB, while there was no correlation between OLSSB and the severity of pain, lower extremity alignment, and Q angle on the symptomatic side.

Conclusions: OLSSB and quadriceps and hamstring strength decreased and Q angle increased on the symptomatic side in PFPS patients. A relationship between OLSSB and pain, Q angle, and lower extremity alignment was not detected, while there was a correlation between the strength of the quadriceps and hamstring and OLSSB.

Clinical Relevance: A quadriceps and hamstring strengthening may be beneficial to improve OLSSB in patients with PFPS.
Heart Transplantation for Congenital Heart Disease
Authors: Pauliks Linda B. , Ündar Akif
Published: October 2011

Congenital heart disease affects 0.8% of all live-born infants. Some of the malformed hearts can at best be palliated by conventional surgical or catheter interventions from the start. Others fail slowly from chronic overloading. Patients with congenital heart disease have been among the first transplant recipients since 1967. Primary therapy with infant heart transplant is a convincing concept from an immunological perspective but large-scale implementation is limited by donor organ shortages. Another growing area is rescue therapy for older patients with end-stage heart failure after palliative procedures, particularly those with single-ventricle hearts, systemic right ventricles, and associated arrhythmias.
The Role of Methylene Blue in the Pediatric Patient With Vasoplegic Syndrome
Authors: Bhalla Tarun , Sawardekar Amod , Russell Hyde , Tobias Joseph D.
Published: October 2011

Patients with vasoplegic syndrome (VPS) in the post-cardiopulmonary bypass setting usually require escalating vasopressor support. The utilization of methylene blue (MB) in the treatment of VPS in the adult population has been well described. We present a 5-year-old girl who developed vasodilatory shock due to VPS that was resistant to escalating doses of adrenergic agonists following cardiac transplantation. After receiving 1 mg/kg of MB, there was a significant improvement in the patient’s mean arterial pressure which allowed for progressive weaning of the vasopressor support. To date, there are limited data regarding the use of MB in pediatric patients with VPS following cardiothoracic surgery. The cellular mechanisms of MB in VPS are discussed and reports of its use in the adult and pediatric population are reviewed. Dosing regimens and potential adverse effects of MB are presented.
Near-Infrared Spectroscopy Monitoring to Predict Postoperative Renal Insufficiency Following Repair of Congenital Heart Disease
Authors: Colasacco Colby , Worthen Mike , Peterson Brad , Lamberti John , Spear Robert
Published: October 2011

Background: Infants undergoing repair or palliation of congenital heart disease are at risk of renal insufficiency. Development of renal insufficiency increases mortality. This project seeks to determine whether intra- and postoperative renal near-infrared spectroscopy (NIRS) monitoring can reliably predict renal insufficiency after cardiac surgery in infants. Methods: In this prospective, observational cohort study 48 patients undergoing repair or palliation of congenital heart disease in the first 6 months of life were studied intraoperatively and on postoperative day 1 and 2. The NIRS mean and nadir were recorded for the 3 time periods, as were urine output, fluid balance, and serum creatinine. Renal insufficiency was defined as rise in creatinine ≥40% from baseline or oliguria for >4 hours. Near-infrared spectroscopy data were compared to creatinine increase, oliguria, and fluid balance on postoperative day 0, 1, and 2 by regression analysis. Results: Mean renal regional saturation on postoperative day 1 has a strong correlation with increase in creatinine ( P < .001 and R 2 = .6). Mean renal saturation less than 80% predicts renal insufficiency with a sensitivity of 100% and a specificity of 75% ( P < .001). Conclusion: Monitoring of intra- and postoperative renal regional saturation may provide an early, noninvasive marker of renal insufficiency after cardiac surgery in infants. This would be clinically significant if interventions to improve renal regional saturation prevent renal insufficiency.
Blalock-Taussig Shunt Thrombosis Prophylaxis in a Patient With Jacobsen Syndrome and Thrombocytopenia
Authors: Casadonte Joseph R. , Kim Jennifer M. , Dadlani Gul H. , Jacobs Jeffrey P. , Cooper David S. , Stapleton Gary E.
Published: October 2011

Jacobsen syndrome (JS) is a rare chromosomal anomaly caused by deletions in the distal long arm of chromosome 11. Features of the syndrome include growth and developmental delays, a distinctive facial appearance, and a variety of physical problems including heart defects and bleeding disorders. Congenital heart defects occur in approximately 50% of children with JS. Hypoplastic left heart syndrome (HLHS) has been occasionally reported in association with JS. In such cases, the hematological abnormalities may influence the outcome from single-ventricle palliation through staged surgical reconstruction. Thrombotic obstruction or occlusion of the modified Blalock-Taussig (BT) shunt is a well-documented cause of interstage mortality following the Norwood operation. Although there is no consensus regarding the therapeutic value of antiplatelet therapy during the interstage period following the first stage of palliation, maintenance of shunt patency is critically important. For patients with JS undergoing single-ventricle palliation, decisions regarding antiplatelet therapy during the interstage period may be further complicated by the presence of thrombocytopenia and platelet dysfunction related to JS. We report the case of a patient with HLHS, JS, and thrombocytopenia who underwent the Norwood procedure, and we describe our strategy for prophylaxis against thrombosis of the BT shunt.
The Transesophageal Echocardiography Probe: An Unusual Source of Pulmonary Venous Obstruction
Authors: Altarabsheh Salah Eldien , Burkhart Harold M. , Deo Salil , Cetta Frank
Published: October 2011

We present a newborn patient who had surgical correction of supracardiac total anomalous pulmonary venous connection repair with an unusual cause of residual postoperative pulmonary venous obstruction secondary to compression from the transesophageal echocardiography (TEE) probe.
Use of an Administrative Database to Determine Clinical Management and Outcomes in Congenital Heart Disease
Authors: Gutgesell Howard P. , Hillman Diane G. , McHugh Kimberly E. , Dean Peter , Matherne G. Paul
Published: October 2011

We review our 16-year experience using the large, multi-institutional database of the University HealthSystem Consortium to study management and outcomes in congenital heart surgery for hypoplastic left heart syndrome, transposition of the great arteries, and neonatal coarctation. The advantages, limitations, and use of administrative databases by others to study congenital heart surgery are reviewed.
Medical Test Results Do Not Tell the Whole Story
Authors: Wray Jo , Brown Kate , Marino Bradley S. , Franklin Rodney
Published: October 2011

Children born today with congenital heart disease (CHD) are likely to reach adulthood, even those with complex disease. As survival rates have increased, attention has focused on the longer-term morbidity associated with CHD and its treatment, but this has largely addressed the physical and physiological outcomes rather than psychosocial morbidity and health-related quality of life (QoL). The purpose of this article is to outline the arguments in favor of routine evaluation of health-related QoL, describe how such measurements might be used, and the barriers and challenges associated with the collection of the data. Finally, a strategy is suggested for the routine collection and use of health-related QoL data with children and adolescents with CHD.
A Novel Provisional Aortopulmonary Shunt May Help Avoid Neonatal Cardiopulmonary Bypass
Authors: Altin Firat H. , Karaci Ali Riza , Jacobs Jeffrey Phillip , Yekeler Ibrahim
Published: October 2011

A novel temporary aortopulmonary shunt, constructed between the aorta and main pulmonary artery with flexible cannulas, was used to facilitate right ventricular outflow tract reconstruction in one neonate and creation of a central aortopulmonary shunt in a second neonate. Although cardiopulmonary bypass is readily available in Turkey, the strategy described in the case report may prove especially useful in developing nations with limited access to cardiopulmonary bypass (CPB).
Using Statistical Process Control to Identify Early Growth Failure Among Infants With Hypoplastic Left Heart Syndrome
Authors: Iyer Srikant B. , Anderson Jeffrey B. , Slicker Julie , Beekman Robert H. , Lannon Carole
Published: October 2011

Although interventions to improve outcomes for children with congenital heart disease may be designed and tested, the rarity of any one specific defect presents a barrier to using traditional statistical methods to measure the effects of these interventions. The purpose of this report is to describe the innovative statistical approach taken by the Joint Council on Congenital Heart Disease (JCCHD) National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) to measure outcomes for infants with hypoplastic left heart syndrome—a relatively rare disease. We report our experience with the application of statistical process control methods to generate measures capable of identifying statistically significant change in the incidence of early growth failure—a clinically important outcome in this relatively small patient population.
ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia
Authors: Rousseau Julie , Gagné Vincent , Labuda Malgorzata , Beaubois Cyrielle , Sinnett Daniel , Laverdière Caroline , Moghrabi Albert , Sallan Stephen E. , Silverman Lewis B. , Neuberg Donna , Kutok Jeffery L. , Krajinovic Maja
Published: October 2011

Asparaginase is a standard and critical component in the therapy of childhood acute lymphoblastic leukemia. Asparagine synthetase (ASNS) and the basic region leucine zipper activating transcription factor 5 (ATF5) and arginosuccinate synthase 1 (ASS1) have been shown to mediate the antileukemic effect of asparaginase and to display variable expression between leukemia cells that are resistant and sensitive to treatment. Fourteen polymorphisms in the regulatory and coding regions of these genes were investigated for an association with acute lymphoblastic leukemia outcome. Lower event-free survival (EFS) was associated with ATF5 T1562C, tandem-repeat ASNS polymorphism, derived haplotype, and ASS1 G1343T and G34T substitutions (P ≤ .03). Associations were limited to patients who received Escherichia coli asparaginase. Variations that sustained correction for multiple testing (ATF5 T1562C, P = .005; ASNS tandem-repeat and related haplotype, P ≤ .01) were subsequently analyzed in the replication cohort. The E coli–dependent association of the ATF5 T1562 allele with reduced EFS was confirmed (P = .01). A gene-reporter assay showed that the haplotype tagged by T1562 had higher promoter activity (P ≤ .01). The remaining regulatory polymorphisms also appeared to affect ATF5 function; 2 additional high-activity haplotypes were identified (P ≤ .02) and were further corroborated by quantitative mRNA analysis in lymphoblastoid cell lines. The ATF5-regulated increase in ASNS expression in response to more efficacious E coli–induced asparagine depletion may explain our observed results.
Fractionation statistics
Authors: Wang Baoyong , Zheng Chunfang , Sankoff David
Published: October 2011

Background

Paralog reduction, the loss of duplicate genes after whole genome duplication (WGD) is a pervasive process. Whether this loss proceeds gene by gene or through deletion of multi-gene DNA segments is controversial, as is the question of fractionation bias, namely whether one homeologous chromosome is more vulnerable to gene deletion than the other.

Results

As a null hypothesis, we first assume deletion events, on one homeolog only, excise a geometrically distributed number of genes with unknown mean µ, and these events combine to produce deleted runs of length l, distributed approximately as a negative binomial with unknown parameter r, itself a random variable with distribution π(·). A more realistic model requires deletion events on both homeologs distributed as a truncated geometric. We simulate the distribution of run lengths l in both models, as well as the underlying π(r), as a function of µ, and show how sampling l allows us to estimate µ. We apply this to data on a total of 15 genomes descended from 6 distinct WGD events and show how to correct the bias towards shorter runs caused by genome rearrangements. Because of the difficulty in deriving π(·) analytically, we develop a deterministic recurrence to calculate each π(r) as a function of µ and the proportion of unreduced paralog pairs.

Conclusions

The parameter µ can be estimated based on run lengths of single-copy regions. Estimates of µ in real data do not exclude the possibility that duplicate gene deletion is largely gene by gene, although it may sometimes involve longer segments.
Wolbachia infections that reduce immature insect survival: Predicted impacts on population replacement
Authors: Crain Philip R , Mains James W , Suh Eunho , Huang Yunxin , Crowley Philip H , Dobson Stephen L
Published: October 2011

Background

The evolutionary success of Wolbachia bacteria, infections of which are widespread in invertebrates, is largely attributed to an ability to manipulate host reproduction without imposing substantial fitness costs. Here, we describe a stage-structured model with deterministic immature lifestages and a stochastic adult female lifestage. Simulations were conducted to better understand Wolbachia invasions into uninfected host populations. The model includes conventional Wolbachia parameters (the level of cytoplasmic incompatibility, maternal inheritance, the relative fecundity of infected females, and the initial Wolbachia infection frequency) and a new parameter termed relative larval viability (RLV), which is the survival of infected larvae relative to uninfected larvae.

Results

The results predict the RLV parameter to be the most important determinant for Wolbachia invasion and establishment. Specifically, the fitness of infected immature hosts must be close to equal to that of uninfected hosts before population replacement can occur. Furthermore, minute decreases in RLV inhibit the invasion of Wolbachia despite high levels of cytoplasmic incompatibility, maternal inheritance, and low adult fitness costs.

Conclusions

The model described here takes a novel approach to understanding the spread of Wolbachia through a population with explicit dynamics. By combining a stochastic female adult lifestage and deterministic immature/adult male lifestages, the model predicts that even those Wolbachia infections that cause minor decreases in immature survival are unlikely to invade and spread within the host population. The results are discussed in relation to recent theoretical and empirical studies of natural population replacement events and proposed applied research, which would use Wolbachia as a tool to manipulate insect populations.
Duodenal and faecal microbiota of celiac children: molecular, phenotype and metabolome characterization
Authors: Di Cagno Raffaella , De Angelis Maria , De Pasquale Ilaria , Ndagijimana Maurice , Vernocchi Pamela , Ricciuti Patrizia , Gagliardi Francesca , Laghi Luca , Crecchio Carmine , Guerzoni Maria Elisabetta , Gobbetti Marco , Francavilla Ruggiero
Published: October 2011

Background

Epidemiology of celiac disease (CD) is increasing. CD mainly presents in early childhood with small intestinal villous atrophy and signs of malabsorption. Compared to healthy individuals, CD patients seemed to be characterized by higher numbers of Gram-negative bacteria and lower numbers Gram-positive bacteria.

Results

This study aimed at investigating the microbiota and metabolome of 19 celiac disease children under gluten-free diet (treated celiac disease, T-CD) and 15 non-celiac children (HC). PCR-denaturing gradient gel electrophoresis (DGGE) analyses by universal and group-specific primers were carried out in duodenal biopsies and faecal samples. Based on the number of PCR-DGGE bands, the diversity of Eubacteria was the higher in duodenal biopsies of T-CD than HC children. Bifidobacteria were only found in faecal samples. With a few exceptions, PCR-DGGE profiles of faecal samples for Lactobacillus and Bifidobacteria differed between T-CD and HC. As shown by culture-dependent methods, the levels of Lactobacillus, Enterococcus and Bifidobacteria were confirmed to be significantly higher (P = 0.028; P = 0.019; and P = 0.023, respectively) in fecal samples of HC than in T-CD children. On the contrary, cell counts (CFU/ml) of presumptive Bacteroides, Staphylococcus, Salmonella, Shighella and Klebsiella were significantly higher (P = 0.014) in T-CD compared to HC children. Enterococcus faecium and Lactobacillus plantarum were the species most diffusely identified. This latter species was also found in all duodenal biopsies of T-CD and HC children. Other bacterial species were identified only in T-CD or HC faecal samples. As shown by Randomly Amplified Polymorphic DNA-PCR analysis, the percentage of strains identified as lactobacilli significantly (P = 0.011) differed between T-CD (ca. 26.5%) and HC (ca. 34.6%) groups. The metabolome of T-CD and HC children was studied using faecal and urine samples which were analyzed by gas-chromatography mass spectrometry-solid-phase microextraction and 1H-Nuclear Magnetic Resonance. As shown by Canonical Discriminant Analysis of Principal Coordinates, the levels of volatile organic compounds and free amino acids in faecal and/or urine samples were markedly affected by CD.

Conclusion

As shown by the parallel microbiology and metabolome approach, the gluten-free diet lasting at least two years did not completely restore the microbiota and, consequently, the metabolome of CD children. Some molecules (e.g., ethyl-acetate and octyl-acetate, some short chain fatty acids and free amino acids, and glutamine) seems to be metabolic signatures of CD.
Efficacy of epidermal growth factor receptor targeting in advanced chordoma: case report and literature review
Authors: Launay Simon G , Chetaille Bruno , Medina Fanny , Perrot Delphine , Nazarian Serge , Guiramand Jérôme , Moureau-Zabotto Laurence , Bertucci François
Published: October 2011

Background

Chordomas are very rare low-grade malignant bone tumors that arise from the embryonic rests of the notochord. They are characterized by slow growth and long history with frequent local relapses, and sometimes metastases. While chemotherapy is not efficient, imatinib has shown antitumor activity.

Case presentation

We report on a 76-year-old patient with EGFR-overexpressing advanced chordoma that progressed on imatinib and subsequently responded to erlotinib during 12 months.

Conclusions

We report the fourth case of advanced chordoma treated with an EGFR inhibitor. We also review the literature concerning the rationale and potential of EGFR targeting in chordoma.
HNF1α inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines
Authors: Pelletier Laura , Rebouissou Sandra , Vignjevic Danijela , Bioulac-Sage Paulette , Zucman-Rossi Jessica
Published: October 2011

Background

Hepatocyte Nuclear Factor 1α (HNF1α) is an atypical homeodomain-containing transcription factor that transactivates liver-specific genes including albumin, α-1-antitrypsin and α- and β-fibrinogen. Biallelic inactivating mutations of HNF1A have been frequently identified in hepatocellular adenomas (HCA), rare benign liver tumors usually developed in women under oral contraceptives, and in rare cases of hepatocellular carcinomas developed in non-cirrhotic liver. HNF1α-mutated HCA (H-HCA) are characterized by a marked steatosis and show activation of glycolysis, lipogenesis, translational machinery and mTOR pathway. We studied the consequences of HNF1α silencing in hepatic cell lines, HepG2 and Hep3B and we reproduced most of the deregulations identified in H-HCA.

Methods

We transfected hepatoma cell lines HepG2 and Hep3B with siRNA targeting HNF1α and obtained a strong inhibition of HNF1α expression. We then looked at the phenotypic changes by microscopy and studied changes in gene expression using qRT-PCR and Western Blot.

Results

Hepatocytes transfected with HNF1α siRNA underwent severe phenotypic changes with loss of cell-cell contacts and development of migration structures. In HNF1α-inhibited cells, hepatocyte and epithelial markers were diminished and mesenchymal markers were over-expressed. This epithelial-mesenchymal transition (EMT) was related to the up regulation of several EMT transcription factors, in particular SNAIL and SLUG. We also found an overexpression of TGFβ1, an EMT initiator, in both cells transfected with HNF1α siRNA and H-HCA. Moreover, TGFβ1 expression is strongly correlated to HNF1α expression in cell models, suggesting regulation of TGFβ1 expression by HNF1α.

Conclusion

Our results suggest that HNF1α is not only important for hepatocyte differentiation, but has also a role in the maintenance of epithelial phenotype in hepatocytes.
Identification of stromal proteins overexpressed in nodular sclerosis Hodgkin lymphoma
Authors: Kischel Philippe , Waltregny David , Greffe Yannick , Mazzucchelli Gabriel , De Pauw Edwin , de Leval Laurence , Castronovo Vincent
Published: October 2011

Hodgkin lymphoma (HL) represents a category of lymphoid neoplasms with unique features, notably the usual scarcity of tumour cells in involved tissues. The most common subtype of classical HL, nodular sclerosis HL, characteristically comprises abundant fibrous tissue stroma. Little information is available about the protein composition of the stromal environment from HL. Moreover, the identification of valid protein targets, specifically and abundantly expressed in HL, would be of utmost importance for targeted therapies and imaging, yet the biomarkers must necessarily be accessible from the bloodstream. To characterize HL stroma and to identify potentially accessible proteins, we used a chemical proteomic approach, consisting in the labelling of accessible proteins and their subsequent purification and identification by mass spectrometry. We performed an analysis of potentially accessible proteins in lymph node biopsies from HL and reactive lymphoid tissues, and in total, more than 1400 proteins were identified in 7 samples. We have identified several extracellular matrix proteins overexpressed in HL, such as versican, fibulin-1, periostin, and other proteins such as S100-A8. These proteins were validated by immunohistochemistry on a larger series of biopsy samples, and bear the potential to become targets for antibody-based anti-cancer therapies.
Quercetin 7-rhamnoside reduces porcine epidemic diarrhea virus replication via independent pathway of viral induced reactive oxygen species
Authors: Song Jae Hyoung , Shim Jae Kwon , Choi Hwa Jung
Published: October 2011

Background

On the base of our previous study we were observed relevant studies on the hypothesis that the antiviral activity of quercetin 7-rhamnoside (Q7R), a flavonoid, won't relate ability of its antioxidant.

Methods

We were investigated the effects of Q7R on the cytopathic effects (CPE) by CPE reduction assay. Production of DNA fragment and reactive oxygen species (ROS) induced by PEDV infection were studied using DNA fragmentation assay and flow cytometry.

Results

In the course of this study it was discovered that Q7R is an extremely potent compound against PEDV. The addition of Q7R to PEDV-infected Vero cells directly reduced the formation of a visible cytopathic effect (CPE). Also, Q7R did not induce DNA fragmentation. Furthermore, ROS increased the infection of PEDV, which was strongly decreased by N-acetyl-L-cysteins (NAC). However, the increased ROS was not decreased by Q7R. Antiviral activity of antioxidants such as NAC, pyrrolidine dithiocarbamate (PDTC), and the vitamin E derivative, trolox, were hardly noticed.

Conclusions

We concluded that the inhibition of PEDV production by Q7R is not simply due to a general action as an antioxidants and is highly specific, as several other antioxidants (NAC, PDTC, trolox) are inactive against PEDV infection.
Dietary fat and not calcium supplementation or dairy product consumption is associated with changes in anthropometrics during a randomized, placebo-controlled energy-restriction trial
Authors: Smilowitz Jennifer T , Wiest Michelle M , Teegarden Dorothy , Zemel Michael B , German J Bruce , Van Loan Marta D
Published: October 2011

Insufficient calcium intake has been proposed to cause unbalanced energy partitioning leading to obesity. However, weight loss interventions including dietary calcium or dairy product consumption have not reported changes in lipid metabolism measured by the plasma lipidome.

Methods

The objective of this study was to determine the relationships between dairy product or supplemental calcium intake with changes in the plasma lipidome and body composition during energy restriction. A secondary objective of this study was to explore the relationships among calculated macronutrient composition of the energy restricted diet to changes in the plasma lipidome, and body composition during energy restriction. Overweight adults (n = 61) were randomized into one of three intervention groups including a deficit of 500kcal/d: 1) placebo; 2) 900 mg/d calcium supplement; and 3) 3-4 servings of dairy products/d plus a placebo supplement. Plasma fatty acid methyl esters of cholesterol ester, diacylglycerol, free fatty acids, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine and triacylglycerol were quantified by capillary gas chromatography.

Results

After adjustments for energy and protein (g/d) intake, there was no significant effect of treatment on changes in weight, waist circumference or body composition. Plasma lipidome did not differ among dietary treatment groups. Stepwise regression identified correlations between reported intake of monounsaturated fat (% of energy) and changes in % lean mass (r = -0.44, P < 0.01) and % body fat (r = 0.48, P < 0.001). Polyunsaturated fat intake was associated with the % change in waist circumference (r = 0.44, P < 0.01). Dietary saturated fat was not associated with any changes in anthropometrics or the plasma lipidome.

Conclusions

Dairy product consumption or calcium supplementation during energy restriction over the course of 12 weeks did not affect plasma lipids. Independent of calcium and dairy product consumption, short-term energy restriction altered body composition. Reported dietary fat composition of energy restricted diets was associated with the degree of change in body composition in these overweight and obese individuals.