bluuebunny/crossref_metadata_2025 huggingface dataset:
Governance and natural disasters: addressing flooding in Saint Louis, Senegal
Authors: Diagne Khady
Published: October 2007

This paper describes an initiative to develop responses to flooding in the city of Saint Louis that focused both on reducing risks and on better preparedness in a city with very limited investment capacity. The initiative was developed by ENDA—Tiers Monde, an international NGO whose headquarters are in Senegal. It focused on building responses that drew on local knowledge and on supporting the engagement of all stakeholders in identifying causes and local solutions both to reduce risks and to reduce people's vulnerability to them.
Piaget No `Remedy' for Kuhn, But the Two Should be Read Together
Authors: Burman Jeremy Trevelyan
Published: October 2007

In arguing that the philosophical works of Jean Piaget could be used as a `remedy' for the flaws in those of Thomas Kuhn, Tsou overlooked some crucial aspects of the problem: the early history between them, the biological foundation supporting Piaget's method, and a preexisting suggestion regarding the intended future extension of his work. There was also no mention of the existence of a `lost' manuscript by Kuhn, which supposedly presents the mature articulation of his theory. This comment therefore proposes some `friendly amendments' to Tsou's exposition, with a view to helping achieve his synthetic vision once the `lost' work has finally been published. Yet the basic message, in anticipation of this future endeavor, is also exceedingly simple: the implicit direction of Piaget's (and Kuhn's) epistemological constructivism can be characterized as evolutionary-developmental `progress from,' rather than vitalist-teleological `progress toward.'
Disintegrating Qualitative Research
Authors: Frosh Stephen
Published: October 2007

This paper explores a tension in qualitative psychology between, on the one hand, a deconstructionist framework in which the human subject is understood as positioned in and through competing discourses and, on the other, a humanistic framework in which the integrity of the subject is taken to be both a starting- and end-point of analysis. This paper offers a critique of the tendency for qualitative research to seek to produce integrated `narratives' of experience and argues for the importance of maintaining the vision of a subject in fragments. It does so by taking up the notion of there being `things that can't be said' and suggesting that this refers to two distinct issues: the multiplicity of possible accounts of experience and the way language systematically excludes some `abjected' material. It finishes with an illustrative analysis of an interview text.
A Theoretical Model for Interpreting Suicidal Behaviour as Communication
Authors: Loa Knizek Birthe , Hjelmeland Heidi
Published: October 2007

Theoretical publications have been relatively few and far between in suicidology. This paper is a contribution to the theoretical development of this field. A model of suicidal behaviour as communication (MoSBaC) is elaborated through a combination of Scandinavian theories within the framework of communication theory and semiotics. The model is functional as it can be used as a tool to analyse both verbal and non-verbal data. It is also flexible in the sense that a variety of qualitative data can be analysed systematically by this model. The typology of the model also is suitable for quantitative approaches. The scientific and multidisciplinary grounds on which a model should be built, what requirements it has to meet, as well as the methodological consequences of this, are also discussed.
Randomized trials for the real world: making as few and as reasonable assumptions as possible
Authors: Baker Stuart G , Kramer Barnett S
Published: October 2007

The strength of the randomized trial to yield conclusions not dependent on assumptions applies only in an ideal setting. In the real world various complications such as loss-to-follow-up, missing outcomes, noncompliance and nonrandom selection into a trial force a reliance on assumptions. To handle real world complications, it is desirable to make as few and as reasonable assumptions as possible. This article reviews four techniques for using a few reasonable assumptions to design or analyse randomized trials in the presence of specific real world complications: 1) a double sampling design for survival data to avoid strong assumptions about informative censoring, 2) sensitivity analysis for partially missing binary outcomes that uses the randomization to reduce the number of parameters specified by the investigator, 3) an estimate of the effect of treatment received in the presence of all-or-none compliance that requires reasonable assumptions, and 4) statistics for binary outcomes that avoid some assumptions for generalizing results to a target population.
Disciplined analyses in clinical trials: the dark heart of the matter
Authors: Moyé Lemuel A
Published: October 2007

Clinical research analyses must balance the desire to `learn all that is learnable' from the database with the observation that sample-based data commonly lead to conclusions that are perfectly correct for the sample, but wholly incorrect for the population from which the data were based.

Investigators who defend exploratory analyses as reliable, misuse important tools that have taken over three hundred years to develop. Statistical estimators in clinical trials function appropriately when they incorporate random data that is gathered in response to a “xed research question. Their prediction ability degrades rapidly when the selection of the research question is itself random, that is, left to the data. Operating like blind guides, these estimators mislead the medical community about what it would see in the population, based on sample observations. The result is a wavering research focus, leaping from one provocative but misleading “nding to the next on the powerful waves of sampling error. Therefore, a primary purpose of the prospective design is to “x the research questions prospectively, thereby anchoring the analysis plan.

Prospective statements of the research questions and rejection of tempting databased changes to the protocol preserve the best estimates of effect sizes, standard errors, con“dence intervals and p-values. Embracing these principles promotes the prosecution of a successful research program, that is, the construction and protection of a research environment that permits an objective assessment of the therapy or exposure being studied. If there is any “xed star in the research constellation, it is that sample-based research must be hypothesis-driven and concordantly executed to have real meaning for both the scienti“c community and the patient populations that we serve.
Evaluation of networks of randomized trials
Authors: Salanti Georgia , Higgins Julian PT , Ades AE , Ioannidis John PA
Published: October 2007

Randomized trials may be designed and interpreted as single experiments or they may be seen in the context of other similar or relevant evidence. The amount and complexity of available randomized evidence vary for different topics. Systematic reviews may be useful in identifying gaps in the existing randomized evidence, pointing to discrepancies between trials, and planning future trials. A new, promising, but also very much debated extension of systematic reviews, mixed treatment comparison (MTC) meta-analysis, has become increasingly popular recently. MTC meta-analysis may have value in interpreting the available randomized evidence from networks of trials and can rank many different treatments, going beyond focusing on simple pairwise-comparisons. Nevertheless, the evaluation of networks also presents special challenges and caveats. In this article, we review the statistical methodology for MTC meta-analysis. We discuss the concept of inconsistency and methods that have been proposed to evaluate it as well as the methodological gaps that remain. We introduce the concepts of network geometry and asymmetry, and propose metrics for the evaluation of the asymmetry. Finally, we discuss the implications of inconsistency, network geometry and asymmetry in informing the planning of future trials.
Health Information—Seeking Behavior
Authors: Lambert Sylvie D. , Loiselle Carmen G.
Published: October 2007

Seeking information about one's health is increasingly documented as a key coping strategy in health-promotive activities and psychosocial adjustment to illness. In this article, the authors critically examine the scientific literature from 1982 to 2006 on the concept of health information—seeking behavior (HISB) to determine its level of maturity and clarify the concept's essential characteristics. A principle-based method of concept analysis provides the framework for exploring the nature of HISB. The authors reviewed approximately 100 published articles and five books reporting on HISB. Although HISB is a popular concept used in various contexts, most HISB definitions provide little insight into the concept's specific meanings. The authors describe the concept's characteristics, contributing to a clearer understanding of HISB, and discuss operationalizations, antecedents, and outcomes of HISB. Such an analysis of HISB might guide further theorizing on this highly relevant concept and assist health care providers in designing optimal informational interventions.
Enacting Personal HIV Disclosure Policies for Sexual Situations: HIV-Positive Gay Men's Experiences
Authors: Rutledge Scott Edward
Published: October 2007

Given successes in treating HIV/AIDS, there are increasing numbers of sexually active HIV-positive people. Although there is a current public health emphasis on testing interventions to reduce HIV transmission by people who know they are HIV positive, understanding how people enact decisions to disclose their HIV seropositivity is needed. HIV Disclosure Decision Making in Sexual Situations, a grounded theory based on interviews with 15 HIV-positive gay men, hypothesizes and interprets a two-part process wherein HIV-positive gay men form personal disclosure policies that they contextualize to various dating and sexual situations. In this article, the author depicts the second part of the grounded theory with its five interlocking components of the process of enacting HIV disclosure in sexual situations.
Power Brokering, Empowering, and Educating: The Role of Home-Based Care Professionals in the Reduction of HIV-Related Stigma in Kenya
Authors: Waterman Heather , Griffiths Jane , Gellard Len , O'Keefe Catherine , Olang Grace , Ayuyo James , Obwanda Elly , Ogwethe Vitalis , Ondiege Joshua
Published: October 2007

In this article the authors report on how home-based care (HBC) professionals reduce stigmatizing behavior in Kenya. This study was part of an action research project that evaluated the introduction of HBC. HBC professionals coordinate the delivery of HIV/AIDS services at a district level and educate community-based health workers in HBC. Understanding how HBC professionals reduce stigma is crucial to reduce, prevent, and treat HIV/AIDS. Fifty HBC professionals participated in 27 focus group interviews over 18 months. Stigma featured strongly when they discussed barriers to the introduction of HBC. Using sociological theory, the authors organized the data into five themes: Power broking and mobilization, Stigma as a social construction, Community and structural interventions, Educating and training people, and Historical context. The HBC professionals appear to operate at mostly individual and community levels in their efforts to challenge stigma, and in spite of the difficulties they appear to be having some impact.
Habitus, Stress, and the Body: The Everyday Production of Health and Cardiovascular Risk
Authors: Angus Jan , Rukholm Ellen , Onge Renée St. , Michel Isabelle , Nolan Robert P. , Lapum Jennifer , Evans Sarah
Published: October 2007

The incidence of coronary heart disease (CHD) and the distribution of contributory risk factors are closely linked with social patterns of advantage and disadvantage. The authors conducted eight focus groups in urban, northern, and rural sites in Ontario, Canada. Participants were all at high absolute risk for or had been diagnosed with CHD. Analysis centered on habitus, which forms the pivotal link between the person and “place.” The authors focused on participants' dialogue about stress because it dealt with the impingements of the social world and resultant constraints on health-related activities in everyday places. Participants described four types of places or social positions in their “stress talk”: work-places, transitional spaces, gendered situations, and exclusions. Places can support or constrain health related activities in many ways. Habits and practices linked with stress by participants were enduringly associated with these contexts, suggesting that place, body, and health are inseparable and coconstituted.
First Nations People's Challenge in Managing Coronary Artery Disease Risk
Authors: King Kathryn M. , Sanguins Julianne , McGregor Lisa , LeBlanc Pamela
Published: October 2007

First Nations peoples bring a particular history and cultural perspective to healing and well-being that significantly influences their health behaviors. The authors used grounded theory methods to describe and explain how ethnocultural affiliation and gender influence the process that 22 First Nations people underwent when making lifestyle changes related to their coronary artery disease (CAD) risk. The transcribed interviews revealed a core variable, meeting the challenge. Meeting the challenge of CAD risk management was influenced by intrapersonal, interpersonal (relationships with others), extrapersonal (i.e., the community and government), sociodemographic, and gendered factors. Salient elements for the participants included their beliefs about origins of illness, the role of family, challenges to accessing information, financial and resource management, and the gendered element of body image. Health care providers need to understand the historical, social, and culturally embedded factors that influence First Nations people's appraisal of their CAD.
A New Theoretical Model for Cooperation in Public Health Settings: The RDIC Model
Authors: de Rijk Angelique , van Raak Arno , van der Made Jan
Published: October 2007

The Resource Dependence Institutional Cooperation (RDIC) model was constructed from four combined theories: network, organizational behavior, resource dependence, and new institutional. The authors developed the model in an effort to better understand cooperation in public health settings, and tested its validity in two different types of networks related to occupational health. Two qualitative studies were performed in the Netherlands. The first study included 11 respondents dealing with the sickness absence of 4 employees. The second study included 11 respondents from 5 organizations involved in developing sickness absence policy. Document analyses and semistructured interviews were performed. The results indicate that the RDIC model coincided with empirical patterns of cooperation in both types of networks. Though they recommend further empirical research, the authors conclude that the model appears to be a valid instrument for understanding cooperation. They assert that the RDIC model can facilitate the management of cooperation in various public health settings.
Maslow Revisited: Constructing a Road Map of Human Nature
Authors: O'Connor Dennis , Yballe Leodones
Published: October 2007

Given the scope and intent of Maslow's work, the current textbook treatment is wanting. Therefore, an inductive exercise has been created and is o fered here to build “the road map of human nature.” This age-old, philosophic focus on our true nature has been a way to successfully engage and inspire both our students and our pedagogy. In the spirit of Maslow, the meaning of self-actualization is explored, and the understanding and managing of motivation is embedded into the larger context of leadership, for example, quality, spirituality, ethics, self-awareness, and personal growth.
Discovering Your Personality: A Group Exercise In Personal Sensemaking
Authors: Anderson Marc H.
Published: October 2007

Personality affects a wide variety of issues in organizational behavior, human resource management, and strategic management. Instructors teaching personality often have students take personality tests and then give them their scores. This passive approach to giving test feedback suffers from several weaknesses dealing with distinct perceptual biases. The author presents an experiential group exercise that helps overcome these problems and that has a broad range of applications in management and social science courses that discuss personality.
“We the People”
Authors: Lee Teten Ryan
Published: October 2007

This article examines the usage of popular address rhetoric within all the State of the Union Addresses to determine whether presidents have consistently used this rhetorical tool, or whether the introduction of going public is indeed a “modern” development that was little used in the rhetorical past of the presidency. By looking at instances in which the president identifies himself with the people, Congress, or as president, the author finds that many formerly “traditional” presidents exhibit “modern” tendencies, which suggests inconsistencies with the “traditional/modern” divide that is a commonly utilized paradigm in presidential study.
Modeling, H∞ Control and Stability Analysis for Structural Systems Using Takagi-Sugeno Fuzzy Model
Authors: Chen Cheng-Wu , Yeh Ken , Chiang Wei-Ling , Chen Chen-Yuan , Wu Deh-Juan
Published: October 2007

This article proposes a design method for producing H∞ control performance for structural systems using the Tagagi-Sugeno (T-S) fuzzy model. A structural system with a tuned mass damper is modeled using a T-S type fuzzy model. Using the parallel distributed compensation (PDC) scheme, we design a nonlinear fuzzy controller for the tuned mass damper system. A sufficient stability condition for the control system is derived in terms of Lyapunov theory and this control problem is reformulated into solving the linear matrix inequalities (LMI) problem. Finally, the tuned mass damper is designed based on the first modal frequency of the control system and a fuzzy controller to stabilize the structural system is then found using the Matlab LMI toolbox. A simulation example is given to show the feasibility of the proposed fuzzy controller design method.
Fuzzy Logic Control of a Non-linear Structural System against Earthquake Induced Vibration
Authors: Guclu Rahmi , Yazici Hakan
Published: October 2007

In this paper, the problem of active vibration control of multi-degree-of-freedom structures is considered. Fuzzy logic and PID controllers are designed to suppress structural vibrations against earthquakes under the non-linear soil-structure interaction. The advantage of the fuzzy logic approach is the ability to handle the non-linear behavior of the system. Non-linear behavior of the soil is modeled in the dynamics of the structural system with non-linear hysteric restoring forces. The simulated system has fifteen degrees of freedom, which is modeled using spring-mass-damper subsystems. A structural system was simulated against the ground motion of the destructive Kocaeli earthquake (M w = 7.4) in Turkey on 17 August 1999. At the end of the study the time history of the storey displacements and accelerations, the control voltages and forces, and the frequency responses of both the uncontrolled and the controlled structures are presented. The performance of designed fuzzy logic control is checked using the changing mass parameters of each storey and the results are discussed. These results show that the proposed fuzzy logic controller has great potential in active structural control.
Adaptive Variable Structure and Active Vibration Reduction for Flexible Spacecraft under Input Nonlinearity
Authors: Hu Qinglei , Xie Lihua , Gao Huijun
Published: October 2007

This paper is concerned with vibration control of a flexible spacecraft in the presence of parametric uncertainty/external disturbances as well as control input nonlinearity through distributed piezoelectric sensor/actuator technology. To satisfy pointing requirements and simultaneously suppress vibrations, two separate control loops are adopted. The first uses piezoceramics as sensors and actuators to actively suppress certain flexible modes by designing suboptimal positive position feedback (SOPPF) compensators which add damping to the flexible structures in certain critical modes. The problem of determining the SOPPF gain is formulated as static output feedback problem. The second feedback loop is designed based on an output feedback sliding mode control (OFSMC) design where control input nonlinearity is taken into consideration. The controller has the ability to reject the disturbance, deal with uncertainty and to ensure that the system trajectories globally converge to the sliding mode. Furthermore, an adaptive version of the proposed controller is achieved through releasing the limitation of knowing the bounds of the uncertainties and perturbations in advance. Simulation studies for the proposed control strategy on a flexible spacecraft have been carried out which demonstrate the effectiveness of the proposed approach.
Modeling and Robust Active Control of a Pneumatic Vibration Isolator
Authors: Chen Ping-Chang , Shih Ming-Chang
Published: October 2007

The accelerated development of precision technology has spurred an increasing requirement for vibration isolation equipment in recent years. Passive pneumatic vibration isolators are popular for avoiding vibration disturbance from the floor. However, the low-frequency resonance ( <3 Hz) is an unavoidable disadvantage when employing this approach. Therefore, this investigation develops an active pneumatic isolator with an active control method to suppress the resonant peak of the passive isolator. The linearized mathematical model is derived to obtain the nominal model of the isolation system in the beginning. Then, through the comparison between experiment and simulation, the unknown parameters of the rubber diaphragm can be identified. The active controller is designed to suppress the vibration disturbance based on the robust H∞ control theory. Hence, the weighting functions are selected appropriately according to desired specifications and taken into consideration during controller design procedures. Finally, the controller is obtained with off-line calculation, and the closed-loop system is achieved using the velocity feedback. The experimental results clearly reveal that the active control method improves the performance in the low frequency range and the resonant peak of passive isolator is reduced effectively.
Impact of Organizational Attributes on Nurse Satisfaction in Home Health
Authors: Mensik Jennifer
Published: October 2007

With the nursing shortage continuing to worsen, the retainment of current nursing staff becomes increasingly important for health care organizations. Specific organizational attributes have been found to have a significant relationship with nurse satisfaction in the acute care setting. Results from this study demonstrate a significant relationship between certain organizational attributes and nurse satisfaction in the home health care setting.
Precepting a Student? Here are the Job Descriptions
Authors: Fitzgerald Dorcas C. , McAllen Patricia A.
Published: October 2007

Often a community health nurse is asked to precept a nursing student. Having a student accompany a nurse into patients' homes and clinics provides valuable learning experiences for the student. In this one-to-one, apprentice-type relationship with a community-skilled nurse, the student synthesizes clinical knowledge by learning skills, roles, responsibilities, and standards of care outside the acute care setting and enhances assessment, decision-making, and communication skills. In addition, preceptor experiences are opportunities to ignite professional enthusiasm, as well as serve as recruitment and retention modalities. To assist in implementing and/or continuing preceptor practicums with nursing schools, this article lists the job descriptions for all those involved in preceptorships.
Asthma Home Visit Program: A Valuable Piece to a Complex Puzzle
Authors: Stabinski Jodie W.
Published: October 2007

This article provides an update on the status of asthma and its impact on the quality of life, as well as the financial impacts. Alternatives to care are discussed that address the decreased use of health care dollars that concurrently enhance the quality of life for children with asthma and their families.
Factors Influencing the Successful Utilization of Home Health Care in the Treatment of Children and Adolescents With Cancer
Authors: Kandsberger Donna
Published: October 2007

Because of ongoing developments in available therapies, supportive care, and medical technology, as well as psychosocial and financial considerations, children and adolescents with cancer are undergoing a greater variety of treatments in a greater variety of settings with a greater chance for cure of their diseases than ever before. Choice of venue for various components of an individual child's treatment must take into account the nature of the therapy, available resources, and burden for the child and family. This article will review recent literature illustrating factors to be considered for the successful utilization of home care services in the overall care of children and adolescents with cancer.
Introduction: person-reference in conversation analytic research
Authors: Lerner Gene H. , Kitzinger Celia
Published: October 2007

In this introduction to the special issue of Discourse Studies on `Referring to Self and Others in Conversation' we briefly survey the history of conversation analytic work on reference to persons from Sacks and Schegloff's (1979) pioneering seven-page paper to the most recently published work. We then introduce the contributions to the special issue.
Categories in action: person-reference and membership categorization
Authors: Schegloff Emanuel A.
Published: October 2007

The article begins with an effort to clarify and differentiate a variety of terms used by analysts in dealing with mentions of persons in conversation and other forms of talk-in-interaction — such terms as person-reference, identifying, describing, categorizing, and the like. This effort leads to the observation that `reference to persons' and `membership categorization' are quite distinct sets of practices, with most reference to persons not being done by membership categories, and most uses of membership categorization devices being in the service of actions other than referring. Two interactional sequences whose analysis turns on a connection to talk earlier in the occasion (a configuration termed `interactional threads') are then examined; first, to establish what is going on interactionally without respect to the mentioning of persons, and then as exercises in examining the various ways person-reference and membership categorization can figure in a stretch of interaction.
Broad-Based Fellowships: A Cornerstone of Minimally Invasive Surgery Education and Dissemination
Authors: Balaa F. , Moloo H. , Poulin E.C. , Haggar F. , Trottier D.C. , Boushey R.P. , Mamazza J.
Published: October 2007

Aware of the trends in surgery and of public demand, many residents completing a 5-year training program seek fellowships in minimally invasive surgery (MIS) because of inadequate exposure to advanced MIS during their residency. A survey was designed to evaluate the effectiveness of a broad-based fellowship in advanced laparoscopic surgery offered in an academic health science center. The questionnaire was mailed to all graduates. Data on demographics, comfort level with specific laparoscopic procedures, and opinions regarding the best methods of acquiring these skills were collected. Most of the surgeons entered the fellowship directly after residency. The majority of these surgeons are academic surgeons. Fellows performed a median of 187 cases by the end of their training and felt comfortable operating on foregut, hindgut, and end organ. A full year of training was found to be the best format for appropriate skill transfer. A broad-based MIS fellowship meets the needs of both academic and community surgeons desiring to perform advanced laparoscopic procedures.
Characterization of Heavyweight and Lightweight Polypropylene Prosthetic Mesh Explants From a Single Patient
Authors: Costello C.R. , Bachman S.L. , Grant S.A. , Cleveland D.S. , Loy T.S. , Ramshaw B.J.
Published: October 2007

Although polypropylene has been used as a hernia repair material for nearly 50 years, very little science has been applied to studying the body's effect on this material. It is possible that oxidation of mesh occurs as a result of the chemical structure of polypropylene and the physiological conditions to which it is subjected; this leads to embrittlement of the material, impaired abdominal movement, and chronic pain. It is also possible that lightweight polypropylene meshes undergo less oxidation due to a reduced inflammatory reaction. The objective of this study was to characterize explanted hernia meshes using techniques such as scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, and compliance testing to determine whether the mesh density of polypropylene affects the oxidative degradation of the material. The hypothesis was that heavyweight polypropylene would incite a more intense inflammatory response than lightweight polypropylene and thus undergo greater oxidative degradation. Overall, the results support this theory.
Misclassification of Hospital Volume With Surveillance, Epidemiology, and End Results—Medicare Data
Authors: Hollenbeck Brent K. , Hong Ji  , Zaojun Ye  , Birkmeyer John D.
Published: October 2007

Surveillance, Epidemiology, and End Results (SEER)— Medicare data are frequently used for studying relationships between volume and outcomes after cancer surgery; however, because patients often cross SEER boundaries for treatment, SEER-Medicare data may misclassify hospital volume. Thus, we measured the agreement of hospital volume as determined by SEER-Medicare and 100% national Medicare data and determined the extent to which misclassification alters the apparent relationship between volume and operative mortality. This is a retrospective cohort study of SEER-Medicare patients undergoing a major cancer surgery for colon, lung, bladder, and esophageal cancers between 1994 and 1999. Hospital procedure volumes were assessed with both SEER-Medicare and 100% national Medicare data and sorted into terciles. Logistic regression models were fit using generalized estimating equations to assess associations between mortality and volume, as determined from each data source. Compared with 100% Medicare data, SEER-Medicare data misclassified 13% (colectomy) to 36% (esophagectomy) of patients; however, fewer than 3% of patients were misclassified by more than 1 volume stratum. For cystectomy, the apparent association between volume and mortality was relatively weak and not statistically significant based on SEER-Medicare data (adjusted odds ratio, low vs high volume 1.41, 95% confidence interval, 0.89-2.23), but stronger and significant when volume was obtained from 100% Medicare data (odds ratio, 1.82; 95% confidence interval, 1.17 to 2.84). For the other 3 procedures, apparent volume/outcome relationships were similar when volume was assessed from the 2 data sources. Hospital volumes are frequently misclassified with SEER-Medicare data. Such misclassification generally biases volume/outcome associations toward the null, but this effect seems to be small for many procedures. Investigators should be cognizant of this bias and exercise caution when interpreting these relationships when using SEER-Medicare data alone.
Innovative Dynamic Minimally Invasive Training Environment (DynaMITE)
Authors: Bell Audrey K. , Saide Matthew B. , Johanas Jacqueline T. , Leisk Gary G. , Schwaitzberg Steven D. , Cao Caroline G.L.
Published: October 2007

Existing laparoscopic box trainers consist only of static tasks and do not adequately prepare surgeons to navigate the dynamic surgical environment. This paper describes an innovative design using controlled motorized target movements to enhance the training of dynamic motor skills. The prototype was tested using 15 subjects with different surgical experience levels. The task required accurate contact, using a laparoscopic tool, with targets moving in 5 different movement trajectories: (1) static, (2) horizontal, (3) vertical, (4) slow hourglass-shaped, and (5) fast hourglass-shaped. Expert surgeons were significantly faster than novices in the static, horizontal, and slow hourglass target conditions. Intermediate experienced subjects (PGY2s) were faster than novices in the horizontal target condition only. In the fast hourglass condition, experts were not faster than less experienced and novice subjects, but they were more accurate. There is the potential to train hand-eye coordination of even expert surgeons using this dynamic environment.
Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage–specific FAK knockout
Authors: Hitchcock Ian S. , Fox Norma E. , Prévost Nicolas , Sear Katherine , Shattil Sanford J. , Kaushansky Kenneth
Published: October 2007

Focal adhesion kinase (FAK) plays a key role in mediating signaling downstream of integrins and growth factor receptors. In this study, we determined the roles of FAK in vivo by generating a megakaryocyte lineage–specific FAK-null mouse (Pf4-Cre/FAK-floxed). Megakaryocyte and platelet FAK expression was ablated in Pf4-Cre/FAK-floxed mice without affecting expression of the FAK homologue PYK2, although PYK2 phosphorylation was increased in FAK−/− megakaryocytes in response to fibrinogen. Megakaryopoiesis is greatly enhanced in Pf4-Cre/FAK-floxed mice, with significant increases in megakaryocytic progenitors (CFU-MK), mature megakaryocytes, megakaryocyte ploidy, and moderate increases in resting platelet number and platelet recovery following a thrombocytopenic stress. Thrombopoietin (Tpo)–mediated activation of Lyn kinase, a negative regulator of megakaryopoiesis, is severely attenuated in FAK-null megakaryocytes compared with wild-type controls. In contrast, Tpo-mediated activation of positive megakaryopoiesis regulators such as ERK1/2 and AKT is increased in FAK-null megakaryocytes, providing a plausible explanation for the observed increases in megakaryopoiesis in these mice. In Pf4-Cre/FAK-floxed mice, rebleeding times are significantly increased, and FAK-null platelets exhibit diminished spreading on immobilized fibrinogen. These studies establish clear roles for FAK in megakaryocyte growth and platelet function, setting the stage for manipulation of this component of the Tpo signaling apparatus for therapeutic benefit.
Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis
Authors: Eiring Anna M. , Neviani Paolo , Santhanam Ramasamy , Oaks Joshua J. , Chang Ji Suk , Notari Mario , Willis William , Gambacorti-Passerini Carlo , Volinia Stefano , Marcucci Guido , Caligiuri Michael A. , Leone Gustavo W. , Perrotti Danilo
Published: October 2007

Several RNA binding proteins (RBPs) have been implicated in the progression of chronic myelogenous leukemia (CML) from the indolent chronic phase to the aggressively fatal blast crisis. In the latter phase, expression and function of specific RBPs are aberrantly regulated at transcriptional or posttranslational levels by the constitutive kinase activity of the BCR/ABL oncoprotein. As a result, altered expression/function of RBPs leads to increased resistance to apoptotic stimuli, enhanced survival, growth advantage, and differentiation arrest of CD34+ progenitors from patients in CML blast crisis. Here, we identify the mRNAs bound to the hnRNP-A1, hnRNP-E2, hnRNP-K, and La/SSB RBPs in BCR/ABLtransformed myeloid cells. Interestingly, we found that the mRNA encoding the transcription factor E2F3 associates to hnRNP-A1 through a conserved binding site located in the E2F3 3′ untranslated region (UTR). E2F3 levels were up-regulated in CML-BCCD34+ in a BCR/ABL kinase– and hnRNP-A1 shuttling–dependent manner. Moreover, by using shRNA-mediated E2F3 knock-down and BCR/ABL-transduced lineage-negative bone marrow cells from E2F3+/+ and E2F3−/− mice, we show that E2F3 expression is important for BCR/ABL clonogenic activity and in vivo leukemogenic potential. Thus, the complexity of the mRNA/RBP network, together with the discovery of E2F3 as an hnRNP-A1–regulated factor, outlines the relevant role played by RBPs in posttranscriptional regulation of CML development and progression.
PGE2-induced metalloproteinase-9 is essential for dendritic cell migration
Authors: Yen Jui-Hung , Khayrullina Tanzilya , Ganea Doina
Published: October 2007

Following antigen acquisition and maturation, dendritic cells (DCs) disengage from the extracellular matrix, cross basement membranes, and travel to draining lymph nodes to activate T cells. CCR7 expression is necessary but not sufficient for the directional migration of DCs. Prostaglandin E2 (PGE2), present in inflammatory sites, induces DC migration, presumably by enacting a migration-permissive gene expression program. Since regulation of DC migration is highly important for their use in vaccination and therapy, we examined the PGE2-induced changes in the expression of metalloproteinases (MMPs). Our results indicate that PGE2 significantly up-regulates MMP-9 expression, induces both secreted and membrane-bound MMP-9, and that in turn, DC-derived MMP-9 is essential for DC chemotaxis in response to the CCR7 ligand CCL19, Matrigel migration, and in vivo migration in both wild-type and MMP-9–deficient hosts. We conclude that DCs matured within inflammatory sites require both CCR7 and PGE2-induced MMP-9 for their directional migration to draining lymph nodes.
Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study
Authors: Boehrer Simone , Adès Lionel , Braun Thorsten , Galluzzi Lorenzo , Grosjean Jennifer , Fabre Claire , Le Roux Génèviève , Gardin Claude , Martin Antoine , de Botton Stéphane , Fenaux Pierre , Kroemer Guido
Published: October 2007

Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR), induces differentiation, cell-cycle arrest, and apoptosis of EGFR-negative myeloblasts of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), as well as in EGFR-negative cell lines representing these diseases (P39, KG-1, and HL 60). This off-target effect can be explained by inhibitory effects on JAK2. Apoptosis induction coupled to mitochondrial membrane permeabilization occurred independently from phenotypic differentiation. In apoptosis-sensitive AML cells, erlotinib caused a rapid (within less than 1 hour) nucleocytoplasmic translocation of nucleophosmin-1 (NPM-1) and p14ARF. Apoptosis-insensitive myeloblasts failed to manifest this translocation yet became sensitive to apoptosis induction by erlotinib when NPM-1 was depleted by RNA interference. Moreover, erlotinib reduced the growth of xenografted human AML cells in vivo. Erlotinib also killed CD34+ bone marrow blasts from MDS and AML patients while sparing normal CD34+ progenitors. This ex vivo therapeutic effect was once more associated with the nucleocytoplasmic translocation of NPM-1 and p14ARF. One patient afflicted with both MDS and non–small cell lung cancer manifested hematologic improvement in response to erlotinib. In summary, we here provide novel evidence in vitro, ex vivo, and in vivo for the potential therapeutic efficacy of erlotinib in the treatment of high-risk MDS and AML.
Biomarkers in newly diagnosed pediatric-extensive chronic graft-versus-host disease: a report from the Children's Oncology Group
Authors: Fujii Hisaki , Cuvelier Geoff , She Kevin , Aslanian Soudabeh , Shimizu Hiromi , Kariminia Amina , Krailo Mark , Chen Zhengjia , McMaster Rob , Bergman Axel , Goldman Frederick , Grupp Stephen A. , Wall Donna A. , Gilman Andrew L. , Schultz Kirk R.
Published: October 2007

Numerous chronic graft-versus-host disease (cGVHD) biomarkers have been identified in limited, single-institution studies without validation. We hypothesized that plasma-derived biomarkers could diagnose, classify, and evaluate response in children with cGVHD. We performed a concomitant analysis of a number of known and predicted peripheral blood cGVHD biomarkers from a Children's Oncology Group (COG) phase 3 cGVHD therapeutic trial. A total of 52 newly diagnosed patients with extensive cGVHD were compared for time of onset after blood and marrow transplantation (BMT) (early, 3-8 months; late, ≥ 9 months) with 28 time-matched controls with no cGVHD (early, 6 months after BMT; late, 12 months after BMT). Soluble B-cell activation factor (sBAFF), anti-dsDNA antibody, soluble IL-2 receptor alpha (sIL-2Rα), and soluble CD13 (sCD13) were elevated in patients with early-onset cGVHD compared with controls. sBAFF and anti-dsDNA were elevated in patients with late-onset cGVHD. Some of the biomarkers correlated with specific organ involvement and with therapeutic response. These 4 biomarkers had high specificity with higher sensitivity in combination. Changes in biomarker concentrations with immune reconstitution after transplantation significantly affected interpretation of results. The identified biomarkers have the potential for improved classification, early response evaluation, and direction of cGVHD treatment, but require validation in larger studies. This study is registered at www.cancer.gov/clinicaltrials as no. COG-ASCT0031.
Inhibition of neutrophil activity improves cardiac function after cardiopulmonary bypass
Authors: Abdel-Rahman Ulf , Margraf Stefan , Aybek Tayfun , Lögters Tim , Bitu-Moreno José , Francischetti Ieda , Kranert Tilmann , Grünwald Frank , Windolf Joachim , Moritz Anton , Scholz Martin
Published: October 2007

Background

The arterial in line application of the leukocyte inhibition module (LIM) in the cardiopulmonary bypass (CPB) limits overshooting leukocyte activity during cardiac surgery. We studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB.

Methods

German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion) without (group I; n = 6) or with LIM (group II; n = 6). The cardiac indices (CI) and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs.

Results

LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 ± 0.31; pre: 4.05 ± 0.45 l/min/m2; p < 0.01). In group II, the CI was only slightly reduced (post: 3.86 ± 0.49; pre 4.21 ± 1.32 l/min/m2; p = 0.23). Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p < 0.05) which was in conjunction with higher pre-load independent endsystolic pressure volume relationship (ESPVR) values (group I: 1.57 ± 0.18; group II: 1.93 ± 0.16; p < 0.001). Moreover, the systemic vascular resistance and pulmonary vascular resistance were lower in the LIM group. LIM appeared to accelerate the sequestration of hyperactivated neutrophils in the spleen and to reduce neutrophil infiltration of heart and lung.

Conclusion

Our data provides strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen.
Resveratrol potently reduces prostaglandin E2production and free radical formation in lipopolysaccharide-activated primary rat microglia
Authors: Candelario-Jalil Eduardo , de Oliveira Antonio C Pinheiro , Gräf Sybille , Bhatia Harsharan S , Hüll Michael , Muñoz Eduardo , Fiebich Bernd L
Published: October 2007

Background

Neuroinflammatory responses are triggered by diverse ethiologies and can provide either beneficial or harmful results. Microglial cells are the major cell type involved in neuroinflammation, releasing several mediators, which contribute to the neuronal demise in several diseases including cerebral ischemia and neurodegenerative disorders. Attenuation of microglial activation has been shown to confer protection against different types of brain injury. Recent evidence suggests that resveratrol has anti-inflammatory and potent antioxidant properties. It has been also shown that resveratrol is a potent inhibitor of cyclooxygenase (COX)-1 activity. Previous findings have demonstrated that this compound is able to reduce neuronal injury in different models, both in vitro and in vivo. The aim of this study was to examine whether resveratrol is able to reduce prostaglandin E2 (PGE2) and 8-iso-prostaglandin F2α (8-iso-PGF2α) production by lipopolysaccharide (LPS)-activated primary rat microglia.

Methods

Primary microglial cell cultures were prepared from cerebral cortices of neonatal rats. Microglial cells were stimulated with 10 ng/ml of LPS in the presence or absence of different concentrations of resveratrol (1–50 μM). After 24 h incubation, culture media were collected to measure the production of PGE2 and 8-iso-PGF2α using enzyme immunoassays. Protein levels of COX-1, COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) were studied by Western blotting after 24 h of incubation with LPS. Expression of mPGES-1 at the mRNA level was investigated using reverse transcription-polymerase chain reaction (RT-PCR) analysis.

Results

Our results indicate that resveratrol potently reduced LPS-induced PGE2 synthesis and the formation of 8-iso-PGF2α, a measure of free radical production. Interestingly, resveratrol dose-dependently reduced the expression (mRNA and protein) of mPGES-1, which is a key enzyme responsible for the synthesis of PGE2 by activated microglia, whereas resveratrol did not affect the expression of COX-2. Resveratrol is therefore the first known inhibitor which specifically prevents mPGES-1 expression without affecting COX-2 levels. Another important observation of the present study is that other COX-1 selective inhibitors (SC-560 and Valeroyl Salicylate) potently reduced PGE2 and 8-iso-PGF2α production by LPS-activated microglia.

Conclusion

These findings suggest that the naturally occurring polyphenol resveratrol is able to reduce microglial activation, an effect that might help to explain its neuroprotective effects in several in vivo models of brain injury.