bluuebunny/crossref_metadata_2025 huggingface dataset:
CYT997: a novel orally active tubulin polymerization inhibitor with potent cytotoxic and vascular disrupting activity in vitro and in vivo
Authors: Burns Christopher J. , Fantino Emmanuelle , Phillips Ian D. , Su Stephen , Harte Michael F. , Bukczynska Patricia E. , Frazzetto Mark , Joffe Max , Kruszelnicki Irma , Wang Bing , Wang Yue , Wilson Neil , Dilley Rodney J. , Wan Soo S. , Charman Susan A. , Shackleford David M. , Fida Rosa , Malcontenti-Wilson Cathy , Wilks Andrew F.
Published: November 2009

CYT997 is a wholly synthetic compound that possesses highly potent cytotoxic activity in vitro through inhibition of microtubule polymerization. CYT997 blocks the cell cycle at the G2-M boundary, and Western blot analysis indicates an increase in phosphorylated Bcl-2, along with increased expression of cyclin B1. Caspase-3 activation is also observed in cells treated with CYT997 along with the generation of poly(ADP-ribose) polymerase. The compound possesses favorable pharmacokinetic properties, is orally bioavailable, and is efficacious per os in a range of in vivo cancer models, including some refractory to paclitaxel treatment. CYT997 exhibits vascular disrupting activity as measured in vitro by effects on the permeability of human umbilical vein endothelial cell monolayers, and in vivo by effects on tumor blood flow. CYT997 possesses a useful combination of pharmacologic and pharmacokinetic properties and has considerable potential as a novel anticancer agent. [Mol Cancer Ther 2009;8(11):3036–45]
JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia
Authors: Manthey Carl L. , Johnson Dana L. , Illig Carl R. , Tuman Robert W. , Zhou Zhao , Baker Judith F. , Chaikin Margery A. , Donatelli Robert R. , Franks Carol F. , Zeng Lee , Crysler Carl , Chen Yanmin , Yurkow Edward J. , Boczon Lisa , Meegalla Sanath K. , Wilson Kenneth J. , Wall Mark J. , Chen Jinsheng , Ballentine Shelley K. , Ott Heidi , Baumann Christian , Lawrence Danielle , Tomczuk Bruce E. , Molloy Christopher J.
Published: November 2009

There is increasing evidence that tumor-associated macrophages promote the malignancy of some cancers. Colony-stimulating factor-1 (CSF-1) is expressed by many tumors and is a growth factor for macrophages and mediates osteoclast differentiation. Herein, we report the efficacy of a novel orally active CSF-1 receptor (CSF-1R) kinase inhibitor, JNJ-28312141, in proof of concept studies of solid tumor growth and tumor-induced bone erosion. H460 lung adenocarcinoma cells did not express CSF-1R and were not growth inhibited by JNJ-28312141 in vitro. Nevertheless, daily p.o. administration of JNJ-28312141 caused dose-dependent suppression of H460 tumor growth in nude mice that correlated with marked reductions in F4/80+ tumor-associated macrophages and with increased plasma CSF-1, a possible biomarker of CSF-1R inhibition. Furthermore, the tumor microvasculature was reduced in JNJ-28312141–treated mice, consistent with a role for macrophages in tumor angiogenesis. In separate studies, JNJ-28312141 was compared with zoledronate in a model in which MRMT-1 mammary carcinoma cells inoculated into the tibias of rats led to severe cortical and trabecular bone lesions. Both agents reduced tumor growth and preserved bone. However, JNJ-28312141 reduced the number of tumor-associated osteoclasts superior to zoledronate. JNJ-28312141 exhibited additional activity against FMS-related receptor tyrosine kinase-3 (FLT3). To more fully define the therapeutic potential of this new agent, JNJ-28312141 was evaluated in a FLT3-dependent acute myeloid leukemia tumor xenograft model and caused tumor regression. In summary, this novel CSF-1R/FLT3 inhibitor represents a new agent with potential therapeutic activity in acute myeloid leukemia and in settings where CSF-1–dependent macrophages and osteoclasts contribute to tumor growth and skeletal events. [Mol Cancer Ther 2009;8(11):3151–61]
Small interfering RNA library screen of human kinases and phosphatases identifies polo-like kinase 1 as a promising new target for the treatment of pediatric rhabdomyosarcomas
Authors: Hu Kaiji , Lee Cathy , Qiu Dexin , Fotovati Abbas , Davies Alastair , Abu-Ali Samah , Wai Daniel , Lawlor Elizabeth R. , Triche Timothy J. , Pallen Catherine J. , Dunn Sandra E.
Published: November 2009

Rhabdomyosarcoma, consisting of alveolar (aRMS) and embryonal (eRMS) subtypes, is the most common type of sarcoma in children. Currently, there are no targeted drug therapies available for rhabdomyosarcoma. In searching for new molecular therapeutic targets, we carried out genome-wide small interfering RNA (siRNA) library screens targeting human phosphatases (n = 206) and kinases (n = 691) initially against an aRMS cell line, RH30. Sixteen phosphatases and 50 kinases were identified based on growth inhibition after 72 hours. Inhibiting polo-like kinase 1 (PLK1) had the most remarkable impact on growth inhibition (∼80%) and apoptosis on all three rhabdomyosarcoma cell lines tested, namely, RH30, CW9019 (aRMS), and RD (eRMS), whereas there was no effect on normal muscle cells. The loss of PLK1 expression and subsequent growth inhibition correlated with decreased p-CDC25C and Cyclin B1. Increased expression of WEE 1 was also noted. The induction of apoptosis after PLK1 silencing was confirmed by increased p-H2AX, propidium iodide uptake, and chromatin condensation, as well as caspase-3 and poly(ADP-ribose) polymerase cleavage. Pediatric Ewing's sarcoma (TC-32), neuroblastoma (IMR32 and KCNR), and glioblastoma (SF188) models were also highly sensitive to PLK1 inhibition. Finally, based on cDNA microarray analyses, PLK1 mRNA was overexpressed (>1.5 fold) in 10 of 10 rhabdomyosarcoma cell lines and in 47% and 51% of primary aRMS (17 of 36 samples) and eRMS (21 of 41 samples) tumors, respectively, compared with normal muscles. Similarly, pediatric Ewing's sarcoma, neuroblastoma, and osteosarcoma tumors expressed high PLK1. We conclude that PLK1 could be a promising therapeutic target for the treatment of a wide range of pediatric solid tumors including rhabdomyosarcoma. [Mol Cancer Ther 2009;8(11):3024–35]
Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer
Authors: Qamri Zahida , Preet Anju , Nasser Mohd W. , Bass Caroline E. , Leone Gustavo , Barsky Sanford H. , Ganju Ramesh K.
Published: November 2009

Cannabinoids have been reported to possess antitumorogenic activity. Not much is known, however, about the effects and mechanism of action of synthetic nonpsychotic cannabinoids on breast cancer growth and metastasis. We have shown that the cannabinoid receptors CB1 and CB2 are overexpressed in primary human breast tumors compared with normal breast tissue. We have also observed that the breast cancer cell lines MDA-MB231, MDA-MB231-luc, and MDA-MB468 express CB1 and CB2 receptors. Furthermore, we have shown that the CB2 synthetic agonist JWH-133 and the CB1 and CB2 agonist WIN-55,212-2 inhibit cell proliferation and migration under in vitro conditions. These results were confirmed in vivo in various mouse model systems. Mice treated with JWH-133 or WIN-55,212-2 showed a 40% to 50% reduction in tumor growth and a 65% to 80% reduction in lung metastasis. These effects were reversed by CB1 and CB2 antagonists AM 251 and SR144528, respectively, suggesting involvement of CB1 and CB2 receptors. In addition, the CB2 agonist JWH-133 was shown to delay and reduce mammary gland tumors in the polyoma middle T oncoprotein (PyMT) transgenic mouse model system. Upon further elucidation, we observed that JWH-133 and WIN-55,212-2 mediate the breast tumor-suppressive effects via a coordinated regulation of cyclooxygenase-2/prostaglandin E2 signaling pathways and induction of apoptosis. These results indicate that CB1 and CB2 receptors could be used to develop novel therapeutic strategies against breast cancer growth and metastasis. [Mol Cancer Ther 2009;8(11):3117–29]
Omega-3 polyunsaturated fatty acids inhibit hepatocellular carcinoma cell growth through blocking β-catenin and cyclooxygenase-2
Authors: Lim Kyu , Han Chang , Dai Yifan , Shen Miaoda , Wu Tong
Published: November 2009

Hepatocellular carcinoma (HCC) is a common human cancer with high mortality, and currently, there is no effective chemoprevention or systematic treatment. Recent evidence suggests that cyclooxygenase-2 (COX-2)–derived PGE2 and Wnt/β-catenin signaling pathways are implicated in hepatocarcinogenesis. Here, we report that ω-3 polyunsaturated fatty acids (PUFA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) inhibit HCC growth through simultaneously inhibition of COX-2 and β-catenin. DHA and EPA treatment resulted in a dose-dependent reduction of cell viability with cleavage of poly ADP ribose polymerase, caspase-3, and caspase-9 in three human HCC cell lines (Hep3B, Huh-7, HepG2). In contrast, AA, a ω-6 PUFA, exhibited no significant effect. DHA and EPA treatment caused dephosphorylation and thus activation of GSK-3β, leading to β-catenin degradation in Hep3B cells. The GSK-3β inhibitor, LiCl, partially prevented DHA-induced β-catenin protein degradation and apoptosis. Additionally, DHA induced the formation of β-catenin/Axin/GSK-3β binding complex, which serves as a parallel mechanism for β-catenin degradation. Furthermore, DHA inhibited PGE2 signaling through downregulation of COX-2 and upregulation of the COX-2 antagonist, 15-hydroxyprostaglandin dehydrogenase. Finally, the growth of HCC in vivo was significantly reduced when mouse HCCs (Hepa1-6) were inoculated into the Fat-1 transgenic mice, which express a Caenorhabditis elegans desaturase converting ω-6 to ω-3 PUFAs endogenously. These findings provide important preclinical evidence and molecular insight for utilization of ω-3 PUFAs for the chemoprevention and treatment of human HCC. [Mol Cancer Ther 2009;8(11):3046–55]
Selective metastatic tumor labeling with green fluorescent protein and killing by systemic administration of telomerase-dependent adenoviruses
Authors: Kishimoto Hiroyuki , Urata Yasuo , Tanaka Noriaki , Fujiwara Toshiyoshi , Hoffman Robert M.
Published: November 2009

We previously constructed telomerase-dependent, replication-selective adenoviruses OBP-301 (Telomelysin) and OBP-401 [Telomelysin-green fluorescent protein (GFP); TelomeScan], the replication of which is regulated by the human telomerase reverse transcriptase promoter. By intratumoral injection, these viruses could replicate within the primary tumor and subsequent lymph node metastasis. The aim of the present study was to evaluate the possibility of systemic administration of these telomerase-dependent adenoviruses. We assessed the antitumor efficacy of OBP-301 and the ability of OBP-401 to deliver GFP in hepatocellular carcinoma (HCC) and metastatic colon cancer nude mouse models. We showed that i.v. administration of OBP-301 significantly inhibited colon cancer liver metastases and orthotopically implanted HCC. Further, we showed that OBP-401 could visualize liver metastases by tumor-specific expression of the GFP gene after portal venous or i.v. administration. Thus, systemic administration of these adenoviral vectors should have clinical potential to treat and detect liver metastasis and HCC. [Mol Cancer Ther 2009;8(11):3001–8]
Outcomes Among Patients With ST-Segment–Elevation Myocardial Infarction Presenting to Interventional Hospitals With and Without On-Site Cardiac Surgery
Authors: Pride Yuri B. , Canto John G. , Frederick Paul D. , Gibson C. Michael
Published: November 2009

Background—

Primary percutaneous coronary intervention (pPCI) is the preferred reperfusion strategy for patients with ST-segment–elevation myocardial infarction (STEMI). The quality of care and safety and efficacy of pPCI at hospitals without on-site open heart surgery (No-OHS hospitals) remains an area of active investigation.

Methods and Results—

The National Registry of Myocardial Infarction enrolled 58 821 STEMI patients from 214 OHS hospitals (n=54 076) and 52 No-OHS hospitals (n=4745) with PCI capabilities from 2004 to 2006. Patients presenting to OHS hospitals had substantially lower in-hospital mortality (7.0% versus 9.8%,
P
<0.001) and were more likely to receive any form of acute reperfusion therapy (80.8% versus 70.8%,
P
<0.001). Patients who presented to OHS hospitals were more likely to receive guideline recommended medications within 24 hours of arrival. In a propensity score model matching for patient characteristics and transfer status, in-hospital mortality remained significantly lower among patients presenting to OHS hospitals (7.2% versus 9.3%,
P
=0.025). When this model was further adjusted for differences in the use of acute reperfusion therapy, medications administered within 24 hours and hospital characteristics, the mortality difference was of borderline significance (hazard ratio, 0.87; 95% CI, 0.75 to 1.01;
P
=0.067). When the propensity score analysis was restricted to patients who underwent pPCI, there was no significant difference in mortality (3.8% versus 3.3%,
P
=0.44).

Conclusions—

STEMI patients presenting to No-OHS hospitals have substantially higher mortality, are less likely to receive guideline recommended medications within 24 hours, and are less likely to undergo acute reperfusion therapy, although this difference was of borderline significance after adjusting for hospital and treatment variables. There was no difference in mortality among patients undergoing pPCI.
Cost-Consequences of Ultrafiltration for Acute Heart Failure
Authors: Bradley Steven M. , Levy Wayne C. , Veenstra David L.
Published: November 2009

Background—

Ultrafiltration for heart failure may reduce costs associated with acute heart failure by decreasing rehospitalization rates compared to intravenous diuretics.

Methods and Results—

We developed a decision-analytic model to explore the clinical outcomes and associated costs of ultrafiltration compared to intravenous diuretics for index and subsequent acute heart failure hospitalizations to 90 days from index hospitalization. We evaluated the model from societal, Medicare, and hospital payer perspectives. Base-case probabilities and costs were derived from the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure clinical trial, Medicare reimbursement schedules, and published data. From a societal perspective, treatment with ultrafiltration had an 86% probability of being more expensive than intravenous diuretics in probabilistic sensitivity analysis, with a base-case estimate of $13 469 per patient treated with ultrafiltration compared to $11 610 per patient treated with intravenous diuretics. Cost estimates were most influenced by length of index hospitalization, daily cost of rehospitalization, number of days rehospitalized, and number and cost of ultrafiltration filters. From a Medicare payer perspective, ultrafiltration had a >99% probability of being cost saving. From a hospital perspective, there was a 97% probability ultrafiltration was more expensive. Our model suggested similar 90-day mortality rates between treatment arms.

Conclusion—

Despite a reduction in rehospitalization rates, it is unlikely ultrafiltration results in cost savings from a societal perspective. The discordance in cost between societal, Medicare, and hospital perspectives underscores the importance of payer perspective in formulating strategies and reimbursement structures to reduce heart failure hospitalizations.
Of Pastors and Petticoats: Humor and Authority in Puritan New England
Authors: Horton Shaun
Published: November 2009

Early Puritan humor usually endorsed Puritanism at the expense of non-Puritans, but during the eighteenth century, Puritans made bolder jokes at the expense of their own ministers. This article examines how Puritans used humor to undermine social authority and how changes in New England society led to changes in Puritan humor.
Is the Prose Tale of Job in Late Biblical Hebrew?
Authors: Young Ian
Published: November 2009

An influential article published in 1974 by Avi Hurvitz argues that the language of the Prose Tale of Job (Job 1:1-2:13; 42:7-17) is incompatible with a date prior to the exile. Hurvitz's suggested Late Biblical Hebrew (LBH) linguistic forms are examined, and while some forms are rejected, Hurvitz's judgement that the Prose Tale contains LBH linguistic elements is found to be correct. However, these do not occur in a sufficient accumulation for the text to be considered LBH according to Hurvitz's own methodology, but rather the accumulation is consistent with a classification as Early Biblical Hebrew (EBH). This conclusion has no chronological implications, however, since EBH and LBH represent not two chronological phases but co-existing styles of Hebrew in the post-exilic and quite possibly pre-exilic periods.
Justice in the Sermon on the Mount: An Aristotelian Reading
Authors: Thom Johan
Published: November 2009

The frequent occurrence of the term δıκαıoσυνη ("righteousness, justice") in the Sermon of the Mount (Matt 5-7) (SM) indicates one of the main themes of the text. This impression is strengthened by the fact that the term is found in strategically important locations in the composition of the SM. This article does not, however, focus on the meaning and use of δıκαıoσυνη as such. Instead, I discuss the role justice, an important component of δıκαıoσυνη, plays in the SM. To help us gain perspective on how justice was popularly conceived, a brief survey of one of the most influential ancient analyses of justice, that by Aristotle in bk. 5 of his Nicomachean Ethics, is provided. Against this background, the way the notion of justice operates in selected passages of the SM is investigated. I try to show that the text frequently manipulates and overturns conventional conceptions of justice and that this reinforces the SM's demand for a δıκαıoσυνη exceeding popular expectations.
The Septuagint Version of Isaiah 53 and the Early Christian Formula "He Was Delivered for Our Trespasses"
Authors: Breytenbach Cilliers
Published: November 2009

Did Isaiah 53 (LXX) and its παραδıδóναı-terminology influence the early Christian notion of Jesus being delivered "for our sins" (Rom 4:25 etc.)? And if so, is that to be understood as a specific Jewish backdrop for the interpretation of the death of Jesus? The way in which the Septuagint deviates from the Hebrew text suggests another view. To render various terms of his Vorlage the translator of the LXX made use of the widespread Greek notion of delivering somebody unto a hostile force. If early Christian explication of the death of Jesus drew on Isaiah 53, it was influenced by its Greek translation.
Fractal Transition Model in Predicting Static Friction Coefficient
Authors: Changfu Sui , Xuanyu Sheng
Published: November 2009

There is a fractal characteristic in most engineering surfaces. Effects of the surface fractal parameters D, G and the material parameter φ on the static friction coefficient are discussed. The predicted static friction coefficient increases with the increase of normal load. This coincides with the fact that static friction coefficient is very low under very small normal load condition. Second, a fractal transition model is proposed which takes into account the change of fractal dimension D. The load‐contact area relationship based on fractal transition model is not simply an exponential function, and the prediction correlates well with the experimental results. The predicted static friction coefficient based on fractal transition model first increases with the increase of load, and then decrease with the increase of load. The transition point is near D=1.5.
Regression of Post-orthodontic Lesions by a Remineralizing Cream
Authors: Bailey D.L. , Adams G.G. , Tsao C.E. , Hyslop A. , Escobar K. , Manton D. J. , Reynolds E.C. , Morgan M.V.
Published: November 2009

Orthodontic patients have an increased risk of white-spot lesion formation. A clinical trial was conducted to test whether, in a post-orthodontic population using fluoride toothpastes and receiving supervised fluoride mouthrinses, more lesions would regress in participants using a remineralizing cream containing casein phosphopeptide- amorphous calcium phosphate compared with a placebo. Forty-five participants (aged 12–18 yrs) with 408 white-spot lesions were recruited, with 23 participants randomized to the remineralizing cream and 22 to the placebo. Product was applied twice daily after fluoride toothpaste use for 12 weeks. Clinical assessments were performed according to ICDAS II criteria. Transitions between examinations were coded as progressing, regressing, or stable. Ninety-two percent of lesions were assessed as code 2 or 3. For these lesions, 31% more had regressed with the remineralizing cream than with the placebo (OR = 2.3, P = 0.04) at 12 weeks. Significantly more post-orthodontic white-spot lesions regressed with the remineralizing cream compared with a placebo over 12 weeks.
Defining Dialect, Perceiving Dialect, and New Dialect Formation: Sarah Palin’s Speech
Authors: Purnell Thomas , Raimy Eric , Salmons Joseph
Published: November 2009

Nonlinguists prove surprisingly good at recognizing dialects, even as dialects rapidly evolve. During the 2008 U.S. presidential election, Republican vice presidential candidate Sarah Palin’s speech was intensely discussed among linguists, the media, and laypeople. Though Palin is from Alaska, her speech was often identified with the Upper Midwest.The authors explore what this mismatch can tell us about dialects and their perception, starting from a description of Palin’s speech as commented on in the media.They review some pragmatic features and provide quantitative treatment of her “g-dropping.” Then, they undertake acoustic analysis of Palin’s vowels and final /z/ devoicing, including Western features and features that create an impression of her speech as Upper Midwestern. Regional settlement history, research on “new dialect formation,” and research on perception of variation inform the authors’ finding that a few acoustic and other characteristics trigger a specific national perception of Palin’s verbal behavior.
Cancer Risk Assessment Approaches at the FDA/CDER: Is the Era of the 2-Year Bioassay Drawing to a Close?
Authors: Jacobson-Kram David
Published: November 2009

Determining the carcinogenic potential of materials to which humans have significant exposures is an important, complex, and imperfect exercise. Not only are the methods for such determinations protracted and expensive and use large numbers of animals, extrapolation of data from such studies to human risk is imprecise. With improved understanding of oncogene activation and tumor suppressor gene inactivation, a number of animal models have been developed to dramatically reduce latency for chemically induced cancers and has led to the development and use of shorter carcinogenicity assays. Recent studies by a number of investigators suggest that specific gene signature patterns seen after short-term exposure of rats to test chemicals can predict long-term outcomes in cancer bioassays with relatively high accuracy. In addition, a recent survey performed by PhRMA member companies examined two hundred drug years to determine whether histological biomarkers seen at the end of a six- or twelve-month toxicology study in rats can predict the outcome of a two-year carcinogenicity study. With only a handful of exceptions, chronic studies appear capable of predicting effects at the end of two years with good accuracy. It is hoped that the combination of results from transgenic mouse assays and six-month rat studies will soon supplant the need for most two-year bioassays.
Communicating and accentuating the aesthetic and expressive dimension in choral conducting
Authors: Durrant Colin
Published: November 2009

This article considers the issues that are involved in effective choral conducting from an aesthetic dimension. Drawing upon research, theories and practice, it provides some insight into the nature of communication and the significance of gesture on vocal outcome as well as qualities of leadership concomitant with such musical activity. The article also reports on a research study that investigated the professional development of students and teachers in the area of choral conducting, focusing on their attitudes, skill acquisition and the importance attached to reflection on practice. The findings reveal that consideration of what counts as effective conducting gesture and communication skill can promote better conducting and, consequently, better, more expressive singing. In addition, the positive impact of self- and peer reflection on progress (both face-to-face and within a virtual learning environment) was also acknowledged. Certain suggestions for promoting effective musical leadership in the area of choral conducting are provided, in order to ground theoretical perspectives in practice.
Reflective practice: a tool for measuring the development of generic skills in the training of professional musicians
Authors: Brown Judith Elizabeth
Published: November 2009

The 2006 ISME Commission for the Education of the Professional Musician (CEPROM) provided a unique forum for a number of important debates surrounding the preparation of young musicians for a professional career in the performing arts. One such debate considered the imperative of ensuring young professional musicians graduated from tertiary music institutions with skills beyond those of just performance practice: the more general or ‘generic’ skills that can be transferred into the many types of work situations they will inevitably face after their formal studies have been completed. Driven by the new imperatives surrounding work and changing careers, this debate dominated many of the discussions at the 2006 CEPROM. Building upon this debate, this article outlines a case study on the use of reflective journal writing as a curriculum tool to encourage music students to develop the generic skills of critical, creative and self-regulated thinking. Within the context of an Australian university landscape that is increasingly placing more emphasis on generic graduate outcomes, this article draws on the work of a number of educational theorists to provide a theoretical underpinning and rationale for reflective journal writing as a tool for embedding these generic skills in the music curriculum. The article concludes with some discussion of further research challenges and implications for curriculum design in tertiary music.
‘I’ll sing with my buddies’ — Fostering the possible selves of male choral singers
Authors: Freer Patrick K.
Published: November 2009

The stories of three high school boys about their experiences in school-based choral music provide the framework for a discussion of the role music educators can play in retaining male singers. The ‘possible selves’ construct (Markus & Nurius, 1986) is explored alongside research-based implications about specific steps toward developing boys’ identities as choral musicians. Possible selves are future conceptions of the self that are either positive (hoped-for) or negative (feared). The changing of the adolescent male voice occurs at approximately the same time as major social, academic, and other physical changes. It is thought that these issues coincide in a manner that discourages boys from participation in choral music (Freer, 2007). Drawing upon a successful non-musical model, the author proposes a variant of the ‘Possible Selves Program’ (Hock, Deshler, & Schumaker, 2006) for use in music settings.
Working with Children in End-of-Life Decision Making
Authors: Whitty-Rogers Joanne , Alex Marion , MacDonald Cathy , Pierrynowski Gallant Donna , Austin Wendy
Published: November 2009

Traditionally, physicians and parents made decisions about children’s health care based on western practices. More recently, with legal and ethical development of informed consent and recognition for decision making, children are becoming active participants in their care. The extent to which this is happening is however blurred by lack of clarity about what children — of diverse levels of cognitive development — are capable of understanding. Moreover, when there are multiple surrogate decision makers, parental and professional conflict can arise concerning children’s ‘best interest’. Giving children a voice and offering choice promotes their dignity and quality of life. Nevertheless, it also presents with many challenges. Case studies using pseudonyms and changed situational identities are used in this article to illuminate the complexity of ethical challenges facing nurses in end-of-life care with children and families.
Generosity and the Moral Imagination in the Practice of Teamwork
Authors: Arber Anne , Gallagher Ann
Published: November 2009

In this article we discuss generosity, a virtue that has received little attention in relation to nursing practice. We make a distinction between material generosity and generosity of spirit. The moral imagination is central to our analysis of generosity of spirit. We discuss data taken from a team meeting and identify the components of generosity, for example, the role of the moral imagination in interrupting value judgements, protecting the identity of the chronically ill patient through use of the psychosocial format, and displaying empathetic maturity. The talk of the team enables us to understand and make visible the link between generosity, moral imagination and identity construction. The topic of generosity, although contextualized in a UK setting, has relevance to other cultural contexts.
Nursing Ethics in the Seventh-Day Adventist Religious Tradition
Authors: Johnston Taylor Elizabeth , Carr Mark F
Published: November 2009

Nurses’ religious beliefs influence their motivations and perspectives, including their practice of ethics in nursing care. When the impact of these beliefs is not recognized, great potential for unethical nursing care exists. Thus, this article examines how the theology of one religious tradition, Seventh-day Adventism (SDA), could affect nurses. An overview of SDA history and beliefs is presented, which explains why ‘medical missionary’ work is central to SDAs. Theological foundations that would permeate an SDA nurse’s view of the nursing metaparadigm concepts of person, health, environment (i.e. community), and nursing (i.e. service) are presented. The ethical principles guiding SDA nurses (i.e. principled, case-based, and care ethics) and the implications of these theological foundations for nurses are noted in a case study.
Technologically-Mediated Nursing Care: the Impact on Moral Agency
Authors: O'Keefe-McCarthy Sheila
Published: November 2009

Technology is pervasive and overwhelming in the intensive care setting. It has the power to inform and direct the nursing care of critically ill patients. Technology changes the moral and social dynamics within nurse—patient encounters. Nurses use technology as the main reference point to interpret and evaluate clinical patient outcomes. This shapes nurses’ understanding and the kind of care provided. Technology inserts itself between patients and nurses, thus distancing nurses from patients. This situates nurses into positions of power, granting them epistemic authority, which constrains them as moral agents. Technology serves to categorize and marginalize patients’ illness experience. In this article, moral agency is examined within the technologically-mediated context of the intensive care unit. Uncritical use of technology has a negative impact on patient care and nurses’ view of patients, thus limiting moral agency. Through examination of technology as it frames cardiac patients, it is demonstrated how technology changes the way nurses understand and conceptualize moral agency. This article offers a new perspective on the ethical discussion of technology and its impact on nurses’ moral agency. Employing reflective analysis using the technique of embodied reflection may help to ensure that patients remain at the centre of nurses’ moral practice. Embodied reflection invites nurses critically to examine how technology has reshaped conceptualization, understanding, and the underlying motivation governing nurses’ moral agency.
A Review of Studies Comparing Methods for Determining Transcranial Magnetic Stimulation Motor Threshold: Observation of Movement or Electromyography Assisted
Authors: Anderson Berry S. , George Mark S.
Published: November 2009

BACKGROUND: Early in the development of transcranial magnetic stimulation (TMS) as a research tool, scientists developed the concept of motor threshold (MT) as a method of quantifying dose and establishing safety. Neurophysiologists determined the MT with the aid of peripheral electromyography (EMG). More recently, clinicians started substituting the EMG with observed movements (OM) of the hand or digits. It is unclear whether the two approaches (EMG and OM) reach similar conclusions about an individual’s cortical excitability and when best to use each approach. OBJECTIVE: To review TMS studies directly comparing the EMG and OM MT methods. DESIGN: A systematic search of the literature on Medline from January 1995 through April 2008. RESULTS: Four articles directly compared the two approaches, reaching different and opposing findings. CONCLUSION S : The evidence supporting the substitution of EMG with OM is sparse and conflicting. Clinicians stimulating at or near safety guidelines should use the EMG method.
An Urban Food Store Intervention Positively Affects Food-Related Psychosocial Variables and Food Behaviors
Authors: Gittelsohn Joel , Song Hee-Jung , Suratkar Sonali , Kumar Mohan B. , Henry Elizabeth G. , Sharma Sangita , Mattingly Megan , Anliker Jean A.
Published: November 2009

Obesity and other diet-related chronic diseases are more prevalent in low-income urban areas, which commonly have limited access to healthy foods. The authors implemented an intervention trial in nine food stores, including two supermarkets and seven corner stores, in a low-income, predominantly African American area of Baltimore City, with a comparison group of eight stores in another low-income area of the city. The intervention (Baltimore Healthy Stores; BHS) included an environmental component to increase stocks of more nutritious foods and provided point-of-purchase promotions including signage for healthy choices and interactive nutrition education sessions. Using pre- and postassessments, the authors evaluated the impact of the program on 84 respondents sampled from the intervention and comparison areas. Exposure to intervention materials was modest in the intervention area, and overall healthy food purchasing scores, food knowledge, and self-efficacy did not show significant improvements associated with intervention status. However, based on adjusted multivariate regression results, the BHS program had a positive impact on healthfulness of food preparation methods and showed a trend toward improved intentions to make healthy food choices. Respondents in the intervention areas were significantly more likely to report purchasing promoted foods because of the presence of a BHS shelf label. This is the first food store intervention trial in low-income urban communities to show positive impacts at the consumer level.
Operation Stacking for Ensemble Computations With Variable Convergence
Authors: Belgin Mehmet , Back Godmar , Ribbens Calvin J.
Published: November 2009

Sparse matrix operations achieve only small fractions of peak CPU speeds because of the use of specialized, index-based matrix representations, which degrade cache utilization by imposing irregular memory accesses and increasing the number of overall accesses. Compounding the problem, the small number of floating-point operations in a single sparse iteration leads to low floating-point pipeline utilization. Operation stacking addresses these problems for large ensemble computations that solve multiple systems of linear equations with identical sparsity structure. By combining the data of multiple problems and solving them as one, operation stacking improves locality, reduces cache misses, and increases floating-point pipeline utilization. Operation stacking also requires less memory bandwidth because it involves fewer index array accesses. In this paper we present the Operation Stacking Framework (OSF), an object-oriented framework that provides runtime and code generation support for the development of stacked iterative solvers. OSF’s runtime component provides an iteration engine that supports efficient ejection of converged problems from the stack. It separates the specific solver algorithm from the coding conventions and data representations that are necessary to implement stacking. Stacked solvers created with OSF can be used transparently without requiring significant changes to existing applications. Our results show that stacking can provide speedups up to 1.94× with an average of 1.46×, even in scenarios in which the number of iterations required to converge varies widely within a stack of problems. Our evaluation shows that these improvements correlate with better cache utilization, improved floating-point utilization, and reduced memory accesses.
Never Say ‘‘Always’’? Extreme Item Wording Effects on Scalar Invariance and Item Response Curves
Authors: Nye Christopher D. , Newman Daniel A. , Joseph Dana L.
Published: November 2009

When writing items for survey measures, common advice dictates that one should avoid using extreme words like ‘‘always.’’ However, the systematic study of extreme wording effects is rare. The current study applies confirmatory factor analysis (CFA) and item response theory (IRT) methods to assess the effects of extreme item wording (i.e., the word ‘‘always’’) on item-level, response option-level, and scale- (or test) level invariance. The authors hypothesized that including the word ‘‘always’’ in an item stem would affect responses such that individuals would be less likely to strongly agree with these items. To test this hypothesis, six items with extreme wording from the Wong and Law Emotional Intelligence Scale (WLEIS) were compared with more moderately worded versions of the same items. Although an effect was found for item wording, the magnitude of nonequivalence was small and is unlikely to have a strong influence on scale-level measurement outcomes. Implications for evaluating survey psychometric properties are discussed.
Work-Related Musculoskeletal Disorders (WRMSD) Among Registered Diagnostic Medical Sonographers and Vascular Technologists
Authors: Evans Kevin , Roll Shawn , Baker Joan
Published: November 2009

Literature indicates a significant history of work-related musculoskeletal disorders (WRMSD) among diagnostic medical sonographers (DMS) and vascular technologist (VTs). To gather current data related to this historical trend, the authors administered a survey to a random and convenient sample of 5200 registered DMS and VTs. The invitation to complete the survey on a secure Web site yielded the largest participant sample to date of 2963 completed surveys (57% response). Data relative to the prevalence of WRMSD were analyzed and compared to other WRMSD research over the past decade. Results indicated that 90% of respondents were scanning in pain, a 9% increase since the last large-scale survey in 1997. Across all demographics, shoulder pain is most common, with older and more experienced sonographers having more finger, hand, and wrist pain than other groups. Pain continues to be related to pressure applied to the transducer, abduction of the arm, and twisting of the neck and trunk. Ergonomic equipment and education are provided by application specialists, but the incidence of WRMSD appears to be unabated. Higher order research, including randomized trials, with education and ergonomic interventions is needed to protect DMS and VTs who are necessary to meet increasing health care demands.
Heterozygous deletion of the PU.1 locus in human AML
Authors: Bonadies Nicola , Pabst Thomas , Mueller Beatrice U.
Published: November 2009

The transcription factor PU.1 is essential for myeloid development. Targeted disruption of an upstream regulatory element (URE) decreases PU.1 expression by 80% and leads to acute myeloid leukemia (AML) in mice. Here, we sequenced the URE sequences of PU.1 in 120 AML patients. Four polymorphisms (single nucleotide polymorphisms [SNPs]) in the URE were observed, with homozygosity in all SNPs in 37 patients. Among them, we compared samples at diagnosis and remission, and one patient with cytogenetically normal acute myeloid leukemia M2 was identified with heterozygosity in 3 of the SNPs in the URE at remission. Loss of heterozygosity was further found in this patient at 2 polymorphic sites in the 5′ promoter region and in 2 intronic sites flanking exon 4, thus suggesting loss of heterozygosity covering at least 40 kb of the PU.1 locus. Consistently, PU.1 expression in this patient was markedly reduced. Our study suggests that heterozygous deletion of the PU.1 locus can be associated with human AML.
The contribution of cyclooxygenase-1 and -2 to persistent thromboxane biosynthesis in aspirin-treated essential thrombocythemia: implications for antiplatelet therapy
Authors: Dragani Alfredo , Pascale Silvia , Recchiuti Antonio , Mattoscio Domenico , Lattanzio Stefano , Petrucci Giovanna , Mucci Luciana , Ferrante Elisabetta , Habib Aida , Ranelletti Franco O. , Ciabattoni Giovanni , Davì Giovanni , Patrono Carlo , Rocca Bianca
Published: November 2009

We tested whether cyclooxygenase 2 (COX-2) expression and unacetylated COX-1 in newly formed platelets might contribute to persistent thromboxane (TX) biosynthesis in aspirin-treated essential thrombocythemia (ET). Forty-one patients on chronic aspirin (100 mg/day) and 24 healthy subjects were studied. Platelet COX-2 expression was significantly increased in patients and correlated with thiazole orange–positive platelets (r = 0.71, P < .001). The rate of TXA2 biosynthesis in vivo, as reflected by urinary 11-dehydro-TXB2 (TXM) excretion, and the maximal biosynthetic capacity of platelets, as reflected by serum TXB2, were higher in patients compared with aspirin-treated healthy volunteers. Serum TXB2 was significantly reduced by the selective COX-2 inhibitor NS-398 added in vitro. Patients were randomized to adding the selective COX-2 inhibitor, etoricoxib, or continuing aspirin for 7 days. Etoricoxib significantly reduced by approximately 25% TXM excretion and serum TXB2. Fourteen of the 41 patients were studied again 21 (± 7) months after the first visit. Serum TXB2 was consistently reduced by approximately 30% by adding NS398 in vitro, while it was completely suppressed with 50μM aspirin. Accelerated platelet regeneration in most aspirin-treated ET patients may explain aspirin-persistent TXA2 biosynthesis through enhanced COX-2 activity and faster renewal of unacetylated COX-1. These findings may help in reassessing the optimal antiplatelet strategy in ET.
Osteoclasts are important for bone angiogenesis
Authors: Cackowski Frank C. , Anderson Judith L. , Patrene Kenneth D. , Choksi Rushir J. , Shapiro Steven D. , Windle Jolene J. , Blair Harry C. , Roodman G. David
Published: November 2009

Increased osteoclastogenesis and angiogenesis occur in physiologic and pathologic conditions. However, it is unclear if or how these processes are linked. To test the hypothesis that osteoclasts stimulate angiogenesis, we modulated osteoclast formation in fetal mouse metatarsal explants or in adult mice and determined the effect on angiogenesis. Suppression of osteoclast formation with osteoprotegerin dose-dependently inhibited angiogenesis and osteoclastogenesis in metatarsal explants. Conversely, treatment with parathyroid hormone related protein (PTHrP) increased explant angiogenesis, which was completely blocked by osteoprotegerin. Further, treatment of mice with receptor activator of nuclear factor-κB ligand (RANKL) or PTHrP in vivo increased calvarial vessel density and osteoclast number. We next determined whether matrix metalloproteinase-9 (MMP-9), an angiogenic factor predominantly produced by osteoclasts in bone, was important for osteoclast-stimulated angiogenesis. The pro-angiogenic effects of PTHrP or RANKL were absent in metatarsal explants or calvaria in vivo, respectively, from Mmp9−/− mice, demonstrating the importance of MMP-9 for osteoclast-stimulated angiogenesis. Lack of MMP-9 decreased osteoclast numbers and abrogated angiogenesis in response to PTHrP or RANKL in explants and in vivo but did not decrease osteoclast differentiation in vitro. Thus, MMP-9 modulates osteoclast-stimulated angiogenesis primarily by affecting osteoclasts, most probably by previously reported migratory effects on osteoclasts. These results clearly demonstrate that osteoclasts stimulate angiogenesis in vivo through MMP-9.
Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease
Authors: Provatopoulou Xeni , Gounaris Antonia , Kalogera Eleni , Zagouri Flora , Flessas Ioannis , Goussetis Evgenios , Nonni Afroditi , Papassotiriou Ioannis , Zografos George
Published: November 2009

Background

Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity.

Methods

The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays.

Results

Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients.

Conclusion

These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.