bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional Variation in Health Status among Chronic Obstructive Pulmonary Disease Patients
Authors: Fan Vincent S. , Bridevaux Pierre-Olivier , McDonell Mary B. , Fihn Stephan D. , Besser Lilah M. , Au David H.
Published: August 2010

Background: Little is known about geographic differences in health status among patients with chronic obstructive pulmonary disease (COPD). Objectives: The aim of this study was to examine regional variations in self-reported health status of COPD patients at 7 Veterans Affairs clinics. Methods: The Ambulatory Care Quality Improvement Project was a multicenter, randomized trial conducted from 1997 to 2000 that evaluated a quality improvement intervention in the primary care setting. Four thousand and nine participants with COPD (age ≧45 years) completed the Seattle Obstructive Lung Disease Questionnaire (SOLDQ) and 2,991 also completed the Medical Outcomes Study 36-item short form (SF-36). The unadjusted maximal difference in health status scores is reported as the ratio of the highest and lowest site prevalence. We report the maximal site difference in mean health status scores after adjusting for demographics, comorbidities, utilization, medication use and clinic factors. Results: Subjects were predominantly older (66.5 ± 9.2 years) Caucasian (83.2%) men (97.9%). After adjustment, the maximal site difference for each health status score was significant (p < 0.01) but larger for the SOLDQ (physical 11.2, emotional 9.7, coping skills 7.6) than for the SF-36 (physical component summary 4.7, mental component summary 2.6). Most of the health status variation was explained by individual or clinic level factors, not clinic site. Conclusions: Our models explained <30% of variation in health status measures; therefore, future studies should consider additional predictors of health status such as physical performance, social determinants of health, COPD treatment and environmental factors. Despite its limitations, this study suggests a need to consider regional differences in health status when comparing COPD health outcomes in diverse geographic areas.
C-Reactive Protein and Mortality in Hemodialysis Patients: The Dialysis Outcomes and Practice Patterns Study (DOPPS)
Authors: Kawaguchi Takehiko , Tong Lin , Robinson Bruce M. , Sen Ananda , Fukuhara Shunichi , Kurokawa Kiyoshi , Canaud Bernard , Lameire Norbert , Port Friedrich K. , Pisoni Ronald L.
Published: August 2010

Background: We examined associations of C-reactive protein (CRP) levels with mortality in Japanese hemodialysis patients and trends in prevalence of CRP measurement at hemodialysis facilities internationally. To assess whether measurement of CRP may influence outcomes, we examined associations of facility prevalence of CRP measurement with mortality. Methods: CRP measurements were from a cross-section of patients in the international Dialysis Outcomes and Practice Patterns Study (n = 610 facilities, 16,355 patients). Cox proportional hazards models assessed associations of mortality with CRP in Japan, and with a facility’s frequency of measuring CRP internationally, (except in the USA and Canada). Results: From 2002–2004, CRP was measured in 0–19% of patients in each country, except Japan (55%). From 2005–2007, CRP was measured in ≧50% of country patients except in Canada (15%) and the USA (2%). After multivariable adjustment, the hazard ratio (HR) of death was 1.6- to 2.4-fold higher (p < 0.05) for various categories of CRP levels >3 mg/l (vs. <1.0 mg/l). Cardiovascular mortality risk was lower in facilities measuring CRP for ≧50% of patients (HR = 0.72, p = 0.01) in multivariable-adjusted analyses. Conclusions: CRP is informative regarding mortality risk beyond that provided by other inflammatory and nutritional markers, with significantly higher risk seen at CRP >3 mg/l. Greater use of CRP may lead to improved patient care as suggested by the association of greater CRP measurement with lower cardiovascular mortality.
Serotype Distribution and Antimicrobial Resistance of Adult Streptococcus pneumoniae Clinical Isolates over the Period 2001–2008 in Crete, Greece
Authors: Maraki S. , Mantadakis E. , Samonis G.
Published: August 2010

Background: We report on the serotype distribution and the antimicrobial susceptibility patterns (ASP) to 19 antibiotics of 195 Streptococcus pneumoniae isolates (41 invasive) collected over the period 2001–2008 from adult patients. Material and Methods: Pneumococcal isolates were serotyped by the Quellung reaction, and ASP testing was performed using E-test. Results: Isolates with intermediate and high-level resistance to penicillin increased from 17 and 12.4% over the period 2001–2004 to 31.1 and 16.7% over the years 2005–2008, respectively (p = 0.03). Macrolide resistance increased from 27.6 to 38.9%, but this was not significant (p = 0.13), while resistance to trimethoprim-sulfamethoxazole did not change over time, with approximately one fourth of the isolates being resistant. Only one isolate was resistant to fluoroquinolones. Multi-resistance was observed among 42 (58.1%) penicillin non-susceptible strains. The isolates tested belonged to 20 different serotypes. Serotypes 19F and 19A were the most common among penicillin-resistant isolates. The currently licensed 23-valent pneumococcal polysaccharide vaccine covered 98.4% of all 186 typeable S. pneumoniae strains. Conclusion: Our study emphasizes the importance of continued serotyping and surveillance of antimicrobial susceptibility of all S. pneumoniae clinical isolates, especially invasive ones, in order to guide the clinician in the choice of appropriate empirical antibiotic therapy for serious pneumococcal infections.
Evaluation of Anti-Quorum-Sensing Activity of Edible Plants and Fruits through Inhibition of the N-Acyl-Homoserine Lactone System in Chromobacterium violaceum and Pseudomonas aeruginosa
Authors: Musthafa K. Syed , Ravi A. Veera , Annapoorani A. , Packiavathy I. Sybiya Vasantha , Pandian S. Karutha
Published: August 2010

Background: To find out an alternative strategy to antibiotic usage against bacterial infection. Materials and Methods: The purpose of this study is to describe the quorum-sensing (QS) inhibitory activity of edible plants and fruits against N-acyl-homoserine lactone (AHL)-mediated violacein production in Chromobacterium violaceum and virulence factor expression in Pseudomonas aeruginosa PAO1. Results: Aqueous extracts of Ananas comosus (Bromeliaceae), Musa paradiciaca (Musaceae), Manilkara zapota (Sapotaceae) and Ocimum sanctum (Lamiaceae) were prepared and anti-QS activity of each extract was tested against AHL-mediated phenotypic expressions of C. violaceum and PAO1. Most of these extracts showed significant reduction in AHL-mediated violacein production in C. violaceum as well as pyocyanin pigment, staphylolytic protease, elastase production and biofilm formation in PAO1. However, these extracts were not inhibitory to bacterial growth, revealing that the QS inhibition by the extracts is not related to static or killing effects on the bacteria. Conclusions: The present study identified the anti-QS activity of A. comosus, M. paradiciaca, M. zapota and O. sanctum. An AHL-inactivating compound from these plant sources can be used as an alternative to antibiotic compounds to prevent AHL-mediated bacterial infection in higher organisms.
Prospective Study of Vinorelbine and Capecitabine Combination Therapy in Chinese Patients with Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes
Authors: Fan Ying , Xu Binghe , Yuan Peng , Wang Jiayu , Ma Fei , Li Qing , Zhang Pin , Li Qiao , Cai Ruigang
Published: August 2010

Aims: This phase II study prospectively evaluated the feasibility of vinorelbine in combination with capecitabine in Chinese patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. Methods: Vinorelbine (25 mg/m2 intravenous infusion on days 1 and 8) and capecitabine (1,000 mg/m2 b.i.d., days 1–14) were administered to eligible MBC patients previously treated with anthracyclines and taxanes every 3 weeks for up to 6 cycles, until disease progression or unacceptable toxicity. The primary endpoint was objective response. Results: Seventy-two patients were enrolled. In total, 297 cycles were given (median 4 cycles, range 2–6). The overall response rate was 45.8% (95% CI 34.2–57.4%), including 5 complete (6.9%) and 28 partial responses (38.9%). With median follow-up of 22 months, median time to progression was 7.7 months (95% CI 5.5–10.0) and median survival was 26.1 months (95% CI 19.6–32.6). The response rate was 53.8% in patients resistant to anthracyclines and taxanes combination. The most common hematologic adverse events were leukopenia (81.9%) with grade 3/4 incidence of 41.7%; nausea was the most frequent non-hematologic toxicity (62.5%). Hand-foot syndrome occurred in 12.5% of patients, and diarrhea was rare. Conclusions: Capecitabine 1,000 mg/m2 b.i.d. combined with vinorelbine 25 mg/m2 is an effective and safe treatment for MBC patients, no matter if anthracycline and taxane pretreated or resistant.
Difficulties in the Treatment of Intestinal Amoebiasis in Mentally Disabled Individuals at a Rehabilitation Institution for the Intellectually Impaired in Japan
Authors: Fujishima Tsukasa , Nishise Shoichi , Ichihara Masahiro , Kobayashi Seiki , Takeuchi Tsutomu
Published: August 2010

Background: A mass Entamoeba histolytica infection recurred despite repeated treatments with metronidazole at a rehabilitation institution for individuals with intellectual impairments. Methods: Diloxanide furoate was administered to improve intractable intestinal amoebiasis after a recurring amoebic infection that tends to occur via coprophagy in mentally disabled individuals infected with E. histolytica at an institution (the prevalence rate and positive serology rate were 38.2 and 67.1%, respectively). The therapeutic effect of the drugs was judged by microscopic stool examination and an E. histolytica antigen detection kit. Results: The mass infection was eliminated through the administration of metronidazole and subsequent use of diloxanide furoate. Conclusions: Combination therapy successfully cured and prevented transmission of the mass E. histolytica infection at the institution.
Optimal Medical Therapy for Non–ST-Segment–Elevation Acute Coronary Syndromes
Authors: Bagnall Alan J. , Yan Andrew T. , Yan Raymond T. , Lee Cindy H. , Tan Mary , Baer Carolyn , Polasek Petr , Fitchett David H. , Langer Anatoly , Goodman Shaun G. ,   for the Canadian Acute Coronary Syndromes Registry II Investigators
Published: August 2010

Background—

Acute coronary syndrome (ACS) patients in the highest risk categories are least likely to receive evidence-based treatments (EBTs). We sought to determine why physicians do not prescribe EBTs for patients with non–ST-segment–elevation ACSs and the factors determining use of these treatments after 1 year.

Methods and Results—

One thousand nine hundred fifty-six non–ST-segment-elevation ACS patients were enrolled in the prospective, multicenter Canadian ACS registry II between October 2002 and December 2003. Each patient's physician gave reasons why guideline-indicated medication(s) was not prescribed during hospitalization. Medication use and reason(s) for discontinuation after 1 year were obtained by telephone interview of the patients. The commonest reason for not prescribing EBTs was “not high-enough risk” or “no evidence/guidelines to support use.” However, Global Registry of Acute Coronary Events scores of patients not treated for this reason were often similar to or higher than those of patients prescribed such treatment. After 1 year, 77% of patients not on optimal ACS treatment at discharge remained without optimal treatment, and overall antiplatelet, β-blocker, and angiotensin-converting enzyme inhibitor use declined. Approximately one third of patients not taking EBTs had stopped their medication without instruction from their doctor.

Conclusions—

Nonprovision of EBTs may be due to subjective underestimation of patient risk and hence, likely treatment benefit. Oversights in care delivery were also apparent. Objective risk stratification, combined with efforts to ensure provision and adherence to EBTs, should be encouraged.
Prediction of 1-Year Mortality With Different Measures of ST-Segment Recovery in All-Comers After Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction
Authors: Verouden Niels J.W. , Haeck Joost D.E. , Kuijt Wichert J. , van Geloven Nan , Koch Karel T. , Henriques José P.S. , Baan Jan , Vis Marije M. , Piek Jan J. , Tijssen Jan G.P. , de Winter Robbert J.
Published: August 2010

Background—

Post hoc analyses from several randomized, controlled trials have established the prognostic importance of different measures of ST-segment recovery in highly selected patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment–elevation myocardial infarction (STEMI). In this single-center registry, we investigated whether various measures of ST-segment recovery can be applied to unselected STEMI patients undergoing primary PCI.

Methods and Results—

We analyzed 12-lead ECGs from 2124 consecutive STEMI patients who underwent primary PCI at our institution between November 1, 2000, and January 1, 2007. ECGs were recorded at the catheterization laboratory immediately before arterial puncture and at the end of PCI. We examined measures assessing ST-segment recovery on the postprocedural ECG and measures comparing both ECGs and related these to 1-year, all-cause mortality. Cumulative ST-segment recovery (∑ST-D resolution) at a 50% cutoff had the highest unadjusted accuracy (C statistic, 0.646; 95% confidence interval, 0.602 to 0.689;
P
<0.001) as compared with the other 8 measures evaluated. Furthermore, ∑ST-D resolution was the strongest contributor to both the net reclassification and integrated discrimination improvement.

Conclusions—

Although each measure of ST-segment recovery provided univariable prognostic information, the ∑ST-D resolution measure comparing summed ST-segment deviations on the preprocedural and postprocedural ECG was the best independent predictor of 1-year mortality in all-comer STEMI patients after primary PCI.
Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors Versus β-Blockers as Second-Line Therapy for Hypertension
Authors: Magid David J. , Shetterly Susan M. , Margolis Karen L. , Tavel Heather M. , O'Connor Patrick J. , Selby Joe V. , Ho P. Michael
Published: August 2010

Background—

Trials comparing hypertension monotherapies have found either no difference or modest differences in blood pressure (BP) and cardiovascular events. However, no trial has assessed the comparative effectiveness of 2nd-line therapy in patients whose BP was not controlled with a thiazide diuretic.

Methods and Results—

This was an observational study conducted with a hypertension registry of adults enrolled in 3 large integrated health care delivery systems from 2002 to 2007. Patients newly started on thiazide monotherapy whose BP remained uncontrolled were observed after addition of either an angiotensin-converting enzyme (ACE) inhibitor or β-blocker for subsequent BP control and cardiovascular events. Patients for whom either add-on drug was indicated or contraindicated were excluded. After adjustment for patient characteristics and study year, BP control during the subsequent 6 to 18 months was comparable for the 2 agents (70.5% ACE, 69.0% β-blockers;
P
=0.09). Rates of incident myocardial infarction (hazard ratio, 1.05; 95% confidence interval, 0.69 to 1.58) and stroke (hazard ratio, 1.01; 95% confidence interval, 0.68 to 1.52) were also similar for the ACE inhibitor and β-blocker groups during an average of 2.3 years of follow-up. There were also no differences in heart failure or renal function.

Conclusions—

ACE inhibitors and β-blockers are equally effective in lowering BP and preventing cardiovascular events for patients whose BP is not controlled with a thiazide diuretic alone and who have no compelling indication for a specific 2nd-line agent.
Social work practitioners and subjective well-being: Personal factors that contribute to high levels of subjective well-being
Authors: Graham John R. , Shier Micheal L.
Published: August 2010

Based on interviews with social workers possessing the highest level of subjective well-being (SWB) from a 2006 Canadian survey, this research identifies personal factors, including personal behaviors, interpersonal relationships and manifestations of self beyond their workplace and identity as social workers, as positively influencing social work practitioners’ high levels of subjective well-being. The conclusion considers implications for social work practice, education, and research.
Understanding non-governmental organizations in community development: Strengths, limitations and suggestions
Authors: Jiyoung Kang
Published: August 2010

Despite the widely recognized importance of non-governmental organizations (NGOs) in community development, few studies have shown a holistic picture of their diverse aspects. This article contributes to a comprehensive understanding of community development NGOs by examining their strengths and limitations and by suggesting strategies to improve their performance.
Biodegradation and mildew resistance of naturally colored cottons
Authors: Chen Hsiou-Lien , Cluver Brigitte
Published: August 2010

Naturally colored cottons contain significantly higher amounts of wax and have a different wax constitution and connectivity with cellulose than conventional cotton. Researchers have proposed that this wax content, together with the natural pigmentation, may serve as a defense against soil-borne pathogens. The purpose of this research is to study the biodegradation and mildew resistance characteristics of naturally colored cotton compared to conventional white and dyed cotton under field soil burial and laboratory mildew culture conditions. Laboratory culture results show that naturally brown and green colored cotton fabrics resist the growth of Aspergillius niger. However, after soil burial, both naturally brown and green cotton specimens showed severe degradation, manifested by significant loss of fabric strength as well as fiber structural damage. This suggests that naturally colored cottons are biodegradable. However, the rate of biodegradation of naturally colored cottons, especially green cotton, is much lower than that of white cotton or conventional dyed cotton.
Cultural Aesthetics and Teacher Improvisation: An Epistemology of Providing Culturally Responsive Service by African American Professors
Authors: Mitchell Roland
Published: August 2010

This research documents and analyzes the nature and content of the knowledge that enables professors to foster learning for Black students. Specifically, it suggests that knowledge of the discourses of a students’ community of origin, discourses often based on collective experience, are a valuable resource to professors in their efforts to promote educational equity. Data were drawn from interviews, observations, focus groups, and follow-up interviews with professors who have shown a particular interest in serving Black students for this study. The resulting conception of teacher knowledge has specific implications for teacher education practice and policy concerning targeted hiring practices, professional development for all teachers, and higher education policy makers in general.
“Cuz They Care About the People Who Goes There”: The Multiple Roles of a Community-Based Youth Center in Providing “Youth (Comm)Unity” for Low-Income Chinese American Youth
Authors: Wong Nga-Wing Anjela
Published: August 2010

This article will explore the role of “CYC,” a community-based youth center, in providing a sense of what I call “Youth (Comm)Unity” for Chinese American youth from low-income immigrant families. While CYC combines the youths’ home and school worlds, it is also distinct from these worlds by forming a new and hybrid culture/space. In doing so, I argue Youth (Comm)Unity consists of three critical concepts: (a) the Multiple Worlds model developed by Patricia Phelan et al. (1991, 1993, 1998); (b) Angela Valenzuela’s “authentic caring” (1999); and (c) similar to Gloria Ladson-Billings’s “culturally relevant pedagogy,” “culturally relevant” understanding (1994; 1995a; 1995b). Through providing the youth with a sense of Youth (Comm)Unity, CYC is able to offer the following kinds of social and emotional support: sense of trust and caring, sense of ethnic self and identity, sense of home and safe space, serving as role models, and sense of being a teenager. Data for this article is drawn from a larger study based on 15 weeks of ethnographic-based research. As this article illustrates, community-based organizations bridge such gaps for youth from low-income and working-class immigrant families, and Youth (Comm)-Unity is key in order to better serve low-income students of color.
Classroom Management in Diverse Classrooms
Authors: Milner H. Richard , Tenore F. Blake
Published: August 2010

Classroom management continues to be a serious concern for teachers and especially in urban and diverse learning environments. The authors present the culturally responsive classroom management practices of two teachers from an urban and diverse middle school to extend the construct, culturally responsive classroom management. The principles that emerged in this study included the importance and centrality of teachers’ (a) understanding equity and equality, (b) understanding power structures among students, (c) immersion into students’ life worlds, (d) understanding the Self in relation to Others, (e) granting students entry into their worlds, and (f) conceiving school as a community with family members. The authors conclude the discussion with implications for teachers and researchers.
The Process of Trust Building Between University Researchers and Urban School Personnel
Authors: Barnett Michael , Anderson Janice , Houle Meredith , Higginbotham Thomas , Gatling Ann
Published: August 2010

A wide range of research has examined trust building within corporations, businesses, and schools, and between and within organizations, but little research has been conducted that examines trust formation between university researchers and classroom-based teachers. Using a qualitative methodological approach, the authors examined the development of trusting relationships between their educational research team and a series of urban science teachers after 3 years of partnerships. It was found that teachers were initially cautiously optimistic about working with the research team, not wanting to invest much effort in the partnership until the research team had proven they were open, honest, and, most importantly, dedicated to helping their students. It was also found that the process of trust building began with an initial tentative and hesitant frontstage persona and eventually progressed to the point where they felt comfortable dropping their frontstage mask to engage in backstage conversations. The authors discovered that the trust-building process was transformative, in that, as trust was developed, it fostered the blurring of their social identities with the teachers as the teachers became teacher/researchers and the research team likewise became researcher/teachers.
Identifying the Causes of Mayoral Control in Urban Public School Systems
Authors: McGlynn Adam J.
Published: August 2010

Absent from the literature on mayoral control of urban public schools are quantitative studies that create a coherent theory of why mayoral control occurs. This article attempts to fill this gap by analyzing 47 urban school districts from 1991 to 2002, using a Cox Proportional Hazards model to assess the effects of political, economic, and district demographic variables on the risk of adopting mayoral control. The author finds that districts in states with Republican legislatures and large impoverished populations are most likely to adopt mayoral control. Lastly, over time, large union membership actually increases the likelihood of adoption, contrary to the conventional wisdom that teachers’ unions obstruct education reform.
Applying Budd’s model to partnership
Authors: Johnstone Stewart , Wilkinson Adrian , Ackers Peter
Published: August 2010

Over the last decade, the notions of workplace partnership and labour—management cooperation have resulted in distinctive and vociferous debates regarding forms of employee voice in the UK. It is proposed that there is a need to reconsider how we actually evaluate both the process and outcomes of partnership. This article reports on detailed case studies conducted in three diverse banking organizations in order to understand more about the process and outcomes of partnership. The study then applies the ‘efficiency, equity, voice’ framework developed by Budd, which has not been widely employed in industrial relations research. Accordingly, the article examines if and how partnership contributes to the balancing of efficiency, equity and voice. Judged in this light, the case studies demonstrate various degrees of success in terms of the extent to which partnership has facilitated voice and promoted more considered decision-making, for both management and employees. The article also demonstrates the usefulness of the Budd framework as a device in analysing employment relations processes and outcomes.
The Influence of Mood on Attribution
Authors: Avramova Yana R. , Stapel Diederik A. , Lerouge Davy
Published: August 2010

Four studies show that mood systematically affects attributions of observed behavior by altering relative attention to actor and context. When the actor is more salient, sad people are more inclined to perceive an actor in stable trait terms and favor dispositional over situational explanations, whereas the opposite is true for happy people (Studies 1-3). However, when the context is made more salient, this pattern reverses, such that those in a negative mood make more situational attributions than those in a positive mood (Study 4). Taken together, these findings provide strong support for our hypothesis that mood and salience interact to affect attributions.
Educational perceptions of requirements of the information profession in China
Authors: Guoqiu Li  , Fuling Li  , Xun Li  , Ingwersen Peter
Published: August 2010

The aim of this study is to analyse the perceptions and demands concerning educational and working requirements of the information profession from the perspectives of employers andemployees in the Chinese public and private information sectors, with focus on information science and information management (IS/IM) training and skills. The paper introduces recent developments of Chinese information education as background for two surveys, one targeting 49 employers of information professionals in public institutions and small, medium and large enterprises, and one aiming at 68 employees from the same sectors, all with academic degrees in IS/IM. Central findings demonstrate a mismatch between the perceptions of the employees with IS/IM background and those of the employers concerning central work functions, actual positions, importance to and status in institutions and enterprises. IS/IM staff are primarily employed for their information retrieval skills, but are also used in clerical work; in contrast, the employers perceive market analytic skills and industrial expertise as most central for the information profession. (Dis)advantages of the current curriculum and proposals for specific reforms of the Chinese IS/IM educational objectives, structure and curriculum are discussed.
Insights into translation students’ information literacy using the IL-HUMASS survey
Authors: Pinto María , Sales Dora
Published: August 2010

In the context of information literacy studies, the research put forward in this paper is focused on the individual and subjective levels of motivation and self-efficacy, together with the sources of learning used by a population of translation students from three Spanish universities. The data were collected by means of the self-evaluating and specific IL-HUMASS survey, and are analysed using a mixed (quantitative and qualitative) case study methodology. From the 26 variables of the survey, the most and least consistent and important ones with regard to motivation and self-efficacy are detected. In general, central tendency scores regarding motivation and self-efficacy increase as respondents advance academically. The most striking opportunities for improvement emerged in relation to the following issues: using bibliographic reference managers, knowing the laws on the use of information, using database managers and communicating in other languages. The surveyed population prefer autonomous learning, with the library being a much underused source of learning.
Drug-induced Valvulopathy: An Update
Authors: Elangbam Chandikumar S.
Published: August 2010

Drug-induced valvulopathy is a serious liability for certain compound classes in development and for some marketed drugs intended for human use. Reports of valvulopathy led to the withdrawal of fenfluramines (anorexigens) and pergolide (antiparkinson drug) from the United States market in 1997 and 2007, respectively. The mechanism responsible for the pathogenesis of valvulopathy by these drugs is likely a result of an “off-target” effect via activation of 5-hydroxytryptamine (5-HT) 2B receptor (5-HT2BR) expressed on heart valve leaflets. Microscopically, the affected valve leaflets showed plaques of proliferative myofibroblasts in an abundant extracellular matrix, composed primarily of glycosaminoglycans. However, the valvular effects caused by fenfluramines and pergolide were not initially predicted from routine preclinical toxicity studies, and to date there are no specific validated animal models or preclinical/toxicologic screens to accurately predict drug-induced valvulopathy. This review covers the structure and function of heart valves and highlights major advances toward understanding the 5-HT2BR-mediated pathogenesis of the lesion and subsequently, development of appropriate animal models using novel techniques/experiments, use of functional screens against 5-HT2BR, and more consistent sampling and pathologic evaluation of valves in preclinical studies that will aid in avoidance of future drug-induced valvulopathy in humans.
Biomarkers of Endothelial Cell Activation Serve as Potential Surrogate Markers for Drug-induced Vascular Injury
Authors: Zhang Jun , DeFelice Albert F. , Hanig Joseph P. , Colatsky Thomas
Published: August 2010

Drug-induced vascular injury (DIVI) is a nonclinical finding that often confounds the toxicological evaluation of investigational drugs, but there is an absence of qualified biomarkers that can be used to detect and monitor its appearance in animals and patients during drug development and clinical use. It is well known that endothelial cell (EC) activation plays a key role in the expression and evolution of DIVI, and the various immunological and inflammatory factors involved in its expression may serve as potential biomarker candidates. Activated ECs change their morphology and gene expression, generating endothelial adhesion molecules, pro-coagulant molecules, cytokines, chemokines, vasodilators, nitric oxide, and acute-phase reactants. This review provides a brief historical background of EC activation and the search for biomarkers of early EC activation for monitoring DIVI. At present, no biomarkers of EC activation have been qualified to predict DIVI in the nonclinical or clinical context, and a robust pathologic foundation for their use is still lacking. We propose three categories of EC activation biomarkers: recommended surrogate markers, potentially useful markers, and emerging candidate markers. This review alerts pharmaceutical companies, research institutions, and regulatory agencies to the continuing need for reliable biomarkers of EC activation in drug development.
Evaluation of Novel Biomarkers of Nephrotoxicity in Two Strains of Rat Treated with Cisplatin
Authors: Gautier Jean-Charles , Riefke Björn , Walter Jakob , Kurth Petra , Mylecraine Lou , Guilpin Valérie , Barlow Norman , Gury Thierry , Hoffman David , Ennulat Daniela , Schuster Kerstin , Harpur Ernie , Pettit Syril
Published: August 2010

Cisplatin is an anticancer agent that induces renal proximal tubule lesions in many species. Studies were conducted in Sprague-Dawley and Han-Wistar rats to evaluate the utility of novel preclinical biomarkers of nephrotoxicity for renal lesions caused by this compound. Groups of 10 males of each strain were given a single intraperitoneal injection of 0.3, 1, or 3 mg/kg cisplatin and were sacrificed on days 2, 3, and 5. The novel biomarkers α-glutathione-S-transferase (α-GST) (for proximal tubular injury), μ-glutathione-S-transferase (μ-GST) (for distal tubular injury), clusterin (for general kidney injury), and renal papillary antigen-1 (RPA-1) (for collecting duct injury) were measured in urine by enzyme immunoassay. Histologically, degeneration and necrosis of the S3 segment of the renal proximal tubule were observed on day 2 (Han-Wistar) and days 3 and 5 (both strains) at 1 and 3 mg/kg. Results showed that in both strains of rats, urinary α-GST and clusterin can be detected in urine soon after injury, are more sensitive than BUN and serum creatinine, and therefore are usable as noninvasive biomarkers of proximal tubule injury. Changes in both μ-GST or RPA-1 were considered to represent secondary minor effects of proximal tubular injury on distal segments of the nephron.
Decisional Involvement: Staff Nurse and Nurse Manager Perceptions
Authors: Scherb Cindy A. , Specht Janet K. P. , Loes Jean L. , Reed David
Published: August 2010

Enhancing involvement in organizational decisions is one strategy to improve the work environment of registered nurses and to increase their recruitment and retention. Little is known about the type of decision making and the level of involvement nurses desire. This was a descriptive study exploring staff nurse and nurse manager ratings of actual and preferred decisional involvement and differences between staff nurses and nurse managers. A sample of 320 RNs from a Midwestern health care network was surveyed using the Decisional Involvement Scale. Nurse managers and staff nurses had statistically significant differences in their perceptions of who was involved in actual decision making in the areas of unit governance and leadership and collaboration or liaison activities. There were statistically significant differences in preferred decisional involvement between staff nurses and nurse managers in the overall DIS scale and the subscales of unit governance and leadership and quality of support staff practice.
Implicit and explicit selective attention to smoking cues in smokers indexed by brain potentials
Authors: Littel Marianne , Franken Ingmar HA
Published: August 2010

Substance use disorders are characterized by cognitive processing biases, such as automatically detecting and orienting attention towards drug-related stimuli. However, it is unclear how, when and what kind of attention (i.e. implicit, explicit) interacts with the processing of these stimuli. In addition, it is unclear whether smokers are hypersensitive to emotionally significant cues in general or to smoking-related cues in particular. The present event-related potential study aimed to enhance insight in drug-related processing biases by manipulating attention for smoking and other motivationally relevant (emotional) cues in smokers and non-smokers using a visual oddball task. Each of the stimulus categories served as a target (explicit attention; counting) or as a non-target (implicit attention; oddball) category. Compared with non-smokers, smokers’ P300 (350–600 ms) was enhanced to smoking pictures under both attentional conditions. P300 amplitude did not differ between groups in response to positive, negative, and neutral cues. It can be concluded from this study that attention manipulation affects the P300 differently in smokers and non-smokers. Smokers display a specific bias to smoking-related cues, and this bias is present during both explicit and implicit attentional processing. Overall, it can be concluded that both explicit and implicit attentional processes appear to play an important role in drug-related processing bias.
Save Now [Y/N]? Machine Memory at War in Iain Banks’ Look to Windward
Authors: Blackmore Tim
Published: August 2010

Creating memory during and after wartime trauma is vexed by state attempts to control public and private discourse. Science fiction author Iain Banks’ novel Look to Windward proposes different ways of preserving memory and culture, from posthuman memory devices, to artwork, to architecture, to personal, local ways of remembering.
Commentary
Authors: Schoeb T. R. , McConnell E. E.
Published: August 2010

The authors recently assessed the likelihood that lifetime cancer bioassays of aspartame, methanol, and methyl tertiary butyl ether conducted with conventional (not specific pathogen free) Sprague–Dawley rats were compromised by Mycoplasma pulmonis disease. From the tumor data and other information, the authors concluded that the rats used in these bioassays likely had M pulmonis disease and that lesions of the disease were plausibly interpreted as lymphoma. Subsequently, they analyzed the nonneoplastic lesion data from these bioassays for occurrence of inflammatory lesions and found that 2,267 of 2,960 rats (76.6%) were reported to have bronchitis, the signature lesion of M pulmonis disease, and that 633 rats (21.4%) were reported to have otitis, another common lesion of the disease. Also, documentation is now available containing serologic evidence of mycoplasma infection in the rats. In contrast, the reports of 6 National Toxicology Program bioassays based on specific pathogen–free Sprague–Dawley rats listed no instances of bronchitis or otitis. These findings provide substantial additional evidence that the bioassays in question were compromised by M pulmonis disease. Therefore, the reported induction of lymphoma in these studies should not be considered in cancer risk assessments. The authors also found that inflammatory lesions were prevalent in lymph nodes, thymus, pleura, and brain. Finally, they found that of all 328 cases of lymphoimmunoblastic lymphoma affecting the lung (the primary form of lymphoma reported), 218 (66.5%) occurred within the first 104 weeks of the studies, showing that occurrence of such lesions was not due to appearance in rats surviving beyond that interval.
Chills in different sensory domains: Frisson elicited by acoustical, visual, tactile and gustatory stimuli
Authors: Grewe Oliver , Katzur Björn , Kopiez Reinhard , Altenmüller Eckart
Published: August 2010

‘Chills’ (frisson manifested as goose bumps or shivers) have been used in an increasing number of studies as indicators of emotions in response to music (e.g., Craig, 2005; Guhn, Hamm, & Zentner, 2007; McCrae, 2007; Panksepp, 1995; Sloboda, 1991). In this study we present evidence that chills can be induced through aural, visual, tactile, and gustatory stimulation. Additionally, chills were elicited by mere mental self-stimulation — even without any external stimulus. Subjective ratings and physiological responses (i.e., skin conductance response, heart rate, breathing rate) of 36 participants reporting chills were recorded in response to stimuli of the named sensory domains. Chills in response to all external stimuli showed similar physiological correlates. However, they differed in the subjective affective perception: more chills occurred in response to negative valent and arousing sounds and pictures, while more chills were reported for positive valent music independent of arousal. These findings suggest that the chill phenomenon could be a valuable indicator of strong emotions. However, the measurement of chills should be combined with other methods of emotion measurement, since chills can be a response to psychological events of different affective value.
Adverse events and placebo effects: African scientists, HIV, and ethics in the ‘global health sciences’
Authors: Crane Johanna
Published: August 2010

This paper builds on the growing literature in ‘postcolonial technoscience’ by examining how science and ethics travel in transnational HIV research. I use examples of two controversial US-funded studies of mother-to-child transmission in Africa as case studies through which to explore quandaries of difference and inequality in global health research. My aim is not to adjudicate the debates over these studies, but rather to raise some questions about transnational research, science, and ethics that often get lost in public controversies over the moral status of such trials. Using interviews conducted with American and Ugandan HIV researchers as well as relevant material published in the popular and medical press, I argue that debates over research practice and the conditions under which practices are deemed ethically legitimate or questionable reflect the challenges faced by African researchers seeking to participate in global health science. In doing so, I show how questions of scientific legitimacy and authority are played out in debates over who decides what constitutes ‘the normal’ in human biological research and who can legitimately ‘speak for Africa’ regarding the ethics of research design and practice. I conclude that researchers from ‘resource-poor settings’ must often walk a tightrope between claims of difference from the global North and assertions of sameness, in which a claim too forceful in either direction can undermine the ethical — and thus scientific — legitimacy of their research.
All-Inside Meniscal Repair with Bioabsorbable Meniscal Screws or with Bioabsorbable Meniscus Arrows
Authors: Järvelä Sally , Sihvonen Raine , Sirkeoja Hannu , Järvelä Timo
Published: August 2010

Background

All-inside meniscal repairs have gained popularity in the past few years. However, only a few prospective, randomized clinical studies have been done to compare different all-inside meniscal repair techniques.

Hypothesis

Meniscal repair with bioabsorbable meniscal screws and arrows results in similar clinical outcome on short-term follow-up.

Study Design

Randomized controlled trial; Level of evidence, 2.

Methods

Forty-two patients were prospectively randomized to have all-inside meniscal repair either by using bioabsorbable meniscal screws or bioabsorbable meniscus arrows (21 patients, 23 meniscal repairs in each group) for the fixation. The evaluation methods were clinical examination, Lysholm score, the International Knee Documentation Committee (IKDC) knee score, and magnetic resonance arthrography (MRA) evaluation. The average follow-up time was 27 months (standard deviation, 8).

Results

There were no differences between the study groups preoperatively. All 42 patients (100%) were available for the follow-up. However, during the follow-up, 11 patients had clinical failure, confirmed at second-look arthroscopy, of the repair leading to partial meniscal resection. Four failures (all on the medial meniscus) were observed with the use of meniscal screw fixation (17%), and 7 (4 on the medial meniscus, and 3 on the lateral meniscus) with the use of meniscus arrow fixation (30%) (P = .242). Six patients with meniscus arrows (29%) had chondral damage on the femoral condyles evaluated by MRA or at second-look arthroscopy, while none of the patients with the meniscal screws had the same (P = .018). However, the Lysholm and the IKDC scores were similar in both groups at follow-up.

Conclusion

All-inside meniscal repair with bioabsorbable meniscal screws and arrows resulted in similar clinical outcome, although significantly more chondral damage was observed when using bioabsorbable meniscus arrows for fixation.
Medial Patellofemoral Ligament Repair for Recurrent Patellar Dislocation
Authors: Camp Christopher L. , Krych Aaron J. , Dahm Diane L. , Levy Bruce A. , Stuart Michael J.
Published: August 2010

Background

The medial patellofemoral ligament (MPFL) is the primary restraint to extreme lateral displacement and is typically disrupted with an acute lateral patellar dislocation. Patients who fail a comprehensive nonoperative program and experience recurrent lateral patellar instability episodes are candidates for surgical treatment. Current surgical procedures include a variety of proximal realignment techniques, including repair or reconstruction of the MPFL along with distal realignment of the tibial tubercle when indicated.

Purpose

The objective of this study was to review the clinical, functional, and radiographic outcomes of isolated MPFL repair for recurrent lateral patellar dislocation.

Study Design

Case series; Level of evidence, 4.

Methods

The records of all patients undergoing MPFL repair for recurrent patellar dislocation at the Mayo Clinic from 2001 to 2006 were retrospectively reviewed. Twenty-seven patients (29 knees) with an average age of 19 years (range, 11-32 years) were included in this study. Clinical, functional, and radiographic outcomes were assessed at an average of 4 years after surgery (range, 2-7 years), using recurrent instability as the primary end point.

Results

The success rate of MPFL repair for preventing recurrent dislocations was 72% (21 of 29 knees). Eight patients (28%) experienced a recurrent lateral patellar dislocation. Five of these patients required a reoperation, including two MPFL reconstructions, 1 tibial tubercle osteotomy with MPFL reconstruction, 1 tibial tubercle osteotomy with revision MPFL repair, and 1 revision MPFL repair. At final follow-up, the mean Lysholm and Kujala scores were 86 (range, 42-100) and 92 (range, 57-105), respectively. Postoperative radiographs revealed a mean patellofemoral congruence angle improvement of 27° (range, 5°-44°). The only statistically significant risk factor for failure was nonanatomical MPFL repair at the medial femoral condyle (P = .004).

Conclusion

Isolated repair of the MPFL for recurrent patellar instability is associated with a relatively high failure rate, but remains a viable surgical option if surgical technique principles are followed. The clinical success of this operation depends on restoration of the anatomical origin of the MPFL and careful patient selection.