bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study of nurses’ ethical climate perceptions
Authors: Humphries Anne , Woods Martin 
Published: January 2015

Background: Acting ethically, in accordance with professional and personal moral values, lies at the heart of nursing practice. However, contextual factors, or obstacles within the work environment, can constrain nurses in their ethical practice – hence the importance of the workplace ethical climate. Interest in nurse workplace ethical climates has snowballed in recent years because the ethical climate has emerged as a key variable in the experience of nurse moral distress. Significantly, this study appears to be the first of its kind carried out in New Zealand. Aim/objective: The purpose of this study was to explore and describe how registered nurses working on a medical ward in a New Zealand hospital perceive their workplace ethical climate. Research design/participants/context: This was a small, qualitative descriptive study. Seven registered nurses were interviewed in two focus group meetings. An inductive method of thematic data analysis was used for this research. Ethical considerations: Ethics approval for this study was granted by the New Zealand Ministry of Health’s Central Regional Health and Disability Ethics Committee on 14 June 2012. Findings: The themes identified in the data centred on three dominant elements that – together – shaped the prevailing ethical climate: staffing levels, patient throughput and the attitude of some managers towards nursing staff. Discussion: While findings from this study regarding staffing levels and the power dynamics between nurses and managers support those from other ethical climate studies, of note is the impact of patient throughput on local nurses’ ethical practice. This issue has not been singled out as having a detrimental influence on ethical climates elsewhere. Conclusion: Moral distress is inevitable in an ethical climate where the organisation’s main priorities are perceived by nursing staff to be budget and patient throughput, rather than patient safety and care.
Normativity under change
Authors: Svanholm Jette Rolf , Nielsen Jens Cosedis , Mortensen Peter Thomas , Christensen Charlotte Fuglesang , Birkelund Regner 
Published: January 2015

Background: In modern society, death has become ‘forbidden’ fed by the medical technology to conquer death. The technological paradigm is challenged by a social-liberal political ideology in postmodern Western societies. The question raised in this study was as follows: Which arguments, attitudes, values and paradoxes between modern and postmodern tendencies concerning treatment and care of older persons with an implantable cardioverter defibrillator appear in the literature? Aims: The aim of this study was to describe and interpret how the field of tension concerning older persons with an implantable cardioverter defibrillator – especially end-of-life issues – has been expressed in the literature throughout the last decade. Methods: Paul Ricoeur’s reflexive interpretive approach was used to extract the meaningful content of the literature involving qualitative, quantitative and normative literature. Analysis and interpretation involved naive reading, structural analysis and critical interpretation. Ethical considerations: The investigation complied with the principles outlined in the Declaration of Helsinki. Findings and discussions: The unifying theme was ‘Normativity under change’. The sub-themes were ‘Death has become legitimate’, ‘The technological imperative is challenged’ and ‘Patients and healthcare professionals need to talk about end-of-life issues’. There seems to be a considerable distance between the normative approach of how practice ought to be and findings in empirical studies. Conclusion: Modern as well as postmodern attitudes and perceptions illustrate contradictory tendencies regarding deactivation of the implantable cardioverter defibrillator and replacement of the implantable cardioverter defibrillator in older persons nearing the end of life. The tendencies challenge each other in a struggle to gain position. On the other hand, they can also complement each other because professionalism and health professional expertise cannot stand alone when the patient’s life is at stake but must be unfolded in an alliance with the patient who needs to be understood and accepted in his vulnerability.
Risk factors for developing cardiotoxicity of trastuzumab in breast cancer patients: An observational single-centre study
Authors: Gunaldi Meral , Duman Berna Bozkurt , Afsar Cigdem Usul , Paydas Semra , Erkisi Melek , Kara I Oguz , Sahin Berksoy 
Published: January 2015

Background Trastuzumab is a recombinant humanized monoclonal antibody used to treat human epidermal growth factor receptor 2 positive breast cancer, with recognized associated cardiotoxicity. In this retrospective observational study, we investigated associated cardiotoxicity on clinical outcomes using trastuzumab in women referred to our clinic. Materials and methods The study was made up of 111 women with human epidermal growth factor receptor 2-overexpressing breast cancer who received trastuzumab in the Medical Oncology Department, between 2010 and 2013. Results A > 10% reduction of the baseline fraction of the left ventricular ejection fraction was observed in 18 (16.21%) women. Two individuals (1.8%) suffered from symptomatic heart failure, seven women showed cardiac symptoms and nine women showed asymptomatic decline of left ventricular ejection fraction. Risk factors for cardiotoxicity in the group included: postmenopausal status ( p = 0.01), hypertension ( p = 0.002), obesity ( p = 0.0001), previously diagnosed coronary artery disease ( p = 0.0001) and smoking ( p = 0.03). Conclusion The aforementioned factors pose a risk for cardiotoxicity. We found postmenopausal status, hypertension, obesity, previous coronary artery disease and smoking to be associated with an increased risk of cardiac dysfunction in women using trastuzumab. While administering trastuzumab to women who have these conditions, one must be aware of the risk of cardiotoxicity of trastuzumab.
The -93T/G LPL Promoter Polymorphism Is Associated With Lower Third-Trimester Triglycerides in Pregnant African American Women
Authors: Schmella Mandy J. , Ferrell Robert E. , Gallaher Marcia J. , Lykins David L. , Althouse Andrew D. , Roberts James M. , Hubel Carl A. 
Published: January 2015

Background: Hypertriglyceridemia is a risk factor for cardiovascular disease and several pregnancy complications. Lipoprotein lipase ( LPL) genetic variation modulates nonpregnancy plasma triglycerides, but its effects during pregnancy are unknown. The G allele of the LPL -93T/G promoter polymorphism is 16–23 times more prevalent in Blacks than in Whites, contributing to lower triglycerides in nonpregnant African Americans by increasing LPL expression. Purpose: This study investigated whether the triglyceride-lowering effect of -93G is observed in African Americans during pregnancy. Methods: Genotyping was performed on 124 African American women with uncomplicated pregnancies for common functional LPL polymorphisms/mutations (-93T/G, D9N, N291S, and S447X). Third-trimester plasma triglyceride, high- and low-density lipoprotein cholesterol, apolipoprotein B, and free fatty acid concentrations were measured with colorimetric assays. Clinical characteristics and lipid values were compared across the -93T/G genotypes. Results: Triglycerides were significantly lower in women with the -93GG compared to the -93TT genotype, both with ( n = 124, p = .02) and without ( n = 108, p = .03) inclusion of participants with other LPL variant alleles. Triglyceride differences persisted after adjustment for prepregnancy body mass index, gestational age at delivery, and smoking. There were no significant differences in the other lipids or apolipoprotein B by -93T/G genotype. Conclusions: Despite the considerable metabolic changes accompanying pregnancy, the triglyceride-lowering effect associated with the -93GG LPL genotype in African Americans persists during late pregnancy. The -93GG genotype might protect against pregnancy complications stemming from hypertriglyceridemia, but the overall increased risk of pregnancy complications in African American women points to complex, multifactorial relationships among risk factors, race, and adverse pregnancy outcomes.
Surgical complications following 1670 consecutive adult renal transplantations: a single center study
Authors: Lempinen M. , Stenman J. , Kyllönen L. , Salmela K. 
Published: January 2015

Background and Aims: The aim of the study was to clarify the frequency and the sequel of surgical complications occurring within 1 year after renal transplantation. Patients and Methods: Surgical complications after 1670 consecutive adult kidney transplantations performed between 2000 and 2009 were retrospectively analyzed. In 2%, a living-related allograft was used, and 10% were retransplantations. An intravesical technique without stenting was used for the ureteric implantation. Results: There were 282 surgical complications occurring in 259 (15.5%) transplantations. Ureteral obstruction occurred in 53 (3.1%), lymphoceles in 39 (1.5%), postoperative hemorrhage in 36 (2.1%), and renal vein thrombosis in 22 (1.3%) patients, respectively. Out of the 17 lung emboli, 4 were fatal. Male recipients had twice as much ureteral stenosis as female (2.4 vs 1.2%, p < 0.05), and the opposite was true of urinary leakage (1.8% vs 4.0%, p < 0.025). Five-year patient and graft survival was impaired in patients with complications compared with patients without complications. Five-year patient survival was 92% versus 88% and graft survival 87% versus 74%. Conclusion: Surgical complications impair patient and graft survival after kidney transplantation.
Suspension of accrual in phase II cancer clinical trials
Authors: Li Yimei , Mick Rosemarie , Heitjan Daniel F 
Published: January 2015

Purpose: Phase II cancer clinical trial designs commonly incorporate an interim analysis for lack of efficacy. To strictly and ethically implement such designs, one should suspend accrual in cases where pending patient outcomes can affect early termination decisions. This article aims to evaluate various options for accrual suspension and illustrate how the suspension strategy affects operating characteristics of the trial. Methods: We define a strict suspension strategy for determining whether one should continue, suspend, or restart accrual at any point within the trial. The strategy is compared to a naive implementation of suspension and a strategy of no suspension. We evaluate the methods’ operating characteristics by simulation. Results: The suspension strategy has little effect on type I error, power, and early termination probability. Methods that involve stricter suspension policies generally lead to smaller but longer trials. Differences across strategies are substantial when the ratio of enrollment rate to outcome availability rate is high. Conclusion: The suspension strategy is most relevant in trials that accrue rapidly and require lengthy observation of each subject. The choice of suspension strategy involves a tradeoff between the cost of implementing a potentially complex suspension algorithm in real time versus the cost of enrolling more patients and exposing them to a potentially toxic and ineffective treatment regimen.
Are nurses more likely to report providing care plans for chronic disease patients than doctors? Findings from a New Zealand study
Authors: Doolan-Noble Fiona , Gauld Robin , Waters Debra L 
Published: January 2015

Objectives The main aim of this study was to compare the perceptions of general practitioners (GPs) and primary care nurses (PCNs) in the Southern Region of New Zealand regarding their provision of chronic illness care. Whether PCNs rated their frequency of providing aspects of chronic illness care higher than GPs was a key question. Methods The modified version of the Patient Assessment of Chronic Illness Care (PACIC) was used to compare the perceptions of GPs and PCNs. Results Surveys were received from 77% of practices in the Southern region. Responding PCNs were more likely than their GP counterparts to document they provided aspects of chronic illness care ‘most of the time’ or ‘always’ in 18 activities from the six M-PACIC domains. Their level of providing patients with formal care plans was surprisingly low. Conclusion This level of engagement of PCNs with chronic illness care was no surprise. The low number reporting they provided patients with a care plan, most of the time or always, was unexpected. Aspects of care planning, however, were reported as taking place more frequently. This discrepancy between the process of care planning and the outcome, a care plan, is not unique to this region of New Zealand and warrants further research.
Triple modality testing by endoscopic retrograde cholangiopancreatography for the diagnosis of cholangiocarcinoma
Authors: Nanda Arjun , Brown Jason M. , Berger Stephen H. , Lewis Melinda M. , Barr Fritcher Emily G. , Gores Gregory J. , Keilin Steven A. , Woods Kevin E. , Cai Qiang , Willingham Field F. 
Published: January 2015

Objectives: Brush cytology has a low sensitivity for the diagnosis of cholangiocarcinoma. This study aimed to compare the standard approach (brush cytology) with a triple modality approach utilizing brush cytology, forceps biopsy and fluorescence in situ hybridization in terms of sensitivity and specificity for the diagnosis of cholangiocarcinoma. Methods: In a retrospective study at a single academic center, 50 patients underwent triple modality testing. Additionally, 61 patients underwent brush cytology alone. Intervention was endoscopic retrograde cholangiopancreatography with brush cytology, fluorescence in situ hybridization, and forceps biopsy. The main outcome measures included sensitivity, specificity, positive predictive value and negative predictive value. Results: Overall, 50 patients underwent triple tissue sampling, and 61 patients underwent brush cytology alone. Twenty-two patients were eventually diagnosed with cholangiocarcinoma. Brush cytology had a sensitivity of 42%, specificity of 100%, positive predictive value of 100% and negative predictive value of 88%. Triple tissue sampling had an overall sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 87%. Within the triple test group, brush cytology had a sensitivity of 27%, forceps biopsy had a sensitivity of 50%, and fluorescence in situ hybridization analysis had a sensitivity of 59%. Conclusions: A triple modality approach results in a marked increase in sensitivity for the diagnosis of cholangiocarcinoma compared with single modality testing such as brush cytology and should be considered in the evaluation of indeterminate or suspicious biliary strictures.
The Impact of Measurement Frequency on the Domains of Glycemic Control in the Critically Ill-A Monte Carlo Simulation
Authors: Krinsley James S. , Bruns David E. , Boyd James C. 
Published: January 2015

Background: The role of blood glucose (BG) measurement frequency on the domains of glycemic control is not well defined. Methods: This Monte Carlo mathematical simulation of glycemic control in a cohort of critically ill patients modeled sets of 100 patients with simulated BG-measuring devices having 5 levels of measurement imprecision, using 2 published insulin infusion protocols, for 200 hours, with 3 different BG-measurement intervals—15 minutes (Q15’), 1 hour (Q1h), and 2 hours (Q2h)—resulting in 1 100 000 BG measurements for 3000 simulated patients. The model varied insulin sensitivity, initial BG value and rate of gluconeogenesis. The primary outcomes included rates of hyperglycemia (BG > 180 mg/dL), hypoglycemia (BG < 70 and 40 mg/dL), proportion of patients with elevated glucose variability (within-patient coefficient of variation [CV] > 20%), and time in range (BG ranges 80-150 mg/dL and 80-180 mg/dL). Results: Percentages of hyperglycemia, hypoglycemia at both thresholds, and patients with elevated glucose variability as well as time outside glycemic targets were substantially higher in simulations with measurement interval Q2h compared to those with measurement interval Q1h and moderately higher in simulations with Q1h than in those with Q15’. Higher measurement frequency mitigated the deleterious effect of high measurement imprecision, defined as CV ≥ 15%. Conclusions: This Monte Carlo simulation suggests that glycemic control in critically ill patients is more optimal with a BG measurement interval no longer than 1h, with further benefit obtained with use of measurement interval of 15’. These findings have important implications for the development of glycemic control standards.
Patterns and Predictors of First-Line Antiretroviral Therapy Modification in HIV-1-Infected Adults in a Large Urban Outpatient Cohort in Nigeria
Authors: Abah Isaac Okoh , Darin Kristin M. , Ebonyi Augustine Odo , Ugoagwu Placcid , Ojeh Victor Bazim , Nasir Naima , Falang Kakjing D. , Olaitan Oluremi , Agbaji Oche , Idoko John , Kanki Phyllis 
Published: January 2015

Objective: We described the magnitude, type, and factors associated with first-line antiretroviral therapy (ART) modification in HIV-1-infected adults on ART in Jos, Nigeria. Method: Data on 6309 patients initiated on first-line ART between January 2004 and December 2006 were analyzed retrospectively. Factors predictive of modification to initial ART were assessed by chi-square and multivariable logistic regression analysis. Results: Overall, 5212 (83%) included patients incurred a modification (73.3% drug substitution and 9.7% drug switch) to their initial first-line ARV regimen during a median (interquartile range) follow-up period of 7 (3-8) years. Drug substitutions of zidovudine (ZDV) were less likely than of tenofovir (TDF; adjusted odd ratio [AOR] 0.6; 95% confidence interval [CI]: 0.51-0.71), and Drug substitutions of efavirenz (EFV) were more likely than of nevirapine (NVP)-containing (AOR 1.82; 95% CI: 1.42-2.33) regimens. Predictors of switch to second-line regimen include older age (AOR 2.05; 95% CI: 1.68-2.51), CD4 count ≤100 cells/mm3 (AOR 1.89; 95% CI: 1.49-2.37), EFV compared to NVP (AOR 1.38; 95% CI: 1.02-1.88), and drug toxicity (AOR 1.90; 95% CI: 1.48-2.43). Conclusion: Modification to initial ART was common in this study. Further evaluation of the contribution of guideline changes on regimen modification and treatment outcomes is recommended.
Acetylation of C/EBPε is a prerequisite for terminal neutrophil differentiation
Authors: Bartels Marije , Govers Anita M. , Fleskens Veerle , Lourenço Ana Rita , Pals Cornelieke E. , Vervoort Stephin J. , van Gent Rogier , Brenkman Arjan B. , Bierings Marc B. , Ackerman Steven J. , van Loosdregt Jorg , Coffer Paul J. 
Published: January 2015

Key Points
C/EBPε acetylation regulates C/EBPε transcriptional activity. C/EBPε acetylation is required for neutrophil differentiation and the formation of neutrophil-specific granules.
LMP1 mediates multinuclearity through downregulation of shelterin proteins and formation of telomeric aggregates
Authors: Lajoie Valérie , Lemieux Bruno , Sawan Bassem , Lichtensztejn Daniel , Lichtensztejn Zelda , Wellinger Raymund , Mai Sabine , Knecht Hans 
Published: January 2015

Key PointsLMP1 expression in post germinal center B cells results in downregulation of shelterin proteins, telomeric aggregates, and multinuclearity. LMP1 targets TRF1, TRF2, and POT1 reversibly at the transcriptional/translational level, and TRF2 is essential to block multinuclearity.
Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis
Authors: Giuliano Mario , Herrera Sabrina , Christiny Pavel , Shaw Chad , Creighton Chad J , Mitchell Tamika , Bhat Raksha , Zhang Xiaomei , Mao Sufeng , Dobrolecki Lacey E , Al-rawi Ahmed , Chen Fengju , Veneziani Bianca M , Zhang Xiang H-F , Hilsenbeck Susan G , Contreras Alejandro , Gutierrez Carolina , Jeselsohn Rinath M , Rimawi Mothaffar F , Osborne C Kent , Lewis Michael T , Schiff Rachel , Trivedi Meghana V 
Published: January 2015

Abstract
Introduction
Real-time monitoring of biologic changes in tumors may be possible by investigating the transitional cells such as circulating tumor cells (CTCs) and disseminated tumor cells in bone marrow (BM-DTCs). However, the small numbers of CTCs and the limited access to bone marrow aspirates in cancer patients pose major hurdles. The goal of this study was to determine whether breast cancer (BC) patient-derived xenograft (PDX) mice could provide a constant and renewable source of CTCs and BM-DTCs, thereby representing a unique system for the study of metastatic processes.

Methods
CTCs and BM-DTCs, isolated from BC PDX-bearing mice, were identified by immunostaining for human pan-cytokeratin and nuclear counterstaining of red blood cell-lysed blood and bone marrow fractions, respectively. The rate of lung metastases (LM) was previously reported in these lines. Associations between the presence of CTCs, BM-DTCs, and LM were assessed by the Fisher’s Exact and Cochran-Mantel-Haenszel tests. Two separate genetic signatures associated with the presence of CTC clusters and with lung metastatic potential were computed by using the expression arrays of primary tumors from different PDX lines and subsequently overlapped to identify common genes.

Results
In total, 18 BC PDX lines were evaluated. CTCs and BM-DTCs, present as either single cells or clusters, were detected in 83% (15 of 18) and 62.5% (10 to16) of the lines, respectively. A positive association was noted between the presence of CTCs and BM-DTCs within the same mice. LM was previously found in 9 of 18 (50%) lines, of which all nine had detectable CTCs. The presence of LM was strongly associated with the detection of CTC clusters but not with individual cells or detection of BM-DTCs. Overlapping of the two genetic signatures of the primary PDX tumors associated with the presence of CTC clusters and with lung metastatic potential identified four genes (HLA-DP1A, GJA1, PEG3, and XIST). This four-gene profile predicted distant metastases-free survival in publicly available datasets of early BC patients.

Conclusion
This study suggests that CTCs and BM-DTCs detected in BC PDX-bearing mice may represent a valuable and unique preclinical model for investigating the role of these rare cells in tumor metastases.
Genome-Wide Identification of CBX2 Targets: Insights in the Human Sex Development Network
Authors: Eid Wassim , Opitz Lennart , Biason-Lauber Anna 
Published: January 2015

Abstract
Chromobox homolog 2 (CBX2) is a chromatin modifier that plays an important role in sexual development and its disorders (disorders of sex development [DSD]), yet the exact rank and function of human CBX2 in this pathway remains unclear. Here, we performed large-scale mapping and analysis of in vivo target loci of the protein CBX2 in Sertoli-like NT-2D1 cells, using the DNA adenine methyltransferase identification technique. We identified close to 1600 direct targets for CBX2. Intriguingly, validation of selected candidate genes using qRT-PCR in cells overexpressing CBX2 or in which CBX2 has been knocked down indicated that several CBX2-responsive genes encode proteins that are involved in DSD. We further validated these effects on the candidate genes using a mutated CBX2 causing DSD in human patient. Overall, our findings suggest that CBX2 role in the sex development cascade is to stimulate the male pathway and concurrently inhibit the female pathway. These data provide fundamental insights into potential etiology of DSD.