bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Not another safety culture survey’: using the Canadian patient safety climate survey (Can-PSCS) to measure provider perceptions of PSC across health settings
Authors: Ginsburg Liane R , Tregunno Deborah , Norton Peter G , Mitchell Jonathan I , Howley Heather 
Published: October 2013

BackgroundThe importance of a strong safety culture for enhancing patient safety has been stated for over a decade in healthcare. However, this complex construct continues to face definitional and measurement challenges. Continuing improvements in the measurement of this construct are necessary for enhancing the utility of patient safety climate surveys (PSCS) in research and in practice. This study examines the revised Canadian PSCS (Can-PSCS) for use across a range of care settings.MethodsConfirmatory factor analytical approaches are used to extensively test the Can-PSCS. Initial and cross-validation samples include 13 126 and 6324 direct care providers from 119 and 35 health settings across Canada, respectively.ResultsResults support a parsimonious model of direct care provider perceptions of patient safety climate (PSC) with 19 items in six dimensions: (1) organisational leadership support for safety; (2) incident follow-up; (3) supervisory leadership for safety; (4) unit learning culture; (5) enabling open communication I: judgement-free environment; (6) enabling open communication II: job repercussions of error. Results also support the validity of the Can-PSCS across a range of care settings.ConclusionsThe Can-PSCS has several advantages: (1) it is a theory-based instrument with a small number of actionable dimensions central to the construct of PSC; (2) it has robust psychometric properties; (3) it is validated for use across a range of care settings, therefore suitable for use in regionalised health delivery systems and can help to raise expectations about acceptable levels of PSC across the system; (4) it has been tested in a publicly funded universal health insurance system and may be suitable for similar international systems.
The ‘who are all these people?’ study
Authors: Gilligan Peadar , Joseph Danny , Bartlett Matthew , Morris Aoife , Mahajan Ajay , McHugh Karen , Hillary Fiona , O'Kelly Patrick 
Published: October 2013

BackgroundOvercrowding of emergency departments (EDs) adversely affects the delivery of emergency care and results in increased patient mortality.Objective and methodsTo examine what contributes to the ED crowd and to specifically examine the patient associated population. The ED in which the research was performed is consistently one of the most overcrowded in Ireland.ResultsOn average 66.7% of the patients in the ED during the study period were boarded awaiting a hospital bed following full processing by the ED staff and agreement by the on-call team that admission was required. The most overcrowded part of the department was the majors area. In this area 55.5% of those present were patients, visitors accounted for 16.6% of occupants, nursing staff 11%, on-call teams 7% and the ED doctors 6.3%.ConclusionsKnowing who the people in the crowd are helps to guide management decisions about how the crowd might be reduced. Our department now has a strict accompanying person/visitor policy that limits the number of visitors to patients and limits visiting times for those relatives with a patient who is experiencing a prolonged stay in the ED.
No gender-related bias in acute musculoskeletal pain management in the emergency department
Authors: Uri Ofir , Elias Shlomo , Behrbalk Eyal , Halpern Pinchas 
Published: October 2013

IntroductionPatients’ gender remains a contributor for bias in pain management. Implementation of standardised analgesic protocols has been shown to minimise bias in analgesic care. The purpose of this study was to assess whether gender-related bias in pain management exists in our emergency department (ED) setting, where a standardised pain management protocol based on patients’ subjective pain rating is routinely used.MethodsPain management measures (ie, analgesia administration, waiting time for analgesia, pain relief and patients’ satisfaction) were prospectively assessed in 328 patients (150 women and 178 men, average age 36±18 years) who were treated in our ED for acute musculoskeletal pain.ResultsPatients’ subjective pain rating on arrival were similar for men and women (59±24 mm vs 61±26 mm, respectively; p=0.47). Interestingly, physicians using the same scale assessed the women's pain level to be higher than that of men (75±25 mm vs 63±22 mm, respectively; p<0.001) and higher than that of women's subjective pain rating (75±25 mm vs 61±26 mm respectively; p<0.001). Nevertheless, the rates of analgesia administration, waiting time for analgesia, pain relief and patient satisfaction were similar for both genders. Physicians’ own gender did not affect analgesic care.ConclusionsOur findings suggest that a standardised pain management protocol based on patients’ subjective pain rating may reduce gender-related bias in acute musculoskeletal pain management.
The association between on-scene blood pressure and early neurological deterioration in patients with spontaneous intracerebral haemorrhage
Authors: Fan Ju-Sing , Chen Yen-Chia , Huang Hsien-Hao , How Chorng-Kuang , Yen David Hung-Tsang , Huang Mu-Shun 
Published: October 2013

ObjectiveTo determine whether on-scene BP is associated with early neurological deterioration (END) in patients with spontaneous intracerebral haemorrhage (SICH).MethodsThis retrospective cohort study enrolled consecutive ambulance-transported adult SICH patients treated at our emergency department (ED) from January 2007 through December 2012. END was defined as a ≥2-point decrease in GCS within 24 h of ED arrival. The exact relationship between on-scene BP and END was assessed using multiple logistic regression analyses for adjusting age, gender, Charlson Index, aspirin use, smoking, elapsed time, consciousness level on ED arrival, haematoma size, intraventricular extension, midline shift and infratentorial ICH. We further calculated the −2 log-likelihood decrease for each regression model incorporated with the BP values measured at different times to compare model fitness.ResultsAfter adjusting for the covariates, on-scene systolic BP (by 10 mm Hg incremental: OR = 1.126, 95% CI 1.015 to 1.265), diastolic BP (by 10 mm Hg incremental: OR=1.146, 95% CI 1.019 to 1.303) and mean arterial pressure (MAP) (by 10 mm Hg incremental: OR=1.225, 95% CI 1.057 to 1.443) were significantly associated with END; adding on-scene MAP into the regression model yielded the highest model fitness increase. Adding on-scene BPs into the regression model yielded higher model fitness increase than adding ED and admission BPs.ConclusionsFew on-scene BP indices were associated with neuroworsening within 24 h after ED arrival in non-comatose SICH patients. Compared with BP measured on ED arrival or admission, on-scene BP had a stronger correlation with END.
Reducing radiation dose while maintaining diagnostic image quality of cerebral three-dimensional digital subtraction angiography: an in vivo study in swine
Authors: Pearl Monica S , Torok Collin M , Messina Steven A , Radvany Martin , Rao Swati N , Ehtiati Tina , Thompson Carol B , Gailloud Philippe 
Published: October 2013

BackgroundThree-dimensional digital subtraction angiography (3D-DSA) is a modern technique that allows for better appreciation of complex vascular lesions. This study evaluates the impact of various dose reduction strategies on 3D-DSA image quality.MethodsThe standard manufacturer 5 s 0.36 μGy/frame setting was modified to create lower dose 3D-DSA protocols by varying the acquisition time (5 or 3 s) and/or dose per frame (0.36, 0.24, 0.17, and 0.10 μGy/f). All protocols were evaluated in three swine. Four raters measured a segment of the external carotid artery on two-dimensional multiplanar reconstruction images. The raters were also presented with three-dimensional volume rendered images from all protocols in a blinded manner and asked to choose the superior image. A full model analysis of variance with repeated measure factors was performed to compare mean differences in measurements between protocols.ResultsMeasurement differences between the standard and low dose protocols were not clinically significant (<0.5 mm). All raters demonstrated high inter-rater reliability. The 5 s protocols were considered as qualitatively superior to the 3 s protocols. Delivered system doses ranged from 43.8 to 6.5 mGy. The 5 s 0.10 μGy/frame protocols generated 65–68% less delivered dose compared with the 5 s 0.36 μGy/frame setting.ConclusionsLow dose 3D-DSA protocols with preserved image quality are achievable, and can help reduce unnecessary radiation exposure to both patients and operators. The 5 s low dose protocols generated clinically acceptable and superior images compared with the 3 s protocols, suggesting a more important role for acquisition time than dose per frame to maintain image quality.
Glioblastoma Stem Cells Are Regulated by Interleukin-8 Signaling in a Tumoral Perivascular Niche
Authors: Infanger David W. , Cho YouJin , Lopez Brina S. , Mohanan Sunish , Liu S. Chris , Gursel Demirkan , Boockvar John A. , Fischbach Claudia 
Published: October 2013

Abstract
Glioblastoma multiforme contains a subpopulation of cancer stem–like cells (CSC) believed to underlie tumorigenesis and therapeutic resistance. Recent studies have localized CSCs in this disease adjacent to endothelial cells (EC) in what has been termed a perivascular niche, spurring investigation into the role of EC–CSC interactions in glioblastoma multiforme pathobiology. However, these studies have been limited by a lack of in vitro models of three-dimensional disease that can recapitulate the relevant conditions of the niche. In this study, we engineered a scaffold-based culture system enabling brain endothelial cells to form vascular networks. Using this system, we showed that vascular assembly induces CSC maintenance and growth in vitro and accelerates tumor growth in vivo through paracrine interleukin (IL)-8 signaling. Relative to conventional monolayers, endothelial cells cultured in this three-dimensional system not only secreted enhanced levels of IL-8 but also induced CSCs to upregulate the IL-8 cognate receptors CXCR1 and CXCR2, which collectively enhanced CSC migration, growth, and stemness properties. CXCR2 silencing in CSCs abolished the tumor-promoting effects of endothelial cells in vivo, confirming a critical role for this signaling pathway in GMB pathogenesis. Together, our results reveal synergistic interactions between endothelial cells and CSCs that promote the malignant properties of CSCs in an IL-8–dependent manner. Furthermore, our findings underscore the relevance of tissue-engineered cell culture platforms to fully analyze signaling mechanisms in the tumor microenvironment. Cancer Res; 73(23); 7079–89. ©2013 AACR.
Androgen Glucuronidation: An Unexpected Target for Androgen Deprivation Therapy, with Prognosis and Diagnostic Implications
Authors: Grosse Laurent , Pâquet Sophie , Caron Patrick , Fazli Ladan , Rennie Paul S. , Bélanger Alain , Barbier Olivier 
Published: October 2013

Abstract
Androgen deprivation therapy (ADTh) remains a mainstay of prostate cancer treatment, but its efficacy is bypassed by mechanisms that are not fully understood. In human prostate cancer cells, androgen glucuronidation, catalyzed by the two UDP-glucuronosyltransferase (UGT) enzymes UGT2B15 and UGT2B17, is the major androgen inactivation pathway. In this study, we investigated the effect of ADTh on androgen glucuronidation to evaluate its potential clinical utility for prostate cancer prognosis or therapy. UGT2B15 and UGT2B17 expression was evaluated in prostate cancer specimens from untreated or treated patients and in cell models of prostate cancer exposed to clinically relevant antiandrogens. UGT2B15 and UGT2B17 protein levels in prostate were increased after 5 months of ADTh when compared with specimens from untreated patients. UGT2B15 expression remained elevated for up to 12 months, but UGT2B17 returned to initial levels as soon as after 6 months. Several androgen receptor (AR) antagonists tested caused a dose- and time-dependent stimulation of UGT2B15 and UGT2B17 expression and androgen glucuronidation in prostate cancer cell lines. The role of AR in these regulatory events was confirmed using AR-deficient LNCaP cells, in which UGT2B attenuation reduced the antiproliferative effects of AR pharmacologic antagonists. Through this combination of clinical and functional investigations, our work revealed that ADTh stimulates a local androgen metabolism in prostate cells, establishing a foundation to evaluate the potential of UGT2B15 and UGT2B17 as drug targets and/or molecular markers for ADTh responsiveness and maintenance in prostate cancer. Cancer Res; 73(23); 6963–71. ©2013 AACR.
In Vivo MAPK Reporting Reveals the Heterogeneity in Tumoral Selection of Resistance to RAF Inhibitors
Authors: Basile Kevin J. , Abel Ethan V. , Dadpey Neda , Hartsough Edward J. , Fortina Paolo , Aplin Andrew E. 
Published: October 2013

Abstract
Activation of the ERK1/2 mitogen-activated protein kinases (MAPK) confers resistance to the RAF inhibitors vemurafenib and dabrafenib in mutant BRAF-driven melanomas. Methods to understand how resistance develops are important to optimize the clinical use of RAF inhibitors in patients. Here, we report the development of a novel ERK1/2 reporter system that provides a noninvasive, quantitative, and temporal analysis of RAF inhibitor efficacy in vivo. Use of this system revealed heterogeneity in the level of ERK1/2 reactivation associated with acquired resistance to RAF inhibition. We identified several distinct novel and known molecular changes in resistant tumors emerging from treatment-naïve cell populations including BRAF V600E variants and HRAS mutation, both of which were required and sufficient for ERK1/2 reactivation and drug resistance. Our work offers an advance in understanding RAF inhibitor resistance and the heterogeneity in resistance mechanisms, which emerge from a malignant cell population. Cancer Res; 73(23); 7101–10. ©2013 AACR.
Neuropilin-2 Is Upregulated in Lung Cancer Cells during TGF-β1–Induced Epithelial–Mesenchymal Transition
Authors: Nasarre Patrick , Gemmill Robert M. , Potiron Vincent A. , Roche Joëlle , Lu Xian , Barón Anna E. , Korch Christopher , Garrett-Mayer Elizabeth , Lagana Alessandro , Howe Philip H. , Drabkin Harry A. 
Published: October 2013

Abstract
The epithelial–mesenchymal transition (EMT) and its reversal, mesenchymal–epithelial transition (MET), are fundamental processes involved in tumor cell invasion and metastasis. SEMA3F is a secreted semaphorin and tumor suppressor downregulated by TGF-β1 and ZEB1-induced EMT. Here, we report that neuropilin (NRP)-2, the high-affinity receptor for SEMA3F and a coreceptor for certain growth factors, is upregulated during TGF-β1–driven EMT in lung cancer cells. Mechanistically, NRP2 upregulation was TβRI dependent and SMAD independent, occurring mainly at a posttranscriptional level involving increased association of mRNA with polyribosomes. Extracellular signal—regulated kinase (ERK) and AKT inhibition blocked NRP2 upregulation, whereas RNA interference-mediated attenuation of ZEB1 reduced steady-state NRP2 levels. In addition, NRP2 attenuation inhibited TGF-β1–driven morphologic transformation, migration/invasion, ERK activation, growth suppression, and changes in gene expression. In a mouse xenograft model of lung cancer, NRP2 attenuation also inhibited locally invasive features of the tumor and reversed TGF-β1–mediated growth inhibition. In support of these results, human lung cancer specimens with the highest NRP2 expression were predominantly E-cadherin negative. Furthermore, the presence of NRP2 staining strengthened the association of E-cadherin loss with high-grade tumors. Together, our results demonstrate that NRP2 contributes significantly to TGF-β1–induced EMT in lung cancer. Cancer Res; 73(23); 7111–21. ©2013 AACR.
Molecular Pathways: SWI/SNF (BAF) Complexes Are Frequently Mutated in Cancer—Mechanisms and Potential Therapeutic Insights
Authors: Wang Xiaofeng , Haswell Jeffrey R. , Roberts Charles W.M. 
Published: October 2013

Abstract
SWI/SNF chromatin remodeling complexes are pleomorphic multisubunit cellular machines that utilize the energy of ATP hydrolysis to modulate chromatin structure. The complexes interact with transcription factors at promoters and enhancers to modulate gene expression and contribute to lineage specification, differentiation, and development. Initial clues to a role in tumor suppression for SWI/SNF complexes came over a decade ago when the gene encoding the SMARCB1/SNF5 core subunit was found specifically inactivated in nearly all pediatric rhabdoid tumors. In the last three years, cancer-genome sequencing efforts have revealed an unexpectedly high mutation rate of SWI/SNF subunit genes, which are collectively mutated in 20% of all human cancers and approach the frequency of p53 mutations. Here, we provide a background on these newly recognized tumor suppressor complexes, discuss mechanisms implicated in the tumor suppressor activity, and highlight findings that may lead to potential therapeutic targets for SWI/SNF-mutant cancers. Clin Cancer Res; 20(1); 21–27. ©2013 AACR.
KAVA Chalcone, Flavokawain A, Inhibits Urothelial Tumorigenesis in the UPII-SV40T Transgenic Mouse Model
Authors: Liu Zhongbo , Xu Xia , Li Xuesen , Liu Shuman , Simoneau Anne R. , He Feng , Wu Xue-Ru , Zi Xiaolin 
Published: October 2013

Abstract
Flavokawain A (FKA) is the predominant chalcone identified from the kava plant. We have previously shown that FKA preferentially inhibits the growth of p53 defective bladder cancer cell lines. Here, we examined whether FKA could inhibit bladder cancer development and progression in vivo in the UPII-SV40T transgenic model that resembles human urothelial cell carcinoma (UCC) with defects in the p53 and the retinoblastoma (Rb) protein pathways. Genotyped UPII-SV40T mice were fed orally with vehicle control (AIN-93M) or FKA (6 g/kg food; 0.6%) for 318 days starting at 28 days of age. More than 64% of the male mice fed with FKA-containing food survived beyond 318 days of age, whereas only about 38% of the male mice fed with vehicle control food survived to that age (P = 0.0383). The mean bladder weights of surviving male transgenic mice with the control diet versus the FKA diet were 234.6 ± 72.5 versus 96.1 ± 69.4 mg (P = 0.0002). FKA was excreted primarily through the urinary tract and concentrated in the urine up to 8.4 μmol/L, averaging about 38 times (males) and 15 times (females) more concentrated than in the plasma (P = 0.0001). FKA treatment inhibited the occurrence of high-grade papillary UCC, a precursor to invasive urothelial cancer, by 42.1%. A decreased expression of Ki67, survivin, and X-linked inhibitor of apoptotic proteins (XIAP) and increased expression of p27 and DR5, and the number of terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL)-positive apoptotic cells were observed in the urothelial tissue of FKA-fed mice. These results suggest a potential of FKA in preventing the recurrence and progression of non–muscle-invasive UCC. Cancer Prev Res; 6(12); 1365–75. ©2013 AACR.
The Semantics of בי״ן in the qal and hiphil
Authors: Garr W. Randall 
Published: October 2013

Abstract
This paper argues that the morphological difference between qal and non-causative hiphil forms of בי״ן has a semantic correlate. The qal expresses perception, lower degrees of mental activity, and a lower degree of agentivity. It denotes sense-based perception, awareness, and cognizance The hiphil expresses a higher level of agentivity as well as a higher, more complex, and more demanding mental activity. It involves disentangling, decipherment, comprehension, as well as practical application.
Is Fear of the Lord the Source of Wisdom or Vice Versa?
Authors: Schwáb Zoltán 
Published: October 2013

Abstract
Despite the diverse interpretations of Prov. 1:7; 9:10, and related verses, scholars have agreed on a crucial point: these verses teach that wisdom stems from the fear of the Lord. Stuart Weeks has challenged this consensus recently, claiming that the relationship works the other way: the fear of the Lord follows from wisdom. I will argue that much of Weeks’ critique of the “traditional” interpretation is correct. Nevertheless, I will also argue that, if it is put carefully, a certain form of the usual understanding of Prov. 1:7 and 9:10 can still be maintained.
Conversion and Autobiography: Telling Tales before the Roman Inquisition
Authors: Fosi Irene 
Published: October 2013

Abstract
The goal of this article is to analyze the mechanisms used by Catholic Church authorities during the early modern period to control and repress heresies, as well as the ways in which foreign heretics were converted and eventually assimilated into local society when they came to Rome. Generally speaking, papal policies encouraged foreigners to hide their religious identity, with the aim of giving a superficial appearance of assimilation, in order to avoid any scandal. Although the guidelines established in papal bulls did allow for some exceptions, the high risk of being expelled or persecuted encouraged foreigners to present themselves before the Holy Office and disavow their religious beliefs. Their confessions before the tribunal were filed by the officials of the Inquisition according to stereotypes that filtered the memories of foreigners. How “genuine” were these stories? Do they simply respond to the expectations and manipulative tactics of the judges? The fragile boundary between true and false, between biography and autobiography, poses a question, one that always underlies any study on religious conversion: to what extent can we analyze the “real” motivations underlying any religious conversion?
Magic, Medicine and Authority in Mid-Seventeenth-Century Muscovy: Andreas Engelhardt (d. 1683) and the Role of the Western Physician at the Court of Tsar Aleksei Mikhailovich, 1656-1666
Authors: Collis Robert 
Published: October 2013

In Early Modern Europe court physicians exerted great influence in service to their royal patrons. These medical practitioners acted as learned conduits, whose knowledge of natural philosophy, which often included occult theories of healing, natural magic and astrology, was able to serve the broad interests of their patrons. Thus, in addition to being charged with maintaining the health of a ruler, physicians were often exploited by monarchs seeking to enhance the general health of their body politic.
This case study of the German physician Andreas Engelhardt examines his decade-long service in Moscow between 1656 and 1666 at the court of Aleksei Mikhailovich. This study of Engelhardt’s role at court at a time of increased Western influence in Muscovy aims to reveal how the tsar sought to utilize the learning of his German physician in a variety of ways. Engelhardt not only administered Western medical remedies, including the use of unicorn horns, to the royal family, but was also instructed to ascertain whether various Russian and Siberian folk remedies possessed beneficent qualities. This process of legitimization and containment of medical knowledge coincided with an attempt to suppress the authority of folk healers, thereby reflecting the autocratic nature of Aleksei Mikhailovich’s reign. Furthermore, this article demonstrates that the tsar drew on Engelhardt’s supposed expertise in astrology and divination in order to know how Muscovy would be affected by the appearance of a comet in the winter of 1664-1665.