bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of intention to leave among non-medical employees after a nuclear disaster: a cross-sectional study
Authors: Takeda Saeka , Orita Makiko , Fukushima Yoshiko , Kudo Takashi , Takamura Noboru 
Published: July 2016

ObjectiveTo conduct a survey among non-medical employees working at the time of the Fukushima Daiichi Nuclear Power Station accident, in order to determine the factors associated with their intentions to leave their jobs during the nuclear disaster.ParticipantsWe asked 287 employees (166 men and 121 women) in the study.MethodsWe asked about their intentions to leave their jobs after the nuclear disaster. We also asked about relevant factors, including the participants’ demographic factors, living situations and working environments.ResultsWe found that in employees younger than 40 (OR=4.73, 95% CI 1.74 to 12.85, p=0.002), being married (OR=3.18, 95% CI 1.03 to 9.79, p=0.044), measurements of the ambient dose rates in their homes after the accident (OR=5.32, 95% CI 1.65 to 17.14, p=0.005), anxiety about their relationships with their colleagues after the accident (OR=3.91, 95% CI 1.51 to 10.16, p=0.005) and the influence of radiation on the workplace (OR=0.33, 95% CI 0.14 to 0.80, p=0.014) were independently associated with the non-medical employees’ intentions to leave their jobs after the nuclear disaster.ConclusionsOur results suggest the need for continuous risk communication regarding such factors and the provision of information about the health effects of radiation exposure to non-medical employees after nuclear disasters.
Ionised calcium levels in major trauma patients who received blood in the Emergency Department
Authors: Webster Stacey , Todd Samuel , Redhead Julian , Wright Chris 
Published: July 2016

BackgroundExsanguination and coagulopathy remain one of the leading causes of preventable trauma related death. Low ionised calcium levels have been associated with hypotension and increased mortality and may inhibit clot formation. Blood product contains citrate that acts as a chelating agent. We hypothesised that trauma patients who have bled are at risk of hypocalcaemia and that receiving any amount of blood product can exacerbate this state.MethodsA retrospective cohort analysis was performed on all trauma patients who had received early blood product in the ED of a single urban major trauma centre in the UK between 2013 and 2014. Ionised calcium levels were taken from venous blood gases from before and after blood product had been transfused.ResultsThe study included 55 patients; 36 male (65%), age 33 (16–92) years, median injury severity score (ISS) 24 (4–50), units of blood product received 2 (1–16), overall mortality 18%. Fifty-five per cent patients were hypocalcaemic on arrival, 89% patients were hypocalcaemic after receiving any amount of blood product. There was a statistically significant difference in ionised calcium levels after receiving blood product, pretransfusion 1.11 mmol/L (95% CI 1.09 to 1.14), post-transfusion 0.98 mmol/L (95% CI 0.93 to 1.02) (p<0.001). A fall in calcium was seen after receiving just one unit and the more units of blood product received the greater the fall seen.ConclusionsTrauma patients that have sustained blood loss are at risk of hypocalcaemia. Ionised calcium levels fall significantly further even after receiving a small amount of blood product. Prompt recognition and early targeted treatment is needed from arrival.
Thrombocytosis and STAT5 activation in chronic myelogenous leukaemia are not associated withJAK2V617F or calreticulin mutations
Authors: Turakhia Samir K , Murugesan Gurunathan , Cotta Claudiu V , Theil Karl S 
Published: July 2016

AimsMarked thrombocytosis is uncommon in chronic myelogenous leukaemia (CML) but may be associated with mutation ofJAK2V617F, calreticulin (CALR) and/or phospho-STAT5 (p-STAT5) activation in other myeloproliferative neoplasms (MPNs), particularly essential thrombocythaemia (ET). We investigated theJAK2V617F,CALRand STAT5 activation status in patients with CML and thrombocytosis (CML-T) that mimicked ET, trying to identify a common mechanism for thrombocytosis in MPN.MethodsBlood and bone marrow morphological findings were reviewed from seven CML-T, four otherwise typical CML and one CML in blast phase. All cases were analysed forBCR-ABL1,JAK2V617F andCALRexon 9 mutation and p-STAT5 expression.ResultsFour of seven cases of CML-T had marked thrombocytosis (>1000×109/L). Eleven of 12 cases had megakaryocyte morphology typical for CML. All cases wereBCR-ABL1positive. Eleven of 12 cases were negative forJAK2V617F, while STAT5 was activated in six of seven CML-T and in four of five CML cases. No case had a detectableCALRexon 9 mutation. One case of CML developed ET-like morphology and hadJAK2V617F detected while in molecular remission for CML.ConclusionsDetection ofBCR-ABL1is critical in the distinction of ET from CML. Thrombocytosis and STAT5 activation in CML-T are not consistently associated withCALRexon 9 orJAK2V617F mutation.
Knowledge Sharing and Learning in Organizations: Role of Incentives and Information Systems
Authors: Sundaresan Shankar , Zhang Zuopeng Justin 
Published: July 2016

Knowledge sharing and learning play a fundamental role in the success of knowledge management (KM). While information technologies facilitate learning and sharing of knowledge in organizations, incentive systems help to align organizational and individual goals. Applying a modeling framework that captures the characteristics of both information systems and incentives in a team-based organization, we demonstrate that an output allocation rule linear in output, and sharing-learning incentive rewards linear in the amounts being shared and learned can be optimally designed. Broad conditions for implementing such incentive systems are derived. The incentives facilitate desirable KM goals such as knowledge sharing (learning) alignment and full-knowledge transfer. Deriving an optimal level of knowledge management systems (KMS), we determine a threshold level required to achieve complete-knowledge enablement to facilitate high performance teams. We explore how investment in information technologies impacts incentives and their combined role, and find conditions under which they substitute or complement each other. Moreover, we demonstrate that IT can help organizations narrow the gap between the profits the firm can make under the two cases — when worker’s knowledge levels are known and unknown. We extend the model to multiple dimensions of knowledge, study a mandatory learning policy, and compare the team-based results to a non-team based setting. Our research provides guidelines for matching investments in information technology with appropriate incentives.
Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder
Authors: Wang Wei-Jan , Li Chien-Feng , Chu Yu-Yi , Wang Yu-Hui , Hour Tzyh-Chyuan , Yen Chia-Jui , Chang Wen-Chang , Wang Ju-Ming 
Published: July 2016

AbstractPurpose: Cisplatin (CDDP) is frequently used in combination chemotherapy with paclitaxel for treating urothelial carcinoma of the urinary bladder (UCUB). CDDP cross-resistance has been suggested to develop with paclitaxel, thus hindering successful UCUB treatment. Therefore, elucidating the mechanisms underlying CDDP-induced anticancer drug resistance is imperative and may provide an insight in developing novel therapeutic strategy.Experimental Design: Loss-of-function assays were performed to elucidate the role of the EGFR and STAT3 in CDDP-induced CCAAT/enhancer-binding protein delta (CEBPD) expression in UCUB cells. Reporter and in vivo DNA-binding assays were employed to determine whether CEBPD directly regulates ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily C member 2 (ABCC2) activation. Finally, a xenograft animal assay was used to examine the abilities of gefitinib and S3I-201 (a STAT3 inhibitor) to reverse CDDP and paclitaxel sensitivity.Results: CEBPD expression was maintained in postoperative chemotherapy patients, and this expression was induced by CDDP even in CDDP-resistant UCUB cells. Upon CDDP treatment, CEBPD activated ABCB1 and ABCC2. Furthermore, the EGFR/STAT3 pathway contributed to CDDP-induced CEBPD expression in UCUB cells. Gefitinib and S3I-201 treatment significantly reduced the expression of CEBPD and enhanced the sensitivity of CDDP-resistant UCUB cells to CDDP and paclitaxel.Conclusions: Our results revealed the risk of CEBPD activation in CDDP-resistant UCUB cells and suggested a therapeutic strategy for patients with UCUB or UCUB resisted to CDDP and paclitaxel by combination with either gefitinib or S3I-201. Clin Cancer Res; 23(2); 503–13. ©2016 AACR.
Molecular Pathways: Immune Checkpoint Antibodies and their Toxicities
Authors: Cousin Sophie , Italiano Antoine 
Published: July 2016

Abstract
The emergence of immune checkpoint inhibitors for solid tumor treatments represents a major oncologic advance. Since the approval of ipilimumab, a cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) antibody, for the treatment of metastatic melanoma, many drugs, especially those targeting PD-1/PD-L1, have demonstrated promising antitumor effects in many types of cancer. By reactivating the immune system, these immunotherapies have led to the development of new toxicity profiles, also called immune-related adverse events (irAE). IrAEs can involve many organ systems, and their management is radically different from that of cytotoxic drugs; irAEs require immunosuppressive treatments, such as corticoids or TNFα antibody. In addition, the occurrence of irAEs has raised significant questions. Here, we summarize progress that has been made toward answering these questions, focusing on (i) the impact of immunotherapy dose on irAE occurrence, (ii) the correlation between irAE and patient outcome, (iii) the safety of immune checkpoint inhibitors in patients already treated for autoimmune disease, and (iv) the suspected effect on tumor growth of steroids used for the management of irAEs. Clin Cancer Res; 22(18); 4550–5. ©2016 AACR.
Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity
Authors: Ballard Peter , Yates James W.T. , Yang Zhenfan , Kim Dong-Wan , Yang James Chih-Hsin , Cantarini Mireille , Pickup Kathryn , Jordan Angela , Hickey Mike , Grist Matthew , Box Matthew , Johnström Peter , Varnäs Katarina , Malmquist Jonas , Thress Kenneth S. , Jänne Pasi A. , Cross Darren 
Published: July 2016

Abstract
Purpose: Approximately one-third of patients with non–small cell lung cancer (NSCLC) harboring tumors with EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutations (EGFRm) experience disease progression during treatment due to brain metastases. Despite anecdotal reports of EGFR-TKIs providing benefit in some patients with EGFRm NSCLC brain metastases, there is a clinical need for novel EGFR-TKIs with improved efficacy against brain lesions.
Experimental Design: We performed preclinical assessments of brain penetration and activity of osimertinib (AZD9291), an oral, potent, irreversible EGFR-TKI selective for EGFRm and T790M resistance mutations, and other EGFR-TKIs in various animal models of EGFR-mutant NSCLC brain metastases. We also present case reports of previously treated patients with EGFRm-advanced NSCLC and brain metastases who received osimertinib in the phase I/II AURA study (NCT01802632).
Results: Osimertinib demonstrated greater penetration of the mouse blood–brain barrier than gefitinib, rociletinib (CO-1686), or afatinib, and at clinically relevant doses induced sustained tumor regression in an EGFRm PC9 mouse brain metastases model; rociletinib did not achieve tumor regression. Under positron emission tomography micro-dosing conditions, [11C]osimertinib showed markedly greater exposure in the cynomolgus monkey brain than [11C]rociletinib and [11C]gefitinib. Early clinical evidence of osimertinib activity in previously treated patients with EGFRm-advanced NSCLC and brain metastases is also reported.
Conclusions: Osimertinib may represent a clinically significant treatment option for patients with EGFRm NSCLC and brain metastases. Further investigation of osimertinib in this patient population is ongoing. Clin Cancer Res; 22(20); 5130–40. ©2016 AACR.
The Efficacy of Oncolytic Adenovirus Is Mediated by T-cell Responses against Virus and Tumor in Syrian Hamster Model
Authors: Li Xiaozhu , Wang Pengju , Li Hang , Du Xuexiang , Liu Mingyue , Huang Qibin , Wang Yaohe , Wang Shengdian 
Published: July 2016

Abstract
Purpose: Oncolytic adenoviruses (Ad) represent an innovative approach to cancer therapy. Its efficacy depends on multiple actions, including direct tumor lysis and stimulation of antiviral and antitumor immune responses. In this study, we investigated the roles of T-cell responses in oncolytic adenoviral therapy.
Experimental Design: An immunocompetent and viral replication–permissive Syrian hamster tumor model was used. The therapeutic mechanisms of oncolytic Ad were investigated by T-cell deletion, immunohistochemical staining, and CTL assay.
Results: Deletion of T cells with an anti-CD3 antibody completely demolished the antitumor efficacy of oncolytic Ad. Intratumoral injection of Ad induced strong virus- and tumor-specific T-cell responses, as well as antiviral antibody response. Both antiviral and antitumor T-cell responses contributed to the efficacy of oncolytic Ad. Deletion of T cells increased viral replication and extended the persistence of infectious virus within tumors but almost abrogated the antitumor efficacy. Preexisting antiviral immunity promoted the clearance of injected oncolytic Ad from tumors but had no effect on antitumor efficacy. Strikingly, the repeated treatment with oncolytic Ad has strong therapeutic effect on relapsed tumors or tumors insensitive to the primary viral therapy.
Conclusions: These results demonstrate that T cell–mediated immune responses outweigh the direct oncolysis in mediating antitumor efficacy of oncolytic Ad. Our data have a high impact on redesigning the regimen of oncolytic Ad for cancer treatment. Clin Cancer Res; 23(1); 239–49. ©2016 AACR.
Validation of the Attention-Related Driving Errors Scale (ARDES) in an English-Speaking Sample
Authors: Barragán Daniela , Roberts Daniel M. , Baldwin Carryl L. 
Published: July 2016

Objective: The goal for this study was to develop an English translation of the Attention-Related Driving Errors Scale (ARDES-US) and to determine its potential relationship with driver history and other demographic variables. Background: Individual differences in performance on vigilance and cognitive tasks are well documented, but less is known about susceptibility to attention-related errors while driving. The ARDES has been developed and administered in both Spanish and Chinese but to our knowledge has never been administered or examined in an English-speaking population. Method: Two hundred ninety-six English-speaking individuals completed a series of self-report measures, including the ARDES-US, Attention-Related Cognitive Errors Scale, Mindful Attention Awareness Scale, and Cognitive Failures Questionnaire. Results: A confirmatory factor analysis using maximum-likelihood estimates with robust standard errors revealed results largely consistent with previous versions of the ARDES, namely, the ARDES-Spain and ARDES-Argentina. Additionally, a number of new results emerged. Specifically, women, drivers who received traffic tickets within the previous 2 years, and those with a lower level of education all had a greater propensity toward self-reported driver inattention as measured by the ARDES-US. Further analyses revealed that these findings were independent of age, years of driving experience, and driving frequency. Conclusion: These results suggest that the ARDES-US is a valid and reliable measure of driver inattention with an English-speaking American sample. Application: Potential applications of the ARDES-US include identifying individuals who are at greater risk of attention-related errors while driving and suggesting individually tailored training and safety countermeasures.
The characterisation of the values of public ethics: application to territorial public management in the province of Guangxi (China)
Authors: Mériade Laurent 
Published: July 2016

Today, the legitimacy of politicians and public confidence in public decision-making and administration are increasingly dependent on the way in which their ethics are appraised ( Kolthoff et al., 2013 ). The ‘moral pluralism and cultural diversity’ of contemporary society ( Boisvert, 2008 ) make public ethics a new theoretical framework to be explored from the point of view of the compromises it makes between various, often conflicting, values. Yet, in practice, this compromise seems to limit the values of public ethics to principles of good governance formalised around codes of conduct or managerial procedures (Rochet, 2011). Our research question sets out to question the variety of these values; the research objective being to develop a categorisation of the values of public ethics by supplementing the conceptual framework of New Public Value ( Moore, 1995 ; Nabatchi, 2011 ), in particular, by characterising the values of the ethics of interaction not yet illustrated in the literature. Points for practitioners In practical terms, the aim of this article is to identify and characterise more precisely the variety of ethical values mobilised by public managers. To do so, we conducted a survey in two stages among public managers in Guangxi province in China, a country where the expression of personal or cultural ethics in the workplace is described in the literature as relatively natural. Our first results suggest a fairly clear distinction between the ethical values governing the performance of public action, which are relatively well formalised, and the ethical values governing public interaction, which are more informal and closer to cultural and social rituals.
Age- and Sex-Related Normative Data for the Foot Function Index in a German-Speaking Cohort
Authors: Schneider Wolfgang , Jurenitsch Stefan 
Published: July 2016

Background: Despite increasing popularity of the Foot Function Index (FFI), normative values are still unavailable for this self-administered score. This study was designed to generate age- and sex-related normative values for the FFI-total and for both subscales FFI-pain and FFI-disability. Methods: We used the cross-cultural adapted and validated German version of the FFI to generate a data pool using the results of 625 individuals, including staff and visitors to our hospital and excluding persons scheduled for foot surgery or in after-treatment. Results: Mean values for FFI-total were calculated: 15.3 points (95% confidence interval [CI], 13.3-16.9), 14.9 points for FFI-pain (CI, 13.3-16.5), and 15.6 for FFI-disability (CI, 13.8-17.4). Results showed higher values for FFI-total, FFI-pain, and FFI-disability for individuals older than 40 years. In general, normative values showed a tendency for higher values with age. A slightly inconsistent distribution over different age groups with a peak for individuals in their 40s and 50s was observed, especially for FFI-pain. Men had better scores than women. Individuals with previous surgery showed lower scores in their respective score. Conclusions: Our data calculated normative values for a German-speaking cohort for FFI-total as well as for both subscales FFI-pain and FFI-disability. Our data quantified the increase of FFI-total, FFI-pain, and FFI-disability normative values with age but also showed a slightly inconsistent distribution of normative values over all age groups. We demonstrated higher normative values for women and slightly higher normative values for individuals with previous foot or ankle surgery. Level of Evidence: II, prospective comparative study
Role of IL-17-producing lymphocytes in severity of multiple sclerosis upon natalizumab treatment
Authors: Bühler Ulrike , Fleischer Vinzenz , Luessi Felix , Rezk Ayman , Belikan Patrick , Graetz Christiane , Gollan René , Wolf Christina , Lutz Jens , Bar-Or Amit , Siffrin Volker , Zipp Frauke 
Published: July 2016

Objective: Natalizumab is known to prevent T-helper cells entering the central nervous system (CNS). We hypothesize that more pathogenic T-helper cells are present outside the CNS and a possible relationship to disease severity. Methods: Characterization and enrichment of human CD4+IL-17+ cells were performed ex vivo using peripheral blood mononuclear cells from natalizumab-treated relapsing-remitting multiple sclerosis (RRMS) patients ( n = 33), untreated RRMS patients ( n = 13), and healthy controls ( n = 33). Magnetic resonance imaging (MRI) scans were performed routinely for patients. Results: Lymphocytes were elevated in peripheral blood of natalizumab-treated patients compared to untreated patients and healthy controls. Whereas group comparison for CD4+IL-17+ numbers also differed, CD4+IFN-γ+ and CD4+IL-22+ counts were not increased. CD4+IL-17+ cells not only expressed but also secreted IL-17. In natalizumab-treated patients, IL-17+ cell frequency was found to correlate with T1-hypointense lesions, but was not an indicator for rebound activity after treatment discontinuation, except in one patient who experienced a fulminant rebound, and interestingly, in whom the highest IL-17+ cell levels were observed. Conclusion: Increased lymphocytes and CD4+IL-17+ cells in the blood of RRMS patients receiving natalizumab corroborate the drug’s mechanism of action, that is, blocking transmigration to CNS. Correlation between IL-17-expressing lymphocytes and T1-hypointense lesions underlines the important role of these cells in the disease pathology.
Correlation between adenoma detection rate in colonoscopy‐ and fecal immunochemical testing‐based colorectal cancer screening programs
Authors: Cubiella Joaquín , Castells Antoni , Andreu Montserrat , Bujanda Luis , Carballo Fernando , Jover Rodrigo , Lanas Ángel , Morillas Juan Diego , Salas Dolores , Quintero Enrique ,   COLONPREV study investigators
Published: July 2016

BackgroundThe adenoma detection rate (ADR) is the main quality indicator of colonoscopy. The ADR recommended in fecal immunochemical testing (FIT)‐based colorectal cancer screening programs is unknown.MethodsUsing the COLONPREV (NCT00906997) study dataset, we performed a post‐hoc analysis to determine if there was a correlation between the ADR in primary and work‐up colonoscopy, and the equivalent figure to the minimal 20% ADR recommended. Colonoscopy was performed in 5722 individuals: 5059 as primary strategy and 663 after a positive FIT result (OC‐Sensor™; cut‐off level 15 µg/g of feces). We developed a predictive model based on a multivariable lineal regression analysis including confounding variables.ResultsThe median ADR was 31% (range, 14%–51%) in the colonoscopy group and 55% (range, 21%–83%) in the FIT group. There was a positive correlation in the ADR between primary and work‐up colonoscopy (Pearson’s coefficient 0.716; p  < 0.001). ADR in the FIT group was independently related to ADR in the colonoscopy group: regression coefficient for colonoscopy ADR, 0.71 (p  = 0.009); sex, 0.09 (p  = 0.09); age, 0.3 (p  = 0.5); and region 0.00 (p  = 0.9). The equivalent figure to the 20% ADR was 45% (95% confidence interval, 35%–56%).ConclusionsADR in primary and work‐up colonoscopy of a FIT‐positive result are positively and significantly correlated.