bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paramedic-supplied ‘Take Home’ Naloxone: protocol for cluster randomised feasibility study
Authors: Moore Chris , Lloyd Gregory , Oretti Rossana , Russell Ian , Snooks Helen 
Published: March 2014

Introduction‘Take Home’ Naloxone (THN) kits for use by peers in the event of an opioid overdose may reduce further overdose and deaths, but distribution through Drugs Services may not reach those at highest risk. Attendance by paramedics at emergency calls for patients who have suffered an overdose presents an opportunity to distribute THN kits. In this feasibility study we will assess the acceptability of this intervention, and gather data to inform definitive trial planning.Methods and analysisCluster randomised trial with staggered allocation of paramedics (clusters) to groups. We will invite paramedics in an urban area of south Wales, UK to take part. We will randomly allocate those that accept to training sessions during the first 4 months of the trial. Patients attended by paramedics who have been trained and issued THN kits will fall into the intervention group. Patients attended by paramedics following usual practice (until they receive their training and THN kits) will fall into the control group. We will gather data about processes and outcomes of care: numbers of patients eligible for intervention, offered and accepted THN, attended emergency department, suffered further overdose, died within 3 months and about follow-up rates: numbers of patients consented, completed (postal or telephone) questionnaire. We will gather qualitative data about acceptability to patients and paramedics through interviews and focus groups.Ethics and disseminationEthical approval for this study was granted on 7 December 2011, by South East Wales Research Ethics Committee, Panel C. Results of this study will be reported through peer-reviewed scientific journals, conference presentations and internal organisational report. We will also seek to report our findings through local and national substance misuse networks and publications.Trial registration numberISRCTN98216498.
Validation of a teamwork perceptions measure to increase patient safety
Authors: Keebler Joseph R , Dietz Aaron S , Lazzara Elizabeth H , Benishek Lauren E , Almeida Sandra A , Toor Phyllis A , King Heidi B , Salas Eduardo 
Published: March 2014

BackgroundTeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety) is a team-training intervention which shows promise in aiding the mitigation of medical errors. This article examines the construct validity of the TeamSTEPPS Teamwork Perceptions Questionnaire (T-TPQ), a self-report survey that examines multiple dimensions of perceptions of teamwork within healthcare settings.MethodUsing survey-based methods, 1700 multidisciplinary healthcare professionals and support staff were measured on their perceptions of teamwork. Confirmatory factor analysis was conducted to examine the relationship between the five TeamSTEPPS dimensions: Leadership, Mutual Support, Situation Monitoring, Communication, and Team Structure.ResultsThe analysis indicated that the T-TPQ measure is more reliable than previously thought (Cronbach's α=0.978). Further, our final tested model showed a good fit with the data (x2(df) 3601.27 (546), p<0.0001, Tucker–Lewis Index (TLI)=0.942, Comparative fit index (CFI)=0.947, root mean square error of approximation (RMSEA)=0.057), indicating that the measure appears to have construct validity. Further, all dimensions correlated with one another, but were shown to be independent constructs.ConclusionsThe T-TPQ is a construct-valid instrument for measuring perceptions of teamwork. This has beneficial implications for patient safety and future research that studies medical teamwork.
Interventions to improve the management of pain in emergency departments: systematic review and narrative synthesis
Authors: Sampson F C , Goodacre S W , O'Cathain A 
Published: March 2014

IntroductionPain management in emergency departments (ED) is often inadequate despite the availability of effective analgesia, with many patients receiving insufficient and untimely analgesia. We conducted a systematic literature review to identify interventions that could improve pain management in the ED.MethodsWe systematically searched seven databases for studies reporting pain management outcomes after intervention to change professional practice to improve pain management in the ED, compared with pain management before or without intervention. Data was synthesised using principles of narrative synthesis.ResultsWe identified 43 relevant studies, including 40 uncontrolled before-and-after studies. Interventions included implementation of guidelines and protocols, educational interventions, pain scoring tools and changes in nursing roles, with many multifaceted interventions incorporating two or more of these elements. Interventions aimed to improve assessment and documentation of pain, knowledge and awareness of pain management and reduce time to analgesia. Due to the high probability of bias in study design and significant variation between studies, it was not possible to estimate the overall effectiveness of interventions, or identify which had the greatest impact. Intervention to improve pain management was reported to have some positive impact in most studies, but these findings may be explained by limitations in study design.ConclusionsMany interventions reported improvements in pain management, but current evidence is insufficient to recommend any for widespread adoption. In order to improve pain management we need to understand more about the theory underlying interventions, the context in which interventions work, and develop interventions based on this stronger theoretical understanding.
Enterprise stenting for intracranial aneurysm treatment induces dynamic and reversible age-dependent stenosis in cerebral arteries
Authors: Gao Bulang , Safain Mina G , Malek Adel M 
Published: March 2014

BackgroundAlthough intracranial stenting has been associated with in-stent stenosis, the vascular response of cerebral vessels to the deployment of the Enterprise vascular reconstruction device is poorly defined.ObjectiveTo evaluate the change in parent vessel caliber that ensues after Enterprise stent placement.MethodsSeventy-seven patients with 88 aneurysms were treated using Enterprise stent-assisted coil embolization and underwent high-resolution three-dimensional rotational angiography followed by three-dimensional edge-detection filtering to remove windowing-dependence measurement artifact. Orthogonal diameters and cross-sectional areas (CSAs) were measured proximal and distal on either side of the leading stent edge (points A, B), trailing stent edge (points D, E), and at mid-stent (point C).ResultsEnterprise stent deployment caused an instant increase in the parent artery CSA by 8.98% at D, which was followed 4–6 months later by significant in-stent stenosis (15.78% at A, 27.24% at B, 10.68% at C, 32.12% at D, and 28.28% at E) in the stented artery. This time-dependent phenomenon showed resolution which was complete by 12–24 months after treatment. This target vessel stenosis showed significant age dependence with greater response in the young. No flow-limiting stenosis requiring treatment was observed in this series.ConclusionsUse of the Enterprise stent is associated with a significant dynamic and spontaneously resolvable age-dependent in-stent stenosis. Further study is warranted on the clinical impact, if any, of this occurrence.
NEUTRON PRODUCTION IN BLACK HOLE CORONAE AND PROTON LOADING OF JETS
Authors: VILA GABRIELA S. , VIEYRO FLORENCIA L. , ROMERO GUSTAVO E. 
Published: March 2014

We study the production of neutrons in the corona of an accreting black hole through the interaction of locally accelerated protons with matter and radiation. A fraction of these neutrons may escape and penetrate into the base of the jet, later decaying into protons. This is a possible mechanism for loading Poynting-dominated outflows with baryons. We characterize the spatial and energy distribution of neutrons in the corona and that of the protons injected in the jet by neutron decay. We assess the contribution of these protons to the radiative spectrum of the jet. We also investigate the fate of the neutrons that escape the corona into the external medium.
Lunar mare volcanism: lateral heterogeneities in volcanic activity and relationship with crustal structure
Authors: Morota Tomokatsu , Ishihara Yoshiaki , Sasaki Sho , Goossens Sander , Matsumoto Koji , Noda Hirotomo , Araki Hiroshi , Hanada Hideo , Tazawa Seiichi , Kikuchi Fuyuhiko , Ishikawa Toshiaki , Tsuruta Seiitsu , Kamata Shunichi , Otake Hisashi , Haruyama Junichi , Ohtake Makiko 
Published: March 2014

Abstract
Lunar mare basalts are spatially unevenly distributed, and their abundances differ between the nearside and farside of the Moon. Although mare asymmetry has been attributed to thickness variations in the low-density anorthositic crust, the eruptive mechanism of lunar magma remains unknown. In this study, we investigate the relationship between mare distribution and crustal thickness using geological and geophysical data obtained by the SELENE (Kaguya) and the Gravity Recovery and Interior Laboratory spacecraft, and quantitatively re-evaluate the influence of the anorthositic crust on magma eruption. We identify a lateral heterogeneity in the upper limit of crustal thickness that allows magma extrusion to the surface. In the Procellarum KREEP Terrane, where the surface abundances of heat-producing elements are extremely high, magmas can erupt in regions of crustal thickness below about 30 km. In contrast, magma eruptions are limited to regions of crustal thickness below about 20 km in other nearside regions, around 10 km in the South Pole–Aitken Basin and approximately 5 km in the farside Felspathic Highland Terrane. Such heterogeneity may result from lateral variations in magma production in the lunar mantle and/or crustal density.
Modelling of structural and lithological controls on mobility of fluids and gold in orogenic belts, New Zealand
Authors: Upton Phaedra , Craw Dave 
Published: March 2014

Abstract
Numerical models have been run to evaluate the key parameters that affect fluid flow and gold mineralization at a range of scales, from the full thickness of the crust to the mineral grain scale. These models are constrained with real examples of orogenic gold in southern New Zealand. Large scale modelling shows that differences in crustal strength and thickness affect the locus, scale, and rate of crustal fluid flow and hence influence gold deposition. The most vigorous hydrothermal activity and gold mineralization occurs in narrow zones with maximum uplift close to a major crustal boundary. Relatively strong middle crust develops deformation-driven permeability and fluid flow in a broad diffuse zone. Deformation of randomly inhomogeneous rocks under mid-crustal conditions results in horizontal fabric and horizontal shear zones, and these can control fluid flow locally. The addition of graphite to flat shear zones causes an increase in deformation-induced permeability, and this can encourage further graphite deposition in a feedback effect. Fluid flow in these flat shears is very slow (mm/year) compared to fluid flow in fracture-controlled permeability at shallow crustal levels. Rock strength inhomogeneities in mid-crustal shear zones can result in localized decrease in differential stress, facilitating the switching of orientations of principal stress axes and the formation of steeply-dipping quartz veins.
Young Investigator Perspectives. Teaching and the postdoctoral experience: impact on transition to faculty positions
Authors: Uno Jennifer , Walton Kristen L. W. 
Published: March 2014

This editorial continues with our Young Investigator Perspectives series. Drs. Uno and Walton are young investigators who hold faculty positions. They completed a K12 postdoctoral program through the IRACDA (Institutional Research and Career Development Award) program sponsored through the NIGMS institute at NIH. IRACDA programs exist at multiple institutions in the USA to combine postdoctoral training with formal training in academic skills and teaching at partner institutions. I thank Drs. Walton and Uno for a thoughtful perspective on how this experience shaped their career goals to combine teaching and research and inspire undergraduates to science careers. Given the current national dialog on broadening career paths and outcomes for PhD scientists, this is a timely perspective. — P. Kay Lund
Embelin Reduces Colitis-Associated Tumorigenesis through Limiting IL-6/STAT3 Signaling
Authors: Dai Yun , Jiao Hongmei , Teng Guigen , Wang Weihong , Zhang Rongxin , Wang Yunhong , Hebbard Lionel , George Jacob , Qiao Liang 
Published: March 2014

Abstract
The interleukin-6 (IL-6)/STAT3 signaling regulates survival and proliferation of intestinal epithelial cells and plays an important role in the pathogenesis of inflammatory bowel disease and colorectal cancer. Embelin is a small molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP), with antioxidant, anti-inflammatory, and antitumor activities. We previously showed that embelin inhibits the growth of colon cancer cells in vitro, and effectively suppresses 1,2-dimethylhydrazine dihydrochloride-induced colon carcinogenesis in mice. Here, we explored the antitumor effects and mechanisms of embelin on colitis-associated cancer (CAC) using the azoxymethane/dextran sulfate sodium (AOM/DSS) model, with a particular focus on whether embelin exerts its effect through the IL-6/STAT3 pathway. We found that embelin significantly reduced incidence and tumor size in CAC-bearing mice. In addition to inhibiting proliferation of tumor epithelial cells, embelin suppressed colonic IL-6 expression and secretion, and subsequently STAT3 activation in vivo. Importantly, in vitro studies have revealed that in colon cancer cells, embelin diminished both the constitutive and IL-6–induced STAT3 activation by stimulating Src homology domain 2-containing protein tyrosine phosphatase (SHP2) activity. Moreover, embelin protected mice from AOM/DSS-induced colitis before tumor development. Embelin decreased IL-1β, IL-17a, and IL-23a expression as well as the number of CD4+ T cells and macrophages infiltrating the colonic tissues. Thus, our findings demonstrated that embelin suppresses CAC tumorigenesis, and its antitumor effect is partly mediated by limiting IL-6/STAT3 activation and Th17 immune response. Embelin may be a potential agent in the prevention and treatment of CAC. Mol Cancer Ther; 13(5); 1206–16. ©2014 AACR.
MAPK Pathway Inhibition Enhances the Efficacy of an Anti-Endothelin B Receptor Drug Conjugate by Inducing Target Expression in Melanoma
Authors: Asundi Jyoti , Lacap Jennifer A. , Clark Suzanna , Nannini Michelle , Roth Leslie , Polakis Paul 
Published: March 2014

Abstract
Therapies targeting the mitogen-activated protein (MAP) kinase pathway in melanoma have produced significant clinical responses; however, duration of response is limited by acquisition of drug resistance. Rational drug combinations may improve outcomes in this setting. We assessed the therapeutic combination of an antibody–drug conjugate (ADC) targeting the endothelin B receptor (EDNRB) with small-molecule inhibitors of the MAP kinase signaling pathway in melanoma. Cell lines and tumor models containing either mutant BRAF or NRAS, or wild-type for both, were exposed to small-molecule inhibitors of BRAF and MEK. Expression of EDNRB was analyzed and the therapeutic impact of combining the anti-EDNRB ADC with the BRAF and MEK inhibitors was assessed. Increased expression of EDNRB in response to inhibition of BRAF and/or MEK was observed and augmented the antitumor activity of the ADC. Enhanced target expression and ADC antitumor activity were realized irrespective of the response of the tumor model to the BRAF or MEK inhibitors alone and could be achieved in melanoma with mutant NRAS, BRAF, or neither mutation. Cells that acquired resistance to BRAF inhibition through long-term culture retained drug-induced elevated levels of EDNRB expression. Expression of EDNRB was not enhanced in normal human melanocytes by inhibition of BRAF and the combination of the ADC with MAPK inhibitors was well-tolerated in mice. The anti-EDNRB ADC combines well with BRAF and MEK inhibitors and could have therapeutic use in the majority of human melanoma cases. Mol Cancer Ther; 13(6); 1599–610. ©2014 AACR.
Slow Overmethylation of Housekeeping Genes in the Body Mucosa Is Associated with the Risk for Gastric Cancer
Authors: Oh Jung-Hwan , Rhyu Mun-Gan , Jung Sung-Hoon , Choi Sang-Wook , Kim Suk-Il , Hong Seung-Jin 
Published: March 2014

Abstract
Helicobacter pylori infection increases age-related diverse overmethylation in gene-control regions, which increases the risk of gastric cancer. The H. pylori-associated overmethylation changes subsequently disappear when gastric atrophy and cancer develop. To identify cancer-risk epigenotypes, we traced dynamic methylation changes in the background mucosa of the stomach depending on the extent of gastric atrophy. Paired biopsy specimens were obtained from the noncancerous antrum and body mucosa of 102 patients with cancer and 114 H. pylori–positive and 112 H. pylori–negative controls. The grade of gastric atrophy was evaluated using the endoscopic atrophic border score. The methylation-variable sites at the CpG-island margins and near the transcriptional start sites lacking CpG islands were semiquantitatively analyzed by radioisotope-labeling methylation-specific PCR. We selected eight housekeeping genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR retroelements (MMP2, CDKN2A, RUNX2, and RUNX3) and eight stomach-specific genes (TFF2, PGC, ATP4B, TFF1, TFF3, GHRL, PGA, and ATP4A). Analysis of age-related methylation in the H. pylori–positive controls revealed slow overmethylation in the body and in the LTR-adjacent genes. A high-frequency overmethylation defined based on the slowly overmethylated genes was frequently observed in the body of patients with gastric cancer with open-type atrophy (OR, 12.7; 95% confidence interval, 3.2–49.8). The rapidly changing methylation of Alu-adjacent genes was barely increased in the antrum of patients with gastric cancer. Among diverse methylation changes associated with H. pylori infection, an increase in slowly changing methylation could serve as a cancer-risk marker. Cancer Prev Res; 7(6); 585–95. ©2014 AACR.
Predicted for Greatness: 1994 Molecule of the Year—The DNA Repair Enzyme
Authors: Berwick Marianne 
Published: March 2014

Abstract
Lung cancer mortality is the highest of any cancer. Primary prevention has stalled, however, new lung cancer screening trials of low-dose computerized tomography (LDCT) have shown that the mortality from lung cancer can be reduced by up to 20% among current and former smokers. There are potential harms that must be taken into account when evaluating any screening program. With LDCT, there is a 90% rate of false positives and the potential for high doses of radiation from subsequent workup of benign lesions. The development of biomarkers that might refine the ability of screening to identify individuals at high risk for developing and dying from lung cancer is a ripe area for investigation. Sevilya and colleagues have developed a highly promising set of biomarkers of DNA repair capacity that may satisfy that goal. The large estimate of risk, the thoughtful combination of functional assays of DNA repair capacity, and the population-based design of the study make it reasonable to test these biomarkers in a larger study. Cancer Prev Res; 7(4); 375–7. ©2014 AACR.
Disturbed Flow Promotes Endothelial Senescence via a p53-Dependent Pathway
Authors: Warboys Christina M. , de Luca Amalia , Amini Narges , Luong Le , Duckles Hayley , Hsiao Sarah , White Alex , Biswas Shukti , Khamis Ramzi , Chong Chuh K. , Cheung Wai-Mun , Sherwin Spencer J. , Bennett Martin R. , Gil Jesus , Mason Justin C. , Haskard Dorian O. , Evans Paul C. 
Published: March 2014

Objective—
Although atherosclerosis is associated with systemic risk factors such as age, high cholesterol, and obesity, plaque formation occurs predominately at branches and bends that are exposed to disturbed patterns of blood flow. The molecular mechanisms that link disturbed flow–generated mechanical forces with arterial injury are uncertain. To illuminate them, we investigated the effects of flow on endothelial cell (EC) senescence.

Approach and Results—

LDLR
−/−
(low-density lipoprotein receptor
−/−
) mice were exposed to a high-fat diet for 2 to 12 weeks (or to a normal chow diet as a control) before the assessment of cellular senescence in aortic ECs. En face staining revealed that senescence-associated β-galactosidase activity and p53 expression were elevated in ECs at sites of disturbed flow in response to a high-fat diet. By contrast, ECs exposed to undisturbed flow did not express senescence-associated β-galactosidase or p53. Studies of aortae from healthy pigs (aged 6 months) also revealed enhanced senescence-associated β-galactosidase staining at sites of disturbed flow. These data suggest that senescent ECs accumulate at disturbed flow sites during atherogenesis. We used in vitro flow systems to examine whether a causal relationship exists between flow and EC senescence. Exposure of cultured ECs to flow (using either an orbital shaker or a syringe-pump flow bioreactor) revealed that disturbed flow promoted EC senescence compared with static conditions, whereas undisturbed flow reduced senescence. Gene silencing studies demonstrated that disturbed flow induced EC senescence via a p53-p21 signaling pathway. Disturbed flow–induced senescent ECs exhibited reduced migration compared with nonsenescent ECs in a scratch wound closure assay, and thus may be defective for arterial repair. However, pharmacological activation of sirtuin 1 (using resveratrol or SRT1720) protected ECs from disturbed flow–induced senescence.

Conclusions—
Disturbed flow promotes endothelial senescence via a p53-p21–dependent pathway which can be inhibited by activation of sirtuin 1. These observations support the principle that pharmacological activation of sirtuin 1 may promote cardiovascular health by suppressing EC senescence at atheroprone sites.