bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-6 pathway-driven investigation of response to IL-6 receptor inhibition in rheumatoid arthritis
Authors: Wang Jianmei , Platt Adam , Upmanyu Ruchi , Germer Søren , Lei Guiyuan , Rabe Christina , Benayed Ryma , Kenwright Andrew , Hemmings Andrew , Martin Mitchell , Harari Olivier 
Published: August 2013

ObjectivesTo determine whether heterogeneity in interleukin-6 (IL-6), IL-6 receptor and other components of the IL-6 signalling pathway/network, at the gene, transcript and protein levels, correlate with disease activity in patients with rheumatoid arthritis (RA) and with clinical response to tocilizumab.DesignBiomarker samples and clinical data for five phase 3 trials of tocilizumab were analysed using serum (3751 samples), genotype (927 samples) and transcript (217 samples) analyses. Linear regression was then used to assess the association between these markers and either baseline disease activity or treatment response.ResultsHigher baseline serum IL-6 levels were significantly associated (p<0.0001) with higher baseline DAS28, erythrocyte sedimentation rate, C reactive protein and Health Assessment Questionnaire in patients whose responses to disease-modifying antirheumatic drugs (DMARD-IR) and to antitumour necrosis factor (aTNF-IR) were inadequate and patients who were naive/responders to methotrexate (MTX). Higher baseline serum IL-6 levels were also significantly associated with better clinical response to tocilizumab (versus placebo) measured by cDAS28 in the pooled DMARD-IR (p<0.0001) and MTX-naive populations (p=0.04). However, the association with treatment response was weak. A threefold difference in baseline IL-6 level corresponded to only a 0.17-unit difference in DAS28 at week 16. IL-6 pathway single nucleotide polymorphisms and RNA levels also were not strongly associated with treatment response.ConclusionsOur analyses illustrate that the biological activity of a disease-associated molecular pathway may impact the benefit of a therapy targeting that pathway. However, the variation in pathway activity, as measured in blood, may not be a strong predictor. These data suggest that the major contribution to variability in clinical responsiveness to therapeutics in RA remains unknown.
Effects of a team-based assessment and intervention on patient safety culture in general practice: an open randomised controlled trial
Authors: Hoffmann B , Müller V , Rochon J , Gondan M , Müller B , Albay Z , Weppler K , Leifermann M , Mießner C , Güthlin C , Parker D , Hofinger G , Gerlach F M 
Published: August 2013

BackgroundThe measurement of safety culture in healthcare is generally regarded as a first step towards improvement. Based on a self-assessment of safety culture, the Frankfurt Patient Safety Matrix (FraTrix) aims to enable healthcare teams to improve safety culture in their organisations. In this study we assessed the effects of FraTrix on safety culture in general practice.MethodsWe conducted an open randomised controlled trial in 60 general practices. FraTrix was applied over a period of 9 months during three facilitated team sessions in intervention practices. At baseline and after 12 months, scores were allocated for safety culture as expressed in practice structure and processes (indicators), in safety climate and in patient safety incident reporting. The primary outcome was the indicator error management.ResultsDuring the team sessions, practice teams reflected on their safety culture and decided on about 10 actions per practice to improve it. After 12 months, no significant differences were found between intervention and control groups in terms of error management (competing probability=0.48, 95% CI 0.34 to 0.63, p=0.823), 11 further patient safety culture indicators and safety climate scales. Intervention practices showed better reporting of patient safety incidents, reflected in a higher number of incident reports (mean (SD) 4.85 (4.94) vs 3.10 (5.42), p=0.045) and incident reports of higher quality (scoring 2.27 (1.93) vs 1.49 (1.67), p=0.038) than control practices.ConclusionsApplied as a team-based instrument to assess safety culture, FraTrix did not lead to measurable improvements in error management. Comparable studies with more positive results had less robust study designs. In future research, validated combined methods to measure safety culture will be required. In addition, more attention should be paid to evaluation of process parameters. Implemented actions and incident reporting may be more appropriate target endpoints.Trial registrationGerman Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) No. DRKS00000145
Teaching about how doctors think: a longitudinal curriculum in cognitive bias and diagnostic error for residents
Authors: Reilly James B , Ogdie Alexis R , Von Feldt Joan M , Myers Jennifer S 
Published: August 2013

BackgroundTrends in medical education have reflected the patient safety movement's initial focus on systems. While the role of cognitive-based diagnostic errors has been increasingly recognised among safety experts, literature describing strategies to teach about this important problem is scarce.Methods48 PGY-2 internal medicine residents participated in a three-part, 1-year curriculum in cognitive bias and diagnostic error. Residents completed a multiple-choice test designed to assess the recognition and knowledge of common heuristics and biases both before and after the curriculum. Results were compared with PGY-3 residents who did not receive the curriculum. An additional assessment in which residents reviewed video vignettes of clinical scenarios with cognitive bias and debiasing techniques was embedded into the curriculum.Results38 residents completed all three parts of the curriculum and completed all assessments. Performance on the 13-item multiple-choice knowledge test improved post-curriculum when compared to both pre-curriculum performance (9.26 vs 8.26, p=0.002) and the PGY-3 comparator group (9.26 vs 7.69, p<0.001). All residents correctly identified at least one cognitive bias and proposed at least one debiasing strategy in response to the videos.ConclusionsA longitudinal curriculum in diagnostic error and cognitive bias improved internal medicine residents’ knowledge and recognition of cognitive biases as measured by a novel assessment tool. Further study is needed to refine learner assessment tools and examine optimal strategies to teach clinical reasoning and cognitive bias avoidance strategies.
Determinants of assault-related violence in the community: potential for public health interventions in hospitals
Authors: Ramsay S E , Bartley A , Rodger A J 
Published: August 2013

BackgroundData from emergency departments (EDs) in England describe the epidemiology of violent assaults. However, the potential of such data to inform hospital-based public health interventions remains unknown.ObjectiveTo identify determinants of assaults using ED data to inform development of programmes delivered in acute Trusts for reducing assault-related injuries in the community.MethodsData were collected from a large North London acute Trust on assault-related injuries reporting to A&E over 18 months (July 2010–February 2012). Information was recorded on patient demographics and assaults (place of assault, type of assault, relation to assailant) through questionnaires administered by ED reception staff.Results1210 assaults were recorded between July 2010 and February 2012. 18% of assaults were severe (strangling, stabbings, sexual assaults). 75% of assault victims were men, 37% were young adults (20–30 years) and 15% were teenagers. A higher proportion of victims lived in more deprived areas. Apart from public streets (48%), the main location of assaults was at home (20%). Female compared with male victims were significantly more likely to be both assaulted at home (OR 6.13; 95% CI 4.41 to 8.54) and to be assaulted by a known assailant (family member, friend, partner/ex-partner; OR 8.20, 95% CI 5.85 to 11.48).ConclusionsThe results highlight the notable contribution of domestic violence to assaults presenting to hospital ED. Such findings can be used to plan interventions such as screening hospital patients for domestic violence. ED data have the potential to inform hospital-based initiatives to address issues such as assaults in the local population.
Controlling for exposure changes the relationship between ethnicity, deprivation and injury: an observational study of child pedestrian injury rates in London
Authors: Steinbach Rebecca , Edwards Phil , Green Judith 
Published: August 2013

BackgroundResearch has suggested that inequalities in risk exposure may help explain identified ethnic inequalities in child pedestrian injury risk. However, addressing risk exposure in epidemiological research presents theoretical and methodological challenges. This article conceptualises the risk of child pedestrian injury as related to both exposure levels (the quantity of time children spend as pedestrians) and the probability of a hazard where that exposure takes place (the quality of the road environment).ObjectiveTo investigate the sensitivity of results on ethnic inequalities in child pedestrian injury risk in London to control for exposure and hazard levels.MethodsUsing police records of injury 2000–2009, we modelled the relationship between ethnicity, deprivation and child pedestrian injury rates in London using characteristics of the road environment to control for hazard levels and restricting the analysis to the time of the weekday morning commute (7.00–9.00 am), when most children must make a journey to school, to control for exposure levels.ResultsControlling for risk exposure in this way fundamentally changed the nature of the relationship between ethnicity, deprivation and child pedestrian injury. During the time of the morning commute to school, ‘Black’ children were found to have higher pedestrian injury rates in the least-deprived areas.ConclusionsTo inform effective strategies for reducing injury inequality, it is vital that exposure to risk is both acknowledged and considered.
Evaluation of a school-based violence prevention media literacy curriculum
Authors: Fingar Kathryn R , Jolls Tessa 
Published: August 2013

PurposeEvaluate whetherBeyond Blame, a violence prevention media literacy curriculum, is associated with improved knowledge, beliefs and behaviours related to media use and aggression.MethodsUsing a quasi-experimental design, from 2007 to 2008, teachers from schools across Southern California administered the curriculum with or without training or served as controls. Students were tested before and after the curriculum was implemented, and during the fall semester of the next academic year. Multivariate hierarchical regression was used to compare changes from baseline to follow-up between the intervention and control groups.ResultsCompared with controls, at the first post-test, students in the trained and untrained groups reported increased knowledge of five core concepts/key questions of media literacy, increased self-rated exposure to media violence, as well as stronger beliefs that media violence affects viewers and that people can protect themselves by watching less. Regarding behaviours, controls were more likely to report ≥8 h of media consumption at the second post-test than at baseline (OR=2.11; 95% CI 1.13 to 3.97), pushing or shoving another student (OR=2.16; 95% CI 1.16 to 4.02) and threatening to hit or hurt someone (OR=2.32; 95% CI 1.13 to 4.78). In comparison, there was no increase in these behaviours in the trained and untrained groups.ConclusionsThis study suggests media literacy can be feasibly integrated into schools as an approach to improving critical analysis of media, media consumption and aggression. Changing the way youth engage media may impact many aspects of health, and an important next step will be to apply this framework to other topics.
Longitudinal study of correlates of modern contraceptive use and impact of HIV care programmes among HIV concordant and serodiscordant couples in Rakai, Uganda
Authors: Brahmbhatt Heena , Makumbi Fredrick , Lutalo Tom , Sekasanvu Joseph , Serwadda David , Wawer Maria J , Gray Ronald H 
Published: August 2013

ObjectiveTo assess trends and determinants of family planning use and impact of HIV serostatus among couples.MethodsCouples’ data were retrospectively linked from cohort surveys in Rakai, Uganda between 1999 and 2011, and were classified by HIV status as concordant (M+F+/M−F−) or serodiscordant (M−F+/M+F−). HIV care (HIVC) was grouped into three periods, pre-antiretroviral therapy (pre-HIVC) (<2004), HIVC roll-out (2005–2007) and HIVC scale-up (≥2008). Trends in couple contraceptive use were assessed by chi-square test (χ2) for trend, and multinomial logistic regression was used to estimate adjusted odds ratios (ORs) of predictors of contraceptive use.ResultsA toal of 6139 couples contributed 13 709 observations. Hormonal contraception (HC) use increased over time from 22.9% to 33.9%,p<0.001), with significant increases among M−F− (23.2% to 34.8%,p<0.0001) and M+F+ (20.8% to 32.2%,p=0.0005), but not serodiscordant couples. Condom use significantly increased among M+F+ (30.3% to 48.0%,p<0.001) and serodiscordant couples (24.2% to 48.7%,p<0.001), but not among M−F− couples. Dual use of HC and condoms increased over time, irrespective of HIV status. Factors associated with increases in contraceptive use were: higher education, co-resident children, male non-marital relationship and scaled-up HIVC phase. Enrolment into HIVC was associated with increased HC and condom use among HIV+ concordant [adjusted OR (adjOR)=3.03; 95% confidence interval (CI) 1.69–5.44 and adjOR=4.46, 95% CI 2.53–7.86, respectively], and serodiscordant couples (adjOR=2.21; 95% CI 1.25–3.92 and adjOR=4.75; 95% CI 2.89–7.82, respectively).ConclusionsUse of modern contraception and dual method use increased over time, particularly after enrolment into HIVC. Integration of HIV and reproductive health services is critical for prevention of unwanted pregnancies and HIV infection.
Safety and predictors of aneurysm retreatment for remnant intracranial aneurysm after initial endovascular embolization
Authors: Teleb Mohamed S , Pandya Dhruvil J , Castonguay Alicia C , Eckardt Gerald , Sweis Rochelle , Lazzaro Marc A , Issa Mohammed A , Fitzsimmons Brian-Fred , Lynch John R , Zaidat Osama O 
Published: August 2013

IntroductionAneurysmal subarachnoid hemorrhage (SAH) is a rare but devastating form of stroke. Endovascular therapy has been criticized for its higher rate of recanalization and retreatment. The safety and predictors of retreatment are unknown. We report the clinical outcomes, imaging outcomes and predictors for aneurysm retreatment after initial endovascular embolization.MethodWe identified patients who underwent endovascular retreatment from July 2005 through November 2011. Aneurysm and patient data were collected. Periprocedural complications were reported as intraoperative perforation (IOP) or thromboembolic event (TEE). Aneurysm and patient characteristics were compared between aneurysms requiring retreatment and those not requiring retreatment to evaluate aneurysm retreatment predictors.ResultsA total of 111/871 (13%) aneurysms underwent retreatment. Two (0.2%) were retreated for recurrent acute SAH, 82 (74%) aneurysms were located in the anterior circulation, 47 (42%) required stent and 5 (5%) required balloon assist during retreatment. There were a total of 5 (5%) IOP and 6 (5%) TEE from which 2 (2%) and 1 (1%) were symptomatic, respectively. Overall symptomatic events rate were 2.7%. Patients were followed up for an average of 15±14 months. Seven (0.8%) aneurysms required a second retreatment without any recurrent SAH. Multivariable analysis revealed an OR for aneurysms requiring retreatment of 2.965 for aneurysms presenting as aneurysmal SAH, 1.791 for aneurysms in the posterior circulation and 1.053 for aneurysms with large dome size.ConclusionsAneurysm retreatment is a safe option without a significant increase in morbidity or mortality. SAH, posterior circulation aneurysms and larger aneurysm dome size are predictors of aneurysms requiring retreatment.
Spatial and temporal relationships between Eocene sand horizons and iron contamination in stream water in the Thames Basin west of London, UK
Authors: Barrott J.J. , Dudeney A.W.L. , Mason P.J. 
Published: August 2013

Analyses of stream water samples associated with Tertiary (Eocene) sands of the Bracklesham Formation 30–60 km west of London showed numerous occurrences of groundwater containing elevated iron(II) concentrations (1–15 mg/l Fe), which oxidise to red-brown ferrihydrite in localised wetlands and streams and join onward flows towards the River Thames. GIS mapping of iron concentrations in relation to topographical and geological data within a 20×30 km project area indicated some 168 km of iron-contaminated water.
The results are consistent with downward permeation of groundwater through contained Camberley, Windlesham and Bagshot sand horizons and predominant W-E groundwater flow of up to 35 km in the Bagshot horizon, which rests on impermeable London Clay. Glauconite, comprising up to 70% of the sand near the base of the Windlesham horizon, apparently provides the main source of soluble iron in the near-anoxic, near-neutral, conditions normally prevailing. Pyrite is also a possible source, especially where quarrying or other excavation releases water from previously isolated volumes, simultaneously causing elevated sulphate and acidity levels via relatively rapid sulphide oxidation. Mechanisms proposed are underpinned through comparison with reports on analogous systems in the UK and abroad.
Streams and lakes in the vicinity of seepages are highly visible and of decreased biodiversity. However, because of their natural origin, they are not subject to the same public concern and environmental control as compositionally similar near-neutral water from many former coal mines elsewhere - where iron derives primarily from pyrite. Also, while comparatively persistent, they appear destined for rapid depletion in geological terms: the unusual isolation of the sands until the Quaternary indicates a short leaching period and suggests a reason why iron-rich water from natural ferruginous sands is seldom of sufficient significance to be reported.
Hbo1 Is a Cyclin E/CDK2 Substrate That Enriches Breast Cancer Stem-like Cells
Authors: Duong MyLinh T. , Akli Said , Macalou Sira , Biernacka Anna , Debeb Bisrat G. , Yi Min , Hunt Kelly K. , Keyomarsi Khandan 
Published: August 2013

Abstract
Expression of cyclin E proteolytic cleavage products, low-molecular weight cyclin E (LMW-E), is associated with poor clinical outcome in patients with breast cancer and it enhances tumorigenecity in mouse models. Here we report that LMW-E expression in human mammary epithelial cells induces an epithelial-to-mesenchymal transition phenotype, increases the CD44hi/CD24lo population, enhances mammosphere formation, and upregulates aldehyde dehydrogenase expression and activity. We also report that breast tumors expressing LMW-E have a higher proportion of CD44hi/CD24lo tumor cells as compared with tumors expressing only full-length cyclin E. In order to explore how LMW-E enriches cancer stem cells in breast tumors, we conducted a protein microarray analysis that identified the histone acetyltransferase (HAT) Hbo1 as a novel cyclin E/CDK2 substrate. The LMW-E/CDK2 complex phosphorylated Hbo1 at T88 without affecting its HAT activity. When coexpressed with LMW-E/CDK2, wild-type Hbo1 promoted enrichment of cancer stem-like cells (CSC), whereas the T88 Hbo1 mutant reversed the CSC phenotype. Finally, doxorubicin and salinomycin (a CSC-selective cytotoxic agent) synergized to kill cells expressing LMW-E, but not full-length cyclin E. Collectively, our results suggest that the heightened oncogenecity of LMW-E relates to its ability to promote CSC properties, supporting the design of therapeutic strategies to target this unique function. Cancer Res; 73(17); 5556–68. ©2013 AACR.
Formalizing an Integrative, Multidisciplinary Cancer Therapy Discovery Workflow
Authors: McGuire Mary F. , Enderling Heiko , Wallace Dorothy I. , Batra Jaspreet , Jordan Marie , Kumar Sushil , Panetta John C. , Pasquier Eddy 
Published: August 2013

Abstract
Although many clinicians and researchers work to understand cancer, there has been limited success to effectively combine forces and collaborate over time, distance, data, and budget constraints. Here we present a workflow template for multidisciplinary cancer therapy that was developed during the 2nd Annual Workshop on Cancer Systems Biology sponsored by Tufts University, Boston, Massachusetts, in July 2012. The template was applied to the development of a metronomic therapy backbone for neuroblastoma. Three primary groups were identified: clinicians, biologists, and quantitative scientists (mathematicians, computer scientists, and engineers). The workflow described their integrative interactions; parallel or sequential processes; data sources and computational tools at different stages as well as the iterative nature of therapeutic development from clinical observations to in vitro, in vivo, and clinical trials. We found that theoreticians in dialog with experimentalists could develop calibrated and parameterized predictive models that inform and formalize sets of testable hypotheses, thus speeding up discovery and validation while reducing laboratory resources and costs. The developed template outlines an interdisciplinary collaboration workflow designed to systematically investigate the mechanistic underpinnings of a new therapy and validate that therapy to advance development and clinical acceptance. Cancer Res; 73(20); 6111–7. ©2013 AACR.
Adenomatous Polyps Are Driven by Microbe-Instigated Focal Inflammation and Are Controlled by IL-10–Producing T Cells
Authors: Dennis Kristen L. , Wang Yunwei , Blatner Nichole R. , Wang Shuya , Saadalla Abdulrahman , Trudeau Erin , Roers Axel , Weaver Casey T. , Lee James J. , Gilbert Jack A. , Chang Eugene B. , Khazaie Khashayarsha 
Published: August 2013

Abstract
Interleukin (IL)-10 is elevated in cancer and is thought to contribute to immune tolerance and tumor growth. Defying these expectations, the adoptive transfer of IL-10–expressing T cells to mice with polyposis attenuates microbial-induced inflammation and suppresses polyposis. To gain better insights into how IL-10 impacts polyposis, we genetically ablated IL-10 in T cells in APCΔ468 mice and compared the effects of treatment with broad-spectrum antibiotics. We found that T cells and regulatory T cells (Treg) were a major cellular source of IL-10 in both the healthy and polyp-bearing colon. Notably, T cell–specific ablation of IL-10 produced pathologies that were identical to mice with a systemic deficiency in IL-10, in both cases increasing the numbers and growth of colon polyps. Eosinophils were found to densely infiltrate colon polyps, which were enriched similarly for microbiota associated previously with colon cancer. In mice receiving broad-spectrum antibiotics, we observed reductions in microbiota, inflammation, and polyposis. Together, our findings establish that colon polyposis is driven by high densities of microbes that accumulate within polyps and trigger local inflammatory responses. Inflammation, local microbe densities, and polyp growth are suppressed by IL-10 derived specifically from T cells and Tregs. Cancer Res; 73(19); 5905–13. ©2013 AACR.