bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol for a multicentre, cluster randomised, superiority trial evaluating the impact of computerised decision support, audit and feedback on antibiotic use: the COMPuterized Antibiotic Stewardship Study (COMPASS)
Authors: Catho Gaud , De Kraker Marlieke , Waldispühl Suter Brigitte , Valotti Roberta , Harbarth Stephan , Kaiser Laurent , Elzi Luigia , Meyer Rodolphe , Bernasconi Enos , Huttner Benedikt D 
Published: June 2018

IntroductionInappropriate use of antimicrobials in hospitals contributes to antimicrobial resistance. Antimicrobial stewardship (AMS) interventions aim to improve antimicrobial prescribing, but they are often resource and personnel intensive. Computerised decision supportsystems (CDSSs) seem a promising tool to improve antimicrobial prescribing but have been insufficiently studied in clinical trials.Methods and analysisThe COMPuterized Antibiotic Stewardship Study trial, is a publicly funded, open-label, cluster randomised, controlled superiority trial which aims to determine whether a multimodal CDSS intervention integrated in the electronic health record (EHR) reduces overall antibiotic exposure in adult patients hospitalised in wards of two secondary and one tertiary care centre in Switzerland compared with ‘standard-of-care’ AMS. Twenty-four hospital wards will be randomised 1:1 to either intervention or control, using a ‘pair-matching’ approach based on baseline antibiotic use, specialty and centre. The intervention will consist of (1) decision support for the choice of antimicrobial treatment and duration of treatment for selected indications (based on indication entry), (2) accountable justification for deviation from the local guidelines (with regard to the choice of molecules and duration), (3) alerts for self-guided re-evaluation of treatment on calendar day 4 of antimicrobial therapy and (4) monthly ward-level feedback of antimicrobial prescribing indicators. The primary outcome will be the difference in overall systemic antibiotic use measured in days of therapy per admission based on administration data recorded in the EHR over the whole intervention period (12 months), taking into account clustering. Secondary outcomes include qualitative and quantitative antimicrobial use indicators, economic outcomes and clinical, microbiological and patient safety indicators.Ethics and disseminationEthics approval was obtained for all participating sites (Comission Cantonale d'Éthique de la Recherche (CCER)2017–00454). The results of the trial will be submitted for publication in a peer-reviewed journal. Further dissemination activities will be presentations/posters at national and international conferences.Trial registration numberNCT03120975; Pre-results.
Developing a hospital-wide quality and safety dashboard: a qualitative research study
Authors: Weggelaar-Jansen Anne Marie J W M , Broekharst Damien S E , de Bruijne Martine 
Published: June 2018

BackgroundSeveral countries have national policies and programmes requiring hospitals to use quality and safety (QS) indicators. To present an overview of these indicators, hospital-wide QS (HWQS) dashboards are designed. There is little evidence how these dashboards are developed. The challenges faced to develop these dashboards in Dutch hospitals were retrospectively studied.Methods24 focus group interviews were conducted: 12 with hospital managers (n=25; 39.7%) and 12 support staff (n=38; 60.3%) in 12 of the largest Dutch hospitals. Open and axial codings were applied consecutively to analyse the data collected.ResultsA heuristic tool for the general development process for HWQS dashboards containing five phases was identified. In phase 1, hospitals make inventories to determine the available data and focus too much on quantitative data relevant for accountability. In phase 2, hospitals develop dashboard content by translating data into meaningful indicators for different users, which is not easy due to differing demands. In phase 3, hospitals search for layouts that depict the dashboard content suited for users with different cognitive abilities and analytical skills. In phase 4, hospitals try to integrate dashboards into organisational structures to ensure that data are systematically reviewed and acted on. In phase 5, hospitals want to improve the flexibility of their dashboards to make this adaptable under differing circumstances.ConclusionThe literature on dashboards addresses the technical and content aspects of dashboards, but overlooks the organisational development process. This study shows how technical and organisational aspects are relevant in development processes.
Do GPs accurately record date of death? A UK observational analysis
Authors: Harshfield Amelia , Abel Gary A , Barclay Stephen , Payne Rupert A 
Published: June 2018

ObjectiveTo examine the concordance between dates of death recorded in UK primary care and national mortality records.MethodsUK primary care data from the Clinical Practice Research Datalink were linked to Office for National Statistics (ONS) data, for 118 571 patients who died between September 2010 and September 2015. Logistic regression was used to examine factors associated with discrepancy in death dates between data sets.ResultsDeath dates matched in 76.8% of cases with primary care dates preceding ONS date in 2.9%, and following in 20.3% of cases; 92.2% of cases differed by <2 weeks. Primary care date was >4 weeks later than ONS in 1.5% of cases and occurred more frequently with deaths categorised as ‘external’ (15.8% vs 0.8% for cancer), and in younger patients (15.9% vs 1% for 18–29 and 80–89 years, respectively). General practices with the greatest discrepancies (97.5th percentile) had around 200 times higher odds of recording substantially discordant dates than practices with the lowest discrepancies (2.5th percentile).ConclusionDates of death in primary care records often disagree with national records and should be treated with caution. There is marked variation between practices, and studies involving young patients, unexplained deaths and where precise date of death is important are particularly vulnerable to these issues.
Efficacy and safety of dabigatran versus warfarin from the RE-LY trial
Authors: Avezum Alvaro , Oliveira Gustavo Bernardes de Figueiredo , Diaz Rafael , Hermosillo Jesus Antonio Gonzalez , Oldgren Jonas , Ripoll Ernesto Ferreiros , Noack Herbert , Piegas Leopoldo Soares , Connolly Stuart J 
Published: June 2018

BackgroundCurrent data for atrial fibrillation (AF) and stroke are predominantly derived from North American and European patients. Although the burden of AF is high in Latin America (LA), little is known about current management of AF in the region.MethodsWe aimed to assess the consistency of efficacy and safety outcomes associated with dabigatran etexilate (DE) versus warfarin in patients with AF in LA from the RE-LY (Randomised Evaluation of Long-Term Anticoagulant Therapy) trial. Data from 956 LA patients and 17 157 non-LA patients were included in this analysis. χ2test and Cox proportional regression analysis were performed. The primary efficacy outcome included all strokes or systemic embolism (SE). Main safety outcome was major bleeding.ResultsLA patients were more often female, had higher proportion of permanent AF and lower creatinine clearance, among other characteristics. Vitamin K antagonist use at randomisation and time in therapeutic range were lower in LA than in non-LA patients (44% vs 63%, p<0.001; and 61.3±22.6% vs 64.6±19.6%, p=0.015, respectively). Efficacy endpoints were 0.91% versus 1.68% for DE 150 mg twice daily versus warfarin, respectively. Stroke/SE risk was lower in LA patients treated with DE 150 mg twice daily compared with warfarin, although not significant (HR 0.54; 95% CI 0.18 to 1.62). The annual stroke/SE rates for DE 110 mg twice daily versus warfarin were 1.82 versus 1.68, also not significantly different (HR 1.09; CI 0.44 to 2.67). There were no treatment-by-region interactions for either dose of DE on efficacy and safety outcomes.ConclusionDespite differences in the clinical profile and AF management, the efficacy and safety benefits of dabigatran over warfarin in LA patients relative to non-LA patients are consistent with those observed in the main RE-LY trial.
Employment and the role of personal factors among patients with ankylosing spondylitis: a Dutch cross-sectional case-control study
Authors: Webers Casper , Vanhoof Laura , van Genderen Simon , Heuft Liesbeth , van de Laar Mart , Luime Jolanda , van der Heijde Désirée , van Gaalen Floris A , Spoorenberg Anneke , Boonen Annelies 
Published: June 2018

ObjectivesTo update the knowledge on employment and the role of mastery, a personal factor reflecting the level of control over life and disease, among Dutch patients with ankylosing spondylitis (AS) compared to general population subjects.MethodsData of persons ≤65 years participating in a Dutch cross-sectional multicentre study on social participation in AS were used. Being employed was the main outcome. Standardised employment ratios (SERs) were calculated using indirect standardisation after adjusting for age, gender and education and repeated after stratification by symptom duration tertiles. Modified Poisson regressions were performed to understand the role of mastery (Pearlin’s scale) independent of sociodemographic and health-related factors.Results214 patients and 470 controls (127 (59.3%) and 323 (68.7%) males; mean age 48.3 (SD 10.4) and 39.3 (SD 12.7) years, respectively) completed an online questionnaire. SER (95%CI) in patients was 0.83 (0.69–0.98); 0.84 (0.67–1.04) in males; 0.83 (0.59–1.07) in females. Adjusted absolute employment of patients compared to controls was 69% versus 84%; 73% versus 86% for males; 62% versus 78% for females. In multivariable analyses stratified for patients and controls, mastery was associated with being employed in patients, but only in those with low education. In controls, not mastery but higher education was associated with being employed.ConclusionOur study reveals that patients suffering from AS compared to population controls are less likely to be employed. Mastery is an important personal factor associated with employment in patients but not in controls. Interventions aimed at improving employment of patients with AS should likely account for mastery.
A composite and deformable honeycomb acoustic metamaterial
Authors: Gao Nansha , Hou Hong , Wu Jiu Hui 
Published: June 2018

This paper reports the design of a deformable honeycomb acoustic metamaterial, which consists of honeycomb structures and ethylene-vinyl acetate (EVA) copolymer films stacked on each other. The FEA results agree well with the experiment analysis, and it is proved that the proposed structure can break the acoustic mass law below 1000 Hz. This paper reveals that dislocation, compression, and tensile deformation can regulate the sound transmission loss (STL) in a wider frequency range. It is concluded that the STL of a bilayer structure is, on average, 10 dB higher than that of a monolayer structure at low-frequencies. When the dislocation distance b = 1.5 mm, the corresponding STLs reach their maximum values. The FEA and experiment results prove that compression and tensile deformation can considerably improve the sound insulation effect. Such a deformable honeycomb acoustic metamaterial with high STL provides a new concept for engineering noise control.
We are done with 'hacking'
Authors: Bugayenko Yegor 
Published: June 2018

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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http://cacm.acm.org/blogs/blog-cacm
Today's programmers offer more valuable skills than simply being able to hack algorithms and make data structures, says Yegor Bugayenko.
Extracellular waveforms reveal an axonal origin of spikelets in pyramidal neurons
Authors: Michalikova Martina , Remme Michiel W. H. , Kempter Richard 
Published: June 2018

Spikelets are small spike-like membrane depolarizations measured at the soma whose origin in pyramidal neurons is still unresolved. We investigated the mechanism of spikelet generation using detailed models of pyramidal neurons. We simulated extracellular waveforms associated with action potentials and spikelets and compared these with experimental data obtained by Chorev and Brecht ( J Neurophysiol 108: 1584–1593, 2012) from hippocampal pyramidal neurons in vivo. We considered spikelets originating in the axon of a single cell as well as spikelets generated in two cells coupled with gap junctions. We found that in both cases the experimental data can be explained by an axonal origin of spikelets: in the single-cell case, action potentials are generated in the axon but fail to activate the soma. Such spikelets can be evoked by dendritic input. Alternatively, spikelets resulting from axoaxonal gap junction coupling with a large (greater than several hundred μm) distance between the somata of the coupled cells are also consistent with the data. Our results demonstrate that a cell firing a somatic spikelet generates a detectable extracellular potential that is different from the action potential-correlated extracellular waveform generated by the same cell and recorded at the same location. This, together with the absence of a refractory period between action potentials and spikelets, implies that spikelets and action potentials generated in one cell may easily get misclassified in extracellular recordings as two different cells, albeit they both constitute the output of a single pyramidal neuron. NEW & NOTEWORTHY We addressed the origin of spikelets, using compartmental models of pyramidal neurons. Comparing our simulation results with published extracellular spikelet recordings revealed an axonal origin of spikelets. Our results imply that action potential- and spikelet-associated extracellular waveforms may easily get misclassified as two different cells, albeit they both constitute the output of a single pyramidal cell.
Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial
Authors: Kyi Chrisann , Roudko Vladimir , Sabado Rachel , Saenger Yvonne , Loging William , Mandeli John , Thin Tin Htwe , Lehrer Deborah , Donovan Michael , Posner Marshall , Misiukiewicz Krzysztof , Greenbaum Benjamin , Salazar Andres , Friedlander Philip , Bhardwaj Nina 
Published: June 2018

Abstract
Purpose: Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC), a synthetic double-stranded RNA complex, is a ligand for toll-like receptor-3 and MDA-5 that can activate immune cells, such as dendritic cells, and trigger natural killer cells to kill tumor cells.
Patients and Methods: In this pilot study, eligible patients included those with recurrent metastatic disease in whom prior systemic therapy (head and neck squamous cell cancer and melanoma) failed. Patients received 2 treatment cycles, each cycle consisting of 1 mg poly-ICLC 3× weekly intratumorally (IT) for 2 weeks followed by intramuscular (IM) boosters biweekly for 7 weeks, with a 1-week rest period. Immune response was evaluated by immunohistochemistry (IHC) and RNA sequencing (RNA-seq) in tumor and blood.
Results: Two patients completed 2 cycles of IT treatments, and 1 achieved clinical benefit (stable disease, progression-free survival 6 months), whereas the remainder had progressive disease. Poly-ICLC was well tolerated, with principal side effects of fatigue and inflammation at injection site (&lt;grade 2). In the patient with clinical benefit, IHC analysis of tumor showed increased CD4, CD8, PD1, and PD-L1 levels compared with patients with progressive disease. RNA-seq analysis of the same patient's tumor and peripheral blood mononuclear cells showed dramatic changes in response to poly-ICLC treatment, including upregulation of genes associated with chemokine activity, T-cell activation, and antigen presentation.
Conclusions: Poly-ICLC was well tolerated in patients with solid cancer and generated local and systemic immune responses, as evident in the patient achieving clinical benefit. These results warrant further investigation and are currently being explored in a multicenter phase II clinical trial (NCT02423863). Clin Cancer Res; 24(20); 4937–48. ©2018 AACR.
The Role of Adding Somatostatin Analogues to Peptide Receptor Radionuclide Therapy as a Combination and Maintenance Therapy
Authors: Yordanova Anna , Wicharz Marcel M. , Mayer Karin , Brossart Peter , Gonzalez-Carmona Maria A. , Strassburg Christian P. , Fimmers Rolf , Essler Markus , Ahmadzadehfar Hojjat 
Published: June 2018

Abstract
Purpose: Although somatostatin analogues (SSA) and peptide receptor radionuclide therapy (PRRT) are validated therapies in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NET), it remains unclear whether SSA combined with PRRT or as maintenance therapy can provide prolonged survival compared with patients treated with PRRT alone. In this retrospective study, we aimed to investigate whether there is a survival benefit to adding SSA to PRRT as a combination therapy and/or maintenance therapy.
Patients and Methods: The investigation included 168 patients with unresectable GEP-NETs treated at the University Hospital Bonn, Bonn, Germany. The patients were divided into two main groups: PRRT monotherapy (N = 81, group 1) and PRRT plus SSA (N = 87, group 2) as combined therapy with PRRT and/or as maintenance therapy after PRRT.
Results: Data for overall survival (OS) were available from 168 patients, of whom 160 had data for progression-free survival (PFS). The median PFS was 27 months in group 1 versus 48 months in group 2 (P = 0.012). The median OS rates were 47 months in group 1 and 91 months in group 2 (P &lt; 0.001). The death-event rates were lower in group 2 (26%) than in group 1 (63%). SSA as a combination therapy with PRRT and/or as a maintenance therapy showed a clinical benefit rate (objective response or stable disease) of 95%, which was significantly higher than group 1 (79%).
Conclusions: SSA as a combination therapy and/or maintenance therapy may play a significant role in tumor control in patients with GEP-NET who underwent a PRRT. Clin Cancer Res; 24(19); 4672–9. ©2018 AACR.
Genetic Regulation of Fibroblast Activation and Proliferation in Cardiac Fibrosis
Authors: Park Shuin , Ranjbarvaziri Sara , Lay Fides D. , Zhao Peng , Miller Mark J. , Dhaliwal Jasmeet S. , Huertas-Vazquez Adriana , Wu Xiuju , Qiao Rong , Soffer Justin M. , Rau Christoph , Wang Yibin , Mikkola Hanna K.A. , Lusis Aldons J. , Ardehali Reza 
Published: June 2018

Background:
Genetic diversity and the heterogeneous nature of cardiac fibroblasts (CFbs) have hindered characterization of the molecular mechanisms that regulate cardiac fibrosis. The Hybrid Mouse Diversity Panel offers a valuable tool to examine genetically diverse cardiac fibroblasts and their role in fibrosis.

Methods:
Three strains of mice (C57BL/6J, C3H/HeJ, and KK/HlJ) were selected from the Hybrid Mouse Diversity Panel and treated with either isoproterenol (ISO) or saline by an intraperitoneally implanted osmotic pump. After 21 days, cardiac function and levels of fibrosis were measured by echocardiography and trichrome staining, respectively. Activation and proliferation of CFbs were measured by in vitro and in vivo assays under normal and injury conditions. RNA sequencing was done on isolated CFbs from each strain. Results were analyzed by Ingenuity Pathway Analysis and validated by reverse transcription-qPCR, immunohistochemistry, and ELISA.

Results:

ISO treatment in C57BL/6J, C3H/HeJ, and KK/HlJ mice resulted in minimal, moderate, and extensive levels of fibrosis, respectively (n=7–8 hearts per condition). Isolated CFbs treated with ISO exhibited strain-specific increases in the levels of activation but showed comparable levels of proliferation. Similar results were found in vivo, with fibroblast activation, and not proliferation, correlating with the differential levels of cardiac fibrosis after ISO treatment. RNA sequencing revealed that CFbs from each strain exhibit unique gene expression changes in response to ISO. We identified
Ltbp2
as a commonly upregulated gene after ISO treatment. Expression of LTBP2 was elevated and specifically localized in the fibrotic regions of the myocardium after injury in mice and in human heart failure patients.

Conclusions:
This study highlights the importance of genetic variation in cardiac fibrosis by using multiple inbred mouse strains to characterize CFbs and their response to ISO treatment. Our data suggest that, although fibroblast activation is a response that parallels the extent of scar formation, proliferation may not necessarily correlate with levels of fibrosis. In addition, by comparing CFbs from multiple strains, we identified pathways as potential therapeutic targets and LTBP2 as a marker for fibrosis, with relevance to patients with underlying myocardial fibrosis.
What is Protestant Art
Authors: Coates Andrew T. 
Published: June 2018

AbstractWhat is Protestant Art?offers a brief introduction to the field of Protestant visual culture. It argues that the diversity of images and visual practices throughout Protestant history might better be described by the term ‘visual culture’ than the term ‘art.’ Examining images from the Reformation to the twentieth century, this review essay showcases the breadth of ways Protestants have put images to work in their religious practices. Containing dozens of illustrations,What is Protestant Art?provides the reader with an overview of current research on Protestant visual culture, as well as discussions of representative examples from five hundred years of Protestant imagery.
Positive Health Benefits of Peer Support and Connections for College Students With Type 1 Diabetes Mellitus
Authors: Saylor Jennifer , Lee Sara , Ness Michelle , Ambrosino Jodie M. , Ike Emily , Ziegler Melissa , Roth Christina L. , Calamaro Christina 
Published: June 2018

Purpose The purpose of this study is to examine the characteristics and health outcomes of college students with type 1 diabetes mellitus (T1DM) as it relates to membership in a local university-based diabetes student organization. Methods This descriptive, correlational research design is a secondary analysis of data. The sample consisted of nationally representative young adults in college (n = 317) between 18 and 30 years of age who were diagnosed with T1DM. Data were collected during April 2017 using a secure electronic diabetes management survey to inquire about self-reported barriers to diabetes management, hypoglycemia, and diabetic ketoacidosis of members of a diabetes organization. Results Students were evenly distributed from freshman to senior year of college with a slight decrease at the graduate level. Students who were affiliated members of a student-led diabetes student organization were less likely to report increased levels of isolation, depressive symptoms, and anxiety related to their diabetes than were general members. Conclusion Participation in a university-based diabetes student organization on campus and connecting with other college students with diabetes may have health benefits. In conclusion, the current study underscores the potential importance of peer-led, diabetes-specific support for adolescents emerging into adulthood.