bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of delayed‐release dimethyl fumarate on no evidence of disease activity in relapsing–remitting multiple sclerosis: integrated analysis of the phaseIII DEFINEandCONFIRMstudies
Authors: Havrdova E. , Giovannoni G. , Gold R. , Fox R. J. , Kappos L. , Phillips J. Theodore , Okwuokenye M. , Marantz J. L. 
Published: March 2017

Background and purposeSignificant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing–remitting multiple sclerosis treated with delayed‐release dimethyl fumarate (DMF) in phaseIII DEFINE/CONFIRMtrials. We conducted apost hocanalysis of integrated data fromDEFINE/CONFIRMto evaluate the effect ofDMFon achieving no evidence of disease activity (NEDA) in patients with relapsing–remitting multiple sclerosis.MethodsThe analysis included patients randomized toDMF240 mg twice daily, placebo or glatiramer acetate (CONFIRMonly) for ≤2 years. A time‐to‐event method was used to estimate the percentage of patients achievingNEDA. ClinicalNEDA(no relapses/no 12‐week confirmed disability progression) was analysed in the intention‐to‐treat (ITT) population. Neuroradiological (no new/newly enlarging T2 hyperintense lesions/no gadolinium‐enhancing lesions) and overall NEDA (clinical and neuroradiologicalNEDA) were analysed in the magnetic resonance imaging (MRI) cohort.ResultsThe ITTandMRIpopulations comprised 1540 and 692 patients, respectively. The percentage of patients with clinicalNEDA(ITTpopulation) and neuroradiologicalNEDA(MRIcohort) was higher withDMFversus placebo over 2 years [clinical NEDA: 38.9% relative reduction; hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.52‐0.72;P< 0.0001; neuroradiologicalNEDA: 40.0% relative reduction;HR, 0.60; 95%CI, 0.49–0.73;P< 0.0001]. The percentage of patients achieving overallNEDA(MRIcohort) was also higher withDMF(26%) versus placebo (12%) over 2 years, with a relative risk reduction of 42.7% (HR, 0.57; 95%CI, 0.48–0.69;P< 0.0001).ConclusionsA significantly higher percentage of patients treated withDMFachievedNEDAstatus over 2 years compared with placebo.
Last Minute Policies and the Incumbency Advantage
Authors: Manzoni Elena , Penczynski Stefan P. 
Published: March 2017

Abstract
This paper models a purely informational mechanism behind the incumbency advantage. In a two-period electoral campaign with two policy issues, an incumbent and a possibly more competent challenger compete for election by voters who are heterogeneously informed about the state of the world. Due to the asymmetries in government responsibility between candidates, the incumbent’s statement may convey information on the relevance of the issues to voters. In equilibrium, the incumbent sometimes strategically releases his statement early and thus signals the importance of his signature issue to the voters. We find that, since the incumbent’s positioning on the issue reveals private information which the challenger can use in later statements, the incumbent’s incentives to distort the campaign are decreasing in his quality, as previously documented by the empirical literature. The distortions arising in equilibrium are decreasing in the incumbent’s true competence; however, the distortions may be increasing in the incumbent’s expected competence on his signature issue.
Clinical evaluation of sofosbuvir/ledipasvir in patients with chronic hepatitis C genotype 1 with and without prior daclatasvir/asunaprevir therapy
Authors: Iio Etsuko , Shimada Noritomo , Takaguchi Koichi , Senoh Tomonori , Eguchi Yuichiro , Atsukawa Masanori , Tsubota Akihito , Abe Hiroshi , Kato Keizo , Kusakabe Atsunori , Miyaki Tomokatsu , Matsuura Kentaro , Matsunami Kayoko , Shinkai Noboru , Fujiwara Kei , Nojiri Shunsuke , Tanaka Yasuhito 
Published: March 2017

AimThis study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy.MethodsOverall, 530 Japanese patients who were infected with hepatitis C virus genotype 1 received SOF/LDV therapy for 12 weeks, and resistance‐associated variants (RAVs) in the hepatitis C virus non‐structural protein (NS)5A and NS5B regions were assessed at baseline and virological relapse by direct sequencing.ResultsSustained virological response (SVR) rates did not significantly differ between patients with and without NS5A Y93H/N (94.2% [113/120] vs. 97.7% [345/353]), but the SVR rate was significantly lower in patients with prior DCV/ASV therapy compared to those without (69.2% [18/26] vs. 98.4% [496/504], P < 0.001). Among 26 patients with prior DCV/ASV therapy, the prevalence of NS5A multi‐RAVs (≥2) was similar between responders and non‐responders (61% [11/18] vs. 75% [5/8]), but all patients without RAVs achieved SVR. Multivariate analysis showed that prior DCV/ASV therapy and history of hepatocellular carcinoma were independently associated with treatment failure (odds ratio, 37.55; 95% confidence interval, 10.78–130.76; P < 0.001 for prior DCV/ASV therapy; odds ratio, 4.42; 95% confidence interval, 1.09–18.04; P = 0.03 for the history of HCC). All SOF/LDV failure patients (n = 8) with prior DCV/ASV treatment had two or more factors of cirrhosis, IL28B unfavorable genotype, and baseline NS5A multi‐RAVs. The multiple NS5A RAVs had increased but NS5B substitutions, C316N/A207T/A218S or L159F, had not changed at the time of relapse.ConclusionsPrior DCV/ASV therapy is associated with failure of SOF/LDV therapy due to multiple RAVs.
Prognostic significance of tumour infiltrating B lymphocytes in breast ductal carcinoma in situ
Authors: Miligy Islam , Mohan Priya , Gaber Ahmed , Aleskandarany Mohammed A , Nolan Christopher C , Diez‐Rodriguez Maria , Mukherjee Abhik , Chapman Caroline , Ellis Ian O , Green Andrew R , Rakha Emad A 
Published: March 2017

AimsTumour‐infiltrating lymphocytes (TILs) are an important component of the immune response to cancer and have a prognostic value in breast cancer. Although several studies have investigated the role of T lymphocytes in breast cancer, the role of B lymphocytes (TIL‐Bs) in ductal carcinoma in situ (DCIS) remains uncertain. This study aimed to assess the role of TIL‐Bs in DCIS.Methods and resultsEighty DCIS cases (36 pure DCIS and 44 mixed with invasive cancer) were stained immunohistochemically for B lineage markers CD19, CD20 and the plasma cell marker CD138. TIL‐Bs density and localization were assessed, including relation to the in‐situ and invasive components. An association with clinicopathological data and patient outcome was performed. Pure DCIS showed a higher number of TIL‐Bs and lymphoid aggregates than DCIS associated with invasion. In pure DCIS, a higher number of peri‐ and paratumoral TIL‐Bs was associated significantly with large tumour size (P = 0.016), hormone receptor (ER/PR) negative (P = 0.008) and HER2+ status (P = 0.010). In tumours with mixed DCIS and invasive components, cases with high‐density B lymphocytes, irrespective of their location or topographic distribution, were associated significantly with variables of poor prognosis, including larger size, high grade, lymphovascular invasion, lymph node metastases, ER/PR‐negative and HER2+ status. Outcome analysis showed that pure DCIS associated with higher numbers of B lymphocytes had shorter recurrence‐free interval (P = 0.04); however, the association was not significant with the CD138+ plasma cell count (P = 0.07).ConclusionAssessment of TIL‐B cells based on location and topographic distribution can provide prognostic information. Validation in a larger cohort is warranted.
The influence of tectonic subsidence on volcaniclastic sedimentation: The Cretaceous upper Daeri Member, Wido Island, Korea
Authors: Gihm Yong Sik , Kim Min‐Cheol , Son Moon , Hwang In Gul 
Published: March 2017

AbstractThe Daeri Member, a Cretaceous volcanic–sedimentary succession, can be divided into lower, middle, and upper parts based on vertical changes in its lithologic characters. The lower Daeri Member is composed of siliciclastic deposits formed in a semi‐arid floodplain environment, which is overlain by the middle Daeri Member consisting mainly of andesite lava flow. After the emplacement of the andesite, activities of intrabasinal normal faults created accommodation on hanging wall blocks together with the development of intrabasinal topographic relief. The upper Daeri Member occurs only in hanging wall blocks and is composed of rhyolitic volcaniclastic sediments formed during an explosive volcanic eruption. Following the eruption, owing to semi‐arid climatic conditions and the destruction of vegetation, the eruptive materials were easily remobilized and deposited by episodic sediment gravity flows, resulting in deposition of the resedimented volcaniclastic deposits with sheet‐like geometry. Away from the intrabasinal normal faults, the resedimented volcaniclastic deposits show a decrease in grain size together with changes in inferred depositional processes from debris flows to hyperconcentrated flows and supercritical sheetfloods. This suggests that the resedimented volcaniclastic deposits were stacked on alluvial fan environments induced by intrabasinal topographic relief associated with normal fault activities. In addition, episodic movement of the faults gave rise to periodic fluctuation of the accommodation and an increase in gradient of the alluvial fan surface, resulting in the development of coarsening‐upward trends in the resedimented volcaniclastic deposits. The development of the alluvial fan and the coarsening‐upward trends indicate that dynamic tectonic subsidence and concomitant changes in the intrabasinal physiographic relief influenced the depositional processes and sizes of the transported volcaniclastic sediments of the upper Daeri Member. Thus, it is necessary to carefully observe tectonic signatures in volcaniclastic successions, particularly the syneruptive lithofacies, in order to reconstruct the tectonic and volcanic histories of receiving basins.
Influence of clinical use on physical–structural surface properties and electrochemical potential of NiTi endodontic instruments
Authors: Pereira E. S. J. , Amaral C. C. F. , Gomes J. A. C. P. , Peters O. A. , Buono V. T. L. , Bahia M. G. A. 
Published: March 2017

AbstractAimTo investigate the surface morphology and electrochemical potential of superelastic (SE), M‐Wire (MW) and shape memory technology (SMT) NiTi instruments before and after single clinical use in vivo.MethodologyA total of 60 ProTaper Universal F2 (PTU‐SE), ProTaper Next X2 (PTN‐MW), Typhoon (TYP), Hyflex (HF) and Vortex Blue (VB), the last three SMT, and size 25, .06 taper (n = 6 of each type) files were examined. Scanning electron microscopy (SEM), X‐ray energy‐dispersive spectroscopy (EDS) and electrochemical potential analysis were employed before and after clinical use. Statistical analysis was performed with one‐way analysis of variance and Bonferroni's post hoc test. Significance was determined at the 95% confidence level for both tests.ResultsSEM observations of new instruments indicated the presence of marks left by the machining process during manufacturing and EDS revealed the existence of an oxide coating on shape memory instruments. After clinical use, the five types were associated with propagation of transverse cracks 3 mm from the tip. The surface oxide layer of TYP, HF and VB instruments had microcracks in multiple directions, whilst TYP and HF had fragmentation in chip form of the oxide layer. EDS analysis demonstrated a significant reduction of the oxide layer in shape memory instruments, except for VB. Electrochemical potentials were higher for shape memory instruments than for M‐Wire and superelastic NiTi instruments, respectively (P < 0.05).ConclusionsIt appears that shape memory technology NiTi instruments have a dysfunctional oxide layer after clinical use. Additionally, they featured higher electrochemical potential relative to NiTi instruments manufactured from M‐Wire, and conventional superelastic NiTi alloy.
The diagnosis and lived experience of polycystic ovary syndrome: A qualitative study
Authors: Tomlinson Julie , Pinkney Jonathan , Adams Linda , Stenhouse Elizabeth , Bendall Alison , Corrigan Oonagh , Letherby Gayle 
Published: March 2017

AbstractAimsTo explore the impact of the diagnosis of polycystic ovary syndrome on health/ill health identity, how women experience this diagnosis and their health beliefs.BackgroundPolycystic ovary syndrome is a common and heterogeneous condition, giving rise to a wide range of different health concerns. Previous research on polycystic ovary syndrome has been dominated by the medical perspective and less is known about the experiences and needs of women.DesignA qualitative study of 32 premenopausal adult women with polycystic ovary syndrome (diagnosis confirmed by Rotterdam criteria), aged between 18 and 45 years, recruited from a primary and secondary care setting.MethodsThematic analysis of transcripts from 11 focus groups conducted between 2013‐2015.Results/FindingsWomen identified a range of concerns affecting personal and reproductive identity, health knowledge and beliefs: (1) delays and barriers to diagnosis; (2) general lack of empathy by the medical profession; (3) difficulty in accessing specialist referral; (4) lack of information from professionals; (5) inconsistent and sometimes unsatisfactory experiences with medications; (6) insufficient help and advice regarding in/fertility; (7) relative lack of awareness or concern about longer term risks such as diabetes; and (8) significant discrepancies between the beliefs of women with polycystic ovary syndrome and how they experienced the attitudes of healthcare professionals.ConclusionsThere appears to be a divergence between women's experience and attitudes of healthcare professionals. The diagnosis, support and lived experience of women with polycystic ovary syndrome could be enhanced by better professional recognition of these concerns, improved knowledge and communication about polycystic ovary syndrome and better access to support and specialist advice.
Towards a symptom cluster model in chronic kidney disease: A structural equation approach
Authors: Almutary Hayfa , Douglas Clint , Bonner Ann 
Published: March 2017

AbstractAimsThe aim of this study was to test a symptom cluster model in chronic kidney disease patients based on the Theory of Unpleasant Symptoms, accounting for the relationships between influencing factors, symptom experience and consequences for quality of life.BackgroundThe evaluation of symptom clusters is a new field of scientific inquiry directed towards more focused symptom management. Yet, little is known about relationships between symptom clusters, predictors and the synergistic effect of multiple symptoms on outcomes.DesignCross‐sectional.MethodsData were collected from 436 patients with advanced stages of chronic kidney disease during July 2013–February 2014 using validated measures of symptom burden and quality of life. Analysis involved structural equation modelling.ResultsThe final model demonstrated good fit with the data and provided strong evidence for the predicted relationships. Psychological distress, stage of chronic kidney disease and age explained most of the variance in symptom experience. Symptom clusters had a strong negative effect on quality of life, with fatigue, sexual symptoms and restless legs being the strongest predictors. Overall, the model explained more than half of the deterioration in quality of life. However, a reciprocal path between quality of life and symptom experience was not found.ConclusionsInterventions targeting symptom clusters could greatly improve quality of life in patients with chronic kidney disease. The symptom cluster model presented has important clinical and heuristic implications, serving as a framework to encourage and guide new lines of intervention research to reduce symptom burden in chronic kidney disease.
Maintaining family life balance while facing a child's imminent death—A mixed methods study
Authors: Eskola Katri , Bergstraesser Eva , Zimmermann Karin , Cignacco Eva 
Published: March 2017

AbstractAimTo understand parents’ experiences and needs during a child's end‐of‐life care at home and to identify systemic factors that influence its provision.BackgroundA child's end‐of‐life phase is an extremely difficult time for the whole family. Parents have specific needs, especially when they care for a dying child at home.DesignConcurrent embedded mixed methods design.MethodsThis sub‐study of the nationwide survey, ‘Paediatric End‐of‐Life Care Needs in Switzerland’ (2012–2015) included 47 children who received EOL care at home from 2011–2012. We extracted quantitative data from patients’ medical charts and obtained information via parental questionnaire and then compared parents whose child died at home or in hospital by computing generalized estimation equations. We thematically analysed interviews with parents who provided EOL care at home.ResultsParents created an intimate lifeworld and a sense of normality for the child at home. They constantly balanced the family's lifeworld with the requirements and challenges posed by the outside world. This work exhausted parents. Parental ‘readiness’ and social support drove EOL care for children at home. Parents needed practical help with housekeeping and had negative experiences when dealing with insurance. In only 34.8% of cases was a child's EOL home care supported by paediatric palliative care team.ConclusionPaediatric end‐of‐life care at home is only feasible if parents make extraordinary efforts. If family‐centred end‐of‐life home care is provided by a hospital‐based paediatric palliative home care team, which includes paid housekeeping help and psychological support, parents' needs could be better met.
Nursing judgement and decision‐making using the Sedation Withdrawal Score (SWS) in children
Authors: Craske Jennie , Carter Bernie , Jarman Ian H. , Tume Lyvonne N 
Published: March 2017

AbstractAimsThe aim of the study was to evaluate registered children's nurses’ approaches to the assessment and management of withdrawal syndrome in children.BackgroundAssessment of withdrawal syndrome is undertaken following critical illness when the child's condition may be unstable with competing differential diagnoses. Assessment tools aim to standardize and improve recognition of withdrawal syndrome. Making the right decisions in complex clinical situations requires a degree of mental effort and it is not known how nurses make decisions when undertaking withdrawal assessments.DesignCognitive interviews with clinical vignettes.MethodsInterviews were undertaken with 12 nurses to explore the cognitive processes they used when assessing children using the Sedation Withdrawal Score (SWS) tool. Interviews took place in Autumn 2013.FindingsEach stage of decision‐making—noticing, interpreting and responding—presented cognitive challenges for nurses. When defining withdrawal behaviours nurses tended to blur the boundaries between Sedation Withdrawal Score signs. Challenges in interpreting behaviours arose from not knowing if the patient's behaviour was a result of withdrawal or other co‐morbidities. Nurses gave a range of diagnoses when interpreting the vignettes, despite being provided with identical information. Treatment responses corresponded to definite withdrawal diagnoses, but varied when nurses were unsure of the diagnosis.ConclusionCognitive interviews with vignettes provided insight into nurses’ judgement and decision‐making. The SWS does not standardize the assessment of withdrawal due to the complexity of the context where assessments take place and the difficulties of determining the cause of equivocal behaviours in children recovering from critical illness.
Application of a Life Cycle Model for European Union Policy‐Driven Waste Management Decision Making in Emerging Economies
Authors: Stanisavljevic Nemanja , Levis James W. , Barlaz Morton A. 
Published: March 2017

SummarySolid waste life cycle modeling has predominantly focused on developed countries, but there are significant opportunities to assist developing and transition economies to minimize the environmental impact of solid waste management (SWM). Serbia is representative of a transition country and most (92%) of its waste is landfilled. As a Candidate European Union (EU) country, Serbia is expected to implement SWM strategies that meet EU directives. The Solid Waste Life‐Cycle Optimization Framework (SWOLF) was used to evaluate scenarios that meet EU goals by 2030. Scenarios included combinations of landfills, anaerobic digestion, composting, material recovery facilities (MRFs), waste‐to‐energy (WTE) combustion, and the use of refuse‐derived fuel in cement kilns. Each scenario was evaluated with and without separate collection of recyclables. Modeled impacts included cost, climate change, cumulative fossil energy demand, acidification, eutrophication, photochemical oxidation, total eco‐toxicity, and total human toxicity. Trade‐offs among the scenarios were evaluated because no scenario performed best in every category. In general, SWM strategies that incorporated processes that recover energy and recyclable materials performed well across categories, whereas scenarios that did not include energy recovery performed poorly. Emissions offsets attributable to energy recovery and reduced energy requirements associated with remanufacturing of recovered recyclables had the strongest influence on the results. The scenarios rankings were robust under parametric sensitivity analysis, except when the marginal electricity fuel source changed from coal to natural gas. Model results showed that the use of existing infrastructure, energy recovery, and efficient recovery of recyclables from mixed waste can reduce environmental emissions at relatively low cost.
SEM‐microphotogrammetry, a new take on an old method for generating high‐resolution 3D models from SEM images
Authors: BALL A.D. , JOB P.A. , WALKER A.E.L. 
Published: March 2017

SummaryThe method we present here uses a scanning electron microscope programmed via macros to automatically capture dozens of images at suitable angles to generate accurate, detailed three‐dimensional (3D) surface models with micron‐scale resolution. We demonstrate that it is possible to use these Scanning Electron Microscope (SEM) images in conjunction with commercially available software originally developed for photogrammetry reconstructions from Digital Single Lens Reflex (DSLR) cameras and to reconstruct 3D models of the specimen. These 3D models can then be exported as polygon meshes and eventually 3D printed.This technique offers the potential to obtain data suitable to reconstruct very tiny features (e.g. diatoms, butterfly scales and mineral fabrics) at nanometre resolution. Ultimately, we foresee this as being a useful tool for better understanding spatial relationships at very high resolution. However, our motivation is also to use it to produce 3D models to be used in public outreach events and exhibitions, especially for the blind or partially sighted.