bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical trial protocol for TRANSFORM‐UK: A therapeutic open‐label study of tocilizumab in the treatment of pulmonary arterial hypertension
Authors: Hernández‐Sánchez Jules , Harlow Louise , Church Colin , Gaine Sean , Knightbridge Emily , Bunclark Kate , Gor Dee , Bedding Alun , Morrell Nicholas , Corris Paul , Toshner Mark 
Published: September 2017

Our aim is to assess the safety and potential efficacy of a novel treatment paradigm in pulmonary arterial hypertension (PAH), immunomodulation by blocking interleukin‐6 (IL6) signaling with the IL6 receptor antagonist, tocilizumab. Inflammation and autoimmunity are established as important in PAH pathophysiology. One of the most robust observations across multiple cohorts in PAH has been an increase in IL6, both in the lung and systemically. Tocilizumab is an IL‐6 receptor antagonist established as safe and effective, primarily in rheumatoid arthritis, and has shown promise in scleroderma. In case reports where the underlying cause of PAH is an inflammatory process such as systemic lupus erythematosus, mixed connective tissue disease (MCTD), and Castleman’s disease, there have been case reports of regression of PAH with tocilizumab. TRANSFORM‐UK is an open‐label study of intravenous (IV) tocilizumab in patients with group 1 PAH. The co‐primary outcome measures will be safety and the change in resting pulmonary vascular resistance (PVR). Clinically relevant secondary outcome measurements include 6‐minute walk distance, WHO functional class, quality of life score, and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). If the data support a potentially useful therapeutic effect with an acceptable risk profile, the study will be used to power a Phase III study to properly address efficacy.
Role of the medial prefrontal cortex and nucleus accumbens in an operant model of checking behaviour and uncertainty
Authors: d’Angelo Camilla , Eagle Dawn M. , Coman Cristina-M. , Robbins Trevor W. 
Published: September 2017

Background: Excessive checking is a common, debilitating symptom of obsessive–compulsive disorder. To further examine cognitive processes underpinning checking behaviour, and clarify how and why checking develops, we designed a novel operant paradigm for rats, the observing response task. The present study used the observing response task to investigate checking behaviour following excitotoxic lesions of the medial prefrontal cortex, nucleus accumbens core and dorsal striatum, brain regions considered to be of relevance to obsessive–compulsive disorder. Methods: In the observing response task, rats pressed an ‘observing’ lever for information (provided by light onset) about the location of an ‘active’ lever that provided food reinforcement. Following training, rats received excitotoxic lesions of the regions described above and performance was evaluated post-operatively before histological processing. Results: Medial prefrontal cortex lesions selectively increased functional checking with a less-prominent effect on non-functional checking and reduced discrimination accuracy during light information periods. Rats with nucleus accumbens core lesions made significantly more checking responses than sham-lesioned rats, including both functional and non-functional checking. Dorsal striatum lesions had no direct effect on checking per se, but reduced both active and inactive lever presses, and therefore changed the relative balance between checking responses and instrumental responses. Conclusions: These results suggest that the medial prefrontal cortex and nucleus accumbens core are important in the control of checking, perhaps via their role in processing uncertainty of reinforcement, and that dysfunction of these regions may therefore promote excessive checking behaviour, possibly relevant to obsessive-compulsive disorder.
Mutation load and an effector T-cell gene signature may distinguish immunologically distinct and clinically relevant lymphoma subsets
Authors: Bolen Christopher R. , McCord Ronald , Huet Sarah , Frampton Garrett M. , Bourgon Richard , Jardin Fabrice , Dartigues Peggy , Punnoose Elizabeth A. , Szafer-Glusman Edith , Xerri Luc , Sujobert Pierre , Salles Gilles , Venstrom Jeffrey M. 
Published: September 2017

Key Points
Low mutation load is associated with a benefit from rituximab maintenance. The Teff signature correlates with high mutation load, is prognostic, and may distinguish immunologically distinct FL subgroups.
Haploidentical transplant in patients with myelodysplastic syndrome
Authors: Robin Marie , Porcher Raphael , Ciceri Fabio , van Lint Maria Teresa , Santarone Stella , Ehninger Gerhard , Blaise Didier , Güllbas Zafer , Gonzáles Muñiz Soledad , Michallet Mauricette , Velardi Andrea , Koster Linda , Maertens Johan , Sierra Jorge , Selleslag Dominik , Radujkovic Aleksandar , Díez-Martin José L. , Kanz Lothar , Arroyo Concepcion Herrera , Niederwieser Dietger , Huang He , McDonald Andrew , de Witte Theo , Koc Yener , Kröger Nicolaus 
Published: September 2017

Key Points
Nonrelapse mortality remains high in MDS patients who underwent haploidentical transplant before 2015. Haplotransplantation using PT-CY and reduced-intensity conditioning seems an acceptable option in MDS patients lacking HLA-matched donors.
Discordance in Human Epidermal Growth Factor Receptor 2 (HER2) Phenotype Between Primary Tumor and Circulating Tumor Cells in Women With HER2-Negative Metastatic Breast Cancer
Authors: De Gregorio Amelie , Friedl Thomas W.P. , Huober Jens , Scholz Christoph , De Gregorio Nikolaus , Rack Brigitte , Trapp Elisabeth , Alunni-Fabbroni Marianna , Riethdorf Sabine , Mueller Volkmar , Schneeweiss Andreas , Pantel Klaus , Meier-Stiegen Franziska , Jaeger Bernadette , Hartkopf Andreas , Taran Florin-Andrei , Fasching Peter A. , Janni Wolfgang , Fehm Tanja 
Published: September 2017

Purpose Discordance in human epidermal growth factor receptor 2 (HER2) status between primary tumor and metastases might have important implications for treatment response and therapy decisions. Here, we evaluate both the frequency of circulating tumor cells (CTCs) and the factors predicting HER2 discordance between primary tumor and CTCs as a potential surrogate for tumor biology and tumor heterogeneity in patients with metastatic breast cancer. Patients and Methods The number of CTCs in 7.5 mL of peripheral blood and HER2 status were evaluated in 1,123 women with HER2-negative metastatic breast cancer. HER2 discordance was defined as the presence of at least one CTC with a strong immunocytochemical HER2 staining intensity. Factors predicting discordance in HER2 phenotype were assessed using multivariable logistic regression. Results Overall, 711 (63.3%) of 1,123 screened patients were positive for CTCs (≥ one CTC). Discordance in HER2 phenotype between primary tumor and CTCs was observed in 134 patients (18.8%) and was significantly associated with histologic type (lobular v ductal; odds ratio [OR], 2.67; 95% CI, 1.63 to 4.39; P < .001), hormone receptor status (positive v negative; OR, 2.84; 95% CI, 1.15 to 7.02; P = .024), and CTC number (≥ five v one to four; OR, 7.64; 95% CI, 3.97 to 14.72; P < .001). Conclusion HER2 discordance between primary tumor and CTCs was observed in 18.8% of patients and was associated with histologic type, hormone receptor status of the primary tumor, and CTC number. The clinical utility of CTCs as liquid biopsy to assess tumor heterogeneity of metastatic disease and guide treatment decisions must be evaluated in prospective randomized trials.
Monte Carlo Simulations Comparing Fisher Exact Test and Unequal Variances t Test for Analysis of Differences Between Groups in Brief Hospital Lengths of Stay
Authors: Dexter Franklin , Bayman Emine O. , Dexter Elisabeth U. 
Published: September 2017

BACKGROUND:We examined type I and II error rates for analysis of (1) mean hospital length of stay (LOS) versus (2) percentage of hospital LOS that are overnight. These 2 end points are suitable for when LOS is treated as a secondary economic end point.METHODS:We repeatedly resampled LOS for 5052 discharges of thoracoscopic wedge resections and lung lobectomy at 26 hospitals.RESULTS:Unequal variancesttest (Welch method) and Fisher exact test both were conservative (ie, type I error rate less than nominal level). The Wilcoxon rank sum test was included as a comparator; the type I error rates did not differ from the nominal level of 0.05 or 0.01. Fisher exact test was more powerful than the unequal variancesttest at detecting differences among hospitals; estimated odds ratio for obtainingP< .05 with Fisher exact test versus unequal variancesttest = 1.94, with 95% confidence interval, 1.31–3.01. Fisher exact test and Wilcoxon-Mann-Whitney had comparable statistical power in terms of differentiating LOS between hospitals.CONCLUSIONS:For studies with LOS to be used as a secondary end point of economic interest, there is currently considerable interest in the planned analysis being for the percentage of patients suitable for ambulatory surgery (ie, hospital LOS equals 0 or 1 midnight). Our results show that there need not be a loss of statistical power when groups are compared using this binary end point, as compared with either Welch method or Wilcoxon rank sum test.
Maternal Death Due to Amniotic Fluid Embolism: A National Study in France
Authors: Bonnet Marie-Pierre , Zlotnik Diane , Saucedo Monica , Chassard Dominique , Bouvier-Colle Marie-Hélène , Deneux-Tharaux Catherine 
Published: September 2017

BACKGROUND:
A structured definition of amniotic fluid embolism (AFE) based on 4 criteria was recently proposed for use in research by the Society for Maternal-Fetal Medicine (SMFM) and the Amniotic Fluid Embolism Foundation. The main objective of this study was to review all AFE-related maternal deaths in France during 2007–2011 according to the presence or not of all these 4 diagnostic criteria.

METHODS:
Maternal deaths due to AFE were identified by the national experts committee of the French Confidential Enquiry into Maternal Deaths during 2007–2011 (n = 39). The maternal mortality ratio for AFE was calculated. We applied the structured definition proposed by the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation to AFE-related maternal deaths identified by the national experts committee. Characteristics of women, pregnancies and deliveries; clinical and biological features of AFE; and specific laboratory tests used were described by the presence or not of all 4 diagnostic criteria. Management of obstetric hemorrhage and quality of care according to the experts were also described.

RESULTS:
The maternal mortality ratio from AFE was 0.95/100,000 live births (95% confidence interval, 0.67–1.3). Detailed clinical data were collected for 36 women who died from AFE: 21 (58%) had all 4 proposed diagnostic criteria and 15 (42%) had 1 or more missing criterion. Documented early disseminated intravascular coagulopathy was missing for 14 women, and 2 women exhibited more than 1 missing criterion. Ten of the 15 women with missing criteria had clinical coagulopathy, with standard hemostasis tests performed in only 3. Specific diagnostic examinations for AFE were performed in similar proportions by the presence or not of all diagnostic criteria. Opportunities to improve care included timely performance of indicated hysterectomy (n = 13) and improved transfusion practices (n = 9). In the context of maternal cardiac arrest, for 5 of 13 women, fetal extraction was performed within 5 minutes.

CONCLUSIONS:
The structured definition of AFE for research studies would exclude more than one-third of AFE-related maternal deaths identified by the national experts committee. Inclusion of clinical coagulopathy as a diagnostic criterion for AFE would reduce this proportion to 14%. There is still room for improvement in the management of obstetric hemorrhage and timely fetal extraction in the context of maternal cardiac arrest, frequently observed in AFE-related maternal death.
Extending voluntary health insurance to the informal sector: experiences and expectations of the informal sector in Kenya
Authors: Barasa Edwine W. , Mwaura Njeri , Rogo Khama , Andrawes Ledia 
Published: September 2017

Background: Kenya has made a policy decision to use contributory health insurance as one of its key pre-payment health financing mechanisms. The National Hospital Insurance Fund (NHIF) is the main health insurer in Kenya. While the NHIF has hitherto focused its efforts on providing health insurance coverage to individuals in the formal sector, it has recently broadened its focus to include individuals in the informal sector. This paper provides an analysis of the perceptions, and experiences of informal sector individuals in Kenya with regard to enrolment with the NHIF. Methods: We collected data through key informant interviews (39) in two purposefully selected counties. Study participants were drawn from healthcare facilities contracted by the NHIF, and current, former, and prospective informal sector members. We analyzed data using a grounded approach. Results: Participants felt that the NHIF provided inadequate information about the registration and membership processes as well as benefit entitlements. There was variable and inconsistent communication by the NHIF. There was also variance between the official benefit package and the actual benefits received by members. The NHIF registration requirements and processes presented an administrative barrier to obtaining membership. The NHIF premium level and contribution mechanism presents a financial barrier to current and prospective members. Healthcare providers discriminated against NHIF members compared to cash-payers or private insurance holders. Conclusions: The NHIF could improve enrolment and retention of informal sector individuals by; 1) using communication strategies that are effective at reaching the informal sector, 2) improving the affordability of the premium rates, 3) simplifying the enrolment requirements and process, and 4) strengthening accountability mechanisms between itself and healthcare facilities to ensure that enrolled members receive the benefits that they are entitled to, and that client experience at healthcare facilities are satisfactory.
Heuristic Solutions to the Facility Location Problem with General Bernoulli Demands
Authors: Albareda-Sambola Maria , Fernández Elena , Saldanha-da-Gama Francisco 
Published: September 2017

In this paper, a heuristic procedure is proposed for the facility location problem with general Bernoulli demands. This is a discrete facility location problem with stochastic demands that can be formulated as a two-stage stochastic program with recourse. In particular, facility locations and customer assignments must be decided here and now, i.e., before knowing the customers who will actually require to be served. In a second stage, service decisions are made according to the actual requests. The heuristic proposed consists of a greedy randomized adaptive search procedure followed by a path relinking. The heterogeneous Bernoulli demands make prohibitive the computational effort for evaluating feasible solutions. Thus the expected cost of a feasible solution is simulated when necessary. The results of extensive computational tests performed for evaluating the quality of the heuristic are reported, showing that high-quality feasible solutions can be obtained for the problem in fairly small computational times. The online supplement is available at https://doi.org/10.1287/ijoc.2017.0755 .
Formulations and Approximation Algorithms for Multilevel Uncapacitated Facility Location
Authors: Ortiz-Astorquiza Camilo , Contreras Ivan , Laporte Gilbert 
Published: September 2017

This paper studies multilevel uncapacitated p-location problems, a general class of facility location problems. We use a combinatorial representation of the general problem where the objective function satisfies the submodular property, and we exploit this characterization to derive worst-case bounds for a greedy heuristic. We also obtain sharper bounds when the setup cost for opening facilities is zero and the allocation profits are nonnegative. Moreover, we introduce a mixed integer linear programming formulation for the problem based on the submodularity property. We present results of computational experiments to assess the performance of the greedy heuristic and that of the formulation. We compare the models with previously studied formulations. The online supplement and data are available at https://doi.org/10.1287/ijoc.2017.0757 .
Does Online Word of Mouth Increase Demand? (And How?) Evidence from a Natural Experiment
Authors: Seiler Stephan , Yao Song , Wang Wenbo 
Published: September 2017

We leverage a temporary block of the Chinese microblogging platform Sina Weibo due to political events to estimate the causal effect of online word-of-mouth content on product demand in the context of TV show viewership. Based on this source of exogenous variation, we estimate an elasticity of TV show ratings (market share in terms of viewership) with respect to the number of relevant comments (comments were disabled during the block) of 0.016. We find that more postshow microblogging activity increases demand, whereas comments posted prior to the show airing do not affect viewership. These patterns are inconsistent with informative or persuasive effects and suggest complementarity between TV consumption and anticipated postshow microblogging activity. Data and the online appendix are available at https://doi.org/10.1287/mksc.2017.1045 .
Promotion of oral health by community nurses
Authors: Garry Brendan , Boran Sue 
Published: September 2017

Aim: To explore the enablers and barriers perceived by community nurses in the promotion of oral health in an adult community trust directorate. Background: Oral health care promotion in community care settings is being neglected. England and Wales have witnessed marked improvements in periodontal disease; however, no improvements have been seen in older people. Method: A qualitative methodology was employed, where eight nurses from Band 5 to 7 were interviewed using a semi-structured approach. The data was analysed thematically. Findings: Data analysis was organised into four themes: professional self-concept and the development of knowledge, skills and attitudes necessary in the promotion of oral health; the impact an organisation has on the promotion of oral health and an exploration of the enablers and barriers identified by the community nurses while delivering care; the relationships between the nurse and patient and the potential impact on oral health promotion; the concept of self-regard in relation to the promotion of oral health and its overall impact. A commitment to improving oral health and requests for additional educational input were apparent. Organisational enablers and barriers were identified, alongside the crucial role a positive self-regard for oral health care may play in the promotion of oral health. Conclusion: Nurses need relevant education, organisational support, adequate resources and support from a multidisciplinary team to deliver optimal oral health promotion.
The Properties of Clay Minerals in Soil Particles from Two Ultisols, China
Authors: Zhang Zhi Yi , Huang Li , Liu Fan , Wang Ming Kuang , Fu Qing Ling , Zhu Jun 
Published: September 2017

AbstractSoil aggregates consist of sand, silt, and clay size particles. Many of the clay size particles in soils are clay minerals, which actively influence soil behavior. The properties of clay minerals may change significantly as soil particle size decreases to the nanoscale; however, little information is available about these properties for the Ultisols in China. In the present study, the clay mineral components and structural characteristics of four particle-size fractions (i.e., <2000, 450–2000, 100–450, and 25–100 nm) of two Ultisol samples (Ult-1 and Ult-2) were investigated using elemental analysis, X-ray diffraction, Fouriertransform infrared spectroscopy, and thermal analysis. The molar SiO2to Al2O3ratios were lower in the nanoscale particle-size fraction (25–100 nm) than in the 450–2000 and <2000 nm fractions. This indicates greater desilicification and allitization of the smaller Ultisol particles. Furthermore, the Fe oxide and Al oxide contents increased and reached a maximum level in the 25–100 nm fraction of the two Ultisols. Goethite was mainly found in the 100–450 nm and 25–100 nm fractions. The dominant clay minerals in the Ultisol 25–100 nm fraction were kaolinite and illite with a small amount of a hydroxy-interlayered mineral in Ult-1 and gibbsite in Ult-2. The kaolinite crystallinity decreased as particle size decreased. The low crystallinity of the kaolinite in the A horizon 25–100 nm fraction was attributed to a reduction in the thickness of coherent scattering domains, as well as to decreases in OH groups and the dimensions of octahedral AlO6sheets. A determination of the chemical and mineralogic properties of the different size fractions of the Ultisols is important to understand the desilicification and Al and Fe oxide enrichment mechanisms during soil formation. The significance of these results can help to reveal the nanoscale transformations of clay minerals. Analysis of clay mineral compositions in nanoparticles can provide the additional data needed to understand the adsorption and mobility of nutrients and pollutants.