bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of daily application of a 0.05% chlorhexidine solution on the incidence of (aspiration) pneumonia in care home residents: design of a multicentre cluster randomised controlled clinical trial
Authors: Hollaar Vanessa , Maarel-Wierink Claar van der , van der Putten Gert-Jan , Swart Bert de , Baat Cees de 
Published: December 2015

IntroductionPneumonia is an important cause of death in care home residents. Dysphagia and poor oral health are significant risk factors for developing aspiration pneumonia. Oral hygiene care reduces the number of oral bacteria and the risk of aspiration pneumonia. However, it is not clear yet which oral hygiene care intervention is most efficacious in reducing the risk of aspiration pneumonia. The aim of the study is to assess whether the application of a 0.05% chlorhexidine-containing solution in addition to the usual daily oral hygiene care reduces the incidence of pneumonia in physically disabled care home residents with dysphagia.Methods and analysisThe study was designed as a multicentre cluster randomised controlled clinical trial, with care homes as units of randomisation. During 1 year, 500 physically disabled care home residents with dysphagia will be followed. The intervention consists of applying a 0.05% chlorhexidine-containing solution twice daily, immediately after the usual oral hygiene care, whereas the control group receives no application after the usual oral hygiene care. The primary outcome is the incidence of pneumonia diagnosed by a physician, using a set of strictly described criteria. The effect of the intervention on the incidence of pneumonia will be determined using a Cox regression analysis. The secondary outcomes are correlations between incidence of pneumonia, age, gender, diagnosed diseases, dysphagia severity, care dependency, actually used medication, number of teeth and implants present and the presence of removable dentures.Ethics and disseminationEthical approval was obtained from the Medical Ethical Committee of Radboud university medical centre: NL.nr: 41990.091.12. Written and informed consent will be obtained from all participating care homes and residents. The study's findings will be published in peer-reviewed journals.Trial registration numberThe trial has been registered in the Netherlands in the National Trial Register: TC=3515.
Safety and efficacy of tiotropium in patients switching from HandiHaler to Respimat in the TIOSPIR trial
Authors: Dahl Ronald , Calverley Peter M A , Anzueto Antonio , Metzdorf Norbert , Fowler Andy , Mueller Achim , Wise Robert , Dusser Daniel 
Published: December 2015

ObjectivesThis post hoc analysis of TIOtropium Safety and Performance In Respimat (TIOSPIR) evaluated safety and exacerbation efficacy in patients with stable (≥2 months) use of tiotropium HandiHaler 18 µg (HH18) prior to study entry, to evaluate whether there was a difference in risk for patients who switched from HH18 to tiotropium Respimat 2.5 µg (R2.5) or 5 µg (R5).SettingTIOSPIR (n=17 135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial.ParticipantsPatients from TIOSPIR with chronic obstructive pulmonary disease (COPD) and postbronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity ≤0.70, receiving HH18 before study entry, were analysed (n=2784).InterventionsPatients were randomised to once-daily tiotropium R2.5 (n=914), R5 (n=918) or HH18 (n=952) for 2–3 years.Primary and secondary outcome measuresPrimary outcomes: time to death (safety) and time to first COPD exacerbation (efficacy). Secondary outcomes: number of exacerbations and time to first major adverse cardiovascular event (MACE).ResultsBaseline characteristics were similar in all groups. Respimat had a similar mortality risk versus HH18 (vital status follow-up, HR; 95% CI R2.5: 0.87; 0.64 to 1.17; R5: 0.79; 0.58 to 1.07) with no significant differences in the risk and rates of exacerbations and severe exacerbations across treatment groups. Risk of MACE and fatal MACE was similar for Respimat versus HH18 (HR; 95% CI MACE R2.5: 0.73; 0.47 to 1.15; R5: 0.69; 0.44 to 1.08; fatal MACE R2.5: 0.57; 0.27 to 1.19; R5: 0.67; 0.33 to 1.34). Overall risk of a fatal event (on treatment) was lower for R5 versus HH18 (HR; 95% CI R2.5: 0.78; 0.55 to 1.09; R5: 0.62; 0.43 to 0.89).ConclusionsThis analysis indicates that it is safe to switch patients from tiotropium HandiHaler to tiotropium Respimat, and that the efficacy is maintained over the switch.Trial registration numberNCT01126437; Post-results.
‘Our Care through Our Eyes’: a mixed-methods, evaluative study of a service-user, co-produced education programme to improve inpatient care of children and young people admitted following self-harm
Authors: Manning Joseph C , Latif Asam , Carter Tim , Cooper Joanne , Horsley Angela , Armstrong Marie , Wharrad Heather 
Published: December 2015

IntroductionWithin Europe, the UK has one of the highest rates of self-harm, with a particularly high prevalence in children and young people (CYP). CYP who are admitted to paediatric hospital wards with self-harm are cared for by registered children's nurses who have been identified to lack specific training in caring for this patient group. This may impede the delivery of high quality care. Therefore, this study aims to co-produce, implement and evaluate an education programme for registered children's nurses to improve their knowledge, attitudes and confidence when caring for CYP admitted with self-harm.Methods and analysisThis mixed-methods evaluative study will involve a three-stage design. Stage 1: A priority-setting workshop will be conducted with 19 registered children's nurses. A Delphi technique will be used to establish consensus of information needs. Stage 2: An online educational intervention will be co-produced with 25 CYP and 19 registered children's nurses based on the priorities identified in Stage 1. Stage 3: The intervention will be implemented and evaluated with 250 registered children's nurses at a single hospital. Online Likert scale questionnaires will be administered at baseline and postintervention to assess levels of knowledge, attitudes and confidence in caring for CYP who self-harm. Descriptive and inferential statistics will be used to analyse the data. Statistical significance will be assessed at the 5% (two-sided) level. One-to-one qualitative interviews will also be undertaken with approximately 25 participants to explore any perceived impact on clinical practice. An interpretive descriptive approach will guide qualitative data collection and analysis.Ethics and disseminationThis study aims to develop, trial and evaluative a service-user, co-produced education programme for acute hospital registered children's nurses to improve the care of CYP admitted due to self-harm. The study has ethical approval from the National Health Services Research Ethics Committee and full governance clearance.
Socioeconomic position in childhood and cancer in adulthood: a rapid-review
Authors: Vohra Jyotsna , Marmot Michael G , Bauld Linda , Hiatt Robert A 
Published: December 2015

BackgroundThe relationship of childhood socioeconomic position (SEP) to adult cancer has been inconsistent in the literature and there has been no review summarising the current evidence focused solely on cancer outcomes.Methods and resultsWe performed a rapid review of the literature, which identified 22 publications from 13 studies, primarily in the UK and northern European countries that specifically analysed individual measures of SEP in childhood and cancer outcomes in adulthood. Most of these studies adjusted for adult SEP as a critical mediator of the relationship of interest.ConclusionsResults confirm that childhood socioeconomic circumstances have a strong influence on stomach cancer and are likely to contribute, along with adult circumstances, to lung cancer through cumulative exposure to smoking. There was also some evidence of increased risk of colorectal, liver, cervical and pancreatic cancers with lower childhood SEP in large studies, but small numbers of cancer deaths made these estimates imprecise. Gaps in knowledge and potential policy implications are presented.
A Performance Comparison of Sort and Scan Libraries for GPUs
Authors: Merry Bruce 
Published: December 2015

Sorting and scanning are two fundamental primitives for constructing highly parallel algorithms. A number of libraries now provide implementations of these primitives for GPUs, but there is relatively little information about the performance of these implementations. We benchmark seven libraries for 32-bit integer scan and sort, and sorting 32-bit values by 32-bit integer keys. We show that there is a large variation in performance between the libraries, and that no one library has both optimal performance and portability.
Origin of the hardest c-axis and softest a-axis and lowest transition pressure of Mo2Ga2C from first principles
Authors: Yang Ze-Jin , Gao Qing-He , Guo Yun-Dong , Xu Zhi-Jun , Tang Ling 
Published: December 2015

The structural properties of Mo2Ga2C are simulated by first-principles under pressure. At 40 GPa, the axial compressibilities of [Formula: see text]- and [Formula: see text]-axes are 0.9763 and 0.9264, respectively, which are the known largest and smallest values in the [Formula: see text] compounds. A phase transition at 48 GPa is observed with an abrupt increase of [Formula: see text]-axis and a rapid decrease of [Formula: see text]-axis. The elastic properties and phonon imaginary frequencies confirmed the structural transition at 48 GPa, which probably should be the lowest-pressure transition in the [Formula: see text] ([Formula: see text], etc.) phases. The anti-expansion of Mo–Mo bond length is responsible for the [Formula: see text]-axis ultra-incompressibility as well as the structural transition at 48 GPa.
Interactive Acoustic Transfer Approximation for Modal Sound
Authors: Li Dingzeyu , Fei Yun , Zheng Changxi 
Published: December 2015

Current linear modal sound models are tightly coupled with their frequency content. Both the modal vibration of object surfaces and the resulting sound radiation depend on the vibration frequency. Whenever the user tweaks modal parameters to adjust frequencies the modal sound model changes completely, necessitating expensive recomputation of modal vibration and sound radiation.
We propose a new method for interactive and continuous editing as well as exploration of modal sound parameters. We start by sampling a number of key points around a vibrating object, and then devise a compact, low-memory representation of frequency-varying acoustic transfer values at each key point using Prony series. We efficiently precompute these series using an adaptive frequency sweeping algorithm and volume-velocity-preserving mesh simplification. At runtime, we approximate acoustic transfer values using standard multipole expansions. Given user-specified modal frequencies, we solve a small least-squares system to estimate the expansion coefficients, and thereby quickly compute the resulting sound pressure value at arbitrary listening locations. We demonstrate the numerical accuracy, the runtime performance of our method on a set of comparisons and examples, and evaluate sound quality with user perception studies.
Implementation of Timing-Event Affinities in Ada/Linux
Authors: Sáez Sergio , Real Jorge , Crespo Alfons 
Published: December 2015

Ada 2012 has introduced mechanisms for exploiting multiprocessor platforms at the application level. These include task afinity control and definition of dispatching domains. However, there are other executable entities defined in the language for which there is no such support to afinity control: event handlers. With event handlers we mean both timing-event and interrupt handlers.
This paper discusses the consequences of this lack of functionality and explores implementation issues related with this ability. We propose a working implementation for afinity of timing-event handlers on top of Linux.
Inflammation in Benign Prostate Tissue and Prostate Cancer in the Finasteride Arm of the Prostate Cancer Prevention Trial
Authors: Murtola Teemu J. , Gurel Bora , Umbehr Martin , Lucia M. Scott , Thompson Ian M. , Goodman Phyllis J. , Kristal Alan R. , Parnes Howard L. , Lippman Scott M. , Sutcliffe Siobhan , Peskoe Sarah B. , Barber John R. , Drake Charles G. , Nelson William G. , De Marzo Angelo M. , Platz Elizabeth A. 
Published: December 2015

Abstract
Background: A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here, we studied these associations in the PCPT finasteride arm.
Methods: Prostate cancer cases (N = 197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N = 248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of hematoxylin and eosin–stained sections. Logistic regression was used for statistical analysis.
Results: In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas (P &lt; 0.001 for difference compared with placebo arm). Overall, the odds of prostate cancer did not differ by prevalence [OR, 0.90; 95% confidence interval (CI), 0.44–1.84] or extent (P trend = 0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR, 1.07; 95% CI, 0.43–2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammation in either cases or controls.
Conclusion: The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer.
Impact: Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation. Cancer Epidemiol Biomarkers Prev; 25(3); 463–9. ©2015 AACR.
Hif1a Deletion Reveals Pro-Neoplastic Function of B Cells in Pancreatic Neoplasia
Authors: Lee Kyoung Eun , Spata Michelle , Bayne Lauren J. , Buza Elizabeth L. , Durham Amy C. , Allman David , Vonderheide Robert H. , Simon M. Celeste 
Published: December 2015

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths worldwide, with an exceedingly low 5-year survival rate. PDAC tumors are characterized by an extensive desmoplastic stromal response and hypovascularity, suggesting that tumor hypoxia could regulate PDAC initiation and/or progression. Using a well-defined, autochthonous KrasG12D-driven murine model, as well as human tumors, we demonstrate that hypoxia and stabilization of hypoxia-inducible factor 1α (HIF1α), a principal mediator of hypoxic adaptation, emerge early during preinvasive stages of PDAC. Surprisingly, pancreas-specific Hif1a deletion drastically accelerated KrasG12D-driven pancreatic neoplasia and was accompanied by significant increases in intrapancreatic B lymphocytes, featuring prominent influx of a rare “B1b” B-cell subtype. Finally, treatment of HIF1α-deficient mice with B cell–depleting αCD20 monoclonal antibodies inhibited progression of pancreatic intraepithelial neoplasia (PanIN). Our data reveal a previously unrecognized role for B cells in promoting pancreatic tumorigenesis and implicate HIF1α as a critical regulator of PDAC development.
Significance: We show here that pancreas-specific Hif1a deletion promotes PDAC initiation, coincident with increased intrapancreatic accumulation of B cells, and that B-cell depletion suppresses pancreatic tumorigenesis. We therefore demonstrate a protective role for HIF1α in pancreatic cancer initiation and uncover a previously unrecognized function of B cells. Cancer Discov; 6(3); 256–69. ©2015 AACR.
See related commentary by Roghanian et al., p. 230.
See related article by Pylayeva-Gupta et al., p. 247.
See related article by Gunderson et al., p. 270.
This article is highlighted in the In This Issue feature, p. 217
Bruton Tyrosine Kinase–Dependent Immune Cell Cross-talk Drives Pancreas Cancer
Authors: Gunderson Andrew J. , Kaneda Megan M. , Tsujikawa Takahiro , Nguyen Abraham V. , Affara Nesrine I. , Ruffell Brian , Gorjestani Sara , Liudahl Shannon M. , Truitt Morgan , Olson Peter , Kim Grace , Hanahan Douglas , Tempero Margaret A. , Sheppard Brett , Irving Bryan , Chang Betty Y. , Varner Judith A. , Coussens Lisa M. 
Published: December 2015

Abstract
Pancreas ductal adenocarcinoma (PDAC) has one of the worst 5-year survival rates of all solid tumors, and thus new treatment strategies are urgently needed. Here, we report that targeting Bruton tyrosine kinase (BTK), a key B-cell and macrophage kinase, restores T cell–dependent antitumor immune responses, thereby inhibiting PDAC growth and improving responsiveness to standard-of-care chemotherapy. We report that PDAC tumor growth depends on cross-talk between B cells and FcRγ+ tumor–associated macrophages, resulting in TH2-type macrophage programming via BTK activation in a PI3Kγ-dependent manner. Treatment of PDAC-bearing mice with the BTK inhibitor PCI32765 (ibrutinib) or by PI3Kγ inhibition reprogrammed macrophages toward a TH1 phenotype that fostered CD8+ T-cell cytotoxicity, and suppressed PDAC growth, indicating that BTK signaling mediates PDAC immunosuppression. These data indicate that pharmacologic inhibition of BTK in PDAC can reactivate adaptive immune responses, presenting a new therapeutic modality for this devastating tumor type.
Significance: We report that BTK regulates B-cell and macrophage-mediated T-cell suppression in pancreas adenocarcinomas. Inhibition of BTK with the FDA-approved inhibitor ibrutinib restores T cell–dependent antitumor immune responses to inhibit PDAC growth and improves responsiveness to chemotherapy, presenting a new therapeutic modality for pancreas cancer. Cancer Discov; 6(3); 270–85. ©2015 AACR.
See related commentary by Roghanian et al., p. 230.
See related article by Pylayeva-Gupta et al., p. 247.
See related article by Lee et al., p. 256.
This article is highlighted in the In This Issue feature, p. 217
Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma
Authors: Girotti Maria Romina , Gremel Gabriela , Lee Rebecca , Galvani Elena , Rothwell Dominic , Viros Amaya , Mandal Amit Kumar , Lim Kok Haw Jonathan , Saturno Grazia , Furney Simon J. , Baenke Franziska , Pedersen Malin , Rogan Jane , Swan Jacqueline , Smith Matthew , Fusi Alberto , Oudit Deemesh , Dhomen Nathalie , Brady Ged , Lorigan Paul , Dive Caroline , Marais Richard 
Published: December 2015

Abstract
Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from ∼9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end, we developed protocols to facilitate individualized treatment decisions for patients with advanced melanoma, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance. WES of tumors revealed potential hypothesis-driven therapeutic strategies for BRAF wild-type and inhibitor-resistant BRAF-mutant tumors, which were then validated in patient-derived xenografts (PDX). We also developed circulating tumor cell–derived xenografts (CDX) as an alternative to PDXs when tumors were inaccessible or difficult to biopsy. Thus, we describe a powerful technology platform for precision medicine in patients with melanoma.
Significance: Although recent developments have revolutionized melanoma care, most patients still die of their disease. To improve melanoma outcomes further, we developed a powerful precision medicine platform to monitor patient responses and to identify and validate hypothesis-driven therapies for patients who do not respond, or who develop resistance to current treatments. Cancer Discov; 6(3); 286–99. ©2015 AACR.
This article is highlighted in the In This Issue feature, p. 217
Responses to nitrate pollution, warming and density in common frog tadpoles (Rana temporaria)
Authors: Egea-Serrano Andrés , Van Buskirk Josh 
Published: December 2015

Amphibians face a variety of anthropogenic environmental perturbations that could act alone or in combination to influence population size. We investigated interactive effects of warming conditions, a moderate pulse of nitrogen pollution, and conspecific density on larvae of the common frog,Rana temporaria. The 16-day experiment had a 2 × 2 × 2 factorial design implemented in 80-l outdoor mesocosms. High density and warm temperature both resulted in reduced activity and visibility; tadpoles grew and developed more quickly at low density and high temperature. The high-nitrogen treatment did not influence behavior, growth, or development rate. We attribute this to several realistic features of our study, including a pulsed treatment application and natural denitrification within the mesocosms. There was only a single interaction among the three factors: higher temperature exacerbated density-dependence in growth rate. These results illustrate that climate warming may benefit temperate amphibians, although the benefits may be counteracted by enhanced larval crowding.
The Effects of Varying Break Length on Attention and Time on Task
Authors: Lim Julian , Kwok Kenneth 
Published: December 2015

Objective: We aimed to discover how varying the length of task breaks would affect the time-on-task effect in subsequent testing periods. Background: An important means of preventing errors and accidents caused by mental fatigue and time on task is to intersperse rest intervals within long work periods. Most studies of rest pauses to date have examined their effects in real-world tasks and settings, and their subtler effects on behavior, as measurable by laboratory paradigms, are not well understood. Method: We studied a group of 71 participants as they completed a 1-hr auditory oddball task with two rest opportunities. Rest intervals were 1, 5, or 10 min long. Results: Improvements in reaction time were significantly positively associated with length of the rest break. However, longer breaks were also associated with steeper decrements in performance in the subsequent task block. Across individuals, the amount of immediate improvement correlated with the extent of later decline. Conclusion: Our results support a resource/effort-allocation model of fatigue, whereby longer breaks bias participants toward greater effort expenditure on resumption of the task when cognitive resources may not have been fully replenished. Application: These findings may have implications for the refinement of work-rest schedules in industries where time-on-task degradation in performance is an important concern.