bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of the days’ supply and the number of refills allowed recorded in Québec prescription claims databases for inhaled corticosteroids
Authors: Blais Lucie , Vilain Anne , Kettani Fatima-Zohra , Forget Amélie , Lalonde Geneviève , Beauchesne Marie-France , Ducharme Francine M , Lemière Catherine 
Published: November 2014

Objectives and hypothesesAdherence to inhaled corticosteroids (ICS) is a major issue in asthma. This study aimed to estimate the accuracy of the days’ supply and number of refills allowed, variables recorded in Québec claims databases and used to estimate adherence, and to develop correction factors, if required. We hypothesised that the accuracy of the days’ supply for ICS would be low whereas the accuracy of the number of refills allowed would be high.Setting40 community pharmacies in Québec (Canada) and a medication registry.ParticipantsWe collected data for 1108 ICS original prescriptions stored in the 40 pharmacies (sample 1), and we obtained a second sample of 2676 ICS prescriptions selected from reMed, a medication registry (sample 2).Primary and secondary outcomesWe estimated the concordance of the days’ supply and number of refills between Québec claims databases and the original prescription from sample 1. We developed a correction factor for the days’ supply in sample 1 and validated it in sample 2. Analyses were stratified by age: 0–11 and 12–64 years.ResultsIn sample 1, the concordance for the days’ supply was 39.6% (95% CI 37.6% to 41.6%) in those aged 0–11 years and 56% (54.9% to 57.2%) in those aged 12–64 years. The concordance increased to 59.4% (58.2% to 60.5%) in those aged 0–11 years and 74.2% (73.5% to 74.9%) in those aged 12–64 years after applying the correction factors in sample 2. The concordance for the refills allowed was 92.1% (91% to 93.1%) in those aged 0–11 years and 93.1% (92.5% to 93.7%) in those aged 12–64 years in sample 1.ConclusionsThe accuracy of the days’ supply was moderate among those aged 0–11 years and substantial among those aged 12–64 years after applying the correction factors. The accuracy of the number of refills was almost perfect in both groups.
Improving physical functional and quality of life in older adults with multiple sclerosis via a DVD-delivered exercise intervention: a study protocol
Authors: Wójcicki Thomas R , Roberts Sarah A , Learmonth Yvonne C , Hubbard Elizabeth A , Kinnett-Hopkins Dominque , Motl Robert W , McAuley Edward 
Published: December 2014

IntroductionThere is a need to identify innovative, low-cost and broad-reaching strategies for promoting exercise and improving physical function in older adults with multiple sclerosis (MS).Methods and analysisThis randomised controlled pilot trial will test the efficacy of a 6-month, DVD-delivered exercise intervention to improve functional performance and quality of life in older adults with MS. Participants will be randomised either into a DVD-delivered exercise condition or an attentional control condition. This novel approach to programme delivery provides participants with detailed exercise instructions which are presented in a progressive manner and includes a variety of modifications to better meet varying levels of physical abilities. The targeted exercises focus on three critical elements of functional fitness: flexibility, strength and balance. It is hypothesised that participants who are randomised to the exercise DVD condition will demonstrate improvements in physical function compared with participants assigned to the attentional control condition. Data analysis will include a 2 (condition)×2 (time) mixed factor analysis of variance (ANOVA) that follows intent-to-treat principles, as well as an examination of effect sizes. Participants will take part in qualitative interviews about perspectives on physical activity and programme participation.Ethics and disseminationThe study protocol was approved by a university institutional review board and registered with a federal database. Participants will be asked to read and sign a detailed informed consent document and will be required to provide a physician's approval to participate in the study. The exercise DVDs include an overview of safety-related concerns and recommendations relative to exercise participation, as well as detailed instructions highlighting the proper execution of each exercise presented on screen. Following completion of this trial, data will be immediately analysed and results will be presented at scientific meetings and published in scholarly journals.Trial registration numberClinical TrialsNCT01993095.
Protocol investigating the clinical utility of an objective measure of activity and attention (QbTest) on diagnostic and treatment decision-making in children and young people with ADHD—‘AssessingQbTestUtility inADHD’ (AQUA): a randomised controlled trial
Authors: Hall Charlotte L , Walker Gemma M , Valentine Althea Z , Guo Boliang , Kaylor-Hughes Catherine , James Marilyn , Daley David , Sayal Kapil , Hollis Chris 
Published: December 2014

IntroductionThe National Institute for Health and Care Excellence (NICE) guidelines for attention deficit/hyperactivity disorder (ADHD) state that young people need to have access to the best evidence-based care to improve outcome. The current ‘gold standard’ ADHD diagnostic assessment combines clinical observation with subjective parent, teacher and self-reports. In routine practice, reports from multiple informants may be unavailable or contradictory, leading to diagnostic uncertainty and delay. The addition of objective tests of attention and activity may help reduce diagnostic uncertainty and delays in initiating treatment leading to improved outcomes. This trial investigates whether providing clinicians with an objective report of levels of attention, impulsivity and activity can lead to an earlier, and more accurate, clinical diagnosis and improved patient outcome.Methods and analysisThis multisite randomised controlled trial will recruit young people (aged 6–17 years old) who have been referred for an ADHD diagnostic assessment at Child and Adolescent Mental Health Services (CAMHS) and Community Paediatric clinics across England. Routine clinical assessment will be augmented by the QbTest, incorporating a continuous performance test (CPT) and infrared motion tracking of activity. The participant will be randomised into one of two study arms: QbOpen (clinician has immediate access to a QbTest report): QbBlind (report is withheld until the study end). Primary outcomes are time to diagnosis and diagnostic accuracy. Secondary outcomes include clinician's diagnostic confidence and routine clinical outcome measures. Cost-effective analysis will be conducted, alongside a qualitative assessment of the feasibility and acceptability of incorporating QbTest in routine practice.Ethics and disseminationThe findings from the study will inform commissioners, clinicians and managers about the feasibility, acceptability, clinical utility and cost-effectiveness of incorporating QbTest into routine diagnostic assessment of young people with ADHD. The results will be submitted for publication in peer-reviewed journals. The study has received ethical approval.Trial registration numberNCT02209116.
Over-the-head two-thumb encircling technique as an alternative to the two-finger technique in the in-hospital infant cardiac arrest setting: a randomised crossover simulation study
Authors: Jo Choong Hyun , Jung Hwan Suk , Cho Gyu Chong , Oh You Jang 
Published: November 2014

ObjectiveTo determine if the over-the-head two-thumb encircling technique (OTTT) provides better quality cardiopulmonary resuscitation (CPR) than the conventional two-finger technique (TFT) when performed by a lone rescuer in an in-hospital infant cardiac arrest setting.MethodsThis prospective, randomised crossover design study recruited 50 nurses who voluntarily performed lone rescuer infant CPR for 2 min on a manikin. Participants who performed OTTT stood at the head of the manikin to compress the chest and provide bag–valve mask ventilations, whereas those who performed TFT stood by the side of the manikin to compress the chest and provide pocket–mask ventilations. Mean hands-off time, mean compression depths and rates, proportion of effective compressions and complete recoil, and fatigue score changes were assessed during the test, and a survey on the ease of use of the techniques was conducted after the test.ResultsHands-off time, total ventilation volume and number of ventilations were not significantly different between the two techniques. OTTT resulted in greater depth of compressions (p<0.001), greater proportion of effective compressions (p<0.001), smaller proportion of complete recoil (p=0.001), and smaller fatigue score change (p=0.003) than TFT. In addition, subjects reported that compression, ventilation and changing compression to ventilation were easier using OTTT than TFT.ConclusionsOTTT performed by a lone rescuer in an in-hospital infant cardiac arrest setting resulted in greater compression depth, with no increase in hands-off time, compared with TFT. OTTT may therefore be a suitable alternative to TFT in the in-hospital infant cardiac arrest setting.
Predictors of emergency service use in adolescents and adults with autism spectrum disorder living with family
Authors: Lunsky Yona , Paquette-Smith Melissa , Weiss Jonathan A , Lee Jacques 
Published: November 2014

IntroductionThe use of emergency services among adolescents and adults with autism spectrum disorder (ASD) transitioning into adult health services has not been well described.ObjectivesTo describe emergency service use including emergency departments (EDs), paramedics, and police involvement among adolescents and adults with ASD and to examine predictors of using emergency services.MethodsCaregivers of 396 adolescents and adults with ASD were recruited through autism advocacy agencies and support programmes in Ontario to complete a survey about their child's health service use. Surveys were completed online, by mail and over the phone between December 2010 and October 2012. Parents were asked to describe their child's emergency service use and provide information about potential predictive factors including predisposing, enabling and clinical need variables.ResultsAccording to parents, 13% of their children with ASD used at least one emergency service in a 2-month period. Sedation or restraints were used 23% of the time. A combination of need and enabling variables predicted emergency service use with previous ED use in the last year (OR 3.4, 95% CI 1.7 to 6.8), a history of hurting others (OR 2.3, 95% 1.2 CI to 4.7) and having no structured daytime activities (OR 3.2, 95% CI 1.4 to 7.0) being the strongest multivariate predictors in the model.ConclusionsPatients with ASD and their families are likely to engage with paramedics or police or visit the ED. Further education and support to families and emergency clinicians are needed to improve and, when possible, prevent such occurrences.
Did Chile’s traffic law reform push police enforcement? Understanding Chile’s traffic fatalities and injuries reduction
Authors: Nazif-Munoz José Ignacio , Quesnel-Vallée Amélie , van den Berg Axel 
Published: November 2014

BackgroundThe objective of the current study is to determine to what extent the reduction of Chile’s traffic fatalities and injuries during 2000–2012 was related to the police traffic enforcement increment registered after the introduction of its 2005 traffic law reform.MethodsA unique dataset with assembled information from public institutions and analyses based on ordinary least square and robust random effects models was carried out. Dependent variables were traffic fatality and severe injury rates per population and vehicle fleet. Independent variables were: (1) presence of new national traffic law; (2) police officers per population; (3) number of traffic tickets per police officer; and (4) interaction effect of number of traffic tickets per police officer with traffic law reform. Oil prices, alcohol consumption, proportion of male population 15–24 years old, unemployment, road infrastructure investment, years’ effects and regions’ effects represented control variables.ResultsEmpirical estimates from instrumental variables suggest that the enactment of the traffic law reform in interaction with number of traffic tickets per police officer is significantly associated with a decrease of 8% in traffic fatalities and 7% in severe injuries. Piecewise regression model results for the 2007–2012 period suggest that police traffic enforcement reduced traffic fatalities by 59% and severe injuries by 37%.ConclusionsFindings suggest that traffic law reforms in order to have an effect on both traffic fatality and injury rates reduction require changes in police enforcement practices. Last, this case also illustrates how the diffusion of successful road safety practices globally promoted by WHO and World Bank can be an important influence for enhancing national road safety practices.
Behavioral software contracts
Authors: Findler Robert Bruce 
Published: December 2014

Programmers embrace contracts. They can use the language they know and love to formulate logical assertions about the behavior of their programs. They can use the existing IDE infrastructure to log contracts, to test, to debug, and to profile their programs.
The keynote presents the challenges and rewards of supporting contracts in a modern, full-spectrum programming language. It covers technical challenges of contracts while demonstrating the non-technical motivation for contract system design choices and showing how contracts and contract research can serve practicing programmers.
The remainder of this article is a literature survey of contract research, with an emphasis on recent work about higher-order contracts and blame.
Parallelization hints via code skeletonization
Authors: Aguston Cfir , Ben Asher Yosi , Haber Gadi 
Published: December 2014

Tools that provide optimization hints for program developers are facing severe obstacles and often unable to provide meaningful guidance on how to parallelize real--life applications. The main reason is due to the high code complexity and its large size when considering commercially valuable code. Such code is often rich with pointers, heavily nested conditional statements, nested while--based loops, function calls, etc. These constructs prevent existing compiler analysis from extracting the full parallelization potential. We propose a new paradigm to overcome this issue by automatically transforming the code into a much simpler skeleton-like form that is more conductive for auto-parallelization. We then apply existing tools of source--level automatic parallelization on the skeletonized code in order to expose possible parallelization patterns. The skeleton code, along with the parallelized version, are then provided to the programmer in the form of an IDE (Integrated Development Environment) recommendation.
The proposed skeletonization algorithm replaces pointers by integer indexes and C-struct references by references to multi-dimensional arrays. This is because automatic parallelizers cannot handle pointer expressions. For example, while(p != NULL){ p->val++; p=p->next; } will be skeletonized to the parallelizable for(Ip=0;Ip<N;Ip++){ Aval[Ip]++; } where Aval[] holds the embedding of the original list. It follows that the main goal of the skeletonization process is to embed pointer-based data structures into arrays. Though the skeletonized code is not semantically equivalent to the original code, it points out a possible parallelization pattern for this code segment and can be used as an effective parallelization hint to the programmer. We applied the method on several representative benchmarks from SPEC CPU 2000 and reached up to 80% performance gain after several sequential code segments had been manually parallelized based on the parallelization patterns of the generated skeletons. In a different set of experiments we tried to estimate the potential of skeletonization for a larger set of programs in SPEC 2000 and obtained an estimation of 27% additional loops that can be parallelized/vectorized due to skeletonization.
Automatic semantic locking
Authors: Golan-Gueta Guy , Ramalingam G. , Sagiv Mooly , Yahav Eran 
Published: December 2014

In this paper, we consider concurrent programs in which the shared state consists of instances of linearizable ADTs (abstract data types). We develop a novel automated approach to concurrency control that addresses a common need: the need to atomically execute a code fragment, which may contain multiple ADT operations on multiple ADT instances. In our approach, each ADT implements ADT-specific semantic locking operations that serve to exploit the semantics of ADT operations. We develop a synthesis algorithm that automatically inserts calls to these locking operations in a set of given code fragments (in a client program) to ensure that these code fragments execute atomically without deadlocks, and without rollbacks.
We have implemented the synthesis algorithm and several general-purpose ADTs with semantic locking. We have applied the synthesis algorithm to several Java programs that use these ADTs. Our results show that our approach enables efficient and scalable synchronization.
Formal semantics for the PACEMAKER system specification
Authors: Larson Brian R. 
Published: December 2014

This paper formally expresses the timing behavior of a cardiac pacemaker as defined in the PACEMAKER System Specification as understood by its principal author.
The PACEMAKER System Specification was publicly released by Boston Scientific to provide a real-world subject for application of formal methods in response to Jim Woodcock's request at FM2006 for an industrial Grand Challenge problem. PACEMAKER's use for purposes other than formal methods has been surprising in its variety. Most ambitious is the Software Certification Consortium's mock regulatory submission, PACEMAKER Grand Challenge, to show that a product with safety-critical software is in fact safe. McMaster University is designing a second-generation hardware platform to execute formally-verified software during system feature test validation with an electrical heart simulator to show correct behavior.
This paper uses first-order predicates, extended with a simple temporal operator, to formally express what the principal author understands to be "correct" behavior defined in PACEMAKER.
Specification of generic APIs, or
Authors: Bagge Anya Helene , Haveraaen Magne 
Published: December 2014

Specification based on Floyd-Hoare logic, using pre- and post-conditions, is common in languages aimed at high integrity software. Such pre/postcondition specifications are geared towards verification of code. While this specification technique has proven quite successful in the past 40 years, it has limitations when applied to API specification, particularly specification of generic interfaces.
API-oriented design and genericity is of particular importance in modern large-scale software development. In this situation, algebraic specification techniques have a significant advantage. Unlike pre/post-based specification, which deals with the inputs and outputs of one operation at a time, algebraic specification deals with the relationships between the different operations in an API, which is needed in the specification of generic APIs.
Crosstalk between KIT and FGFR3 Promotes Gastrointestinal Stromal Tumor Cell Growth and Drug Resistance
Authors: Javidi-Sharifi Nathalie , Traer Elie , Martinez Jacqueline , Gupta Anu , Taguchi Takehiro , Dunlap Jennifer , Heinrich Michael C. , Corless Christopher L. , Rubin Brian P. , Druker Brian J. , Tyner Jeffrey W. 
Published: November 2014

Abstract
Kinase inhibitors such as imatinib have dramatically improved outcomes for patients with gastrointestinal stromal tumor (GIST), but many patients develop resistance to these treatments. Although in some patients this event corresponds with mutations in the GIST driver oncogenic kinase KIT, other patients develop resistance without KIT mutations. In this study, we address this patient subset in reporting a functional dependence of GIST on the FGF receptor FGFR3 and its crosstalk with KIT in GIST cells. Addition of the FGFR3 ligand FGF2 to GIST cells restored KIT phosphorylation during imatinib treatment, allowing sensitive cells to proliferate in the presence of the drug. FGF2 expression was increased in imatinib-resistant GIST cells, the growth of which was blocked by RNAi-mediated silencing of FGFR3. Moreover, combining KIT and FGFR3 inhibitors synergized to block the growth of imatinib-resistant cells. Signaling crosstalk between KIT and FGFR3 activated the MAPK pathway to promote resistance to imatinib. Clinically, an IHC analysis of tumor specimens from imatinib-resistant GIST patients revealed a relative increase in FGF2 levels, with a trend toward increased expression in imatinib-naïve samples consistent with possible involvement in drug resistance. Our findings provide a mechanistic rationale to evaluate existing FGFR inhibitors and multikinase inhibitors that target FGFR3 as promising strategies to improve treatment of patients with GIST with de novo or acquired resistance to imatinib. Cancer Res; 75(5); 880–91. ©2015 AACR.
PI3K/mTOR Dual Inhibitor VS-5584 Preferentially Targets Cancer Stem Cells
Authors: Kolev Vihren N. , Wright Quentin G. , Vidal Christian M. , Ring Jennifer E. , Shapiro Irina M. , Ricono Jill , Weaver David T. , Padval Mahesh V. , Pachter Jonathan A. , Xu Qunli 
Published: November 2014

Abstract
Cancer stem cells (CSC) have been implicated in disease recurrence, metastasis, and therapeutic resistance, but effective targeting strategies for these cells are still wanting. VS-5584 is a potent and selective dual inhibitor of mTORC1/2 and class I PI 3-kinases. Here, we report that VS-5584 is up to 30-fold more potent in inhibiting the proliferation and survival of CSC compared with non-CSC in solid tumor cell populations. VS-5584 preferentially diminished CSC levels in multiple mouse xenograft models of human cancer, as evidenced by marked reduction of tumor-initiating capacity in limiting dilution assays. Likewise, VS-5584 treatment ex vivo preferentially reduced CSC in surgically resected breast and ovarian patient tumors. In contrast, chemotherapeutics such as paclitaxel and cisplatin were less effective in targeting CSC than bulk tumor cells. Mechanistic investigations revealed that preferential targeting of CSC required inhibition of multiple components of the PI3K–mTOR pathway: coordinate RNAi-mediated silencing of PI3Kα, PI3Kβ, and mTOR phenocopied the effect of VS-5584, exhibiting the strongest preferential targeting of CSC, while silencing of individual PI3K isoforms or mTOR failed to replicate the effect of VS-5584. Consistent with CSC ablation, VS-5584 delayed tumor regrowth following chemotherapy in xenograft models of small-cell lung cancer. Taken together, the preferential targeting of CSC prompts a new paradigm for clinical testing of VS-5584: clinical trials designed with CSC-directed endpoints may facilitate demonstration of the therapeutic benefit of VS-5584. We suggest that combining VS-5584 with classic chemotherapy that debulks tumors may engender a more effective strategy to achieve durable remissions in patients with cancer. Cancer Res; 75(2); 446–55. ©2014 AACR.