bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change in prevalence of chronic kidney disease in England over time: comparison of nationally representative cross-sectional surveys from 2003 to 2010
Authors: Aitken Grant R , Roderick Paul J , Fraser Simon , Mindell Jennifer S , O'Donoghue Donal , Day Julie , Moon Graham 
Published: October 2014

ObjectivesTo determine whether the prevalence of chronic kidney disease (CKD) in England has changed over time.DesignCross-sectional analysis of nationally representative Health Survey for England (HSE) random samples.SettingEngland 2003 and 2009/2010.Survey participants13 896 adults aged 16+ participating in HSE, adjusted for sampling and non-response, 2009/2010 surveys combined.Main outcome measureChange in prevalence of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2(as proxy for stage 3–5 CKD), from 2003 to 2009/2010 based on a single serum creatinine measure using an isotope dilution mass spectrometry traceable enzymatic assay in a single laboratory; eGFR derived using Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) eGFR formulae.AnalysisMultivariate logistic regression modelling to adjust time changes for sociodemographic and clinical factors (body mass index, hypertension, diabetes, lipids). A correction factor was applied to the 2003 HSE serum creatinine to account for a storage effect.ResultsNational prevalence of low eGFR (<60) decreased within each age and gender group for both formulae except in men aged 65–74. Prevalence of obesity and diabetes increased in this period, while there was a decrease in hypertension. Adjustment for demographic and clinical factors led to a significant decrease in CKD between the surveyed periods. The fully adjusted OR for eGFR <60 mL/min/1.73 m2was 0.75 (0.61 to 0.92) comparing 2009/2010 with 2003 using the MDRD equation, and was similar using the CKDEPI equation 0.73 (0.57 to 0.93).ConclusionsThe prevalence of a low eGFR indicative of CKD in England appeared to decrease over this 7-year period, despite the rising prevalence of obesity and diabetes, two key causes of CKD. Hypertension prevalence declined and blood pressure control improved but this did not appear to explain the fall. Periodic assessment of eGFR and albuminuria in future HSEs is needed to evaluate trends in CKD.
Short-term use of remifentanil during endotracheal extubation for prophylactic analgesia in neurosurgical patients after craniotomy (SURE after Craniotomy Study): a study protocol and statistical analysis plan for a randomised controlled trial
Authors: Wu Yuan-Xing , Chen Han , Zhou Jian-Xin 
Published: October 2014

IntroductionAcute pain is common during the endotracheal extubation period, and is related to complications and adverse outcomes. Patients with delayed extubation after craniotomy are vulnerable to pain and complications of extubation. However, pain control during extubation is still inadequate. Remifentanil, a new opioid with rapid onset and short duration of action, provides adequate analgesia during procedures with minimal effect of respiratory depression.Methods and analysisThe study is a prospective, randomised, double-blinded, controlled parallel-group design. Patients with delayed extubation after intracranial surgery are screened daily. Adult patients ready for extubation are enrolled and assigned randomly to one of the two treatment study groups, labelled as the ‘Remi group’ or ‘Saline group’. Patients in the Remi group receive an intravenous bolus dose of remifentanil 0.5 μg/kg over 60 s followed by a continuous infusion 0.05 μg/kg/min for 20 min. Patients in the Saline group receive an intravenous infusion of 0.9% sodium chloride at a volume and rate equal to that of remifentanil. Pain intensity is measured by the visual analogue scale (VAS) pain score. Adverse events during drug infusion are documented and reported. Patients will be followed up until hospital discharge, death or 60 days after the trial intervention on a first come, first served basis. Details of the incidence of reintubation and reoperation within 72 h after extubation, length of stay in the intensive care unit and hospital and mortality are collected. The primary end point is the incidence of severe pain (defined as a VAS pain score more than 5 cm) during the periextubation period (defined as the period of time from immediately before extubation to 20 min after extubation).Ethics and disseminationThe study was approved by the Institutional Review Board (IRB) of the Beijing Tiantan Hospital, Capital Medical University. The study findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberClinicalTrials (NCT): ChiCTR-PRC-13003879.
Study protocol for a double blind, randomised, placebo-controlled trial of continuous subpectoral local anaesthetic infusion for pain and shoulder function following mastectomy: SUB-pectoral Local anaesthetic Infusion following MastEctomy (SUBLIME) study
Authors: Langford R , Brown I , Vickery J , Mitchell K , Pritchard C , Creanor S 
Published: October 2014

IntroductionOver 16 000 mastectomies are performed in England and Wales annually. Acute postoperative pain and nausea are common. The most frequently occurring long-term complications are chronic pain (up to 50%) and reduced shoulder function (reported at 35%). Regional techniques that improve acute postoperative pain relief may reduce the incidence of these complications. This study assesses the effectiveness of a 24-hour continuous local anaesthetic in the subpectoral plane in improving postoperative pain and quality of life in patients undergoing mastectomy.Methods and analysisThis is a randomised, double blind, placebo-controlled, two-centre, parallel group trial in women undergoing mastectomy with or without axillary involvement. One hundred and sixty participants will be randomised in a 1:1 ratio to receive either 0.25% levobupivacaine or 0.9% saline by subpectoral infusion postoperatively for 24 h. All participants will be provided with an intravenous morphine patient-controlled analgesia (PCA) system. Participants will be followed-up for 24 h in hospital and at approximately 14 days and 6 months postoperatively. Joint primary outcome measures are total morphine consumption and total pain score (captured via patient-recorded visual analogue scale (VAS) 4 hourly) during the first 24 h postoperatively. Primary statistical analysis of total pain is based on the area under the curve of pain versus time graph. Secondary outcomes include PCA attempts in first 24 h; VAS pain scores and shoulder function by goniometry at 24 h, 14 days (approximately) and 6 months; Verbal Rating Scale pain scores in first 24 h; Brief Pain Inventory and Oxford Shoulder Score at 6 months; duration of hospital stay; incidence of postoperative nausea and vomiting; cost-effectiveness.Ethics and disseminationThe study is approved by the South West England Research Ethics Committee (12/SW/0149).Resultswill be published in a peer-reviewed journal and presented at local, national and international scientific meetings.Trial registrationISRCTN46621916. EudraCT 2011-005775-16.
Key characteristics of successful quality improvement curricula in physician education: a realist review
Authors: Jones Anne C , Shipman Scott A , Ogrinc Greg 
Published: October 2014

PurposeQuality improvement (QI) is a common competency that must be taught in all physician training programmes, yet, there is no clear best approach to teach this content in clinical settings. We conducted a realist systematic review of the existing literature in QI curricula within the clinical setting, highlighting examples of trainees learning QI by doing QI.MethodCandidate theories describing successful QI curricula were articulateda priori. We searched MEDLINE (1 January 2000 to 12 March 2013), the Cochrane Library (2013) and Web of Science (15 March 2013) and reviewed references of prior systematic reviews. Inclusion criteria included study design, setting, population, interventions, clinical and educational outcomes. The data abstraction tool included categories for setting, population, intervention, outcomes and qualitative comments. Themes were iteratively developed and synthesised using realist review methodology. A methodological quality tool assessed the biases, confounders, secular trends, reporting and study quality.ResultsAmong 39 studies, most were before–after design with resident physicians as the primary population. Twenty-one described clinical interventions and 18 described educational interventions with a mean intervention length of 6.58 (SD=9.16) months. Twenty-eight reported successful clinical improvements; no studies reported clinical outcomes that worsened. Characteristics of successful clinical QI curricula include attention to the interface of educational and clinical systems, careful choice of QI work for the trainees and appropriately trained local faculty.ConclusionsThis realist review identified success characteristics to guide training programmes, medical schools, faculty, trainees, accrediting organisations and funders to further develop educational and improvement resources in QI educational programmes.
Efficient application of next-generation sequencing for the diagnosis of rare genetic syndromes
Authors: Madrigal Irene , Alvarez-Mora Maria Isabel , Karlberg Olof , Rodríguez-Revenga Laia , Elurbe Dei M , Rabionet Raquel , Mur Antonio , Pie Juan , Ballesta Francisca , Sauer Sascha , Syvänen Ann-Christine , Milà Montserrat 
Published: October 2014

AimsThe causes of intellectual disability, which affects 1%–3% of the general population, are highly heterogeneous and the genetic defect remains unknown in around 40% of patients. The application of next-generation sequencing is changing the nature of biomedical diagnosis. This technology has quickly become the method of choice for searching for pathogenic mutations in rare uncharacterised genetic diseases.MethodsWhole-exome sequencing was applied to a series of families affected with intellectual disability in order to identify variants underlying disease phenotypes.ResultsWe present data of three families in which we identified the disease-causing mutations and which benefited from receiving a clinical diagnosis: Cornelia de Lange, Cohen syndrome and Dent-2 disease. The genetic heterogeneity and the variability in clinical presentation of these disorders could explain why these patients are difficult to diagnose.ConclusionsThe accessibility to next-generation sequencing allows clinicians to save much time and cost in identifying the aetiology of rare diseases. The presented cases are excellent examples that demonstrate the efficacy of next-generation sequencing in rare disease diagnosis.
Recanalization of acute basilar artery occlusion improves outcomes: a meta-analysis
Authors: Kumar Gyanendra , Shahripour Reza Bavarsad , Alexandrov Andrei V 
Published: October 2014

ObjectiveAcute basilar artery occlusion (BAO) is a catastrophe with high mortality and disability. Randomized controlled trial (RCT) data supporting/refuting reperfusion treatment are sparse in acute BAO. The study objective was to pool risk estimates for death or dependency (DoD), mortality, and intracerebral hemorrhage (ICH) from published studies on BAO.MethodsMedline, Embase, The Cochrane Library, and clinicaltrials.gov were searched through August 2013 for studies of reperfusion therapies in acute BAO. Two independent authors selected studies and abstracted the data. Pooled risk ratios (RR) and mean weighted probabilities (MWP) were calculated using random effects model.Results45 studies (n=2056) met the inclusion criteria. Recanalization was associated with a lower risk of DoD (RR 0.67; number needed to treat (NNT) 3) and mortality (RR 0.49; NNT 2.5). ICH rate (MWP) with acute therapies was 13%. With recanalization, RR for DoD in those treated ≤12 h was 0.63, and for those treated >12 h, it was 0.67. With recanalization, RR for DoD in the intravenous thrombolysis (IVT) subgroup was 0.68; in the intra-arterial/endovascular therapy (IA/EVT) subgroup, DoD RR was 0.67. Recanalization resulted in mortality RR of 0.46 in those treated ≤12 h; for >12 h group, RR was 0.50. Recanalization resulted in mortality RR of 0.53 in the IVT subgroup, and RR of 0.48 in the IA/EVT subgroup. ICH rate for ≤12 h was 10%; ICH rate for >12 h was 14%. With IVT, the ICH rate was 9%, and with IA/EVT the ICH rate was 14%.ConclusionsRecanalization of acute BAO leads to reduction in mortality by two-fold and reduction in the risk of DoD by 1.5-fold. This study underscores the equipoise in acute BAO for comparing systemic and endovascular therapies, and testing different time windows through RCTs.
Global Sparse Analysis Framework
Authors: Oh Hakjoo , Heo Kihong , Lee Wonchan , Lee Woosuk , Park Daejun , Kang Jeehoon , Yi Kwangkeun 
Published: October 2014

In this article, we present a general method for achieving global static analyzers that are precise and sound, yet also scalable. Our method, on top of the abstract interpretation framework, is a general sparse analysis technique that supports relational as well as nonrelational semantics properties for various programming languages. Analysis designers first use the abstract interpretation framework to have a global and correct static analyzer whose scalability is unattended. Upon this underlying sound static analyzer, analysis designers add our generalized sparse analysis techniques to improve its scalability while preserving the precision of the underlying analysis. Our method prescribes what to prove to guarantee that the resulting sparse version should preserve the precision of the underlying analyzer.
We formally present our framework and show that existing sparse analyses are all restricted instances of our framework. In addition, we show more semantically elaborate design examples of sparse nonrelational and relational static analyses. We then present their implementation results that scale to globally analyze up to one million lines of C programs. We also show a set of implementation techniques that turn out to be critical to economically support the sparse analysis process.
A Local Frequency Analysis of Light Scattering and Absorption
Authors: Belcour Laurent , Bala Kavita , Soler Cyril 
Published: October 2014

Rendering participating media requires significant computation, but the effect of volumetric scattering is often eventually smooth. This article proposes an innovative analysis of absorption and scattering of local light fields in the Fourier domain and derives the corresponding set of operators on the covariance matrix of the power spectrum of the light field. This analysis brings an efficient prediction tool for the behavior of light along a light path in participating media. We leverage this analysis to derive proper frequency prediction metrics in 3D by combining per-light path information in the volume.
We demonstrate the use of these metrics to significantly improve the convergence of a variety of existing methods for the simulation of multiple scattering in participating media. First, we propose an efficient computation of second derivatives of the fluence, to be used in methods like irradiance caching. Second, we derive proper filters and adaptive sample densities for image-space adaptive sampling and reconstruction. Third, we propose an adaptive sampling for the integration of scattered illumination to the camera. Finally, we improve the convergence of progressive photon beams by predicting where the radius of light gathering can stop decreasing. Light paths in participating media can be very complex. Our key contribution is to show that analyzing local light fields in the Fourier domain reveals the consistency of illumination in such media and provides a set of simple and useful rules to be used to accelerate existing global illumination methods.
Tesseract
Authors: Arya Kapil , Baskakov Yury , Garthwaite Alex 
Published: October 2014

Double-paging is an often-cited, if unsubstantiated, problem in multi-level scheduling of memory between virtual machines (VMs) and the hypervisor. This problem occurs when both a virtualized guest and the hypervisor overcommit their respective physical address-spaces. When the guest pages out memory previously swapped out by the hypervisor, it initiates an expensive sequence of steps causing the contents to be read in from the hypervisor swapfile only to be written out again, significantly lengthening the time to complete the guest I/O request. As a result, performance rapidly drops.
We present Tesseract, a system that directly and transparently addresses the double-paging problem. Tesseract tracks when guest and hypervisor I/O operations are redundant and modifies these I/Os to create indirections to existing disk blocks containing the page contents. Although our focus is on reconciling I/Os between the guest disks and hypervisor swap, our technique is general and can reconcile, or deduplicate, I/Os for guest pages read or written by the VM.
Deduplication of disk blocks for file contents accessed in a common manner is well-understood. One challenge that our approach faces is that the locality of guest I/Os (reflecting the guest's notion of disk layout) often differs from that of the blocks in the hypervisor swap. This loss of locality through indirection results in significant performance loss on subsequent guest reads. We propose two alternatives to recovering this lost locality, each based on the idea of asynchronously reorganizing the indirected blocks in persistent storage.
We evaluate our system and show that it can significantly reduce the costs of double-paging. We focus our experiments on a synthetic benchmark designed to highlight its effects. In our experiments we observe Tesseract can improve our benchmark's throughput by as much as 200% when using traditional disks and by as much as 30% when using SSD. At the same time worst case application responsiveness can be improved by a factor of 5.
Composable multi-level debugging with Stackdb
Authors: Johnson David , Hibler Mike , Eide Eric 
Published: October 2014

Virtual machine introspection (VMI) allows users to debug software that executes within a virtual machine. To support rich, whole-system analyses, a VMI tool must inspect and control systems at multiple levels of the software stack. Traditional debuggers enable inspection and control, but they limit users to treating a whole system as just one kind of target: e.g., just a kernel, or just a process, but not both.
We created Stackdb, a debugging library with VMI support that allows one to monitor and control a whole system through multiple, coordinated targets. A target corresponds to a particular level of the system's software stack; multiple targets allow a user to observe a VM guest at several levels of abstraction simultaneously. For example, with Stackdb, one can observe a PHP script running in a Linux process in a Xen VM via three coordinated targets at the language, process, and kernel levels. Within Stackdb, higher-level targets are components that utilize lower-level targets; a key contribution of Stackdb is its API that supports multi-level and flexible "stacks" of targets. This paper describes the challenges we faced in creating Stackdb, presents the solutions we devised, and evaluates Stackdb through its application to a security-focused, whole-system case study.
Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade
Authors: Dovedi Simon J. , Adlard Amy L. , Lipowska-Bhalla Grazyna , McKenna Conor , Jones Sherrie , Cheadle Eleanor J. , Stratford Ian J. , Poon Edmund , Morrow Michelle , Stewart Ross , Jones Hazel , Wilkinson Robert W. , Honeychurch Jamie , Illidge Tim M. 
Published: October 2014

Abstract
Radiotherapy is a major part in the treatment of most common cancers, but many patients experience local recurrence with metastatic disease. In evaluating response biomarkers, we found that low doses of fractionated radiotherapy led to PD-L1 upregulation on tumor cells in a variety of syngeneic mouse models of cancer. Notably, fractionated radiotherapy delivered in combination with αPD-1 or αPD-L1 mAbs generated efficacious CD8+ T-cell responses that improved local tumor control, long-term survival, and protection against tumor rechallenge. These favorable outcomes were associated with induction of a tumor antigen–specific memory immune response. Mechanistic investigations showed that IFNγ produced by CD8+ T cells was responsible for mediating PD-L1 upregulation on tumor cells after delivery of fractionated radiotherapy. Scheduling of anti–PD-L1 mAb was important for therapeutic outcome, with concomitant but not sequential administration with fractionated radiotherapy required to improve survival. Taken together, our results reveal the mechanistic basis for an adaptive response by tumor cells that mediates resistance to fractionated radiotherapy and its treatment failure. With attention to scheduling, combination immunoradiotherapy with radiotherapy and PD-1/PD-L1 signaling blockade may offer an immediate strategy for clinical evaluation to improve treatment outcomes. Cancer Res; 74(19); 5458–68. ©2014 AACR.
Host Deficiency in Caveolin-2 Inhibits Lung Carcinoma Tumor Growth by Impairing Tumor Angiogenesis
Authors: Liu Yajun , Jang Sungchan , Xie Leike , Sowa Grzegorz 
Published: October 2014

Abstract
Caveolin-2 (Cav-2), a member of caveolin protein family, is largely different from better known caveolin-1 (Cav-1) and thus might play distinct functions. Here, we provide the first genetic evidence suggesting that host-expressed Cav-2 promotes subcutaneous tumor growth and tumor-induced neovascularization using two independent syngeneic mouse models. Host deficiency in Cav-2 resulted in defective and reduced growth of subcutaneously implanted Lewis lung carcinoma (LLC) and B16-F10 melanoma tumors, respectively. Consistent with the defective growth, LLC and B16-F10 melanoma tumors implanted into Cav-2 KO mice displayed reduced microvascular density (MVD) determined by IHC with anti-CD31 antibodies, suggesting impaired pathologic angiogenesis. Additional studies involving LLC tumors extracted from Cav-2 KO mice just 10 days after implantation determined reduced cell proliferation, massive necrotic cell death, and fibrosis. In contrast with day 10, only MVD but not cell proliferation and survival was reduced in the earliest palpable LLC tumors extracted 6 days after implantation into Cav-2 KO mice, suggesting that impaired angiogenesis is the causative factor. Mechanistically, impaired LLC tumor growth and angiogenesis in Cav-2 KO mice was associated with increased expression levels of antiangiogenic thrombospondin-1 and inhibited S1177 phosphorylation of endothelial nitric oxide synthase. Taken together, our data suggest that host deficiency in Cav-2 impairs tumor-induced angiogenesis, leading to compromised tumor cell survival/proliferation manifested by the defective tumor growth. In conclusion, host-expressed Cav-2 may promote tumor growth via supporting tumor-induced angiogenesis. Thus, Cav-2 expressed in tumor microenvironment may potentially become a novel target for cancer therapy. Cancer Res; 74(22); 6452–62. ©2014 AACR.
A CREB1–TGFβ2 Self-Sustaining Loop in Glioblastoma
Authors: Wotton David 
Published: October 2014

Abstract
Summary: A subset of glioblastomas (GBM) has high levels of TGFβ signaling, and anti-TGFβ therapies are being pursued as treatments for GBM. The work presented here identifies CREB1 as a potential biomarker for TGFβ-dependent GBM. CREB1 integrates signaling from TGFβ and the PI3K pathway and nucleates a self-sustaining signaling loop that maintains TGFβ2 expression in GBM with high CREB1 levels. Cancer Discov; 4(10); 1123–5. ©2014 AACR.
See related article by Rodón et al., p. 1230