bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the management of pain from advanced cancer in the community: study protocol for a pragmatic multicentre randomised controlled trial
Authors: Allsop Matthew J , Wright-Hughes Alexandra , Black Kath , Hartley Suzanne , Fletcher Marie , Ziegler Lucy E , Bewick Bridgette M , Meads David , Hughes Nicholas D , Closs S José , Hulme Claire , Taylor Sally , Flemming Kate , Hackett Julia , O’Dwyer John L , Brown Julia M , Bennett Michael I 
Published: March 2018

IntroductionFor patients with advanced cancer, research shows that pain is frequent, burdensome and undertreated. Evidence-based approaches to support cancer pain management have been developed but have not been implemented within the context of the UK National Health Service. This protocol is for a pragmatic multicentre randomised controlled trial (RCT) to assess feasibility, acceptability, effectiveness and cost-effectiveness for a multicomponent intervention for pain management in patients with advanced cancer.Methods and analysisThis trial will assess the feasibility of implementation and uptake of evidence-based interventions, developed and piloted as part of the Improving the Management of Pain from Advanced Cancer in the Community Programme grant, into routine clinical practice and determine whether there are potential differences with respect to patient-rated pain, patient pain knowledge and experience, healthcare use, quality of life and cost-effectiveness. 160 patients will receive either the intervention (usual care plus supported self-management) delivered within the oncology clinic and palliative care services by locally assigned community palliative care nurses, consisting of a self-management educational intervention and eHealth intervention for routine pain assessment and monitoring; or usual care. The primary outcomes are to assess implementation and uptake of the interventions, and differences in terms of pain severity. Secondary outcomes include pain interference, participant pain knowledge and experience, and cost-effectiveness. Outcome assessment will be blinded and patient-reported outcome measures collected via post at 6 and 12 weeks following randomisation.Ethics and disseminationThis RCT has the potential to significantly influence National Health Service delivery to community-based patients with pain from advanced cancer. We aim to provide definitive evidence of whether two simple interventions delivered by community palliative care nurse in palliative care that support-self-management are clinically effective and cost-effective additions to standard community palliative care.Trial registration numberISRCTN18281271; Pre-results.
Nature-based supportive care opportunities: a conceptual framework
Authors: Blaschke Sarah , O’Callaghan Clare C , Schofield Penelope 
Published: March 2018

ObjectiveGiven preliminary evidence for positive health outcomes related to contact with nature for cancer populations, research is warranted to ascertain possible strategies for incorporating nature-based care opportunities into oncology contexts as additional strategies for addressing multidimensional aspects of cancer patients’ health and recovery needs. The objective of this study was to consolidate existing research related to nature-based supportive care opportunities and generate a conceptual framework for discerning relevant applications in the supportive care setting.MethodsDrawing on research investigating nature-based engagement in oncology contexts, a two-step analytic process was used to construct a conceptual framework for guiding nature-based supportive care design and future research. Concept analysis methodology generated new representations of understanding by extracting and synthesising salient concepts. Newly formulated concepts were transposed to findings from related research about patient-reported and healthcare expert-developed recommendations for nature-based supportive care in oncology.ResultsFive theoretical concepts (themes) were formulated describing patients’ reasons for engaging with nature and the underlying needs these interactions address. These included: connecting with what is genuinely valued, distancing from the cancer experience, meaning-making and reframing the cancer experience, finding comfort and safety, and vital nurturance. Eight shared patient and expert recommendations were compiled, which address the identified needs through nature-based initiatives. Eleven additional patient-reported recommendations attend to beneficial and adverse experiential qualities of patients’ nature-based engagement and complete the framework.ConclusionsThe framework outlines salient findings about helpful nature-based supportive care opportunities for ready access by healthcare practitioners, designers, researchers and patients themselves.
Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome
Authors: Calmels Nadege , Botta Elena , Jia Nan , Fawcett Heather , Nardo Tiziana , Nakazawa Yuka , Lanzafame Manuela , Moriwaki Shinichi , Sugita Katsuo , Kubota Masaya , Obringer Cathy , Spitz Marie-Aude , Stefanini Miria , Laugel Vincent , Orioli Donata , Ogi Tomoo , Lehmann Alan Robert 
Published: March 2018

BackgroundCockayne syndrome (CS) is a rare, autosomal recessive multisystem disorder characterised by prenatal or postnatal growth failure, progressive neurological dysfunction, ocular and skeletal abnormalities and premature ageing. About half of the patients with symptoms diagnostic for CS show cutaneous photosensitivity and an abnormal cellular response to UV light due to mutations in either the ERCC8/CSA or ERCC6/CSB gene. Studies performed thus far have failed to delineate clear genotype-phenotype relationships. We have carried out a four-centre clinical, molecular and cellular analysis of 124 patients with CS.Methods and resultsWe assigned 39 patients to the ERCC8/CSA and 85 to the ERCC6/CSB genes. Most of the genetic variants were truncations. The missense variants were distributed non-randomly with concentrations in relatively short regions of the respective proteins. Our analyses revealed several hotspots and founder mutations in ERCC6/CSB. Although no unequivocal genotype-phenotype relationships could be made, patients were more likely to have severe clinical features if the mutation was downstream of the PiggyBac insertion in intron 5 of ERCC6/CSB than if it was upstream. Also a higher proportion of severely affected patients was found with mutations in ERCC6/CSB than in ERCC8/CSA.ConclusionBy identifying >70 novel homozygous or compound heterozygous genetic variants in 124 patients with CS with different disease severity and ethnic backgrounds, we considerably broaden the CSA and CSB mutation spectrum responsible for CS. Besides providing information relevant for diagnosis of and genetic counselling for this devastating disorder, this study improves the definition of the puzzling genotype-phenotype relationships in patients with CS.
Inframe deletion of human ESPN is associated with deafness, vestibulopathy and vision impairment
Authors: Ahmed Zubair M , Jaworek Thomas J , Sarangdhar Gowri N , Zheng Lili , Gul Khitab , Khan Shaheen N , Friedman Thomas B , Sisk Robert A , Bartles James R , Riazuddin Sheikh , Riazuddin Saima 
Published: March 2018

BackgroundUsher syndrome (USH) is a neurosensory disorder characterised by deafness, variable vestibular areflexia and vision loss. The aim of the study was to identify the genetic defect in a Pakistani family (PKDF1051) segregating USH.MethodsGenome-wide linkage analysis was performed by using an Illumina linkage array followed by Sanger and exome sequencing. Heterologous cells and mouse organ of Corti explant-based transfection assays were used for functional evaluations. Detailed clinical evaluations were performed to characterise the USH phenotype.ResultsThrough homozygosity mapping, we genetically linked the USH phenotype segregating in family PKDF1051 to markers on chromosome 1p36.32-p36.22. The locus was designated USH1M. Using a combination of Sanger sequencing and exome sequencing, we identified a novel homozygous 18 base pair inframe deletion in ESPN. Variants of ESPN, encoding the actin-bundling protein espin, have been previously associated with deafness and vestibular areflexia in humans with no apparent visual deficits. Our functional studies in heterologous cells and in mouse organ of Corti explant cultures revealed that the six deleted residues in affected individuals of family PKDF1051 are essential for the actin bundling function of espin demonstrated by ultracentrifugation actin binding and bundling assays. Funduscopic examination of the affected individuals of family PKDF1051 revealed irregular retinal contour, temporal flecks and disc pallor in both eyes. ERG revealed diminished rod photoreceptor function among affected individuals.ConclusionOur study uncovers an additional USH gene, assigns the USH1 phenotype to a variant of ESPN and provides a 12th molecular component to the USH proteome.
Long-term visual outcome in patients treated by flow diversion for carotid-ophthalmic aneurysms
Authors: Touzé Romain , Touitou Valérie , Shotar Eimad , Gabrieli Joseph , Drir Mehdi , Mathon Bertrand , Sourour Nader-Antoine , Clarençon Frédéric 
Published: March 2018

BackgroundFlow-diverter stents (FDSs) are an upgrade in the treatment of intracranial aneurysms. However, complications concerning covered branches have been reported, especially the ophthalmic artery (OA). The purpose of our study was to evaluate the long-term ophthalmic complication rate of carotid-ophthalmic aneurysms (COA) without visual pathways compression, treated by a FDS covering the OA by performing an exhaustive ophthalmic examination.Material and methodsRetrospective analysis of a single-center database screening the patients treated from October 2009 to April 2015 for an intracranial aneurysm with a FDS. The patients treated for a non-compressive COA with coverage of the OA by the device were studied (n=30). Among these patients, 15 (50%) were excluded. The remaining 15 patients underwent a systematic and extensive ophthalmic examination at least 2 years after the stent placement by two ophthalmologists.ResultsFifteen patients with 16 COAs treated with a FDS were included. Mean follow-up was 4.1±2 years. Six patients (40%), presented ophthalmic complications, including three fugax amauroses (18.8%) and four significant visual field defects (25%). After comparing each eye’s visual field’s patients, we observed a significant difference between the eye on the FDS side compared with the contralateral eye, with a mean deviation of −1.58 dB versus −0.67 dB respectively (P=0.003). Visual acuity was preserved in all patients.ConclusionPatients treated by FDS for COA have a good long-term clinical ophthalmic outcome. However, extensive ophthalmic examination shows a high percentage of minor ophthalmic modifications. Interventional neuroradiologists should be aware of these possible complications when choosing to treat these aneurysms with FDS.
Role of basaltic magmatism within the Parnaíba cratonic basin, NE Brazil
Authors: Klöcking Marthe , White Nicky , MacLennan John 
Published: March 2018

Abstract
The sedimentary fill of the Parnaíba basin in NE Brazil is punctuated by two episodes of basaltic magmatism in Jurassic and Cretaceous times, known as the Mosquito and Sardinha formations, respectively. A quantitative understanding of the depth and degree of melting that generated these basalts should provide useful constraints on the history of vertical motions in this cratonic basin. We carried out forward and inverse modelling of major, trace and rare earth element concentrations for primitive melts from both igneous provinces. We calculated the melt fraction as a function of depth to determine the melt volumes and mantle potential temperatures. Our results suggest that both episodes of magmatism resulted from shallow decompression melting within the asthenospheric mantle. The Mosquito basalts record an excess temperature of 55–75°C and are probably related to the widespread Central Atlantic Magmatic Province associated with the initial break-up of Gondwanaland. By contrast, the Sardinha basalts record localized lithospheric thinning to less than half its original thickness with excess temperatures of 15–25°C. This younger activity is probably part of the Paraná–Etendeka large igneous province, which is linked to rifting between South America and Africa. We suspect that these magmatic episodes are associated with phases of regional epeirogenic uplift affecting the Parnaíba basin.
Orthorhombic faulting in the Beagle Sub-basin, North West Shelf, Australia
Authors: McCormack K. D. , McClay K. R. 
Published: March 2018

Abstract

The Beagle Platform forms a structurally complex outboard boundary to the Mesozoic Beagle Sub-basin in the Northern Carnarvon Basin in 50–1000 m of water
c.
250 km offshore on Australia's North West Shelf. North- and NE-trending conjugate fault systems link to form
c.
5–10 km-wide rhomboidal horsts bound by
c.
5 km-wide graben in complex orthorhombic symmetry.

Interpretation of the Canning TQ3D three-dimensional (3D) seismic survey identified four populations of faults comprising: (1) latest Triassic–Early Cretaceous north–south-striking normal faults (Fault Population I); (2) latest Triassic–Early Cretaceous NE–SW-striking normal faults (Fault Population II); (3) Cretaceous polygonal faults (Fault Population III); and (4) Neogene–present-day north–south- and NE–SW-trending en echelon conjugate fault arrays (Fault Population IV). Structural interpretation, comprising fault seismic interpretation, displacement analyses and fault orientation analysis, illustrates that orthorhombic extensional faulting occurred penecontemporaneously.

Three-dimensional non-plane strain with non-zero intermediate (
σ
2
) extension magnitude controls the near-synchronous displacement of fault population I and II conjugate fault sets in orthorhombic symmetry to create the characteristic rhomboidal fault geometry. Neogene–present-day north–south- and NE–SW-striking en echelon conjugate fault arrays (Fault Population IV) form in response to oblique reactivation of these subjacent latest Triassic–Early Cretaceous polymodal faults (Fault Population I and Fault Population II). Fault Population I, II and IV together form a vertically decoupled (soft-linked) pseudo-conjugate fault system partitioned by a Cretaceous interval characterized by polygonal fault systems (Fault Population III) and monoclinic draping.

The structural interpretation of the Beagle Platform illustrates a seismic-scale orthorhombic fault symmetry accommodating 3D strain and the insufficiency of plane-strain ‘Andersonian’ conjugate fault theory to resolve complex polymodal faulting evolved penecontemporaneously under a single stress regime. Subsequent oblique extension reactivation of these polymodal fault systems also demonstrates that complex soft-linked en echelon extensional conjugate fault arrays form in response to a single stress regime. This research supports the evolution of complex polymodal faulting under simple states of stress, and has implications for understanding the distribution, linkage and age of extensional faults within the Beagle Sub-basin and other extensional basins.
Characterizing and Modeling Patching Practices of Industrial Control Systems
Authors: Wang Brandon , Li Xiaoye , de Aguiar Leandro P. , Menasche Daniel S. , Shafiq Zubair 
Published: March 2018

Industrial Control Systems (ICS) are widely deployed in mission critical infrastructures such as manufacturing, energy, and transportation. The mission critical nature of ICS devices poses important security challenges for ICS vendors and asset owners. In particular, the patching of ICS devices is usually deferred to scheduled production outages so as to prevent potential operational disruption of critical systems. Unfortunately, anecdotal evidence suggests that ICS devices are riddled with security vulnerabilities that are not patched in a timely manner, which leaves them vulnerable to exploitation by hackers, nation states, and hacktivist organizations.
In this paper, we present the results from our longitudinal measurement and characterization study of ICS patching behavior. Our study is based on IP scan data collected from Shodan over the duration of three years for more than 500 known industrial ICS protocols and products. Our longitudinal measurements reveal the impact of vulnerability disclosures on ICS patching. Our analysis of more than 100 thousand Internet-exposed ICS devices reveals that about 50% upgrade to newer patched versions within 60 days of a vulnerability disclosure. Based on our measurement and analysis, we further propose a variation of the Bass model to forecast the patching behavior of ICS devices. The evaluation shows that our proposed models have comparable prediction accuracy when contrasted against traditional ARIMA timeseries forecasting models, while requiring less parameters and being amenable to direct physical interpretation.
Design-Induced Latency Variation in Modern DRAM Chips
Authors: Lee Donghyuk , Khan Samira , Subramanian Lavanya , Ghose Saugata , Ausavarungnirun Rachata , Pekhimenko Gennady , Seshadri Vivek , Mutlu Onur 
Published: March 2018

Variation has been shown to exist across the cells within a modern DRAM chip. Prior work has studied and exploited several forms of variation, such as manufacturing-process- or temperature-induced variation. We empirically demonstrate a new form of variation that exists within a real DRAM chip, induced by the design and placement of different components in the DRAM chip: different regions in DRAM, based on their relative distances from the peripheral structures, require different minimum access latencies for reliable operation. In particular, we show that in most real DRAM chips, cells closer to the peripheral structures can be accessed much faster than cells that are farther. We call this phenomenon design-induced variation in DRAM. Our goals are to i) understand design-induced variation that exists in real, state-of-the-art DRAM chips, ii) exploit it to develop low-cost mechanisms that can dynamically find and use the lowest latency at which to operate a DRAM chip reliably, and, thus, iii) improve overall system performance while ensuring reliable system operation.
To this end, we first experimentally demonstrate and analyze designed-induced variation in modern DRAM devices by testing and characterizing 96 DIMMs (768 DRAM chips). Our characterization identifies DRAM regions that are vulnerable to errors, if operated at lower latency, and finds consistency in their locations across a given DRAM chip generation, due to design-induced variation. Based on our extensive experimental analysis, we develop two mechanisms that reliably reduce DRAM latency. First, DIVA Profiling uses runtime profiling to dynamically identify the lowest DRAM latency that does not introduce failures. DIVA Profiling exploits design-induced variation and periodically profiles only the vulnerable regions to determine the lowest DRAM latency at low cost. It is the first mechanism to dynamically determine the lowest latency that can be used to operate DRAM reliably. DIVA Profiling reduces the latency of read/write requests by 35.1%/57.8%, respectively, at 55°C. Our second mechanism, DIVA Shuffling, shuffles data such that values stored in vulnerable regions are mapped to multiple error-correcting code (ECC) codewords. As a result, DIVA Shuffling can correct 26% more multi-bit errors than conventional ECC. Combined together, our two mechanisms reduce read/write latency by 40.0%/60.5%, which translates to an overall system performance improvement of 14.7%/13.7%/13.8% (in 2-/4-/8-core systems) across a variety of workloads, while ensuring reliable operation.
The CSI Framework for Compiler-Inserted Program Instrumentation
Authors: Schardl Tao B. , Denniston Tyler , Doucet Damon , Kuszmaul Bradley C. , Lee I-Ting Angelina , Leiserson Charles E. 
Published: March 2018

The CSI framework provides comprehensive static instrumentation that a compiler can insert into a program-under-test so that dynamic-analysis tools - memory checkers, race detectors, cache simulators, performance profilers, code-coverage analyzers, etc. - can observe and investigate runtime behavior. Heretofore, tools based on compiler instrumentation would each separately modify the compiler to insert their own instrumentation. In contrast, CSI inserts a standard collection of instrumentation hooks into the program-under-test. Each CSI-tool is implemented as a library that defines relevant hooks, and the remaining hooks are "nulled" out and elided during either compile-time or link-time optimization, resulting in instrumented runtimes on par with custom instrumentation. CSI allows many compiler-based tools to be written as simple libraries without modifying the compiler, lowering the bar for the development of dynamic-analysis tools.
We have defined a standard API for CSI and modified LLVM to insert CSI hooks into the compiler's internal representation (IR) of the program. The API organizes IR objects - such as functions, basic blocks, and memory accesses - into flat and compact ID spaces, which not only simplifies the building of tools, but surprisingly enables faster maintenance of IR-object data than do traditional hash tables. CSI hooks contain a "property" parameter that allows tools to customize behavior based on static information without introducing overhead. CSI provides "forensic" tables that tools can use to associate IR objects with source-code locations and to relate IR objects to each other.
To evaluate the efficacy of CSI, we implemented six demonstration CSI-tools. One of our studies shows that compiling with CSI and linking with the "null" CSI-tool produces a tool-instrumented executable that is as fast as the original uninstrumented code. Another study, using a CSI port of Google's ThreadSanitizer, shows that the CSI-tool rivals the performance of Google's custom compiler-based implementation. All other demonstration CSI tools slow down the execution of the program-under-test by less than 70%.
Efficient and Scalable Graph Parallel Processing With Symbolic Execution
Authors: Zheng Long , Liao Xiaofei , Jin Hai 
Published: March 2018

Existing graph processing essentially relies on the underlying iterative execution with synchronous (Sync) and/or asynchronous (Async) engine. Nevertheless, they both suffer from a wide class of inherent serialization arising from data interdependencies within a graph.
In this article, we present SymGraph, a judicious graph engine with symbolic iteration that enables the parallelism of dependent computation on vertices. SymGraph allows using abstract symbolic value (instead of the concrete value) for the computation if the desired data is unavailable. To maximize the potential of symbolic iteration, we propose a chain of tailored sophisticated techniques, enabling SymGraph to scale out with a new milestone of efficiency for large-scale graph processing. We evaluate SymGraph in comparison to Sync, Async, and a hybrid of Sync and Async engines. Our results on 12 nodes show that SymGraph outperforms all three graph engines by 1.93x (vs. Sync), 1.98x (vs. Async), and 1.57x (vs. Hybrid) on average. In particular, the performance for PageRank on 32 nodes can be dramatically improved by 16.5x (vs. Sync), 23.3x (vs. Async), and 12.1x (vs. Hybrid), respectively. The efficiency of SymGraph is also validated with at least one order of magnitude improvement in contrast to three specialized graph systems (Naiad, GraphX, and PGX.D).