bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of minimal important differences in degenerative knee disease outcomes: a systematic review and case study to informBMJRapid Recommendations
Authors: Devji Tahira , Guyatt Gordon H , Lytvyn Lyubov , Brignardello-Petersen Romina , Foroutan Farid , Sadeghirad Behnam , Buchbinder Rachelle , Poolman Rudolf W , Harris Ian A , Carrasco-Labra Alonso , Siemieniuk Reed A C , Vandvik Per O
Published: May 2017

Objectives

To identify the most credible anchor-based minimal important differences (MIDs) for patient important outcomes in patients with degenerative knee disease, and to informBMJRapid Recommendations for arthroscopic surgery versus conservative management

Design

Systematic review.

Outcome measures

Estimates of anchor-based MIDs, and their credibility, for knee symptoms and health-related quality of life (HRQoL).

Data sources

MEDLINE, EMBASE and PsycINFO.

Eligibility criteria

We included original studies documenting the development of anchor-based MIDs for patient-reported outcomes (PROs) reported in randomised controlled trials included in the linked systematic review and meta-analysis and judged by the parallelBMJRapid Recommendations panel as critically important for informing their recommendation: measures of pain, function and HRQoL.

Results

13 studies reported 95 empirically estimated anchor-based MIDs for 8 PRO instruments and/or their subdomains that measure knee pain, function or HRQoL. All studies used a transition rating (global rating of change) as the anchor to ascertain the MID. Among PROs with more than 1 estimated MID, we found wide variation in MID values. Many studies suffered from serious methodological limitations. We identified the following most credible MIDs: Western Ontario and McMaster University Osteoarthritis Index (WOMAC; pain: 12, function: 13), Knee injury and Osteoarthritis Outcome Score (KOOS; pain: 12, activities of daily living: 8) and EuroQol five dimensions Questionnaire (EQ-5D; 0.15).

Conclusions

We were able to distinguish between more and less credible MID estimates and provide best estimates for key instruments that informed evidence presentation in the associated systematic review and judgements made by the Rapid Recommendation panel.

Trial registration number

CRD42016047912.
Rethinking priorities: experience of an educational initiative to change attitudes, behaviours and clinical practice in end-of-life care
Authors: Edwards Annette , Barros D'Sa Viv , Hicks Fiona
Published: May 2017

To implement the National End of Life Care strategy and enable more people to express and achieve their preferences about care at the end of life, senior clinicians outside palliative medicine need to make it a routine part of their practice. However, it is acknowledged that recognising that people are entering the last phase of their illness is not always straightforward, and having conversations about aims of treatment and planning for future care may not be easy. In order to begin to address these challenges, funding was sought from the Yorkshire and the Humber Strategic Health Authority (SHA), and subsequently Health Education England, Yorkshire and the Humber (HEEYH), to pilot a development programme in 2 acute trusts. 2 palliative medicine consultants shared the trainer role at each site, supporting hospital consultants from a range of specialties, with a GP to give a community perspective. The programme involved individual clinicians identifying their own learning needs and specific issues for end-of-life care in their patients. The group met together monthly in action learning sets to discuss issues in a safe yet challenging environment. Following evaluation using a combination of training needs analyses, feedback questionnaires, audits and service evaluations, it was modified slightly and repiloted in 2 further trusts as ‘Rethinking Priorities’. This paper describes the programme and its outcomes, especially in relation to participants' learning, service development and leadership. It also highlights the challenges, including different learning styles, the concept of action learning, obtaining funding and dedicated time, and how to evaluate the effectiveness of a programme. Overall, it suggests that an educational initiative based on clinicians identifying their own learning needs, and using an action learning approach to explore issues with other colleagues, with the addition of some targeted sessions, can result in positive change in knowledge, behaviour and clinical practice.
Alcohol identification and intervention in English emergency departments
Authors: Patton Robert , Green Ghiselle
Published: May 2017

Aims

In the ED, alcohol identification and brief advice is an effective method of reducing consumption and related harms. Our objective was to conduct a national survey of English EDs to determine current practice regarding alcohol identification and provision of brief advice and to compare changes in activity to a previous National Survey conducted in 2011.

Methods

This was a cross-sectional survey of all consultant-led EDs in England.

Results

Of 180 departments, 147 (81.6%) responded. All departments may question adult patients about their alcohol consumption, with many (63.6%) asking all patients aged over 18 years as part routine care and using a formal screening tool (61.4%). The majority of departments asked young people (aged 11–17 years) about their consumption (83.8%), but only 11.6% did so as a part of routine practice. Compared with the 2011 survey, there have been significant increases in routine screening among adults (15.9%, CI 4.16% to 27.18%; p=0.006), general practitioners being informed about patients’alcohol-related presentations (10.2%, CI 0.64% to 19.58%; p=0.028) and access to an alcohol health worker or a clinical nurse specialist (13.4%, CI 3.64% to 22.91%, p=0.005). Modest (non-significant) changes were also found in access to training on brief advice (9.7%) and the use of formal screening questions on adult patients (9.7%).

Conclusion

Alcohol screening together with referral or intervention is becoming part of routine practice in England. Compared with our previous national survey, increases in alcohol screening and intervention activity are demonstrated, with improvements in routine questioning (among adults), the number of general practitioners being informed about alcohol-related attendances, provision of training, access to specialist services and the use of formal screening tools.
Improved coupled map car-following model considering partial car-to-car communication and its jam analysis
Authors: Shi Y.F. , Yang L.C.
Published: May 2017

The characteristics and the nonlinear phenomenon of traffic flow in the case of car-to-car communication (C2CC) are studied based on an improved coupled map car-following model. The model incorporates the modified optimal velocity function and appropriate control method. The conditions necessary to maintain the system stability and suppress traffic jams are obtained. To describe the car-following dynamics under C2CC accurately, different penetration rates of C2CC vehicles, such as 10%, 30%, and 60% are considered. The simulation results suggest that the improved model can effectively suppress traffic jams. The extent to which traffic jams are suppressed is increasing as the penetration rate increases. Moreover, the car-following stability has a noticeable improvement by analysing the time–space plots.
Experiential knowledge, suffering, and vicissitudes of having malaria in the Brazilian Amazon: An ethnographic study
Authors: Freitas de Souza Luciane Machado
Published: May 2017

This paper focuses on the multiple ways in which people who live along the rivers of the Brazilian Amazon, known as ribeirinhos, experience malaria outside of a clinical setting. It describes the local understanding of malaria, strategies to distinguish the illness from other febrile sicknesses, challenges for detecting the disease through biomedical diagnosis methods, and vicissitudes of having malaria. It draws on cases from ribeirinhos from a peri-urban community of Manaus and a rural community from Careiro, State of Amazonas, Brazil. Although malaria is biomedically characterized by the pathogens causing the disease, ribeirinhos have developed other standards to define malaria, including the intensity of the symptoms, the interval between the infections, and the types of medications dispensed to them. In the riverine communities studied, the etiology of malaria includes mosquitoes, microbes, water, wind, sun, and person-to-person transmission. Symptoms of malaria were found to overlap with other febrile sicknesses; hence, ribeirinhos developed skills to monitor how a malaise unfolds in their bodies. Experiential knowledge plays a key role in the early detection of malaria. Individuals who have no previous experience with malaria were found to spend more time seeking health care. Equally important, ribeirinhos perceive that malaria is part of the landscape they inhabit.
SPES: A new cyclotron-based facility for research and applications with high-intensity beams
Authors: Maggiore M. , Campo D. , Antonini P. , Lombardi A. , Manzolaro M. , Andrighetto A. , Monetti A. , Scarpa D. , Esposito J. , Silvestrin L.
Published: May 2017

In 2016, Laboratori Nazionali di Legnaro (Italy) started the commissioning of a new accelerator facility based on a high-power cyclotron able to deliver proton beams up to 70 MeV of energy and 700 [Formula: see text]A current. Such a machine is the core of the Selective Production of Exotic Species (SPES) project whose main goal is to provide exotics beam for nuclear and astrophysics research and to deliver high-intensity proton beams for medical applications and neutrons generator.
Effect of Ge atoms on crystal structure and optoelectronic properties of hydrogenated Si–Ge films
Authors: Li Tianwei , Zhang Jianjun , Ma Ying , Yu Yunwu , Zhao Ying
Published: May 2017

Optoelectronic and structural properties of hydrogenated microcrystalline silicon–germanium ([Formula: see text]c-Si[Formula: see text]Ge[Formula: see text]:H) alloys prepared by radio-frequency plasma-enhanced chemical vapor deposition (RF-PECVD) were investigated. When the Ge atoms were predominantly incorporated in amorphous matrix, the dark and photo-conductivity decreased due to the reduced crystalline volume fraction of the Si atoms (X[Formula: see text]) and the increased Ge dangling bond density. The photosensitivity decreased monotonously with Ge incorporation under higher hydrogen dilution condition, which was attributed to the increase in both crystallization of Ge and the defect density.
The influence of LED lighting on task accuracy: time of day, gender and myopia effects
Authors: Rao Feng , Chan A. H. S. , Zhu Xi-Fang
Published: May 2017

In this research, task errors were obtained during performance of a marker location task in which the markers were shown on a computer screen under nine LED lighting conditions; three illuminances (100, 300 and 500 lx) and three color temperatures (3000, 4500 and 6500 K). A total of 47 students participated voluntarily in these tasks. The results showed that task errors in the morning were small and nearly constant across the nine lighting conditions. However in the afternoon, the task errors were significantly larger and varied across lighting conditions. The largest errors for the afternoon session occurred when the color temperature was 4500 K and illuminance 500 lx. There were significant differences between task errors in the morning and afternoon sessions. No significant difference between females and males was found. Task errors for high myopia students were significantly larger than for the low myopia students under the same lighting conditions. In summary, the influence of LED lighting on task accuracy during office hours was not gender dependent, but was time of day and myopia dependent.
An efficient method for significant motifs discovery from multiple DNA sequences
Authors: Al-Ssulami Abdulrakeeb M. , Azmi Aqil M. , Mathkour Hassan
Published: May 2017

Identification of transcription factor binding sites or biological motifs is an important step in deciphering the mechanisms of gene regulation. It is a classic problem that has eluded a satisfactory and efficient solution. In this paper, we devise a three-phase algorithm to mine for biologically significant motifs. In the first phase, we generate all the possible string motifs, this phase is followed by a filtering process where we discard all motifs that do not meet the constraints. And in the final phase, motifs are scored and ranked using a combination of stochastic techniques and [Formula: see text]-value. We show that our method outperforms some very well-known motif discovery tools, e.g. MEME and Weeder on well-established benchmark data suites. We also apply the algorithm on the non-coding regions of M. tuberculosis and report significant motifs of size 10 with excellent [Formula: see text]-values in a fraction of the time MEME and MoSDi did. In fact, among the best 10 motifs ([Formula: see text]-value wise) in the non-coding regions of M. tuberculosis reported by the tools MEME, MoSDi and ours, five were discovered by our approach which included the third and the fourth best ones. All this in 1/17 and 1/6 the time which MEME and MoSDi (respectively) took.
Quantitative optical measurement of mitochondrial superoxide dynamics in pulmonary artery endothelial cells
Authors: Ghanian Zahra , Konduri Girija Ganesh , Audi Said Halim , Camara Amadou K. S. , Ranji Mahsa
Published: May 2017

Reactive oxygen species (ROS) play a vital role in cell signaling and redox regulation, but when present in excess, lead to numerous pathologies. Detailed quantitative characterization of mitochondrial superoxide anion (O[Formula: see text] production in fetal pulmonary artery endothelia cells (PAECs) has never been reported. The aim of this study is to assess mitochondrial O[Formula: see text] production in cultured PAECs over time using a novel quantitative optical approach. The rate, the sources, and the dynamics of O[Formula: see text] production were assessed using targeted metabolic modulators of the mitochondrial electron transport chain (ETC) complexes, specifically an uncoupler and inhibitors of the various ETC complexes, and inhibitors of extra-mitochondrial sources of O[Formula: see text]. After stabilization, the cells were loaded with nanomolar mitochondrial-targeted hydroethidine (Mito-HE, MitoSOX) online during the experiment without washout of the residual dye. Time-lapse fluorescence microscopy was used to monitor the dynamic changes in O[Formula: see text] fluorescence intensity over time in PAECs. The transient behaviors of the fluorescence time course showed exponential increases in the rate of O[Formula: see text] production in the presence of the ETC uncoupler or inhibitors. The most dramatic and the fastest increase in O[Formula: see text] production was observed when the cells were treated with the uncoupling agent, PCP. We also showed that only the complex IV inhibitor, KCN, attenuated the marked surge in O[Formula: see text] production induced by PCP. The results showed that mitochondrial respiratory complexes I, III and IV are sources of O[Formula: see text] production in PAECs, and a new observation that ROS production during uncoupling of mitochondrial respiration is mediated in part via complex IV. This novel method can be applied in other studies that examine ROS production under stress condition and during ROS-mediated injuries in vitro.
Dynamic race detection for C++11
Authors: Lidbury Christopher , Donaldson Alastair F.
Published: May 2017

The intricate rules for memory ordering and synchronisation associated with the C/C++11 memory model mean that data races can be difficult to eliminate from concurrent programs. Dynamic data race analysis can pinpoint races in large and complex applications, but the state-of-the-art ThreadSanitizer (tsan) tool for C/C++ considers only sequentially consistent program executions, and does not correctly model synchronisation between C/C++11 atomic operations. We present a scalable dynamic data race analysis for C/C++11 that correctly captures C/C++11 synchronisation, and uses instrumentation to support exploration of a class of non sequentially consistent executions. We concisely define the memory model fragment captured by our instrumentation via a restricted axiomatic semantics, and show that the axiomatic semantics permits exactly those executions explored by our instrumentation. We have implemented our analysis in tsan, and evaluate its effectiveness on benchmark programs, enabling a comparison with the CDSChecker tool, and on two large and highly concurrent applications: the Firefox and Chromium web browsers. Our results show that our method can detect races that are beyond the scope of the original tsan tool, and that the overhead associated with applying our enhanced instrumentation to large applications is tolerable.
Stream fusion, to completeness
Authors: Kiselyov Oleg , Biboudis Aggelos , Palladinos Nick , Smaragdakis Yannis
Published: May 2017

Stream processing is mainstream (again): Widely-used stream libraries are now available for virtually all modern OO and functional languages, from Java to C# to Scala to OCaml to Haskell. Yet expressivity and performance are still lacking. For instance, the popular, well-optimized Java 8 streams do not support the zip operator and are still an order of magnitude slower than hand-written loops.

We present the first approach that represents the full generality of stream processing and eliminates overheads, via the use of staging. It is based on an unusually rich semantic model of stream interaction. We support any combination of zipping, nesting (or flat-mapping), sub-ranging, filtering, mapping—of finite or infinite streams. Our model captures idiosyncrasies that a programmer uses in optimizing stream pipelines, such as rate differences and the choice of a “for” vs. “while” loops. Our approach delivers hand-written–like code, but automatically. It explicitly avoids the reliance on black-box optimizers and sufficiently-smart compilers, offering highest, guaranteed and portable performance.

Our approach relies on high-level concepts that are then readily mapped into an implementation. Accordingly, we have two distinct implementations: an OCaml stream library, staged via MetaOCaml, and a Scala library for the JVM, staged via LMS. In both cases, we derive libraries richer and simultaneously many tens of times faster than past work. We greatly exceed in performance the standard stream libraries available in Java, Scala and OCaml, including the well-optimized Java 8 streams.
Semantic-directed clumping of disjunctive abstract states
Authors: Li Huisong , Berenger Francois , Chang Bor-Yuh Evan , Rival Xavier
Published: May 2017

To infer complex structural invariants, shape analyses rely on expressive families of logical properties. Many such analyses manipulate abstract memory states that consist of separating conjunctions of basic predicates describing atomic blocks or summaries. Moreover, they use finite disjunctions of abstract memory states in order to account for dissimilar shapes. Disjunctions should be kept small for the sake of scalability, though precision often requires to keep additional case splits. In this context, deciding when and how to merge case splits and to replace them with summaries is critical both for the precision and for the efficiency. Existing techniques use sets of syntactic rules, which are tedious to design and prone to failure. In this paper, we design a semantic criterion to clump abstract states based on their silhouette which applies not only to the conservative union of disjuncts, but also to the weakening of separating conjunction of memory predicates into inductive summaries. Our approach allows to define union and widening operators that aim at preserving the case splits that are required for the analysis to succeed. We implement this approach in the MemCAD analyzer, and evaluate it on real-world C codes from existing libraries, including programs dealing with doubly linked lists, red-black trees and AVL-trees.
Modules, abstraction, and parametric polymorphism
Authors: Crary Karl
Published: May 2017

Reynolds's Abstraction theorem forms the mathematical foundation for data abstraction. His setting was the polymorphic lambda calculus. Today, many modern languages, such as the ML family, employ rich module systems designed to give more expressive support for data abstraction than the polymorphic lambda calculus, but analogues of the Abstraction theorem for such module systems have lagged far behind.

We give an account of the Abstraction theorem for a modern module calculus supporting generative and applicative functors, higher-order functors, sealing, and translucent signatures. The main issues to be overcome are: (1) the fact that modules combine both types and terms, so they must be treated as both simultaneously, (2) the effect discipline that models the distinction between transparent and opaque modules, and (3) a very rich language of type constructors supporting singleton kinds. We define logical equivalence for modules and show that it coincides with contextual equivalence. This substantiates the folk theorem that modules are good for data abstraction. All our proofs are formalized in Coq.
Rust: from POPL to practice (keynote)
Authors: Turon Aaron
Published: May 2017

In 2015, a language based fundamentally on substructural typing–Rust–hit its 1.0 release, and less than a year later it has been put into production use in a number of tech companies, including some household names. The language has started a trend, with several other mainstream languages, including C++ and Swift, in the early stages of incorporating ideas about ownership. How did this come about?

Rust’s core focus is safe systems programming. It does not require a runtime system or garbage collector, but guarantees memory safety. It does not stipulate any particular style of concurrent programming, but instead provides the tools needed to guarantee data race freedom even when doing low-level shared-state concurrency. It allows you to build up high-level abstractions without paying a tax; its compilation model ensures that the abstractions boil away.

These benefits derive from two core aspects of Rust: its ownership system (based on substructural typing) and its trait system (a descendant of Haskell’s typeclasses). The talk will cover these two pillars of Rust design, with particular attention to the key innovations that make the language usable at scale. It will highlight the implications for concurrency, where Rust provides a unique perspective. It will also touch on aspects of Rust’s development that tend to get less attention within the POPL community: Rust’s governance and open development process, and design considerations around language and library evolution. Finally, it will mention a few of the myriad open research questions around Rust.
Parallel virtual machines with RPython
Authors: Meier Remigius , Rigo Armin , Gross Thomas R.
Published: May 2017

The RPython framework takes an interpreter for a dynamic language as its input and produces a Virtual Machine (VM) for that language. RPython is being used to develop PyPy, a high-performance Python interpreter. However, the produced VM does not support parallel execution since the framework relies on a Global Interpreter Lock (GIL): PyPy serialises the execution of multi-threaded Python programs.

We describe the rationale and design of a new parallel execution model for RPython that allows the generation of parallel virtual machines while leaving the language semantics unchanged. This model then allows different implementations of concurrency control, and we discuss an implementation based on a GIL and an implementation based on Software Transactional Memory (STM).

To evaluate the benefits of either choice, we adapt PyPy to work with both implementations (GIL and STM). The evaluation shows that PyPy with STM improves the runtime of a set of multi-threaded Python programs over PyPy with a GIL by factors in the range of 1.87x up to 5.96x when executing on a processor with 8 cores.
Clinical Psychology Training: Accreditation and Beyond
Authors: Levenson Robert W.
Published: May 2017

Beginning with efforts in the late 1940s to ensure that clinical psychologists were adequately trained to meet the mental health needs of the veterans of World War II, the accreditation of clinical psychologists has largely been the province of the Commission on Accreditation of the American Psychological Association. However, in 2008 the Psychological Clinical Science Accreditation System began accrediting doctoral programs that adhere to the clinical science training model. This review discusses the goals of accreditation and the history of the accreditation of graduate programs in clinical psychology, and provides an overview of the evaluation procedures used by these two systems. Accreditation is viewed against the backdrop of the slow rate of progress in reducing the burden of mental illness and the changes in clinical psychology training that might help improve this situation. The review concludes with a set of five recommendations for improving accreditation.
Edmund Goodwyn and the first description of diving bradycardia
Authors: Vega Jose L.
Published: May 2017

Diving bradycardia is a primordial oxygen-conserving reflex by which the heart rate of air-breathing vertebrates, including humans, slows down in response to water immersion. Its discovery is attributed to Paul Bert, whose seminal observation was published in 1870 as part of a series of experiments that examined physiological adaptations to asphyxia in ducks and other animals. However, Edmund Goodwyn, a British physician who studied medicine at the University of Edinburgh, had already described this reflex in his doctoral thesis, which was originally published in Latin in 1786 and again in English in 1788. Ironically, even though Goodwyn's work has yet to be recognized in the diving physiology literature, it was referenced in the very publication that contains Bert's original observation. Thus this article brings Goodwyn’s work and its historical context to light and argues that he should be credited with the first description of diving bradycardia.
Protective Effect of 18β‐Glycyrrhetinic Acid against Triptolide‐Induced Hepatotoxicity in Rats
Authors: Yang Guanghua , Wang Lan , Yu Xiuting , Huang Yanfeng , Qu Chang , Zhang Zhenbiao , Luo Dandan , Lin Ji , Zhou Lian , Su Ziren , Zhang Xiaojun , Chen Haiming
Published: May 2017

Triptolide (TP) is the major active component of Tripterygium wilfordii Hook F (TWHF) and possesses multiple pharmacological effects. However, hepatotoxicity of TP which is one of the toxic properties slows its progression in clinical application. 18β‐Glycyrrhetinic acid (GA) is the main bioactive ingredient of Licorice (Glycyrrhiza glabra L.), a herbal medicine famous for its detoxification. This study aims to investigate whether GA possesses protective effect against TP‐induced hepatotoxicity in rats. TP interference markedly elevated serum levels of ALT, AST, and ALP, caused evident liver histopathological changes, and elevated hepatic TNF‐α, IL‐6, IL‐1β, and IFN‐γ as well as nuclear translocation of NF‐κB. TP also significantly elevated liver MDA and declined hepatic activities of SOD, CAT, and GSH‐Px. Assay of TUNEL and apoptosis proteins (Bax, Bcl‐2, and active caspase‐3) showed that TP induced severe hepatocellular apoptosis. In contrast, low‐dose GA (50 mg/kg) significantly reversed TP‐induced changes above. However, high‐dose GA (100 mg/kg) had no such effect. Overall, these findings indicated that low‐dose GA but not high‐dose GA exhibited a protective effect against TP‐induced hepatotoxicity in rats by anti‐inflammation, antioxidation, and antiapoptosis, which suggests that the doses of GA/Licorice should be carefully considered when used together with TWHF or TWHF preparations.
A Novel Double Cluster and Principal Component Analysis-Based Optimization Method for the Orbit Design of Earth Observation Satellites
Authors: Dong Yunfeng , Wei Xiaona , Tian Lu , Liu Fengrui , Xu Guangde
Published: May 2017

The weighted sum and genetic algorithm-based hybrid method (WSGA-based HM), which has been applied to multiobjective orbit optimizations, is negatively influenced by human factors through the artificial choice of the weight coefficients in weighted sum method and the slow convergence of GA. To address these two problems, a cluster and principal component analysis-based optimization method (CPC-based OM) is proposed, in which many candidate orbits are gradually randomly generated until the optimal orbit is obtained using a data mining method, that is, cluster analysis based on principal components. Then, the second cluster analysis of the orbital elements is introduced into CPC-based OM to improve the convergence, developing a novel double cluster and principal component analysis-based optimization method (DCPC-based OM). In DCPC-based OM, the cluster analysis based on principal components has the advantage of reducing the human influences, and the cluster analysis based on six orbital elements can reduce the search space to effectively accelerate convergence. The test results from a multiobjective numerical benchmark function and the orbit design results of an Earth observation satellite show that DCPC-based OM converges more efficiently than WSGA-based HM. And DCPC-based OM, to some degree, reduces the influence of human factors presented in WSGA-based HM.
Visible Light Excited Catalysis and Reusability Performances of TiO2@Pr:Y2SiO5 Upconversion Materials
Authors: Jiao Yan , Wang Yamiao , Li Min , Liu Ying , Mao Ping , Yang Yi
Published: May 2017

To get high efficiency photodegradation on pollutants under visible light, Pr(III) doped Y2SiO5 upconversion materials and anatase TiO2 nanofilm coated Pr:Y2SiO5 composite have been prepared by using a sol-gel method. XRD and SEM test results indicated that TiO2 nanofilm was well coated on Pr:Y2SiO5 to form TiO2@Pr:Y2SiO5 composite particles with the sizes of 0.5–1.0 μm. To avoid secondary pollution resulting from incomplete recovery of catalyst particles, TiO2@Pr:Y2SiO5 was loaded on the glass fiber filters by using a dip-coating method. It is found that the catalyst particles were embedded into the carrier firmly, even after having been reused for 6 times. The luminescence intensities of TiO2@Pr:Y2SiO5 were getting down sharply with the coating contents of TiO2 increased, which was attributed to the adsorption of the luminescence by the TiO2 film in situ. As a result, TiO2@Pr:Y2SiO5 with 4% TiO2, which presented lowest luminescence intensity, showed the highest efficiency on the photodegradation of nitrobenzene wastewater. The catalysts loaded on glass fiber filters showed excellent reusability on the photodegradation of nitrobenzene and presented a photodegradation rate of 95% at the first time and up to 75.9% even after 6 times of reusing by the treatment time of 12 h.
A Novel Approach to Reduction of Frictional Losses in a Heavy-Duty Diesel Engine by Reducing the Hydrodynamic Frictional Losses
Authors: Johansson Staffan , Nilsson Per H. , Ohlsson Robert , Rosén Bengt-Göran
Published: May 2017

An important parameter in the reduction of fuel consumption of heavy-duty diesel engines is the Power Cylinder Unit (PCU); the PCU is the single largest contributor to engine frictional losses. Much attention, from both academia and industry, has been paid to reducing the frictional losses of the PCU in the boundary and mixed lubrication regime. However, previous studies have shown that a large portion of frictional losses in the PCU occur in the hydrodynamic lubrication regime. A novel texturing design with large types of surface features was experimentally analyzed using a tribometer setup. The experimental result shows a significant reduction of friction loss for the textured surfaces. Additionally, the textured surface did not exhibit wear. On the contrary, it was shown that the textured surfaces exhibited a smaller amount of abrasive scratches on the plateaus (compared to the reference plateau honed surface) due to entrapment of wear particles within the textures. The decrease in hydrodynamic friction for the textured surfaces relates to the relative increase of oil film thickness within the textures. A tentative example is given which describes a method of decreasing hydrodynamic frictional losses in the full-scale application.
Epstein–Barr Virus-Induced VEGF and GM-CSF Drive Nasopharyngeal Carcinoma Metastasis via Recruitment and Activation of Macrophages
Authors: Huang Di , Song Shi-Jian , Wu Zi-Zhao , Wu Wei , Cui Xiu-Ying , Chen Jia-Ning , Zeng Mu-Sheng , Su Shi-Cheng
Published: May 2017

Chronic inflammation induced by persistent microbial infection plays an essential role in tumor progression. Although it is well documented that Epstein–Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma (NPC), how EBV-induced inflammation promotes NPC progression remains largely unknown. Here, we report that tumor infiltration of tumor-associated macrophages (TAM) and expression of CCL18, the cytokine preferentially secreted by TAM, closely correlate with serum EBV infection titers and tumor progression in two cohorts of NPC patients. In vitro, compared with EBV− NPC cell lines, EBV+ NPC cell lines exhibited superior capacity to attract monocytes and skew them to differentiate to a TAM-like phenotype. Cytokine profiling analysis revealed that NPC cells with active EBV replications recruited monocytes by VEGF and induced TAM by GM-CSF in an NF-κB–dependent manner. Reciprocally, TAM induced epithelial–mesenchymal transition and furthered NF-κB activation of tumor cells by CCL18. In humanized mice, NPC cells with active EBV replications exhibited increased metastasis, and neutralization of CCL18, GM-CSF, and VEGF significantly reduced metastasis. Collectively, our work defines a feed-forward loop between tumor cells and macrophages in NPC, which shows how metastatic potential can evolve concurrently with virus-induced chronic inflammation. Cancer Res; 77(13); 3591–604. ©2017 AACR.
Sarcoma Eradication by Doxorubicin and Targeted TNF Relies upon CD8+ T-cell Recognition of a Retroviral Antigen
Authors: Probst Philipp , Kopp Janine , Oxenius Annette , Colombo Mario P. , Ritz Danilo , Fugmann Tim , Neri Dario
Published: May 2017

Antibody–cytokine complexes may offer new tools to treat cancer. Here, we show how TNF-linked antibodies, which recognize tumor-selective splice isoforms of fibronectin (F8-TNF), can be exploited to eradicate sarcomas in immunocompetent mice. We treated mice bearing WEHI-164 fibrosarcoma with a combination of F8-TNF and doxorubicin, curing the majority of treated animals (29/37). Notably, cured mice were resistant to rechallenge not only by WEHI-164 cells but also heterologous C51 or CT26 colorectal tumor cells in a CD8+ T-cell–dependent process. Mechanistic analyses revealed that each tumor cell line presented AH1, a common endogenous retroviral peptide. Numbers of AH1-specific CD8+ T cells exhibiting cytotoxic capacity were increased by F8-TNF plus doxorubicin treatment, arguing that cognate CD8+ T cells contributed to tumor eradication. Sequence analysis of T-cell receptors of CD8+ T cells revealed the presence of H-2Ld/AH1-specific T cells and an expansion of sequence diversity in treated mice. Overall, our findings provide evidence that retroviral genes contribute to tumoral immunosurveillance in a process that can be generally boosted by F8-TNF and doxorubicin treatment. Cancer Res; 77(13); 3644–54. ©2017 AACR.
Total and Free Circulating Vitamin D and Vitamin D–Binding Protein in Relation to Colorectal Cancer Risk in a Prospective Study of African Americans
Authors: Andersen Shaneda Warren , Shu Xiao-Ou , Cai Qiuyin , Khankari Nikhil K. , Steinwandel Mark D. , Jurutka Peter W. , Blot William J. , Zheng Wei
Published: May 2017

Background: Previous studies rarely evaluated the associations between vitamin D–binding protein and free vitamin D with colorectal cancer risk. We assessed these biomarkers and total 25-hydroxyvitamin D in relation to colorectal cancer risk in a sample of African Americans.

Methods: Cases comprised 224 African American participants of the Southern Community Cohort Study diagnosed with incident colorectal cancer. Controls (N = 440) were selected through incidence density sampling and matched to cases on age, sex, and race. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for associations between biomarker levels and colorectal cancer risk.

Results: Vitamin D was inversely associated with colorectal cancer risk where the OR per-SD increase in total and free 25-hydroxyvitamin D were 0.82 (95% CI, 0.66–1.02) and 0.82 (95% CI, 0.66–1.01), respectively. Associations were most apparent among cases diagnosed >3 years after blood draw: ORs for the highest tertile versus the lowest were 0.69 (95% CI, 0.21–0.93) for total 25-hydroxyvitamin D and 0.71 (95% CI, 0.53–0.97) for free 25-hydroxyvitamin D. Inverse associations were seen in strata defined by sex, BMI, and anatomic site, although not all findings were statistically significant. Vitamin D–binding protein was not associated with colorectal cancer risk.

Conclusions: Our findings suggest that total and free 25-hydroxyvitamin D may be inversely associated with colorectal cancer risk among African Americans.

Impact: These findings highlight a potential role for vitamin D in colorectal cancer prevention in African Americans. Cancer Epidemiol Biomarkers Prev; 26(8); 1242–7. ©2017 AACR.
Risk Factors for Early Postoperative Small Bowel Obstruction after Elective Colon Cancer Surgery: An Observational Study of 1,244 Consecutive Patients
Authors: Wang Xiao-Jie , Chi Pan , Lin Hui-Ming , Lu Xing-Rong , Huang Ying , Xu Zong-Bin , Huang Sheng-Hui , Sun Yan-Wu , Ye Dao-Xiong
Published: May 2017

Background: Early postoperative small bowel obstruction (EPSBO) is a common complication following colon cancer surgery. EPSBO is associated with increased hospital stays, mortality rates, and healthcare costs. The purpose of this study was to identify risk factors for EPSBO following elective colon cancer surgery. Study Design: We retrospectively reviewed the clinicopathological variables of 1,244 patients with colon cancer who underwent partial colectomy from January 2000 to December 2014. A multivariable logistic regression model was used to identify risk factors for EPSBO. Results: The EPSBO rate was 3.5%. In multivariate analysis, preoperative bowel obstruction (OR 2.378; 95% CI 0.986-5.735, p = 0.054), weight loss >10% of body weight (OR 3.029; 95% CI 1.000-9.178, p = 0.05), albumin level (in g/L; OR 0.966; 95% CI 0.937-0.996, p = 0.024), and surgical duration (in min; OR 1.008; 95% CI 1.003-1.012, p = 0.003) were significant predictors of EPSBO. Conclusion: EPSBO is more likely to develop in the presence of poor systemic conditions (e.g., weight loss >10% of body weight, hypoalbuminemia, and preoperative bowel obstruction) and following operations of longer duration. These predictors may facilitate the stratification of patients at risk for EPSBO following surgery for elective colon cancer.
First-Line Support by Intra-Aortic Balloon Pump in Non-Ischaemic Cardiogenic Shock in the Era of Modern Ventricular Assist Devices
Authors: den Uil Corstiaan A. , Galli Giorgia , Jewbali Lucia S. , Caliskan Kadir , Manintveld Olivier C. , Brugts Jasper J. , van Mieghem Nicolas M. , Lenzen Mattie J. , Boersma Eric , Constantinescu Alina A.
Published: May 2017

Objectives: Little is known about circulatory support in cardiogenic shock (CS) from other causes than the acute coronary syndrome or after cardiotomy. We evaluated the effects of first-line intra-aortic balloon pump (IABP) support in this subpopulation of CS patients. Methods: A retrospective study was performed in 27 patients with CS from end-stage cardiomyopathy supported firstly by IABP in the years 2011-2016. Results: At 24 h, lactate decreased from 3.2 (2.1-6.8) to 1.8 (1.2-2.2) mmol/L (p < 0.001). Eighteen patients (67%) defined as IABP responders were successfully bridged to either recovery (n = 7), left ventricular assist device (n = 5), or heart transplantation (n = 6). IABP failed in 9 patients (non-responders, 33%) who either died (n = 7) or needed support by extracorporeal membrane oxygenation (n = 2). At 24 h of IABP support, urinary output was higher (2,660 [1,835-4,440] vs. 1,200 [649-2,385] mL; p = 0.02) and fluid balance more negative (-1,564 [-2,673 to -1,086] vs. -500 [-930 to +240] mL; p < 0.001) in responders than non-responders. Overall survival at 1 year was 63%. Conclusion: In most patients, first-line support by IABP in end-stage cardiomyopathy is associated with improvement in organ perfusion and clinical stabilisation for at least 24 h allowing time for decision making on next therapies.
Factors Associated with Potassium-Competitive Acid Blocker Non-Response in Patients with Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease
Authors: Okuyama Masatsugu , Nakahara Kenichi , Iwakura Narika , Hasegawa Tomoki , Oyama Maizumi , Inoue Ayumi , Ishizu Hirotaka , Satoh Hiroshi , Fujiwara Yasuhiro
Published: May 2017

Background/Aims: Approximately 20-40% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) treatment. The acid-inhibitory effect of vonoprazan, a novel potassium-competitive acid blocker (P-CAB), is significantly greater when compared to the effect of PPIs. We investigated the efficacy of vonoprazan treatment for PPI-refractory GERD and factors associated with P-CAB non-response. Methods: We enrolled 277 GERD patients receiving continuous PPI therapy. Subjects completed a self-report questionnaire including the frequency scale for the symptoms of GERD (FSSG). Patients with PPI-refractory GERD received 20 mg of vonoprazan once daily for 8 weeks. After that, subjects completed the same questionnaire, and the results were used to identify P-CAB responders and non-responders. Results: Twenty-eight patients were identified as P-CAB responders and 26 were non-responders. Vonoprazan treatment significantly decreased scores of FSSG, nighttime symptom, and Athens Insomnia Scale. Multivariate analysis demonstrated co-existing functional dyspepsia (FD; OR 4.94) and the presence of sleep disturbances (OR 4.34) was associated with P-CAB non-response, whereas alcohol consumption was inversely associated. Conclusions: Vonoprazan treatment might be appropriate as a promising new strategy for PPI-refractory GERD. Co-existing FD, sleep disturbances, and alcohol abstinence were significantly associated with P-CAB non-response. Other therapeutic options should be considered in patients with these factors.
Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression
Authors: Nezu Masahiro , Suzuki Norio , Yamamoto Masayuki
Published: May 2017

Background: Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor for the antioxidative stress response and it activates a variety of cytoprotective genes related to redox and detoxification. NRF2 activity is regulated by the oxidative-stress sensor molecule Kelch-like ECH-associated protein 1 (KEAP1) that induces proteasomal degradation of NRF2 through ubiquitinating NRF2 under unstressed conditions. Because oxidative stress is a major pathogenic and aggravating factor for kidney diseases, the KEAP1-NRF2 system has been proposed to be a therapeutic target for renal protection. Summary: Oxidative-stress molecules, such as reactive oxygen species, accumulate in the kidneys of animal models for acute kidney injury (AKI), in which NRF2 is transiently and slightly activated. Genetic or pharmacological enhancement of NRF2 activity in the renal tubules significantly ameliorates damage related to AKI and prevents AKI progression to chronic kidney disease (CKD) by reducing oxidative stress. These beneficial effects of NRF2 activation highlight the KEAP1-NRF2 system as an important target for kidney disease treatment. However, a phase-3 clinical trial of a KEAP1 inhibitor for patients with stage 4 CKD and type-2 diabetes mellitus (T2DM) was terminated due to the occurrence of cardiovascular events. Because recent basic studies have accumulated positive effects of KEAP1 inhibitors in moderate stages of CKD, phase-2 trials have been restarted. The data from the ongoing projects demonstrate that a KEAP1 inhibitor improves the glomerular filtration rate in patients with stage 3 CKD and T2DM without safety concerns. Key Message: The KEAP1-NRF2 system is one of the most promising therapeutic targets for kidney disease, and KEAP1 inhibitors could be part of critical therapies for kidney disease.
Long Non-Coding RNA XLOC_008466 Functions as an Oncogene in Human Non-Small Cell Lung Cancer by Targeting miR-874
Authors: Yang Rui , Li Ping , Zhang Guojun , Lu Chunya , Wang Huaqi , Zhao Guoqiang
Published: May 2017

Background: The therapy and prognosis of lung cancer are difficult because of multiple genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) have been verified as new mediators of cancer development and progression by virtue of their various functions. Here, we focused on the lncRNA XLOC_008466 based on previous microarray data. However, whether aberrant expression of XLOC_008466 in human non-small cell lung cancer (NSCLC) is correlated with malignancy, metastasis or prognosis has not been elucidated. Methods: We performed real-time PCR, CCK-8, flow cytometry, trans-well, western blotting, luciferase reporter assays, RNA immunoprecipitation (RIP) assay and surface plasmon resonance (SPR) assay to detect the function of XLOC_008466 in NSCLC. Results: Up-regulation of XLOC_008466 in NSCLC patients was related to lymph node metastasis and the TNM stage. In vitro, down-regulation of XLOC_008466 inhibited cell proliferation and invasion of A549 and H460 cells in vitro, but promoted cell apoptosis. Experiments on mechanisms revealed that XLOC_008466 functioned as a ceRNA, directly binding to miR-874, and could affect cell proliferation, apoptosis and invasion through regulation of miR-874 expression as well as by increasing matrix metalloproteinase 2 (MMP2) and X-linked inhibitor of apoptosis (XIAP) expression. Conclusions: XLOC_008466 functions as an oncogene in NSCLC by regulating the miR-874-MMP2/XIAP axis, which indicates that XLOC_008466 may be a useful marker and potential therapeutic target in NSCLC.
Attenuated Spreading in Sanskrit Retroflex Harmony
Authors: Ryan Kevin
Published: May 2017

Drawing on a two-million-word corpus of Sanskrit, the article documents and analyzes two previously unrecognized generalizations concerning the morphoprosodic conditioning of retroflex spreading ( nati). Both reveal harmony to be attenuated across the left boundaries of roots (i.e., between a prefix and a root or between members of a compound), in the sense that while harmony applies across these boundaries, when it does so, it accesses a proper subset of the targets otherwise accessible. This attenuation is analyzed here through the “ganging up” of phonotactics and output-output correspondence in serial Harmonic Grammar. The article also simplifies the core analysis of the spreading rule, primarily through recognizing FLAPOUT, an articulatorily grounded constraint.
Cupid’s Arrows
Authors: Wickkiser Bronwen L.
Published: May 2017

Ovid’s narrative of Apollo and Daphne introduces elements not apparent in earlier extant versions of the myth, such as the involvement of Cupid and his deployment of two distinct arrows, one golden that sets Apollo’s passions aflame, and the other lead that makes Daphne averse to all male advances. The passion-averting arrow in particular is a curious addition to Cupid’s arsenal. This paper will argue that the lead arrow can be better understood when viewed alongside the practices and discourses of ancient magic and medicine, especially the widespread use of lead for erotic defixiones, antaphrodisiacs, and even contraceptives.