bluuebunny/crossref_metadata_2025 huggingface dataset:
Follicle Diameter and Systemic Hormone Interrelationships during Induction of Follicle Collapse with Intrafollicular Prostaglandin E2 and F2α in Mares
Authors: Martínez‐Boví R , Cuervo‐Arango J
Published: March 2016

Contents

The objectives were to determine: (i) whether intrafollicular administration of PGE2 and PGF2α to mares would hasten follicle collapse and (ii) the differences in reproductive hormone characteristics in mares with spontaneous and prostaglandin‐induced follicle collapses. Six mares were followed for two oestrous cycles each: when the mares reached a follicle diameter of 30–35 mm and showed mild‐to‐moderate endometrial oedema, mares were administered a single 0.5 ml dose containing 500 μg PGE2 and 125 μg PGF2α (treatment cycle) or a placebo (0.5 ml of water for injection; control cycle) into the preovulatory follicle (Hour 0). Blood samples were collected, and serial ultrasound examinations were performed until follicle collapse. Treated mares showed follicle collapse significantly earlier (20.0 ± 5.9 h) than the control mares (72.0 ± 10.7 h). The LH, progesterone, total oestrogens and oestradiol concentrations did not differ between groups; however, the progesterone concentration increased more between 48 and 72 h after follicle injection in the treatment compared to the control cycles (P < 0.05). In conclusion, intrafollicular treatment with PGE2 and PGF2α hastened follicle collapse in mares without the simultaneous use of an inductor of ovulation; despite the early induction of follicle collapse, the profiles of LH and oestradiol were not altered. This study provides information on the role of prostaglandins (PGs) in the process of follicle wall rupture and collapse and suggests that this may happen even before the beginning of the sharp rise in circulating LH at the final stage of the ovulatory surge.
The Appalachian ‘Other’: Academic Approaches to the Study of Serpent‐handling Sects
Authors: Gray‐Hildenbrand Jenna
Published: March 2016

Serpent‐handling sects are often portrayed in the media as bizarre Southern cults whose members engage in dangerous primitive rituals. The fact that a religious ritual identified as existing outside the normative boundaries of Christianity, and perhaps religion in general, defines this Christian tradition marks serpent‐handling sects as abnormal or ‘other’. Consequently, scholars investigating why these Christians handle poisonous snakes during religious services must address the boundary between ‘abnormal’ and ‘normal’ religion, the ‘norm’ and the ‘other’. This essay surveys the multi‐disciplinary literature on serpent‐handling sects with a particular eye toward the ways scholars both negotiate and perpetuate this boundary.
The Political Construction of Elder Care Markets: Comparing Denmark, Finland and Italy
Authors: Burau Viola , Zechner Minna , Dahl Hanne Marlene , Ranci Costanzo
Published: March 2016

In Europe over the last two decades, marketization has become an important policy option in elder care. Comparative studies predominantly adopt an institutional perspective and analyze the politics and policies of marketization. This analysis takes a step back and examines the fundamental ideas underpinning the policies of marketization, using the ‘What's the problem?’ approach by Carol Bacchi. The central question is how the market was discursively framed as the solution to the perceived problems of three different systems of elder care, and how such processes are similar or different across the three countries. The analysis includes two extreme types of elder care systems, the Nordic public systems in Denmark and Finland, and the Southern European family‐based model in Italy. Empirically, the analysis offers interesting insights into processes of constructing and legitimating markets at the level of discourse; this occurs by defining specific problem representations, underlying assumptions and silences. In all three countries, marketization is presented as a solution which builds on rather than challenges dominant ideas of care. Conceptually, in addition to its institutions, it is crucial to understand the ideas behind the marketization of elder care. Ideas emerge as a key leverage for making policies and practices of marketization acceptable and which decision makers and other influential political/societal actors use in policy and public debates. The importance of ideas is further underlined by the fact that they do not necessarily relate to the institutions of elder care systems in a linear way.
Scientists Taking a Nature of Science Course: Beliefs and Learning Outcomes of Career Switchers
Authors: Peters‐Burton Erin
Published: March 2016

The purpose of the study was to examine what scientists studying to become teachers know about the nature of science (NOS) before, during and after a course focused on NOS. The 16 scientists had an average of 9.7 years of work experience. The course was structured to teach knowledge about the aspects of NOS, demonstrate effective methods of teaching NOS, provide examples of successful attempts at meaningfully incorporating NOS into science content, and give students an opportunity to design and teach their own lessons incorporating NOS. Data sources collected include a prepost test of Views of Science and Education, electronic discussion postings, written class assignment of a clinical interview with an adolescent about NOS, video recordings of teaching, and individual interviews conducted three months after the course. Quantitative and qualitative data indicate that the scientists entered the course with much knowledge regarding the tentativeness of science and the nature of observations. There were significant gains in sophistication of view of NOS with regard to the following aspects of NOS: (a) knowing that variety of scientific methods exist, (b) the role of theories and laws, (c) the use of imagination, and (d) the role of subjectivity and objectivity in science.
Elementary Teachers: Concerns About Implementing a Science Program
Authors: Dailey Debbie , Robinson Ann
Published: March 2016

The purpose of this study was to examine elementary teachers’ science teaching concerns after participating in a two‐year extensive and sustained science professional development intervention. The intervention consisted of two types of teacher professional development across two years including: (a) summer institutes (60 hours across two years) which provided training on curriculum units, inquiry‐based instructional strategies, problem‐based learning, classroom management, and technology use in the classroom; and (b) coaching (60 hours across two years) which provided teachers support in establishing an investigative classroom and assistance in the implementation of inquiry/problem‐based science units. Teacher data were collected across four different time points: prior to the intervention, after one year of intervention, after two years of intervention, and one year after completion of the intervention. Results from quantitative data supported with qualitative interviews indicated concerns among teachers changed but they were not eliminated. The findings of this study provide evidence that teachers’ concerns may not be eliminated, but with extensive support––concerns become less focused on self and more focused on students.
The Growing Awareness Inventory: Building Capacity for Culturally Responsive Science and Mathematics With a Structured Observation Protocol
Authors: Brown Julie C. , Crippen Kent J.
Published: March 2016

This study represents a first iteration in the design process of the Growing Awareness Inventory (GAIn), a structured observation protocol for building the awareness of preservice teachers (PSTs) for resources in mathematics and science classrooms that can be used for culturally responsive pedagogy (CRP). The GAIn is designed to develop awareness of: how students use language in classrooms; relationships between teacher questioning patterns and student participation; messages conveyed by the classroom environment; and ways to incorporate students’ interests into lesson plans. The methodology took the form of a multiple case study design with fourteen mathematics PSTs as one case and five science PSTs as the other case. The participants' response to the GAIn and lesson plans served as data sources. Findings reveal that the GAIn scaffolded PSTs’ awareness of their students, their own attitudes, and several elements of CRP. However, there were key areas of CRP that were neither explored with the GAIn nor identified by the participants. Consistent with design‐based research, outcomes include a design framework for revision of the GAIn and a theory of action that situates it within a teacher education course that includes a field placement.
Molecular and biochemical characterizations of the monoacylglycerol lipase gene family of Arabidopsis thaliana
Authors: Kim Ryeo Jin , Kim Hae Jin , Shim Donghwan , Suh Mi Chung
Published: March 2016

Monoacylglycerol lipase (MAGL) catalyzes the last step of triacylglycerol breakdown, which is the hydrolysis of monoacylglycerol (MAG) to fatty acid and glycerol. Arabidopsis harbors over 270 genes annotated as ‘lipase’, the largest class of acyl lipid metabolism genes that have not been characterized experimentally. In this study, computational modeling suggested that 16 Arabidopsis putative MAGLs (AtMAGLs) have a three‐dimensional structure that is similar to a human MAGL. Heterologous expression and enzyme assays indicated that 11 of the 16 encoded proteins indeed possess MAG lipase activity. Additionally, AtMAGL4 displayed hydrolase activity with lysophosphatidylcholine and lysophosphatidylethanolamine (LPE) substrates and AtMAGL1 and 2 utilized LPE as a substrate. All recombinant AtMAGLs preferred MAG substrates with unsaturated fatty acids over saturated fatty acids and AtMAGL8 exhibited the highest hydrolase activities with MAG containing 20:1 fatty acids. Except for AtMAGL4, −14 and −16, all AtMAGLs showed similar activity with both sn‐1 and sn‐2 MAG isomers. Spatial, temporal and stress‐induced expression of the 16 AtMAGL genes was analyzed by transcriptome analyses. AtMAGL:eYFP fusion proteins provided initial evidence that AtMAGL1, −3, −6, ‐7, −8, −11, −13, −14 and −16 are targeted to the endoplasmic reticulum and/or Golgi network, AtMAGL10, −12 and −15 to the cytosol and AtMAGL2, −4 and −5 to the chloroplasts. Furthermore, AtMAGL8 was associated with the surface of oil bodies in germinating seeds and leaves accumulating oil bodies. This study provides the broad characterization of one of the least well‐understood groups of Arabidopsis lipid‐related enzymes and will be useful for better understanding their roles in planta.
Acid‐sensing ion channels are tuned to follow high‐frequency stimuli
Authors: MacLean David M. , Jayaraman Vasanthi
Published: March 2016

Key points

Acid‐sensing ion channels (ASICs) act as neurotransmitter receptors by responding to synaptic cleft acidification.

We investigated how ASIC1a homomers and ASIC1a/2a heteromers respond to brief stimuli, jumping from pH 8.0 to 5.0, approximating the time course of neurotransmitter in the cleft.

We find that ASICs deactivate surprisingly fast in response to such brief stimuli from pH 8.0 to 5.0, whereas they desensitize comparatively slowly to prolonged activation.

The combination of unusually fast deactivation with slow desensitzation enables recombinant ASIC1a homomers and ASIC1a/2a heteromers, as well as native ASICs of sensory neurons, to follow trains of such brief pH 8.0 to 5.0 stimuli at high frequencies.

This capacity for high‐frequency signalling persists under a physiological pH of 7.4 with ASIC1a/2a heteromers, suggesting that they may sustain postsynaptic responses when other receptors desensitize.

The neurotransmitter‐gated ion channels that underlie rapid synaptic transmission are often subjected to bursts of very brief neurotransmitter release at high frequencies. When challenged with such short duration high‐frequency stimuli, neurotransmitter‐gated ion channels generally exhibit the common response of desensitization. Recently, acid‐sensing ion channels (ASICs) were shown to act as neurotransmitter‐gated ion channels because postsynaptic ASICs can be activated by the transient acidification of the synaptic cleft accompanying neurotransmission. In the present study, we examined the responses of recombinant ASIC1a homomers, ASIC1a/2a heteromers and native ASICs from sensory neurons to 1 ms acidification stimuli, switching from pH 8.0 to 5.0, as either single pulses or trains of pulses at physiologically relevant frequencies. We found that ASIC deactivation is extremely fast and, in contrast to most other neurotransmitter‐gated ion channels, ASICs show no desensitization during high‐frequency stimulus trains under these conditions. We also found that accelerating ASIC desensitization by anion substitution can induce depression during high‐frequency trains. When using a baseline physiological pH of 7.4, the ASIC1a responses were too small to reliably measure, presumably as a result of steady‐state desensitization. However, ASIC1a/2 heteromers gave robust responses when using a baseline pH of 7.4 and were also able to sustain these responses during high‐frequency stimulus trains. In conclusion, we report that the slow desensitization and fast deactivation of ASIC1a/2a heteromers enables them to sustain postsynaptic responses to bursts at high frequencies at a physiological pH that may desensitize other receptors.
The incretin hormone glucagon‐like peptide 1 increases mitral cell excitability by decreasing conductance of a voltage‐dependent potassium channel
Authors: Thiebaud Nicolas , Llewellyn‐Smith Ida J. , Gribble Fiona , Reimann Frank , Trapp Stefan , Fadool Debra Ann
Published: March 2016

Key points

The gut hormone called glucagon‐like peptide 1 (GLP‐1) is a strong moderator of energy homeostasis and communication between the peripheral organs and the brain.

GLP‐1 signalling occurs in the brain; using a newly developed genetic reporter line of mice, we have discovered GLP‐synthesizing cells in the olfactory bulb.

GLP‐1 increases the firing frequency of neurons (mitral cells) that encode olfactory information by decreasing activity of voltage‐dependent K channels (Kv1.3).

Modifying GLP‐1 levels, either therapeutically or following the ingestion of food, could alter the excitability of neurons in the olfactory bulb in a nutrition or energy state‐dependent manner to influence olfactory detection or metabolic sensing.

The results of the present study uncover a new function for an olfactory bulb neuron (deep short axon cells, Cajal cells) that could be capable of modifying mitral cell activity through the release of GLP‐1. This might be of relevance for the action of GLP‐1 mimetics now widely used in the treatment of diabetes.

The olfactory system is intricately linked with the endocrine system where it may serve as a detector of the internal metabolic state or energy homeostasis in addition to its classical function as a sensor of external olfactory information. The recent development of transgenic mGLU‐yellow fluorescent protein mice that express a genetic reporter under the control of the preproglucagon reporter suggested the presence of the gut hormone, glucagon‐like peptide (GLP‐1), in deep short axon cells (Cajal cells) of the olfactory bulb and its neuromodulatory effect on mitral cell (MC) first‐order neurons. A MC target for the peptide was determined using GLP‐1 receptor binding assays, immunocytochemistry for the receptor and injection of fluorescence‐labelled GLP‐1 analogue exendin‐4. Using patch clamp recording of olfactory bulb slices in the whole‐cell configuration, we report that GLP‐1 and its stable analogue exendin‐4 increase the action potential firing frequency of MCs by decreasing the interburst interval rather than modifying the action potential shape, train length or interspike interval. GLP‐1 decreases Kv1.3 channel contribution to outward currents in voltage clamp recordings as determined by pharmacological blockade of Kv1.3 or utilizing mice with Kv1.3 gene‐targeted deletion as a negative control. Because fluctuations in GLP‐1 concentrations monitored by the olfactory bulb can modify the firing frequency of MCs, olfactory coding could change depending upon nutritional or physiological state. As a regulator of neuronal activity, GLP‐1 or its analogue may comprise a new metabolic factor with a potential therapeutic target in the olfactory bulb (i.e. via intranasal delivery) for controlling an imbalance in energy homeostasis.
Performance Investigation of Dual Layer Yttria-Stabilized Zirconia–Samaria-Doped Ceria Electrolyte for Intermediate Temperature Solid Oxide Fuel Cells
Authors: Milcarek Ryan J. , Wang Kang , Garrett Michael J. , Ahn Jeongmin
Published: March 2016

The performance of yttria-stabilized zirconia (YSZ)–samaria-doped ceria (SDC) dual layer electrolyte anode-supported solid oxide fuel cell (AS-SOFC) was investigated. Tape-casting, lamination, and co-sintering of the NiO–YSZ anode followed by wet powder spraying of the SDC buffer layer and BSCF cathode was proposed for fabrication of these cells as an effective means of reducing the number of sintering stages required. The AS-SOFC showed a significant fuel cell performance of ∼1.9 W cm−2 at 800 °C. The fuel cell performance varies significantly with the sintering temperature of the SDC buffer layer. An optimal buffer layer sintering temperature of 1350 °C occurs due to a balance between the YSZ–SDC contact and densification at low sintering temperature and reactions between YSZ and SDC at high sintering temperatures. At high sintering temperatures, the reactions between YSZ and SDC have a detrimental effect on the fuel cell performance resulting in no power at a sintering temperature of 1500 °C.
Lubricity from Entangled Polymer Networks on Hydrogels
Authors: Pitenis Angela A. , Manuel Urueña Juan , Nixon Ryan M. , Bhattacharjee Tapomoy , Krick Brandon A. , Dunn Alison C. , Angelini Thomas E. , Gregory Sawyer W.
Published: March 2016

Structural hydrogel materials are being considered and investigated for a wide variety of biotribological applications. Unfortunately, most of the mechanical strength and rigidity of these materials comes from high polymer concentrations and correspondingly low polymer mesh size, which results in high friction coefficients in aqueous environments. Recent measurements have revealed that soft, flexible, and large mesh size hydrogels can provide ultra low friction, but this comes at the expense of mechanical strength. In this paper, we have prepared a low friction structural hydrogel sample of polyhydroxyethylmethacrylate (pHEMA) by polymerizing an entangled polymer network on the surface through a solution polymerization route. The entangled polymer network was made entirely from uncrosslinked polyacrylamide (pAAm) that was polymerized from an aqueous solution and had integral entanglement with the pHEMA surface. Measurements revealed that these entangled polymer networks could extend up to ∼200 μm from the surface, and these entangled polymer networks can provide reductions in friction coefficient of almost two orders of magnitude (μ > 0.7 to μ < 0.01).
Superlubricity in Gemini Hydrogels
Authors: Pitenis Angela A. , Manuel Urueña Juan , Cooper Andrew C. , Angelini Thomas E. , Gregory Sawyer W.
Published: March 2016

Gemini hydrogels have repeatedly produced low friction under conditions generally not thought to be favorable to superlubricity: low sliding speeds, low contact pressures, macroscopic contact areas, and room temperature aqueous environments. A proposed explanation for this unique behavior is that thermal fluctuations at the interface are sufficient to separate the surfaces, with solvent (water) shearing in this region being the main source of dissipation. In this paper, we demonstrate that very soft and correspondingly large mesh size Gemini hydrogels show superlubricity with the lowest measured friction coefficient being μ = 0.0013 ± 0.0006.
Vacuum Venting Enhances the Replication of Nano/Microfeatures in Micro-Injection Molding Process
Authors: Ying Choi Seong , Zhang Nan , Toner J. P. , Dunne G. , Gilchrist Michael D.
Published: March 2016

Vacuum venting is a method proposed to improve feature replication in microparts that are fabricated using micro-injection molding (MIM). A qualitative and quantitative study has been carried out to investigate the effect of vacuum venting on the nano/microfeature replication in MIM. Anodized aluminum oxide (AAO) containing nanofeatures and a bulk metallic glass (BMG) tool mold containing microfeatures were used as mold inserts. The effect of vacuum pressure at constant vacuum time, and of vacuum time at constant vacuum pressure on the replication of these features is investigated. It is found that vacuum venting qualitatively enhances the nanoscale feature definition as well as increases the area of feature replication. In the quantitative study, higher aspect ratio (AR) features can be replicated more effectively using vacuum venting. Increasing both vacuum pressure and vacuum time are found to improve the depth of replication, with the vacuum pressure having more influence. Feature orientation and final sample shape could affect the absolute depth of replication of a particular feature within the sample.
Radial Buckling of Tensile Armor Wires in Subsea Flexible Pipe—Numerical Assessment of Key Factors
Authors: Ebrahimi Alireza , Kenny Shawn , Hussein Amgad
Published: March 2016

Flexible pipes can be used as risers, jumpers, and flowlines that may be subject to axial forces and out-of-plane bending motion due to operational and environmental loading conditions. The tensile armor wires provide axial stiffness to resist these loads. Antibirdcaging tape is used to provide circumferential support and prevent a loss of stability for the tension armor wires, in the radial direction. The antibirdcaging tape may be damaged where a condition known as “wet annulus” occurs that may result in the radial buckling (i.e., birdcaging mechanism) of the tensile armor wires. A three-dimensional continuum finite element (FE) model of a 4 in. flexible pipe is developed using abaqus/implicit software package. As a verification case, the radial buckling response is compared with similar but limited experimental work available in the public domain. The modeling procedures represent an improvement over past studies through the increased number of layers and elements to model contact interactions and failure mechanisms. A limited parameter study highlighted the importance of key factors influencing the radial buckling mechanism that includes external pressure, internal pressure, and damage, related to the percentage of wet annulus. The importance of radial contact pressure and shear stress between layers was also identified. The outcomes may be used to improve guidance in the engineering analysis and design of flexible pipelines and to support the improvement of recommended practices.
Load Torque Estimation Method to Design Electric Drivetrains for Offshore Pipe Handling Equipment
Authors: Pawlus Witold , Choux Martin , Hansen Michael R. , Hovland Geir
Published: March 2016

One of the main design objectives for electric drivetrains operating in offshore drilling equipment is to keep them as small, yet as effective, as possible, to minimize space they occupy on drill floor and maximize their performance. However, practical experience shows that typically choices made by design engineers are too conservative due to the lack of enough data characterizing load conditions. This results in too costly and too heavy selected components. Therefore, in the current paper we present a method to estimate required full-scale motor torque using a scaled down experimental setup and its computational model. A gripper arm of an offshore vertical pipe handling machine is selected as a case study for which the practical significance of the current work is demonstrated. The presented method has a potential to aid design of electrically actuated offshore drilling equipment and help design engineers choose correctly dimensioned drivetrain components.
Efficient Dynamic Analysis of a Nonlinear Wave Energy Harvester Model
Authors: Spanos Pol D. , Arena Felice , Richichi Alessandro , Malara Giovanni
Published: March 2016

In recent years, wave energy harvesting systems have received considerable attention as an alternative energy source. Within this class of systems, single-point harvesters are popular at least for preliminary studies and proof-of-concept analyses in particular locations. Unfortunately, the large displacements of a single-point wave energy harvester are described by a set of nonlinear equations. Further, the excitation is often characterized statistically and in terms of a relevant power spectral density (PSD) function. In the context of this complex problem, the development of efficient techniques for the calculation of reliable harvester response statistics is quite desirable, since traditional Monte Carlo techniques involve nontrivial computational cost. The paper proposes a statistical linearization technique for conducting expeditiously random vibration analyses of single-point harvesters. The technique is developed by relying on the determination of a surrogate linear system identified by minimizing the mean square error between the linear system and the nonlinear one. It is shown that the technique can be implemented via an iterative procedure, which allows calculating statistics, PSDs, and probability density functions (PDFs) of the response components. The reliability of the statistical linearization solution is assessed vis-à-vis data from relevant Monte Carlo simulations. This novel approach can be a basis for constructing computationally expeditious assessments of various design alternatives.
Experimental and Analytical Investigations of Dynamic Characteristics of Magnetorheological and Nanomagnetorheological Fluid Film Journal Bearing
Authors: Bompos Dimitrios A. , Nikolakopoulos Pantelis G.
Published: March 2016

The integrity and reliability of a rotor depend significantly on the dynamic characteristics of its bearings. Bearing design has been altered in many ways in order to achieve improvement in terms of damping and stiffness. A promising field in terms of vibration control and overall performance improvement for the journal bearings is the use of smart lubricants. Smart lubricants are fluids with controllable properties. A suitable excitation, such as an electric or a magnetic field, is used as a means of smart fluid properties control. Magnetorheological (MR) fluids consist one category of lubricants with controllable properties, thanks to magnetic particles inside the fluid volume. In this case of material, a magnetostatic field affects the apparent viscosity of the fluid by aligning the magnetic particles into chains. In this work, an MR fluid is produced. An MR fluid film bearing was constructed, which is capable of exciting the MR fluid. These bearing performances are examined experimentally and its dynamic properties are evaluated using an impact excitation method for an SAE-10 W lubricant as well as with the produced MR fluid both in its active and in its inactive state.
Differentiation of crystalline and amorphous phases in photothermorefractive glass by secondary ion mass spectrometry
Authors: Klimov Mikhail , Glebov Leonid , Glebova Larissa
Published: March 2016

Photothermorefractive glass (PTRG) is a complex material combining properties of amorphous and crystalline components in the same matrix. PTRG is one of the leading photosensitive materials in holographic gratings production and is a new optical material for lasers. Even though PTRG application is quite mature, the precise mechanism for induced photosensitivity is still under intense investigation. This paper presents secondary ion mass spectrometry investigation in this question by identifying and optimizing detection of secondary ion clusters that provide not only elemental but also structural information on the composition of the PTRG. The crystalline phase of NaF is presumably responsible for the photosensitivity of PTRG and was differentiated from Na and F bound in amorphous matrix by detection of (NaF)Na+, Cs(NaF)2+, and (NaF)2Na+ secondary ion clusters. Choices of secondary clusters and their sensitivity to NaF crystallinity are discussed. The depth profiles of crystalline NaF on PTRG samples of varying degree of crystallization as well as on a holographic grating are presented.
PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations
Authors: Zou Weiping , Wolchok Jedd D. , Chen Lieping
Published: March 2016

PD pathway blockade elicits durable antitumor responses in a subset of patients with a broad spectrum of cancers.
A dominant gain-of-function mutation in universal tyrosine kinase
SRC
causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies
Authors: Turro Ernest , Greene Daniel , Wijgaerts Anouck , Thys Chantal , Lentaigne Claire , Bariana Tadbir K. , Westbury Sarah K. , Kelly Anne M. , Selleslag Dominik , Stephens Jonathan C. , Papadia Sofia , Simeoni Ilenia , Penkett Christopher J. , Ashford Sofie , Attwood Antony , Austin Steve , Bakchoul Tamam , Collins Peter , Deevi Sri V. V. , Favier Rémi , Kostadima Myrto , Lambert Michele P. , Mathias Mary , Millar Carolyn M. , Peerlinck Kathelijne , Perry David J. , Schulman Sol , Whitehorn Deborah , Wittevrongel Christine ,   BRIDGE-BPD Consortium, De Maeyer Marc , Rendon Augusto , Gomez Keith , Erber Wendy N. , Mumford Andrew D. , Nurden Paquita , Stirrups Kathleen , Bradley John R. , Lucy Raymond F. , Laffan Michael A. , Van Geet Chris , Richardson Sylvia , Freson Kathleen , Ouwehand Willem H.
Published: March 2016

E527K hyperactive SRC results in megakaryocytes with increased podosome formation, thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.
Dendritic cell vaccines based on immunogenic cell death elicit danger signals and T cell–driven rejection of high-grade glioma
Authors: Garg Abhishek D. , Vandenberk Lien , Koks Carolien , Verschuere Tina , Boon Louis , Van Gool Stefaan W. , Agostinis Patrizia
Published: March 2016

Combining an immunogenic cell death inducer with dendritic cell immunotherapy treats high-grade glioma in a preclinical model.
Giant seminal vesicle cyst: an unusual site for a malignant extragastrointestinal stromal tumour
Authors: Boaz Ranil Johann , George Arun Philip , Manoj Kumar Ramani , Devasia Antony
Published: March 2016

Mesenchymal tumours with clinicopathological and molecular profiles similar to gastrointestinal stromal tumours (GISTs) are, on occasion, found in extragastrointestinal locations. Extra GIST (EGIST) is a singular occurrence in the genitourinary tract. A 30-year-old man, catheterised following urinary retention, was found to have a complex pelvic retrovesical cyst on imaging. At operation, origin from the right seminal vesicle was evident with histopathology confirming a GIST. The patient received adjuvant therapy with tyrosine kinase inhibitor and is currently disease free at 2 years. This is only the second report of an EGIST at this anatomic locale. The current literature presents significant uncertainty in defining the true origin of EGISTs, particularly those in the pelvis. We propose the designation origin indeterminate stromal tumour (OIST), to facilitate disambiguation and advance accurate profiling of EGIST; a subject in evolution.
Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials
Authors: Yee Brittany E , Nguyen Nghia H , Jin Minjuan , Lutchman Glen , Lim Joseph K , Nguyen Mindie H
Published: March 2016

Background

High sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of available data evaluating the effectiveness of SMV+SOF±RBV in HCV-1.

Methods

We performed a comprehensive literature search in June 2015 to identify randomised controlled trials (RCTs) and observational studies of HCV-1 patients treated with 12 weeks of SMV+SOF±RBV. Original studies with SVR12 data in ≥5 HCV-1 patients were included. We excluded studies on liver transplant recipients and/or patients co-infected with HIV or hepatitis B/D. We estimated pooled effect sizes using a random-effects model and evaluated heterogeneity with Cochrane Q-test, p≤0.10 and I2statistic ≥50%.

Results

Pooled SVR12 was 85.6% (CI 81.3% to 89.0%) in 1389 HCV-1 patients from 15 studies. On subgroup analysis, SVR12 was 83.9% (CI 79.4% to 87.5%) in observational studies, which was lower than 93.5% (CI 85.7% to 97.2%) in RCTs. A trend showed SVR12 was higher in mild fibrosis, 93.0% (CI 86.2% to 96.6%) compared with advanced fibrosis, 81.5% (CI 75.7% to 86.1%), OR 2.22 (CI 0.79 to 6.25, p=0.131). There was no significant difference in SVR12 rates between HCV-1a, 89.9% (CI 81.9% to 94.6%) and HCV-1b, 89.0% (CI 78.9% to 94.6%) with OR 1.35 (CI 0.75 to 2.42, p=0.322). The most common pooled side effects were: headache 15.2% (n=55/361), fatigue 12.1% (n=78/646), nausea 9.5% (n=50/527) and rash 9.3% (n=68/728).

Conclusions

SMV+SOF±RBV is an effective regimen in HCV-1 patients. The SVR12 rate in observational studies was lower than that in RCTs, which may reflect the more diverse patient population in real-world settings.
Development and validation of a lipase nasogastric tube position test
Authors: Anderson Oliver , Carr Reuben , Harbinson Merrilee , Hanna George Bushra
Published: March 2016

Background

Nasogastric tube position should be checked every day by either aspirate pH or chest radiography to prevent fatal misplaced feeding into the lungs. Many patients do not have acidic gastric aspirates and require daily chest radiographs. We developed and validated a lipase test that was compatible with non-acidic gastric aspirates.

Methods

We conducted evaluations of diagnostic test accuracy at a teaching hospital in development and validation stages.Development: We collected gastric and lung aspirates from 34 consecutive patients. We measured pH and human gastric lipase activity in the laboratory. These data helped us develop the lipase test. Ingenza Ltd (Roslin, Scotland) created tributyrin-coated pH test paper, which human gastric lipase converted into butyric acid, thus correcting false negatives.Validation: We tested nasogastric feeding tube aspirates from 36 consecutive patients with pH and lipase tests, using chest radiography or trial by use as the reference standard.

Results

Development:We demonstrated human gastric lipase activity in the non-acidic stomach aspirates.Validation:The accuracy of the lipase test (sensitivity 97.2%, specificity 100%) was significantly better than pH (sensitivity 65.7%, specificity 100%, p<0.05).

Conclusions

When nasogastric tube stomach aspirates were not acidic and pH was falsely negative, the lipase test showed a true positive and was significantly more accurate.
Hyperbilirubinaemia in HIV–HCV co-infected patients on antiretroviral therapy: drug effect or liver disease severity?
Authors: Kaspar Matthew B , Sterling Richard K
Published: March 2016

Objective

Hyperbilirubinaemia (HB) is common in HIV and hepatitis C virus (HIV–HCV) co-infected patients and poses a unique challenge in management as it may be due to medications such as the protease inhibitors (PIs) or to hepatic dysfunction. There are no data on the relationship of HB to liver histology and PI use in this population. Clinicians caring for these patients are faced with the difficult task of determining whether increasing serum bilirubin is due to drug effects or progression of liver disease.

Methods

To address this gap in knowledge, we performed a retrospective analysis of 344 consecutive HIV–HCV co-infected patients undergoing liver biopsy to identify factors associated with HB. Demographic, clinical, laboratory data were collected. Advanced fibrosis was defined as bridging fibrosis or cirrhosis. Those with hepatitis B virus, hepatic decompensation or hepatocellular carcinoma were excluded.

Results

The prevalence of HB (range 1.3–9.4) was 33% and more common in those on a PI (46%) than those who were not (10%; p≤0.001) and mostly in those on indinavir (40%) or atazanavir (46%). Of the patients on these PIs, HB was not associated with fibrosis grade, demographics, or other clinical variables. Conversely, in those not on a PI, HB was associated with fibrosis grade (p≤0.0001) after adjusting for other clinical and demographic variables.

Conclusions

In the setting of indinavir or atazanavir use, HB is common and unrelated to underlying disease severity and the medications can be continued safely. Conversely, HB in HIV–HCV co-infected patients not on a PI is due to their underlying liver disease and suggests these patients require closer monitoring.
Effect of early goal-directed therapy on mortality in patients with severe sepsis or septic shock: a meta-analysis of randomised controlled trials
Authors: Yu Hong , Chi Dongmei , Wang Siyang , Liu Bin
Published: March 2016

Objective

To determine whether patients with severe sepsis or septic shock could benefit from a strict and early goal-directed therapy (EGDT) protocol recommended by Surviving Sepsis Campaign (SSC) Guidelines.

Methods

MEDLINE/PubMed, EMBASE/OVID and Cochrane Central Register of Controlled Trials (CENTRAL) were searched between March 1983 and March 2015. Eligible studies evaluated the outcomes of EGDT versus usual care or standard therapy in patients with severe sepsis or septic shock. The primary outcomes were mortality within 28 days, 60 days and 90 days. Included studies must report at least one metric of mortality.

Results

5 studies that enrolled 4303 patients with 2144 in the EGDT group and 2159 in the control group were included in this meta-analysis. Overall, there were slight decreases of mortality within 28 days, 60 days and 90 days in the random-effect model in patients with severe sepsis or septic shock receiving EGDT resuscitation. However, none of the differences reached statistical significance (RR=0.86; 95% CI 0.69 to 1.06; p=0.16; p for heterogeneity=0.008, I2=71%; RR=0.94; 95% CI 0.81 to 1.10; p=0.46; p for heterogeneity=0.16, I2=43%; RR=0.98; 95% CI 0.88 to 1.10; p=0.75; p for heterogeneity=0.87, I2=0%, respectively).

Conclusions

The current meta-analysis pooled data from five RCTs and found no survival benefit of EGDT in patients with sepsis. However, the included trials are not sufficiently homogeneous and potential confounding factors in the negative trials (ProCESS, ARISE and ProMISe) might bias the results and diminish the treatment effect of EGDT. Further well-designed studies should eliminate all potential source of bias to determine if EGDT has a mortality benefit.
Association between employment status change and depression in Korean adults
Authors: Yoo Ki-Bong , Park Eun-Cheol , Jang Suk-Yong , Kwon Jeoung A , Kim Sun Jung , Cho Kyoung-hee , Choi Jae-Woo , Kim Jae-Hyun , Park Sohee
Published: March 2016

Objectives

This study investigated the association between employment status and depression.

Methods

Data from the Korea Welfare Panel Study (KOWEPS) collected from 2008 to 2011 were used. A total of 7368 subjects were included in this study after exclusion of subjects with missing data and those who were self-employed or could not work. Depression was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Employment status, age, sex, region, education, marital status, income, head of household, self-rated health, smoking status, drinking habits, and the current year's and the previous year's CES-D scores were included in the model as independent variables. A generalised linear mixed-effects model for longitudinal binary data was used.

Results

Compared with those who were permanently employed, individuals who moved from permanent to precarious employment (OR 1.45, 95% CI 1.23 to 1.70) or to unemployment (OR 1.78, 95% CI 1.30 to 2.43) and from precarious employment to unemployment (OR 1.65, 95% CI 1.32 to 2.06) showed a significantly increased the odds of having depression. Continuing precarious employment (OR 1.54, 95% CI 1.30 to 1.83) or unemployment (OR 1.45, 95% CI 1.23 to 1.70) also significantly increased the odds of having depression. These results were particularly identified in men and head of household women. The effects were not significant among non-head of household women.

Conclusions

Precarious employment and unemployment were clearly associated with having depression. In addition, in view of our findings, policy makers should consider sex and head of household status when developing welfare policies. The inequity between precarious jobs and permanent jobs should be tackled.
Effectiveness of a multicentre nasopharyngeal carcinoma awareness programme in Indonesia
Authors: Fles Renske , Indrasari Sagung R , Herdini Camelia , Martini Santi , Isfandiari Atoillah , Romdhoni Achmad C , Adham Marlinda , Mayangsari Ika D , van Werkhoven Erik , Wildeman Maarten A , Hariwiyanto Bambang , Hermani Bambang , Kentjono Widodo A , Haryana Sofia M , Schmidt Marjanka K , Tan I Bing
Published: March 2016

Objective

To evaluate the effectiveness of a nasopharyngeal carcinoma (NPC) awareness programme on the short-term and long-term improvement of knowledge and referral of patients with NPC by primary healthcare centres (PHCCs) staff in Indonesia.

Design

The NPC awareness programme consisted of 12 symposia including a Train-The-Trainer component, containing lectures about early symptoms and risk factors of NPC, practical examination and the referral system for NPC suspects. Before and after training participants completed a questionnaire. The Indonesian Doctors Association accredited all activities.

Participants

1 representative general practitioner (GP) from each PHCC attended an NPC awareness symposium. On the basis of the Train-The-Trainer principle, GPs received training material and were obligated to train their colleagues in the PHCC.

Results

703 GPs attended the symposia and trained 1349 staff members: 314 other GPs, 685 nurses and 350 midwives. After the training, respondents’ average score regarding the knowledge of NPC symptoms increased from 47 points (of the 100) to 74 points (p<0.001); this increase was similar between symposium and Train-The-Trainer component (p=0.88). At 1½ years after the training, this knowledge remained significantly increased at 59 points (p<0.001).

Conclusions

The initial results of this NPC awareness programme indicate that the programme effectively increases NPC knowledge in the short and long term and therefore should be continued. Effects of the improved knowledge on the stage at diagnoses of the patients with NPC will still need to be scrutinised. This awareness programme can serve as a blueprint for other cancer types in Indonesia and for other developing countries.
Costs, effects and implementation of routine data emergency admission risk prediction models in primary care for patients with, or at risk of, chronic conditions: a systematic review protocol
Authors: Kingston Mark Rhys , Evans Bridie Angela , Nelson Kayleigh , Hutchings Hayley , Russell Ian , Snooks Helen
Published: March 2016

Introduction

Emergency admission risk prediction models are increasingly used to identify patients, typically with one or more chronic conditions, for proactive management in primary care to avoid admissions, save costs and improve patient experience.

Aim

To identify and review the published evidence on the costs, effects and implementation of emergency admission risk prediction models in primary care for patients with, or at risk of, chronic conditions.

Methods

We shall search for studies of healthcare interventions using routine data-generated emergency admission risk models. We shall report: the effects on emergency admissions and health costs; clinician and patient views; and implementation findings. We shall search ASSIA, CINAHL, the Cochrane Library, HMIC, ISI Web of Science, MEDLINE and Scopus from 2005, review references in and citations of included articles, search key journals and contact experts. Study selection, data extraction and quality assessment will be performed by two independent reviewers.

Ethics and dissemination

No ethical permissions are required for this study using published data. Findings will be disseminated widely, including publication in a peer-reviewed journal and through conferences in primary and emergency care and chronic conditions. We judge our results will help a wide audience including primary care practitioners and commissioners, and policymakers.

Trial registration number

CRD42015016874; Pre-results.
How adolescents experience and cope with pain in daily life: a qualitative study on ways to cope and the use of over-the-counter analgesics
Authors: Lagerløv Per , Rosvold Elin Olaug , Holager Tanja , Helseth Sølvi
Published: March 2016

Objective

The aim of this study was to describe how different adolescents experience and manage pain in their daily life, with a focus on their use of over-the-counter analgesics. More specifically, the aim was to explore different patterns among the adolescents in pain descriptions, in the management of pain, in relationships with others, and in their daily life.

Design

Qualitative semistructured interviews on experiences with pain, pain management and involvement of family and friends during pain. Pain and stress management strategies and attachment theory will be in focus for interpretations.

Participants and setting

25 participants aged 15–16-years from six different junior high schools, both genders, with and without immigrant background were interviewed at their local schools in Norway.

Results

We identified 4 groups of adolescents with similarities in attitudes and management strategies to pain: ‘pain is manageable’, ‘pain is communicable’, ‘pain is inevitable’ and ‘pain is all over’. The participants within each group differed in how they engaged their parents in pain; how they perceived, communicated and managed pain; and how they involved emotions and used over-the-counter analgesics.

Conclusions

The adolescents’ different involvement with the family during pain related to their pain perception and management. Knowledge of the different ways of approaching pain is important when supporting adolescents and may be a subject for further research on the use of over-the-counter analgesics in the family.