bluuebunny/crossref_metadata_2025 huggingface dataset:
Facility Integrity Management and Assessment of Associated Risk Conditions
Authors: Jaske Carl E. , Brongers Michiel P. H.
Published: November 2015

This paper reviews the basic elements of a facility integrity management program and describes the process used to assess risk conditions related to a facility. The policies, goals and objectives of the program should be defined before implementing it. The location and details of the facility and all its equipment must be described and the information should be recorded in a computerized database. Important triggers for change management and the minimum features of change management are reviewed. Ensuring the competency and training of personnel responsible for integrity management is essential. The integrity management team must identify hazards associated and ways of controlling them. Once hazards are identified, risk assessment is performed and options for reducing risk are considered. Results of the risk assessment are then used to plan and execute activities of the integrity management program. Needed repairs or replacements are identified, planned and completed. Finally, the integrity management program should incorporate a continuous improvement process and information from investigations of incidents at the facility, at other company locations, and within the industry.
Balanced and Standard Globe Valves Operating Load Profiles With Flow Over the Discs/Plugs
Authors: Ezekoye L. Ike , Matty Terrence J. , Hobbs Matt , Farrell Ronald S.
Published: November 2015

Standard globe valves have one disc and are used for the majority of valve applications in flow isolation and modulation services. However, as the size of the valves get bigger, such as 8 inches or greater; the operating load requirements get much bigger by the square of the plug/disc diameter. The bigger the operating loads, the larger are the actuators, which increase cost. At some point, it makes sense for economic reasons to utilize balanced globe valves to reduce the operating loads and thereby reduce actuator cost. Balanced globe valves have more than one plug/disc. Generally, balanced globe valves have an inner disc often referred to as the pilot and an outer disc often referred to as the main disc. The pilot is used to balance the differential pressure across the main disc which allows the main disc to open at a lower differential pressure and hence results in reduced force to open or close the valve. In this paper, the variation of balanced globe and standard globe valve required operating load profiles in the forward flow over the seat flow direction, are presented. The relationship of the pilot disc area to the main disc area is presented to show how this relationship affects valve performance. The impact of the operating load reversal during valve closing on electric motor actuators will be discussed and recommendations provided to guard against valve stalling during closing. The parameters that can affect the occurrence of peak loads as percent of valve travel for the pilot and the main seat will be discussed. The effect of pilot to main disc area ratio on valve factor will be presented. The results of the studies on the balanced globe valves will be compared against the performance of a standard globe valve (i.e., not balanced) with flow over the disc/plug particularly in area of valve factors.
Calibrating Phase Transformation and Grain Growth Models and Measuring Phase Dependent Material Properties for Use in FE Simulations of Welds
Authors: O’Meara Nicholas , Smith Simon D. , Francis John A.
Published: November 2015

Computer modelling methods are being used to determine the residual stresses in nuclear reactor pressure vessel welds. It has been found that such models need to simulate the effects of solid state phase transformations. Transformations have an associated transformation strain which can significantly influence the evolution of residual stress. The predicted distribution of phases enables structural simulations to account for the distribution of mechanical properties throughout a weld. Factors such as heating or cooling rate and prior austenite grain size must be considered in order to accurately predict the distribution of phases during a transient thermal cycle since they influence transformation kinetics.

In this paper, a model to predict the prior austenite grain size and its effects on phase transformation kinetics is presented and calibrated using free dilatometry data. Validation experiments are conducted using a Gleeble thermo-mechanical simulator and are modelled in a commercial FE package to assess the accuracy of a phase transformation model. Samples have been heat treated to possess specific microstructures and have been tested at different temperatures to establish the properties of the phases that can form during weld thermal cycles.
Stress Intensity Factors of a Three-Point Bend Specimen Under Dynamic Loading
Authors: Chao Yuh J. , Lam Poh-Sang
Published: November 2015

Stress intensity factors for a three-point bend specimen under dynamic loadings are obtained through the displacement fields using digital image correlation (DIC) method. The dynamic loads are generated with a drop weight to impact the specimen while the crack remains stationary in this study. It shows that the stress intensity factor oscillates as a function of time. The experimental details and the comparison with theoretical solutions are presented.
A Study on Leakage Flow Induced Vibration From Engineering Viewpoint
Authors: Inada Fumio
Published: November 2015

Leakage-flow-induced vibration for a relatively short gap is studied analytically to provide useful information to design structures that include a leakage flow. The relationship between the analysis of a one-dimensional system and that of an annular gap is explained first. Then, the mechanism of flutter-type instability is reproduced from previous study after correcting an error. Finally, the self-excited vibration potential of an engineering system is shown from sample calculations. It is shown that an axial flow becomes dominant in the short-gap approximation, and in this case, the analysis of a one-dimensional flow can be expanded to that of an annular flow. The result that negative damping can occur in the case of a divergent passage owing to the delay induced by fluid inertia was obtained from a previous study. It was suggested analytically that the damping ratio could become negative and its absolute value could become more than 10% in a system that is frequently encountered in a plant, if the natural frequency decreases. The value could be sufficient to generate self-excited vibration.
Monitoring Helium Integrity in Welded Canisters
Authors: Liu Y. Y. , Tsai H.-C. , Nutt M.
Published: November 2015

Monitoring the interior of a welded canister containing spent (or used) nuclear fuel for its functional and structural integrity is exceptionally challenging because of the intense levels of heat and radiation and the difficulties of transmitting the sensor signals out through the sealed stainless-steel canister wall. Yet, confirmation of canister integrity is crucial for the aging management of the dry cask storage systems (DCSSs) for extended long-term storage and subsequent transportation of used fuel. A canister breach can lead to serious consequences — release of radioactive contaminants; oxidation of fuel cladding, which could compromise fuel rod integrity and criticality safety; and generation of potentially explosive hydrogen gas. The development of the Remote Area Modular Monitoring (RAMM) technology and 3D simulation of thermal performance of a vertical dry storage cask are reported in this paper, as is a preliminary plan for field-testing and evaluation of multiple prototype RAMM units on selected dry storage casks at an Independent Spent Fuel Storage Installation (ISFSI) site.
Example Analysis for Environmental Fatigue Crack Growth in Austenitic Stainless Steel Piping Using Code Case N-809
Authors: Bamford Warren H. , Cipolla Russell C. , Udyawar Anees , Glunt Nathan L.
Published: November 2015

Reference fatigue crack growth (da/dN) curves for pressurized water reactor (PWR) environments have been proposed for ASME Section XI flaw evaluation applications in Code Case N-809. The reference curves are dependent on temperature, loading rate, mean stress, and cyclic stress range which are all contained in the da/dN model. This paper presents the application of N-809 in a fatigue crack growth analysis for a large diameter austenitic pipe in a PWR Reactor Coolant System main loop using the current analytical evaluation procedures in Appendix C of ASME Section XI. The example problem was used to evaluate the reference fatigue crack growth curves during the development of the code case and the results have been compared with other industry codes.
Experimental Consideration of the Detonation Expansion Wave Limit
Authors: Ligon Thomas C. , Pellman Abby M. , Minichiello John C.
Published: November 2015

The pressure time-history associated with a propagating detonation within a pipe can be reasonably well described using a one-dimensional model. These models describe the advancement of the detonation front and the expansion wave behind the detonation front, over which the pressure decays. The length of the expansion wave, and the corresponding pressure decay period, is a function of the distance the detonation wave has traveled. One-dimensional detonation models typically assume an isentropic expansion behind the detonation front. The consequence of this assumption is that the expansion wave will grow infinitively long in an infinitely long pipe. The loss of energy due to heat transfer, however, has been observed to result in a natural limit in the length of the expansion wave, and corresponding pressure decay.

The implication of this limit on piping design for gaseous detonations is that there is a limit on the pressure-impulse that is applied to the system. When a detonation propagates through a piping system, the detonation pressure produces unbalanced loads at the bends, tees, reducers, and closed-ends. These transient loads are a function of both the peak pressure and the details of the pressure decay. In long piping systems, the decay period of the expansion wave can become sufficiently long that very high loads are imposed on the system. Crediting a natural limit of these loads may have significant implications for the design of the pipe and its supports.

Although the existence of an expansion wave limit has been previously observed, consensus on its length does not currently exist in the literature. This paper describes detonation tests that were performed in both 2-inch and 4-inch 36.6m long pipes using mixtures of hydrogen and nitrous oxide. Pressure transducers were installed at periodic locations along the pipe. The slope of the initial pressure decay of the detonation was used to characterize its shape. The slope of the initial pressure decay was found to exponentially approach a limiting steady state value, and this limiting value was achieved after the detonation had propagated approximately 120 pipe diameters.
Pressure-Pulse Attenuation in a Non-Newtonian Slurry With a Dispersed Non-Condensable Gas Phase
Authors: Jones Ryan E. , Pellman Abby M. , Minichiello John C.
Published: November 2015

The Hanford Tank Waste Treatment and Immobilization Plant (WTP), located in southeastern Washington state, will process waste slurries capable of retaining a dispersed non-condensable gas phase while in a quiescent state. Under postulated conditions, a pressure pulse generated from a deflagration or detonation within a flammable gas pocket may be transmitted into piping systems that contain the gas-liquid slurry. In general, this traveling pressure pulse will impose structural loads on the piping and its associated supports. It is necessary to understand how a pressure pulse attenuates as it propagates through the system in order to properly quantify the structural loading. Simplifications to the general equations are presented in this paper that are applicable to WTP while eliminating the numerical challenges associated with the full set of equations. This alternate set of equations is used to model the propagation and attenuation of a pressure pulse characteristic of those of interest to WTP in a slurry system that contains a small amount of dispersed non-condensable gas. The numerical results are compared to experimental data and are shown to be consistent with experimental observations.
Flashing Phenomena of Liquid Nitrogen in a Pressure Vessel Under Rapid Depressurizations
Authors: Watanabe Toshiaki , Maehara Hironori , Nakamura Makoto , Ohta Hiromitsu , Itoh Shigeru
Published: November 2015

In recent years in Japan, the demand of cryogenic fluids like a LH2, LNG is increasing because of the advance of fuel cell device technology, hydrogen of engine, and stream of consciousness for environmental agreement. The purpose of this study is to clarify some fundamental features of the flashing of cryogenic fluids. Experiments on flashing of liquid nitrogen were conducted to clarify the effect of surface roughness of a vessel. Two types of pressure vessel were used. One is a vessel made of stainless steel, the other is a vessel made of glass. In the case of glass vessel, many types of boiling have been observed. The degree of superheat at the start of boiling was found to depend strongly on the rate of depressurization.
A Proposed Generalized Model for Forming Limit Diagram
Authors: El Domiaty Aly , Mourad Abdel-Hamid I. , Bouzid Abdel-Hakim
Published: November 2015

One of the most significant approaches for predicting formability is the use of forming limit diagrams (FLDs). The development of the generalized model integrates other models. The first model is based on Von-Misses yield criterion (traditionally used for isotropic material) and power law constitutive equation considering the strain hardening exponent. The second model is also based on Von-Misses yield criterion but uses a power law constitutive equation that considers the effect of strain rate sensitivity factor. The third model is based on the modified Hill’s yield criterion (for anisotropic materials) and a power law constitutive equation that considers the strain hardening exponent. The current developed model is a generalized model which is formulated on the basis of the modified Hill yield criterion and a power law constitutive equation considering the effect of strain rate. A new controlling parameter (γ) for the limit strains was exploited. This parameter presents the rate of change of strain rate with respect to strain. As γ increases the level of the FLD raises indicating a better formability of the material.
Can a Weld in Welded Structure Be Made With Zero Residual Stress?
Authors: Tchernov Stanislav , Goldak John A.
Published: November 2015

While solving a sequence of seventeen optimization projects to predict the values of the side heater parameters that would be expected to minimize camber distortion in an edge welded bar, the design parameters that reduced distortion to effectively zero were not unique. This raised the question if any of the designs that minimized the distortion effectively to zero also minimized the residual stress. To answer this question three different measures of residual stress were evaluated for all 1451 designs. The Computational Weld Mechanics (CWM) optimization problem is to find the best point in the 4D space of side heater design parameters: flux, heated area, longitudinal and transverse distance from the weld such that the final residual stress is as low as possible (minimized). To evaluate the objective function for each point in the 4D design space, the associated 3D transient non-linear thermal visco-elastic-plastic stress analyzes was solved. A FEM mesh with 6600 8-node brick elements and 9438 nodes was solved for 166 time steps in 10 minutes of single-core CPU time. In the seventeen optimization projects, 1451 weld analyses were solved in 75 quad-core CPU hours by one person in two calendar weeks. The residual stress was effectively reduced to zero in some designs. These designs also reduced distortion to effectively zero. Whether a design that effectively reduces the residual stress to zero is unique remains an open question.
Are Retirement Villages Promoting Active Aging?
Authors: Holt Annie , Lee Andy H. , Jancey Jonine , Kerr Deborah , Howat Peter
Published: November 2015

Purpose:

This study investigated physical activity (PA) facilities of retirement villages (RVs) and neighborhood PA barriers identified by RV residents in Perth, Australia.

Methods:

An environmental audit of PA facilities was undertaken on 50 RV with 50+ independent living units, using the Audit of Physical Activity Resources for Seniors. Telephone interviews with 200 RV residents were conducted to identify neighborhood barriers to walking, and to obtain information on utilization of facilities and attendance of PA programs.

Results:

Larger size RV appeared to provide significantly more PA facilities and programs. Utilization of PA facilities and program attendance were low (≈ 50%) and not associated with the RV environment (size, age, and facilities). Neighborhood barriers to walking were unsafe streets and hills.

Discussion:

RV offers an attractive residential option with facilities that support active aging, but it is important to understand the barriers and enablers to use such facilities and attend programs offered.
From the Physical to the Social: Twitter as a Pedagogical Innovation in the Sport Communication and Sport Management Classroom
Authors: Sanderson Jimmy , Browning Blair
Published: November 2015

This essay discusses how Twitter can be used as a pedagogical tool for sport communication and sport management courses. Given the prevalence with which Twitter has penetrated the sport industry and the frequency with which college students use social media, Twitter is a complementary and viable classroom component. The essay provides ways in which Twitter can be used for formal assignments in the sport communication and sport management classroom. The essay concludes by discussing some challenges to using Twitter in the classroom, describing strategies for overcoming these barriers, and encouraging sport communication and sport management educators to embrace the culture of convergence that Twitter affords. The appendix offers detailed guidelines for the assignments discussed in the essay.
The Fantasy of Learning: Fantasy Football in a Sports Public Relations Course
Authors: Woo Chang Wan , Davis Michael K.
Published: November 2015

Sports-related programs in higher education need to educate students in the professional use of evolving communication technologies. In addition, students need to develop soft skills, such as problem solving and critical thinking, while improving their practical use of technology. The purpose of this article is to introduce the use of fantasy sports in a sports management class, more specifically a sports public relations class, and discuss how students perceived the use of fantasy sports in course assignments. We explain how the use of fantasy sports assignments promoted social constructivist learning of students and helped students develop soft skills. We also identify the pedagogical challenges the fantasy sports assignments presented to students and instructors. We also offer summaries of students’ class reflections to demonstrate how such reflections echoed course learning outcomes.
Europe's research chief wants scientists to speak up
Authors: Rabesandratana Tania
Published: November 2015

Commissioner Carlos Moedas is confident that science and innovation will bring growth to a divided continent.
Crystalline eyes of chitons inspire materials scientists
Authors: Pennisi Elizabeth
Published: November 2015

Mollusk makes hundreds of eyes from shell mineral.
“Water-in-salt” electrolyte enables high-voltage aqueous lithium-ion chemistries
Authors: Suo Liumin , Borodin Oleg , Gao Tao , Olguin Marco , Ho Janet , Fan Xiulin , Luo Chao , Wang Chunsheng , Xu Kang
Published: November 2015

A concentrated effort for battery safety

Aqueous electrolytes are limited to run below 1.23 V to avoid degradation. Suo
et al.
smash through this limit with an aqueous salt solution containing lithium (Li) bis(trifluoromethane sulfonyl)imide to create an electrolyte that has an electrochemical window of 3 V (see the Perspective by Smith and Dunn). They used extremely high-concentration solutions, which suppressed hydrogen evolution and electrode oxidation. At these concentrations, the Li solvation shell changes because there simply is not enough water to neutralize the Li
+
charge. Thus, flammable organic electrolytes could potentially be replaced with a safer aqueous alternative.

Science
, this issue p.
938
; see also p.
918
Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria
Authors: Mandala Wilson L. , Msefula Chisomo L. , Gondwe Esther N. , Gilchrist James J. , Graham Stephen M. , Pensulo Paul , Mwimaniwa Grace , Banda Meraby , Taylor Terrie E. , Molyneux Elizabeth E. , Drayson Mark T. , Ward Steven A. , Molyneux Malcolm E. , MacLennan Calman A.
Published: November 2015

Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (
n
= 113) and healthy aparasitemic children (
n
= 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69
+
NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4
+
lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria.
Characterization of Samples Identified as Hepatitis C Virus Genotype 1 without Subtype by Abbott RealTi
m
e HCV Genotype II Assay Using the New Abbott HCV Genotype
Plus
RUO Test
Authors: Mokhtari Camelia , Ebel Anne , Reinhardt Birgit , Merlin Sandra , Proust Stéphanie , Roque-Afonso Anne-Marie
Published: November 2015

Hepatitis C virus (HCV) genotyping continues to be relevant for therapeutic strategies. Some samples are reported as genotype 1 (gt 1) without subtype by the Abbott RealTi
m
e HCV Genotype II (GT II) test. To characterize such samples further, the Abbott HCV Genotype
Plus
RUO (Plus) assay, which targets the core region for gt 1a, gt 1b, and gt 6 detection, was evaluated as a reflex test in reference to NS5B or 5′-untranslated region (UTR)/core region sequencing. Of 3,626 routine samples, results of gt 1 without subtype were received for 171 samples (4.7%), accounting for 11.5% of gt 1 specimens. The Plus assay and sequencing were applied to 98 of those samples. NS5B or 5′-UTR/core region sequencing was successful for 91/98 specimens (92.9%). Plus assay and sequencing results were concordant for 87.9% of specimens (80/91 samples). Sequencing confirmed Plus assay results for 82.6%, 85.7%, 100%, and 89.3% of gt 1a, gt 1b, gt 6, and non-gt 1a/1b/6 results, respectively. Notably, 12 gt 6 samples that had been identified previously as gt 1 without subtype were assigned correctly here; for 25/28 samples reported as “not detected” by the Plus assay, sequencing identified the samples as gt 1 with subtypes other than 1a/1b. The genetic variability of HCV continues to present challenges for the current genotyping platforms regardless of the applied methodology. Samples identified by the GT II assay as gt 1 without subtype can be further resolved and reliably characterized by the new Plus assay.
Multicenter Evaluation of MRSASelectII Chromogenic Agar for Identification of Methicillin-Resistant Staphylococcus aureus from Wound and Nasal Specimens
Authors: Hernandez Diana R. , Newton Duane W. , Ledeboer Nathan A. , Buchan Blake , Young Carol , Clark Andrew E. , Connoly Jessica , Wolk Donna M.
Published: November 2015

Hospitals strive to reduce methicillin-resistantStaphylococcus aureus(MRSA) prevalence via active surveillance of inpatient populations. Rapid and inexpensive screening methods are utilized when molecular methods are not operationally feasible. In this multisite clinical trial, the utility of Bio-Rad's MRSASelectII was evaluated for MRSA identification from remnant nares and wound swabs. The prevalence of MRSA was 11.1% (n= 1,384) from nares samples and 18.1% (n= 842) from wound samples. MRSASelectII had an overall concordance of 95.4% (confidence interval [CI] = 94.5% to 96.2%) compared to a broth-enriched reference standard. Comparisons between results, stratified by examination times, exhibited a nonsignificant trend toward increased positivity at prolonged incubation times. Cefoxitin screening of colonies directly from MRSASelectII was 96.7% (95.8% to 97.3%) concordant compared to testing of colonies following broth enrichment. A comparison of MRSASelectand MRSASelectII revealed no statistical differences; however, the latter exhibited earlier positivity, greater selectivity, and more intense indicator staining, which resulted in facilitated differentiation of positive results. MRSASelectII agar is a simple, rapid, and robust method to routinely screen patients for MRSA colonization without the need for additional testing.
Enhanced Tracking of Nosocomial Transmission of Endemic Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Type IV Isolates among Patients and Environmental Sites by Use of Whole-Genome Sequencing
Authors: Kinnevey Peter M. , Shore Anna C. , Mac Aogáin Micheál , Creamer Eilish , Brennan Gráinne I. , Humphreys Hilary , Rogers Thomas R. , O'Connell Brian , Coleman David C.
Published: November 2015

Whole-genome sequencing (WGS) of 41 patient and environmental sequence type 22 methicillin-resistant
Staphylococcus aureus
staphylococcal cassette chromosome
mec
type IV (ST22-MRSA-IV) isolates recovered over 6 weeks in one acute hospital ward in Dublin, Ireland, where ST22-MRSA IV is endemic, revealed 228 pairwise combinations differing by <40 single nucleotide variants corresponding to potential cross-transmission events (CTEs). In contrast, 15 pairwise combinations of isolates representing five CTEs were previously identified by conventional molecular epidemiological typing. WGS enhanced ST22-MRSA-IV tracking and highlighted potential transmission of MRSA via the hospital environment.
Mechanism of Cell Culture Adaptation of an Enteric Calicivirus, the Porcine Sapovirus Cowden Strain
Authors: Lu Zhongyan , Yokoyama Masaru , Chen Ning , Oka Tomoichiro , Jung Kwonil , Chang Kyeong-Ok , Annamalai Thavamathi , Wang Qiuhong , Saif Linda J.
Published: November 2015

The porcine sapovirus (SaV) (PoSaV) Cowden strain is one of only a few culturable enteric caliciviruses. Compared to the wild-type (WT) PoSaV Cowden strain, tissue culture-adapted (TC) PoSaV has two conserved amino acid substitutions in the RNA-dependent RNA polymerase (RdRp) and six in the capsid protein (VP1). By using the reverse-genetics system, we identified that 4 amino acid substitutions in VP1 (residues 178, 289, 324, and 328), but not the substitutions in the RdRp region, were critical for the cell culture adaptation of the PoSaV Cowden strain. The other two substitutions in VP1 (residues 291 and 295) reduced virus replication
in vitro
. Three-dimensional (3D) structural analysis of VP1 showed that residue 178 was located near the dimer-dimer interface, which may affect VP1 assembly and oligomerization; residues 289, 291, 324, and 328 were located at protruding subdomain 2 (P2) of VP1, which may influence virus binding to cellular receptors; and residue 295 was located at the interface of two monomeric VP1 proteins, which may influence VP1 dimerization. Although reversion of the mutation at residue 291 or 295 from that of the TC strain to that of the WT reduced virus replication
in vitro
, it enhanced virus replication
in vivo
, and the revertants induced higher-level serum and mucosal antibody responses than those induced by the TC PoSaV Cowden strain. Our findings reveal the molecular basis for PoSaV adaptation to cell culture. These findings may provide new, critical information for the cell culture adaptation of other PoSaV strains and human SaVs or noroviruses.

IMPORTANCE
The tissue culture-adapted porcine sapovirus Cowden strain is one of only a few culturable enteric caliciviruses. We discovered that 4 amino acid substitutions in VP1 (residues 178, 289, 324, and 328) were critical for its adaptation to LLC-PK cells. Two substitutions in VP1 (residues 291 and 295) reduced virus replication
in vitro
but enhanced virus replication and induced higher-level serum and mucosal antibody responses in gnotobiotic pigs than those induced by the tissue culture-adapted strain. Structural modeling analysis of VP1 suggested that residue 178 may affect VP1 assembly and oligomerization; residues 289, 291, 324, and 328 may influence virus binding to cellular receptors; and residue 295 may influence VP1 dimerization. Our findings will provide new information for the cell culture adaptation of other sapoviruses and possibly noroviruses.
Preventing Cleavage of the Respiratory Syncytial Virus Attachment Protein in Vero Cells Rescues the Infectivity of Progeny Virus for Primary Human Airway Cultures
Authors: Corry Jacqueline , Johnson Sara M. , Cornwell Jessica , Peeples Mark E.
Published: November 2015

All live attenuated respiratory syncytial virus (RSV) vaccines that have advanced to clinical trials have been produced in Vero cells. The attachment (G) glycoprotein in virions produced in these cells is smaller than that produced in other immortalized cells due to cleavage. These virions are 5-fold less infectious for primary well-differentiated human airway epithelial (HAE) cell cultures. Because HAE cells are isolated directly from human airways, Vero cell-grown vaccine virus would very likely be similarly inefficient at initiating infection of the nasal epithelium following vaccination, and therefore, a larger inoculum would be required for effective vaccination. We hypothesized that Vero cell-derived virus containing an intact G protein would be more infectious for HAE cell cultures. Using protease inhibitors with increasing specificity, we identified cathepsin L to be the protease responsible for cleavage. Our evidence suggests that cleavage occurs in the late endosome or lysosome during endocytic recycling. Cathepsin L activity was 100-fold greater in Vero cells than in HeLa cells. In addition, cathepsin L was able to cleave the G protein in Vero cell-grown virions but not in HeLa cell-grown virions, suggesting a difference in G-protein posttranslational modification in the two cell lines. We identified by mutagenesis amino acids important for cleavage, and these amino acids included a likely cathepsin L cleavage site. Virus containing a modified, noncleavable G protein produced in Vero cells was 5-fold more infectious for HAE cells in culture, confirming our hypothesis and indicating the value of including such a mutation in future live attenuated RSV vaccines.

IMPORTANCE
Worldwide, RSV is the second leading infectious cause of infant death, but no vaccine is available. Experimental live attenuated RSV vaccines are grown in Vero cells, but during production the virion attachment (G) glycoprotein is cleaved. Virions containing a cleaved G protein are less infectious for primary airway epithelial cells, the natural RSV target. In the study described here we identified the protease responsible, located the cleavage site, and demonstrated that cleavage likely occurs during endocytic recycling. Moreover, we showed that the infectivity of Vero cell-derived virus for primary airway epithelial cells is increased 5-fold if the virus contains a mutation in the G protein that prevents cleavage. The blocking of cleavage should improve RSV vaccine yield, consequently reducing production costs. Posttranslational cleavage of the fusion glycoprotein of many viruses plays an essential role in activation; however, cleavage of the RSV G protein is a novel example of a detrimental effect of cleavage on virus infectivity.
Knockdown of Autophagy Inhibits Infectious Hepatitis C Virus Release by the Exosomal Pathway
Authors: Shrivastava Shubham , Devhare Pradip , Sujijantarat Nanthiya , Steele Robert , Kwon Young-Chan , Ray Ranjit , Ray Ratna B.
Published: November 2015

Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma in humans. We showed previously that HCV induces autophagy for viral persistence by preventing the innate immune response. Knockdown of autophagy reduces extracellular HCV release, although the precise mechanism remains unknown. In this study, we observed that knockdown of autophagy genes enhances intracellular HCV RNA and accumulates infectious virus particles in cells. Since HCV release is linked with the exosomal pathway, we examined whether autophagy proteins associate with exosomes in HCV-infected cells. We observed an association between HCV and the exosomal marker CD63 in autophagy knockdown cells. Subsequently, we observed that levels of extracellular infectious HCV were significantly lower in exosomes released from autophagy knockdown cells. To understand the mechanism for reduced extracellular infectious HCV in the exosome, we observed that an interferon (IFN)-stimulated BST-2 gene is upregulated in autophagy knockdown cells and associated with the exosome marker CD63, which may inhibit HCV assembly or release. Taken together, our results suggest a novel mechanism involving autophagy and exosome-mediated HCV release from infected hepatocytes.

IMPORTANCE
Autophagy plays an important role in HCV pathogenesis. Autophagy suppresses the innate immune response and promotes survival of virus-infected hepatocytes. The present study examined the role of autophagy in secretion of infectious HCV from hepatocytes. Autophagy promoted HCV trafficking from late endosomes to lysosomes, thus providing a link with the exosome. Inhibition of HCV-induced autophagy could be used as a strategy to block exosome-mediated virus transmission.
Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs
Authors: Bolton Diane L. , Pegu Amarendra , Wang Keyun , McGinnis Kathleen , Nason Martha , Foulds Kathryn , Letukas Valerie , Schmidt Stephen D. , Chen Xuejun , Todd John Paul , Lifson Jeffrey D. , Rao Srinivas , Michael Nelson L. , Robb Merlin L. , Mascola John R. , Koup Richard A.
Published: November 2015

Combination antiretroviral therapy (cART) administered shortly after human immunodeficiency virus type 1 (HIV-1) infection can suppress viremia and limit seeding of the viral reservoir, but lifelong treatment is required for the majority of patients. Highly potent broadly neutralizing HIV-1 monoclonal antibodies (MAbs) can reduce plasma viremia when administered during chronic HIV-1 infection, but the therapeutic potential of these antibodies during acute infection is unknown. We tested the ability of HIV-1 envelope glycoprotein-specific broadly neutralizing MAbs to suppress acute simian-human immunodeficiency virus (SHIV) replication in rhesus macaques. Four groups of macaques were infected with SHIV-SF162P3 and received (i) the CD4-binding-site MAb VRC01; (ii) a combination of a more potent clonal relative of VRC01 (VRC07-523) and a V3 glycan-dependent MAb (PGT121); (iii) daily cART, all on day 10, just prior to expected peak plasma viremia; or (iv) no treatment. Daily cART was initiated 11 days after MAb administration and was continued for 13 weeks in all treated animals. Over a period of 11 days after a single administration, MAb treatment significantly reduced peak viremia, accelerated the decay slope, and reduced total viral replication compared to untreated controls. Proviral DNA in lymph node CD4 T cells was also diminished after treatment with the dual MAb. These data demonstrate the virological effect of potent MAbs and support future clinical trials that investigate HIV-1-neutralizing MAbs as adjunctive therapy with cART during acute HIV-1 infection.

IMPORTANCE
Treatment of chronic HIV-1 infection with potent broadly neutralizing HIV-1 MAbs has been shown to significantly reduce plasma viremia. However, the antiviral effect of MAb treatment during acute HIV-1 infection is unknown. Here, we demonstrate that MAbs targeting the HIV-1 envelope glycoprotein both suppress acute SHIV plasma viremia and limit CD4 T cell-associated viral DNA. These findings provide support for clinical trials of MAbs as adjunctive therapy with antiretroviral therapy during acute HIV-1 infection.
Genetics, Receptor Binding, Replication, and Mammalian Transmission of H4 Avian Influenza Viruses Isolated from Live Poultry Markets in China
Authors: Liang Libin , Deng Guohua , Shi Jianzhong , Wang Shuai , Zhang Qianyi , Kong Huihui , Gu Chunyang , Guan Yuntao , Suzuki Yasuo , Li Yanbing , Jiang Yongping , Tian Guobin , Liu Liling , Li Chengjun , Chen Hualan
Published: November 2015

H4 avian influenza virus (AIV) is one of the most prevalent influenza virus subtypes in the world. However, whether H4 AIVs pose a threat to public health remains largely unclear. Here, we analyzed the phylogenetic relationships, receptor binding properties, replication, and transmissibility in mammals of H4 AIVs isolated from live poultry markets in China between 2009 and 2012. Genomic sequence analysis of 36 representative H4 viruses revealed 32 different genotypes, indicating that these viruses are undergoing complex and frequent reassortment events. All 32 viruses tested could replicate in the respiratory organs of infected mice without prior adaptation. Receptor binding analysis demonstrated that the H4 AIVs bound to α-2,6-linked glycans, although they retained the binding preference for α-2,3-linked glycans. When we tested the direct-contact transmission of 10 H4 viruses in guinea pigs, we found that three viruses did not transmit to any of the contact animals, one virus transmitted to one of three contact animals, and six viruses transmitted to all three contact animals. When we further tested the respiratory droplet transmissibility of four of the viruses that transmitted efficiently via direct contact, we found that three of them could transmit to one or two of the five exposed animals. Our study demonstrates that the current circulating H4 AIVs can infect, replicate in, and transmit to mammalian hosts, thereby posing a potential threat to human health. These findings emphasize the continual need for enhanced surveillance of H4 AIVs.

IMPORTANCE
Numerous surveillance studies have documented the wide distribution of H4 AIVs throughout the world, yet the biological properties of H4 viruses have not been well studied. In this study, we found that multiple genotypes of H4 viruses are cocirculating in the live poultry markets of China and that H4 viruses can replicate in mice, possess human-type receptor binding specificity, and transmit between guinea pigs via direct contact. Strikingly, some H4 strains also can transmit via respiratory droplet, albeit with limited efficiency. These results clearly show the potential threat posed by H4 viruses to public health.
Enhanced Immune Responses to HIV-1 Envelope Elicited by a Vaccine Regimen Consisting of Priming with Newcastle Disease Virus Expressing HIV gp160 and Boosting with gp120 and SOSIP gp140 Proteins
Authors: Khattar Sunil K. , DeVico Anthony L. , LaBranche Celia C. , Panda Aruna , Montefiori David C. , Samal Siba K.
Published: November 2015

Newcastle disease virus (NDV) expressing HIV-1 BaL gp160 was evaluated either alone or with monomeric BaL gp120 and BaL SOSIP gp140 protein in a prime-boost combination in guinea pigs to enhance envelope (Env)-specific humoral and mucosal immune responses. We showed that a regimen consisting of an NDV prime followed by a protein boost elicited stronger serum and mucosal Th-1-biased IgG responses and neutralizing antibody responses than NDV-only immunizations. Additionally, these responses were higher after the gp120 than after the SOSIP gp140 protein boost.
Paediatric cardiac surgery in low-income and middle-income countries: a continuing challenge
Authors: Nguyen Nguyenvu , Leon-Wyss Juan , Iyer Krishna S , Pezzella A Thomas
Published: November 2015

Despite advances in surgical and catheter-based treatment for congenital heart disease (CHD), there remain wide disparities across the globe. Ongoing international humanitarian and in-country programmes are working to address these issues with the ultimate goal to increase the quality and quantity of paediatric cardiac care, particularly in under-served regions of the world. This review aims to illustrate the reasons for these inequalities and suggests novel ways of improving access and sustainability of CHD programmes in low-income and middle-income countries.
Improving fluid balance monitoring on the wards
Authors: Jeyapala Sobanakumari , Gerth Alice , Patel Aarti , Syed Nazia
Published: November 2015

Clinical experience and nursing metrics have consistently identified poor documentation of fluid balance monitoring at Milton Keynes University Hospital, compromising patient safety and quality of care. This project aimed to increase the percentage of fluid balance charts correctly completed on the wards.

Three areas for improvement were identified: understanding the importance of good fluid balance monitoring, correct identification of patients requiring monitoring, and ease of completion of fluid balance charts. Three interventions were deployed on two acute medical awards in consecutive cycles; 1) small group education for staff, 2) creation of board magnets to aid the multidisciplinary team to identify patients requiring monitoring, 3) modification of the current fluid balance chart. Questionnaires were utilised to highlight improvements with current charts and measured staff awareness pre and post education. Each intervention was implemented for one week followed by daily surveys for four days to monitor compliance.

Initial results showed a range of 6-12 charts used daily per ward. Of these 0-45% of them were correctly filled. Post education there was a reduced number of inappropriate charts. Introduction of board magnets improved correlation between doctors and nurses in identification of patients (52% before, 77% after magnets). Following modification there was a subjective improvement in the quality of chart completion.

This study highlighted that understanding and use of fluid balance monitoring can be improved for nurses, health care assistants (HCAs), and doctors. These improvements allow better documentation and safer patient care. As a result, Milton Keynes University Hospital is investing in magnets and modified charts for a Trust-wide pilot.
Exploring the transition from curative care to palliative care: a systematic review of the literature
Authors: Gardiner Clare , Ingleton Christine , Gott Merryn , Ryan Tony
Published: November 2015

Background

UK policy guidance on treatment and care towards the end of life identifies a need to better recognise patients who are likely to be in the last 12 months of life. Health and social care professionals have a key role in initiating and managing a patient's transition from ‘curative care’ to palliative care. The aim of this paper is to provide a systematic review of evidence relating to the transition from curative care to palliative care within UK settings.

Method

Four electronic databases were searched for studies published between 1975 and March 2010. Inclusion criteria were all UK studies relating to the transition from curative care to palliative care in adults over the age of 18. Selected studies were independently reviewed, data were extracted, quality was assessed and data were synthesised using a descriptive thematic approach.

Results

Of the 1464 articles initially identified, 12 papers met the criteria for inclusion. Four themes emerged from the literature: (1) patient and carer experiences of transitions; (2) recognition and identification of the transition phase; (3) optimising and improving transitions; and (4) defining and conceptualising transitions.

Conclusions

The literature suggests that little is known about the potentially complex transition to palliative care. Evidence suggests that continuity of care and multidisciplinary collaboration are crucial in order to improve the experience of patients making the transition. An important role is outlined for generalist providers of palliative care. Incorporating palliative care earlier in the disease trajectory and implementing a phased transition appear key components of optimum care.
Improving care and support for people with progressive illness in primary care
Authors: Harrison N , Cavers D , Campbell C , Murray S A
Published: November 2015

Introduction and aims

The Palliative Care Directed Enhanced Service (DES) was introduced in Scotland in 2008/2009 to stimulate anticipatory care by GP practice teams. We aimed to evaluate how practices were implementing this by assessing how they were

identifying patients for their palliative care register (PCR),

assessing/reviewing needs,

sharing information with out of hours (OOH) providers,

using the Liverpool Care Pathway (LCP).

Methods

Six practices were recruited from three Scottish Health Boards. Data were collected on current palliative care patients and on patients dying in the previous 6 months; semi-structured interviews were conducted with GPs, district nurses (DN) and administrative staff (total 20) and with patients and bereaved relatives (total 11); the researcher observed multidisciplinary practice meetings.

Results

Only 29% of patients were on the PCR prior to death (range 10–38% between practices). Of these, 69% had cancer, 17% organ failure and 14% dementia or physical frailty and 25% died in hospital (cf. 44% of all deaths). 52% on the current PCR had a record of preferred place of care and 35% of resuscitation status. Practices valued better focused and structured palliative care, improved communication with OOH providers and introduction of the LCP but raised some difficulties in including non-cancer patients on the PCR. Patients and relatives appreciated pro-active care.

Conclusion

Despite this initiative few patients were identified for palliative care. However when identified, their multidisciplinary and OOH care improved and hospital admissions to die decreased. Practices must identify more patients earlier for palliative care.