bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermomechanical Analysis of Pressure Vessels With Functionally Graded Material Coating
Authors: Wang Z. W. , Zhang Q. , Xia L. Z. , Wu J. T. , Liu P. Q.
Published: July 2015

Pressure vessels covered with overlaying layer or coating are widely applied due to its strong heat resistance, corrosion resistance, and load-carrying capacity. However, limited work has been reported on investigating the thermomechanical behavior of a pressure vessel with a functionally graded material (FGM) coating. In this study, a closed-form analytical solution was first derived for calculating the stress distribution in a pressure vessel with an FGM coating subjected to an internal pressure and a thermal load. Afterwards, a numerical solution was also established for validating the analytical solution using finite element (FE) method. It was found out that the analytical solution agreed well with the numerical ones, and the thermomechanical properties of FGM coating were also discussed in detail. This work would be helpful for better understanding and scientific design of pressure vessels with an FGM coating or related thin-walled structures.
A Study on Test Pressures for Hot Tap for Large Diameter Pipes
Authors: Saha Subrata , Pisal Abhijit
Published: July 2015

Hot tapping [1–3] is the operation which allows attaching new branch connection on piping system and pipelines containing hydrocarbons under operating conditions. This operation is associated with high level of risk and is undertaken with extreme caution.

A major source of risk from the point of structural integrity is the low limits on value of test pressure as compared to the Code specified test pressures [4]. The reason is pipes are not designed for external pressure and they may “buckle” under external pressure during testing. The current practice is to use curves which are specifically developed by various operating companies [3] and are not generally available in the public domain. The problem becomes severe for large diameter thin pipes where the safe test pressure becomes quite low. This has potential risk as the pressures could be much lower than the operating pressures.

This paper discusses this problem and also details out an analytical method which can be used to obtain higher “Strength test pressure” with respect to ratio of parent pipe diameter and thickness. So that design reliability of the hot tap branch can be increased. Methodology explained in paper gives lot of flexibility to go for higher test pressure. FEA analysis is used to demonstrate these results.

Globally acceptable procedures also advocate using FEM analysis to confirm the strength test pressure. Based on that FEA analysis was done and it is established that hot tap design can sustain higher test pressure than operating. In reality Hot Taps have been performed and tested successfully with the test pressures as per our proposed method which in a way validates our theory.
Remote-Controlled Plugging Technology Minimizes Platform Downtime: Valve Replacement Through SmartPlug® Isolation
Authors: Lie Rolf Gunnar , Muangsuankwan Natthasart
Published: July 2015

Following a planned inline inspection pigging program of its 32-inch gas export pipeline (GEP) on the Bongkot platform in the Gulf of Thailand, PTT Exploration and Production Public Company Limited (PTTEP) discovered that the line’s primary shutdown valve (SDV), last manual isolation valve, and one of the two isolation valves for the line’s pig trap were defective. The issues were creating unacceptable internal passing rates and external leakage to the atmosphere. In addition, the line had severe corrosion at the surface of a 5D bend underneath the deck sealing block. The situation mandated valve repair, removal and replacement operations, while the corroded bend necessitated treatment with composite fiber wrap.

PTTEP planned for their shutdown and maintenance for over a year and it was to take place in April 2014. Faced with two options for safe and reliable isolation of its gas export line, PTTEP could either bleed down the entire line — a protracted and very costly option, or it could pressure isolate the line downstream of the valves and just bleed down the section back to the pig launcher. PTTEP chose SmartPlug pressure isolation with the remote-controlled plugging technology engineered by T.D. Williamson (TDW).

With the export line securely isolated, the SDV and manually operated valves were replaced. Following the replacement of the valves, a hydrotest was carried out against the SmartPlug tool’s third plugging module to verify the integrity of the repair work.

This paper describes the challenges of such an offshore pressure isolation, as well as the steps taken from planning, to site visit and engineering, to safely and successfully executing the isolation.
Challenges and Best Safety Practices in CGD Industry
Authors: Sharma Alok
Published: July 2015

Indraprastha Gas Limited — the largest CGD Company in the country serving more than 11 Lakh customers with uninterrupted gas supply round the clock with largest pipeline network (more than 9200 kms) in the National Capital Region of the Country.

IGL has adopted best safety practices and always strives to ensure safety of employees, workers, consumers, stake holders and general public at large. However IGL’s City Gas Distribution network operations in National Capital Region pose its own very typical challenges in CNG (Compressed Natural Gas – Vehicle Refueling) & PNG (Piped Natural Gas) operations. There are various challenges during Laying of Pipeline as per relevant codes & statutes as obtaining permissions, clearances, NoCs, approvals, etc., availability & retaining of trained & experienced manpower, constraints in laying of pipeline in highly populated area, presence of other utilities, etc. Similarly during the O&M of Pipeline, the organization faces challenges like third party damages leading to gas leak & fire, massive expansion projects of other companies in Delhi/NCR like Delhi Metro/Delhi Jal Board/MTNL, etc. Same is the case with CNG Operations where we are handling incidents/emergencies due to the customers’ negligence like an important issue of CNG cylinder validation, Poor Maintenance of CNG Vehicles and their CNG Kits, Untested and unsafe cylinders is a matter of serious concern, Installation of unauthorized spare parts in CNG Kits of vehicles, leading to serious consequences at our CNG stations.

Based on scientific analysis of the incidents happening on day to day basis, various initiatives are taken to control and avoid their recurrence.
Use of Graphene-Based Composite Pipe Materials for Transportation of Oil and Gas
Authors: Kumawat Hemant
Published: July 2015

Graphene is emerged as superior reinforcing filler for the polymer matrix due to its superior mechanical, electrical and thermal properties. The present study relates to new graphene-based tubes, pipes or risers, whose specificities of geometry, chemical composition, microstructure and mechanical properties allow its use for transporting oil and gas. This technical solution aimed at improving the structural integrity of such tubes, pipes, or risers produced according to an exclusive method of manufacturing, and that have qualities much higher than those without graphene. Such products can be used for petroleum and gas transportation, including in deepwater submarine riser systems (>1500 m), with direct application in the oil industry. This project will be carried out in two stages, first is to establish the high concentration dispersion of graphene using the suitable surfactant, and second is to use this high concentration dispersion of graphene for the preparation of epoxy nanocomposites. The graphene dispersion and its nanocomposites will be characterized using various characterization techniques such as UV-Vis-NIR spectroscopy, Flexural testing, Tensile testing, SEM studies.
Emergency Pipeline Repair System (EPRS) Using Mechanical Connectors
Authors: Mohan Vidit , Ramesh Ashwin P. , Toshniwal Anirudh , Mohan Prakhar
Published: July 2015

In an industry with ever growing concerns of potential failures and increased contingency planning, this paper aims to highlight some of the existing available solutions and future planning options for the emergency repair of subsea pipelines and risers. Focusing on the available technologies and repair scenarios available, the paper will expand to cover the requirements for an Emergency Pipeline Repair System (EPRS), the common gaps and limitations, the philosophy behind the development of a complete EPRS solution and how the use of complementing technologies can be successfully combined. This paper will be supported with a case study of subsea pipeline repairs using mechanical connector. The paper and presentations will be aimed at all levels of pipeline / engineering managers and technical authorities particularly those responsible for their company’s integrity management and contingency planning.
Integrity Management: II — Pipeline Operation and Maintenance
Authors: Dey Rajib Kumar , Iyengar Srivatsan K.
Published: July 2015

Oil & Gas pipeline industry has experience external corrosion and damage impacting its structural integrity for decades. Over 30 years, composite technology has been implemented to strengthen pipelines back to its design condition. The composite application is very common for pipelines of all sizes having operating temperatures from ambient to 60 deg. C.

ONGC – Uran plant is a major facility to process crude oil with associated gas and condensate received from Mumbai High through Subsea pipeline. Regeneration Column was designed for 50 PSI with Design Temperature of 130 Deg. C. and insulated skin. Weather and humidity was accelerating external corrosion around stiffener rings to the point that, it warranted a shutdown to replace either a section or full tower, thereby impacting the production throughput of ONGC-Uran facility.

ONGC hired M/s. EIL as a consulting company to map out extent of corrosion and to identify area needed attention to rehabilitate. Consultant recommended to go for weld build up in identified LML areas (Local Metal Loss) through a planned shutdown of the column.

We were aware about composite technology and further investigation helped to find the right combination of Carbon and High Temperature Epoxy system meeting our requirement through online repair and rehabilitation avoiding shutdown of Regeneration Column.

We selected Carbon with high temperature epoxy based composite system designed for 130 deg. C and installation between 90 to 110 deg. C. Composite application system was designed accordingly and a third party inspection agency was hired to witness prototype tests and composite application techniques. Bonding of Carbon Composite to the Carbon Steel pipe of equivalent grade was successfully tested in the lab.

After infield application, the thickness and hardness of composite system were measured throughout the repaired area during and after the process by TPI. Project was completed by T.D. Williamson in end 2012.
Precise control of defects in graphene using oxygen plasma
Authors: Lee Geonyeop , Kim Jihyun , Kim Kyeounghak , Han Jeong Woo
Published: July 2015

The authors report on a facile method for introducing defects in graphene in a controlled manner. Samples were mounted face down between supports, and exposed to oxygen plasma in a reactive ion etching (RIE) system. Defect density and the rate of defect formation in graphene were analyzed according to the oxygen flow rates and power conditions, using Raman spectroscopy. The mechanism of defect formation was systematically investigated via both experiment and density functional theory (DFT) calculation. Based on our DFT results, sp3 oxygen in the epoxide form would most likely be induced in pristine graphene after exposure to the oxygen plasma. Defect engineering through the fine tuning of the graphene disorder using a conventional RIE system has great potential for use in various graphene-based applications.
An interactive reference framework for modeling a dynamic immune system
Authors: Spitzer Matthew H. , Gherardini Pier Federico , Fragiadakis Gabriela K. , Bhattacharya Nupur , Yuan Robert T. , Hotson Andrew N. , Finck Rachel , Carmi Yaron , Zunder Eli R. , Fantl Wendy J. , Bendall Sean C. , Engleman Edgar G. , Nolan Garry P.
Published: July 2015

Single-cell measurements map immunity

Multiple characteristics of individual cells define cell types and their physiological states. Spitzer
et al.
quantitated the abundance of 39 different cell surface proteins or transcription factors on individual cells of the mouse immune system. They used these measurements to create a map that clustered similar individual cells into groups corresponding to cell type and function. Their extensible experimental platform will allow the inclusion of other data types and data from independent laboratories.

Science
, this issue
10.1126/science.1259425
Bumblebees aren't keeping up with a warming planet
Authors: Carswell Cally
Published: July 2015

Pollinators retreat from south, but don't move north.
Targeting copper to treat breast cancer
Authors: Garber Ken
Published: July 2015

Business obstacles threaten to delay the phase III trial of a copper-depleting drug.
Deep sleep
Authors: Cornwall Warren
Published: July 2015

Boreholes drilled into Earth's crust get a fresh look for nuclear waste disposal.
Rolling out a welcome mat for waste
Authors: Cornwall Warren
Published: July 2015

As feds go looking for somewhere to put nuclear waste, a few willing candidates emerge.
Sea-level rise due to polar ice-sheet mass loss during past warm periods
Authors: Dutton A. , Carlson A. E. , Long A. J. , Milne G. A. , Clark P. U. , DeConto R. , Horton B. P. , Rahmstorf S. , Raymo M. E.
Published: July 2015

Warming climate, melting ice, rising seas

We know that the sea level will rise as climate warms. Nevertheless, accurate projections of how much sea-level rise will occur are difficult to make based solely on modern observations. Determining how ice sheets and sea level have varied in past warm periods can help us better understand how sensitive ice sheets are to higher temperatures. Dutton
et al.
review recent interdisciplinary progress in understanding this issue, based on data from four different warm intervals over the past 3 million years. Their synthesis provides a clear picture of the progress we have made and the hurdles that still exist.

Science
, this issue
10.1126/science.aaa4019
Single-trial spike trains in parietal cortex reveal discrete steps during decision-making
Authors: Latimer Kenneth W. , Yates Jacob L. , Meister Miriam L. R. , Huk Alexander C. , Pillow Jonathan W.
Published: July 2015

A better way to explain neuronal activity

A brain region called the lateral intraparietal (LIP) area is involved in primate decision-making. The dominant model to explain neuronal firing in LIP assumes that neurons slowly accumulate sensory evidence in favor of one choice or another. Latimer
et al.
hypothesized that neurons instead exhibit rapid steps or jumps in their firing rate, reflecting discrete changes in the animal's decision state. They recorded from LIP neurons in macaque monkeys performing a motion-discrimination task. LIP spike trains in most cells involved discrete stepping dynamics rather than slow evidence integration dynamics.

Science
, this issue p.
184
An over-massive black hole in a typical star-forming galaxy, 2 billion years after the Big Bang
Authors: Trakhtenbrot Benny , Urry C. Megan , Civano Francesca , Rosario David J. , Elvis Martin , Schawinski Kevin , Suh Hyewon , Bongiorno Angela , Simmons Brooke D.
Published: July 2015

Black hole out of kilter with theory

It is believed that black holes and their host galaxies coevolve, with the feedback from the black hole inducing star formation. Such a scenario requires certain timing and mass constraints for the black hole and the star-forming gas. Trakhtenbrot
et al.
looked at high–red shift galaxies, when the universe was only about 2 billion years old. They found a black hole that developed to maturity much earlier than would be expected and was about 10% of the total galactic mass—much more than expected. Moreover, star formation continued after it would have been expected to stop.

Science
, this issue p.
168
150 years of Maxwell's equations
Authors: Engheta Nader
Published: July 2015

Powerful tools are available for the manipulation of electromagnetic fields
Exceptionally low daily energy expenditure in the bamboo-eating giant panda
Authors: Nie Yonggang , Speakman John R. , Wu Qi , Zhang Chenglin , Hu Yibo , Xia Maohua , Yan Li , Hambly Catherine , Wang Lu , Wei Wei , Zhang Jinguo , Wei Fuwen
Published: July 2015

Laid-back bamboo eater

Pandas are members of the order Carnivora but are entirely herbivorous, living almost exclusively on bamboo. Unlike most other herbivorous species, however, their digestive tract has not evolved the long twists and turns that facilitate the slower digestion necessary for cellulose-rich plants. Nie
et al.
measured energy expenditure in both wild and captive pandas, which was extremely low, relative to other mammals. The pandas' thyroid hormone levels are also a fraction of the mammalian norm.

Science
, this issue p.
171
Water, bound and mobile
Authors: Brooks J. Renée
Published: July 2015

Isotopic data help to resolve global hydrologic fluxes

[Also see Report by

Good
et al.

]
Beachcomber's delight
Spirals in Time: The Secret Life and Curious Afterlife of Seashells
Helen Scales
Bloomsbury Sigma, 2015. 312 pp.
Authors: Kemp Christopher
Published: July 2015

The hidden mysteries and human history of seashells
Managing mining of the deep seabed
Authors: Wedding L. M. , Reiter S. M. , Smith C. R. , Gjerde K. M. , Kittinger J. N. , Friedlander A. M. , Gaines S. D. , Clark M. R. , Thurnherr A. M. , Hardy S. M. , Crowder L. B.
Published: July 2015

Contracts are being granted, but protections are lagging
Support from Phylogenomic Networks and Subspecies Signatures for Separation of Mycobacterium massiliense from Mycobacterium bolletii
Authors: Tan Joon Liang , Ngeow Yun Fong , Choo Siew Woh
Published: July 2015

Mycobacterium abscessus
subspecies classification has important clinical implications. We used phylogenomic network and amino acid analyses to provide evidence for the separation of
Mycobacterium bolletii
and
Mycobacterium massiliense
into two distinct subspecies which can potentially be differentiated rapidly by their protein signatures.
Multilocus Sequence Analysis of Clinical “Candidatus Neoehrlichia mikurensis” Strains from Europe
Authors: Grankvist Anna , Moore Edward R. B. , Svensson Stadler Liselott , Pekova Sona , Bogdan Christian , Geißdörfer Walter , Grip-Lindén Jenny , Brandström Kenny , Marsal Jan , Andréasson Kristofer , Lewerin Catharina , Welinder-Olsson Christina , Wennerås Christine
Published: July 2015

“
Candidatus
Neoehrlichia mikurensis” is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of “
Ca
. Neoehrlichia” has been studied only by comparing 16S rRNA genes and
groEL
operon sequences. We describe the development and use of a multilocus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinical “
Ca
. Neoehrlichia” strains in Europe and their relatedness to other species within the
Anaplasmataceae
family. Six genes were selected:
ftsZ
,
clpB
,
gatB
,
lipA
,
groEL
, and 16S rRNA. Each MLSA locus was amplified by real-time PCR, and the PCR products were sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed “
Ca
. Neoehrlichia” infection from Sweden (
n
= 9), the Czech Republic (
n
= 2), and Germany (
n
= 1) were analyzed with the MLSA protocol. Three of the Swedish strains exhibited identical
lipA
sequences, while the
lipA
sequences of the strains from the other nine patients were identical to each other. One of the Czech strains had one differing nucleotide in the
clpB
sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16S rRNA,
ftsZ
,
gatB
, and
groEL
. According to the MLSA, among the
Anaplasmataceae
, “
Ca
. Neoehrlichia” is most closely related to
Ehrlichia ruminantium
, less so to
Anaplasma phagocytophilum
, and least to
Wolbachia
endosymbionts. To conclude, three sequence types of infectious “
Ca
. Neoehrlichia” were identified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
Humicola sp. as a Cause of Peritoneal Dialysis-Associated Peritonitis
Authors: Burns Nathan , Arthur Ian , Leung Michael , Ketharanathan Selva , Sandoval-Denis Marcelo , Gené Josepa , Guarro Josep , Chakera Aron
Published: July 2015

Peritoneal dialysis is the renal replacement modality used by ∼20% of patients with end-stage kidney disease (S. McDonald, P. Clayton, and K. Hurst, p. 6.2–6.27,in ANZDATA 2012 Annual Report, 35th ed., 2012). A major complication of peritoneal dialysis is the development of peritonitis. We describe a case ofHumicolasp. causing peritoneal dialysis (PD)-associated peritonitis, successfully treated with a prolonged course of antifungal therapy.
Measles Virus Infection Inactivates Cellular Protein Phosphatase 5 with Consequent Suppression of Sp1 and c-Myc Activities
Authors: Sato Hiroki , Yoneda Misako , Honma Reiko , Ikeda Fusako , Watanabe Shinya , Kai Chieko
Published: July 2015

Measles virus (MeV) causes several unique syndromes, including transient immunosuppression. To clarify the cellular responses to MeV infection, we previously analyzed a MeV-infected epithelial cell line and a lymphoid cell line by microarray and showed that the expression of numerous genes was up- or downregulated in the epithelial cells. In particular, there was a characteristic comprehensive downregulation of housekeeping genes during late stage infection. To identify the mechanism underlying this phenomenon, we examined the phosphorylation status of transcription factors and kinase/phosphatase activities in epithelial cells after infection. MeV infection inactivated cellular protein phosphatase 5 (PP5) that consequently inactivated DNA-dependent protein kinase, which reduced Sp1 phosphorylation levels, and c-Myc degradation, both of which downregulated the expression of many housekeeping genes. In addition, intracellular accumulation of viral nucleocapsid inactivated PP5 and subsequent downstream responses. These findings demonstrate a novel strategy of MeV during infection, which causes the collapse of host cellular functions.

IMPORTANCE
Measles virus (MeV) is one of the most important pathogens in humans. We previously showed that MeV infection induces the comprehensive downregulation of housekeeping genes in epithelial cells. By examining this phenomenon, we clarified the molecular mechanism underlying the constitutive expression of housekeeping genes in cells, which is maintained by cellular protein phosphatase 5 (PP5) and DNA-dependent protein kinase. We also demonstrated that MeV targets PP5 for downregulation in epithelial cells. This is the first report to show how MeV infection triggers a reduction in overall cellular functions of infected host cells. Our findings will help uncover unique pathogenicities caused by MeV.
Enhanced Neutralizing Antibody Response Induced by Respiratory Syncytial Virus Prefusion F Protein Expressed by a Vaccine Candidate
Authors: Liang Bo , Surman Sonja , Amaro-Carambot Emerito , Kabatova Barbora , Mackow Natalie , Lingemann Matthias , Yang Lijuan , McLellan Jason S. , Graham Barney S. , Kwong Peter D. , Schaap-Nutt Anne , Collins Peter L. , Munir Shirin
Published: July 2015

Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. Vaccines are not available, and an RSV vaccine is particularly needed. A live attenuated chimeric recombinant bovine/human PIV3 (rB/HPIV3) vector expressing the RSV fusion (F) glycoprotein from an added gene has been under development as a bivalent vaccine against RSV and HPIV3. Previous clinical evaluation of this vaccine candidate suggested that increased genetic stability and immunogenicity of the RSV F insert were needed. This was investigated in the present study. RSV F expression was enhanced 5-fold by codon optimization and by modifying the amino acid sequence to be identical to that of an early passage of the original clinical isolate. This conferred a hypofusogenic phenotype that presumably reflects the original isolate. We then compared vectors expressing stabilized prefusion and postfusion versions of RSV F. In a hamster model, prefusion F induced increased quantity and quality of RSV-neutralizing serum antibodies and increased protection against wild-type (wt) RSV challenge. In contrast, a vector expressing the postfusion F was less immunogenic and protective. The genetic stability of the RSV F insert was high and was not affected by enhanced expression or the prefusion or postfusion conformation of RSV F. These studies provide an improved version of the previously well-tolerated rB/HPIV3-RSV F vaccine candidate that induces a superior RSV-neutralizing serum antibody response.

IMPORTANCE
Respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are two major causes of pediatric pneumonia and bronchiolitis. The rB/HPIV3 vector expressing RSV F protein is a candidate bivalent live vaccine against HPIV3 and RSV. Previous clinical evaluation indicated the need to increase the immunogenicity and genetic stability of the RSV F insert. Here, we increased RSV F expression by codon optimization and by modifying the RSV F amino acid sequence to conform to that of an early passage of the original isolate. This resulted in a hypofusogenic phenotype, which likely represents the original phenotype before adaptation to cell culture. We also included stabilized versions of prefusion and postfusion RSV F protein. Prefusion RSV F induced a larger quantity and higher quality of RSV-neutralizing serum antibodies and was highly protective. This provides an improved candidate for further clinical evaluation.
Microplitis demolitor Bracovirus Proviral Loci and Clustered Replication Genes Exhibit Distinct DNA Amplification Patterns during Replication
Authors: Burke Gaelen R. , Simmonds Tyler J. , Thomas Sarah A. , Strand Michael R.
Published: July 2015

Polydnaviruses are large, double-stranded DNA viruses that are beneficial symbionts of parasitoid wasps. Polydnaviruses in the genus
Bracovirus
(BVs) persist in wasps as proviruses, and their genomes consist of two functional components referred to as proviral segments and nudivirus-like genes. Prior studies established that the DNA domains where proviral segments reside are amplified during replication and that segments within amplified loci are circularized before packaging into nucleocapsids. One DNA domain where nudivirus-like genes are located is also amplified but never packaged into virions. We recently sequenced the genome of the braconid
Microplitis demolitor
, which carries
M. demolitor
bracovirus (MdBV). Here, we took advantage of this resource to characterize the DNAs that are amplified during MdBV replication using a combination of Illumina and Pacific Biosciences sequencing approaches. The results showed that specific nucleotide sites identify the boundaries of amplification for proviral loci. Surprisingly, however, amplification of loci 3, 4, 6, and 8 produced head-to-tail concatemeric intermediates; loci 1, 2, and 5 produced head-to-head/tail-to-tail concatemers; and locus 7 yielded no identified concatemers. Sequence differences at amplification junctions correlated with the types of amplification intermediates the loci produced, while concatemer processing gave rise to the circularized DNAs that are packaged into nucleocapsids. The MdBV nudivirus-like gene cluster was also amplified, albeit more weakly than most proviral loci and with nondiscrete boundaries. Overall, the MdBV genome exhibited three patterns of DNA amplification during replication. Our data also suggest that PacBio sequencing could be useful in studying the replication intermediates produced by other DNA viruses.

IMPORTANCE
Polydnaviruses are of fundamental interest because they provide a novel example of viruses evolving into beneficial symbionts. All polydnaviruses are associated with insects called parasitoid wasps, which are of additional applied interest because many are biological control agents of pest insects. Polydnaviruses in the genus
Bracovirus
(BVs) evolved ∼100 million years ago from an ancestor related to the baculovirus-nudivirus lineage but have also established many novelties due to their symbiotic lifestyle. These include the fact that BVs are transmitted only vertically as proviruses and produce replication-defective virions that package only a portion of the viral genome. Here, we studied
Microplitis demolitor
bracovirus (MdBV) and report that its genome exhibits three distinct patterns of DNA amplification during replication. We also identify several previously unknown features of BV genomes that correlate with these different amplification patterns.
Insights into Chronic Wasting Disease and Bovine Spongiform Encephalopathy Species Barriers by Use of Real-Time Conversion
Authors: Davenport Kristen A. , Henderson Davin M. , Bian Jifeng , Telling Glenn C. , Mathiason Candace K. , Hoover Edward A.
Published: July 2015

The propensity for transspecies prion transmission is related to the structural characteristics of the enciphering and new host PrP, although the exact mechanism remains incompletely understood. The effects of variability in prion protein on cross-species prion transmission have been studied with animal bioassays, but the influence of prion protein structure versus that of host cofactors (e.g., cellular constituents, trafficking, and innate immune interactions) remains difficult to dissect. To isolate the effects of protein-protein interactions on transspecies conversion, we used recombinant PrP
C
and real-time quaking-induced conversion (RT-QuIC) and compared chronic wasting disease (CWD) and classical bovine spongiform encephalopathy (cBSE) prions. To assess the impact of transmission to a new species, we studied feline CWD (fCWD) and feline BSE (i.e., feline spongiform encephalopathy [FSE]). We cross-seeded fCWD and FSE into each species' full-length, recombinant PrP
C
and measured the time required for conversion to the amyloid (PrP
Res
) form, which we describe here as the rate of amyloid conversion. These studies revealed the following: (i) CWD and BSE seeded their homologous species' PrP best; (ii) fCWD was a more efficient seed for feline rPrP than for white-tailed deer rPrP; (iii) conversely, FSE more efficiently converted bovine than feline rPrP; (iv) and CWD, fCWD, BSE, and FSE all converted human rPrP, although not as efficiently as homologous sCJD prions. These results suggest that (i) at the level of protein-protein interactions, CWD adapts to a new species more readily than does BSE and (ii) the barrier preventing transmission of CWD to humans may be less robust than estimated.

IMPORTANCE
We demonstrate that bovine spongiform encephalopathy prions maintain their transspecies conversion characteristics upon passage to cats but that chronic wasting disease prions adapt to the cat and are distinguishable from the original prion. Additionally, we showed that chronic wasting disease prions are effective at seeding the conversion of normal human prion protein to an amyloid conformation, perhaps the first step in crossing the species barrier.
The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis
Authors: Donaldson David S. , Else Kathryn J. , Mabbott Neil A.
Published: July 2015

Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasiteTrichuris murisin the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease.

IMPORTANCEMany natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the small intestinal GALT are the essential early sites of prion accumulation. Furthermore, congruent infection with a large intestinal helminth (worm) around the time of oral prion exposure did not affect disease pathogenesis. This is important for our understanding of the factors that influence the risk of prion infection and the preclinical diagnosis of disease. The detection of prions within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, our data suggest that using these biopsy specimens may miss individuals in the early stages of oral prion infection and significantly underestimate the disease prevalence.
Aspergillus
Biofilm
In Vitro
and
In Vivo
Authors: Beauvais Anne , Latgé Jean-Paul
Published: July 2015

In vivo, Aspergillus fumigatus
grows as a typical biofilm with hyphae covered by an extracellular matrix (ECM) composed of polysaccharides, galactomannan, and galactosaminogalactan. α1,3 glucans and melanin are also constitutive of the ECM in aspergilloma but not in invasive aspergillosis.
In vitro
, two biofilm models were established to mimic the
in vivo
situation. The first model (model 1) uses submerged liquid conditions and is characterized by slow growth, while the second model (model 2) uses agar medium and aerial conditions and is characterized by rapid growth. The composition of the ECM was studied only in the second model and has been shown to be composed of galactomannan, galactosaminogalactan (GAG), and α1,3 glucans, melanin, antigens, and hydrophobins. The presence of extracellular DNA was detected in model 1 biofilm but not in model 2. Transcriptomic analysis employing both biofilm models showed upregulation of genes coding for proteins involved in the biosynthesis of secondary metabolites, adhesion, and drug resistance. However, most data on
A. fumigatus
biofilms have been obtained
in vitro
and should be confirmed using
in vivo
animal models. There is a need for new therapeutic antibiofilm strategies that focus on the use of combination therapy, since biofilm formation poses an important clinical problem due to their resistance to antifungal agents. Furthermore,
in vivo
investigations of
A. fumigatus
biofilms that incorporate the associated microbiota are needed. Such studies will add another layer of complexity to our understanding of the role of
A. fumigatus
biofilm during lung invasion.
Intermittent daytime mouthpiece ventilation successfully augments nocturnal non-invasive ventilation, controlling ventilatory failure and maintaining patient independence
Authors: Ward Karen , Ford Verity , Ashcroft Helen , Parker Robert
Published: July 2015

A 53-year-old woman with spinal muscular atrophy and a 7-year history of nocturnal non-invasive ventilation (NIV) use via nasal mask and chinstrap was admitted electively. Outpatient review suggested symptomatic hypercapnia and hypoxaemia. Use of her usual NIV resulted in early morning respiratory acidosis due to excess mouth leak, and continuous face mask NIV was instigated while in hospital. Once stabilised, she elected to return to nasal ventilation. At outpatient review, respiratory acidosis reoccurred despite diurnal use of NIV. Using the patient's routine ventilator and a novel mouthpiece and trigger algorithm, intermittent daytime mouthpiece ventilation (MPV) was introduced alongside overnight NIV. Control of respiratory failure was achieved and, vitally, independent living maintained. Intermittent MPV was practicable and effective where the limits of ventilator tolerance had otherwise been reached. MPV may reduce the need for tracheostomy ventilation and this case serves as a reminder of the increasing options routinely available to NIV clinicians.
Sarcoidosis-related hypercalcaemia due to production of parathyroid hormone-related peptide
Authors: Raalte Daniel H van , Goorden Susan M , Kemper Evelien A , Brosens Lodewijk A A , ten Kate Reinier W
Published: July 2015

Hypercalcaemia is frequently observed in patients with sarcoidosis. This is classically attributed to ectopic production of 1,25 dihydroxy vitamin D by sarcoid granulomas. We present a case of sarcoidosis-related hypercalcaemia with normal vitamin D levels. In this patient, production of parathyroid hormone-related peptide (PTHrp) was the cause for sarcoidosis-induced hypercalcaemia. As such, plasma PTHrp levels were increased and bone marrow granulomas stained positively for PTHrp expression. Medium-dose prednisolone treatment improved symptoms of sarcoidosis and normalised serum calcium, and PTHrp concentrations. Thus, production of PTHrp may be the cause for hypercalcaemia in some patients with sarcoidosis.
c.1437G>A intron 9 substitution on acid α-glucosidase gene associated with classic infantile-onset Pompe disease phenotype
Authors: Morales Andrés , Poling Mikaela I , Páez Marco T , Cabrera Julio , McCormick Rodger J
Published: July 2015

Pompe disease, or glycogen storage disease type II (GSD2), an autosomal recessive disease first described by Joannes Cassianus Pompe (1901–1945), causes deficient activity of acid α-glucosidase (GAA) enzyme.GAAcatalyses α 1,4 and α 1,6 glucosidic linkages in lysosomes; destruction of these linkages permits glycogen to be separated into glucose and later used for energy. Without proper function of this enzyme, glycogen accumulates in lysosome, causing muscle hypotonia. We report a previously undescribed association of c.1437G>A intron 9 substitution on theGAAgene with severe infantile-onset Pompe disease in a deceased proband and carrier status in four of five surviving family members. Previous authors have found late-onset or moderate severity infantile-onset Pompe disease associated with this allelic variation. Our proband’s family’s village was suspicious for locally endemic disease. While our proband developed all features of classic infantile onset GSD2, socioeconomic and geographic factors initially suggested an infectious aetiology.
Sustained virological response and its treatment predictors in hepatitis C virus genotype 4 compared to genotypes 1, 2, and 3: a meta-analysis
Authors: Yee Brittany E , Nguyen Nghia H , Zhang Bing , Lin Derek , Vutien Philip , Wong Carrie R , Lutchman Glen A , Nguyen Mindie H
Published: July 2015

Background

Pegylated interferon and ribavirin (PEG-IFN+RBV) may be more cost-effective than direct-acting antivirals in resource-limited settings. Current literature suggests sustained virological response (SVR) in hepatitis C virus genotype 4 (HCV-4) is similar to genotype 1 (HCV-1), but worse than 2 and 3 (HCV-2/3). However, few studies have compared treatment response between these groups and these have been limited by small sample sizes with heterogeneous designs. We performed a meta-analysis of SVR predictors in HCV-4 versus HCV-1, 2, and 3 patients treated with PEG-IFN+RBV.

Methods

In November 2013, we searched for ‘genotype 4’ in MEDLINE/EMBASE databases and scientific conferences. We included original articles with ≥25 treatment-naïve HCV-4 and comparisons to HCV-1, 2, and/or 3 patients treated with PEG-IFN+RBV. Random effects modelling was used with heterogeneity defined by Cochrane Q-test (p value<0.10) and I2statistic (>50%).

Results

Five studies with 20 014 patients (899 HCV-4; 12 033 HCV-1; and 7082 HCV-2/3 patients) were included. SVR was 53% (CI 43% to 62%) for HCV-4, 44% (CI 40% to 47%) for HCV-1; and 73% (CI 58% to 84%) for HCV-2/3. SVR with EVR (early virological response) was 75% (CI 61% to 86%) in HCV-4; 64% (CI 46% to 79%) in HCV-1; and 85% (CI 71% to 93%) in HCV-2/3. SVR without EVR was 10% (CI 6% to 17%) for HCV-4; 13% (CI 12% to 15%) for HCV-1; and 23% (CI 16% to 33%) for HCV-2/3.

Conclusions

SVR rates are similar in HCV-4 (∼50%) and HCV-1 (∼40%). Lack of EVR is a good stopping rule for HCV-4 and HCV-1 since only 10% subsequently achieve SVR. In HCV-4 patients with EVR, three-quarters can expect to achieve SVR with PEG-IFN+RBV.
Evaluation of the fidelity of an interactive face-to-face educational intervention to improve general practitioner management of back pain
Authors: French Simon D , Green Sally E , Francis Jill J , Buchbinder Rachelle , O'Connor Denise A , Grimshaw Jeremy M , Michie Susan
Published: July 2015

Objectives

Implementation intervention effects can only be fully realised and understood if they are faithfully delivered. However the evaluation of implementation intervention fidelity is not commonly undertaken. The IMPLEMENT intervention was designed to improve the management of low back pain by general medical practitioners. It consisted of a two-session interactive workshop, including didactic presentations and small group discussions by trained facilitators. This study aimed to evaluate the fidelity of the IMPLEMENT intervention by assessing: (1) observed facilitator adherence to planned behaviour change techniques (BCTs); (2) comparison of observed and self-reported adherence to planned BCTs and (3) variation across different facilitators and different BCTs.

Design

The study compared planned and actual, and observed versus self-assessed delivery of BCTs during the IMPLEMENT workshops.

Method

Workshop sessions were audiorecorded and transcribed verbatim. Observed adherence of facilitators to the planned intervention was assessed by analysing the workshop transcripts in terms of BCTs delivered. Self-reported adherence was measured using a checklist completed at the end of each workshop session and was compared with the ‘gold standard’ of observed adherence using sensitivity and specificity analyses.

Results

The overall observed adherence to planned BCTs was 79%, representing moderate-to-high intervention fidelity. There was no significant difference in adherence to BCTs between the facilitators. Sensitivity of self-reported adherence was 95% (95% CI 88 to 98) and specificity was 30% (95% CI 11 to 60).

Conclusions

The findings suggest that the IMPLEMENT intervention was delivered with high levels of adherence to the planned intervention protocol.

Trial registration number

The IMPLEMENT trial was registered in the Australian New Zealand Clinical Trials Registry, ACTRN012606000098538 (http://www.anzctr.org.au/trial_view.aspx?ID=1162).
Prospective cohort study protocol to describe the transfer of patients from intensive care units to hospital wards
Authors: Buchner Denise L , Bagshaw Sean M , Dodek Peter , Forster Alan J , Fowler Robert A , Lamontagne François , Turgeon Alexis F , Potestio Melissa , Stelfox Henry T
Published: July 2015

Introduction

The transfer of patient care between the intensive care unit (ICU) and the hospital ward is associated with increased risk of medical error and adverse events. This study will describe patient transfer from ICU to hospital ward by documenting (1) patient, family and provider experiences related to ICU transfer, (2) communication between stakeholders involved in ICU transfer, (3) adverse events that follow ICU transfer and (4) opportunities to improve ICU to hospital ward transfer.

Methods

This is a mixed methods prospective observational study of ICU to hospital ward transfer practices in 10 ICUs across Canada. We will recruit 50 patients at each site (n=500) who are transferred from ICU to hospital ward, and distribute surveys to enrolled patients, family members, and healthcare providers (ICU and ward physicians and nurses) after patient transfer. A random sample of 6 consenting study participants (patients, family members, healthcare providers) from each study site (n=60) will be offered an opportunity to participate in interviews to further describe stakeholders’ experience with ICU to hospital ward transfer. We will abstract information from patient health records to identify clinical data and use of transfer tools, and identify adverse events that are related to the transfer.

Ethics and Dissemination

Research ethics board approval has been obtained at the coordinating study centre (UofC REB13-0021) and 5 study sites (UofA Pro00050646; UBC-PHC H14-01667; Sunnybrook 336-2014; QCH 14-07; Sherbrooke 14-172). Dissemination of the findings will provide a comprehensive description of transfer from ICU to hospital ward in Canada including the uptake of validated or local transfer tools, a conceptual framework of the experiences and needs of stakeholders in the ICU transfer process, a summary of adverse events experienced by patients after transfer from ICU to hospital ward, and opportunities to guide quality improvement efforts.
Republished: Vertebral–venous fistula: an unusual cause for ocular symptoms mimicking a carotid cavernous fistula
Authors: Felbaum Daniel , Chidambaram Swathi , Mason Robert Bryan , Armonda Rocco A , Liu Ai Hsi
Published: July 2015

Vertebral–venous fistulas (VVF), or vertebral–vertebral arteriovenous fistulas, are an uncommon clinical entity. Typically, they present as a result of a direct vascular connection between an extracranial branch of the vertebral artery or its radicular components and the epidural venous plexus. These may manifest with signs and symptoms referable to cervical myelopathy secondary to compression or steal phenomenon. To our knowledge, this is the first case to identify a patient who presented with classic ocular symptoms attributable to a carotid cavernous fistula but secondary to a VVF. We present its treatment and clinical outcome. In addition, we present a brief literature review surrounding this uncommon disease.
Republished: Acute ischemic stroke in a child due to basilar artery occlusion treated successfully with a stent retriever
Authors: Savastano Luis , Gemmete Joseph J , Pandey Aditya S , Roark Christopher , Chaudhary Neeraj
Published: July 2015

Ischemic strokes in childhood are rare. Thrombolytic therapy with intravenous (IV) tissue plasminogen activator (tPA) has been the main intervention for the management of pediatric stroke patients, but safety data are lacking and efficacy has been questioned. Recently, successful endovascular treatments for acute ischemic stroke in children have been reported with increasing frequency, suggesting that mechanical thrombectomy can be a safe and effective treatment. We present the case of a 22-month-old child with acute ischemic stroke due to basilar artery occlusion that was successfully treated with a stent retriever.
Fifty years a vet
Authors: Winter Agnes
Published: July 2015

Agnes Winter wanted to go to Bristol vet school to become a cattle vet, but ended up studying at Liverpool and ultimately became a sheep vet. Here, she discusses the choices she made based on the opportunities available