bluuebunny/crossref_metadata_2025 huggingface dataset:
Transnational Environmental Activism in North America: Wielding Soft Power through Knowledge Sharing?
Authors: Pacheco‐Vega Raul
Published: January 2015

While a majority of scholarship on the study of transnational advocacy networks (TANs) has focused on the role of value‐and‐belief‐sharing as these networks link activists across nations together, less has been written concerning the role of knowledge exchange among environmental nongovernmental organizations (ENGOs) in helping effect policy change. This article examines how transnational coalitions of ENGOs in North America have helped shape environmental policy across the Canada–U.S.–Mexico borders. In the paper, I explore two cases of nonstate actor mobilization: the North American Pollutant Release, and Transfer Registry Project and the Citizen Submission on Enforcement Matters. In this article, I bridge notions of “soft power” with scholarship on knowledge sharing, thereby showing that nonstate actors use it as a model to build stronger transnational coalitions, effecting pressure on industry and intergovernmental actors, and provide policy input in environmental decision making across borders.
Feeling at Home in College: Fortifying School‐Relevant Selves to Reduce Social Class Disparities in Higher Education
Authors: Stephens Nicole M. , Brannon Tiffany N. , Markus Hazel Rose , Nelson Jessica E.
Published: January 2015

Social class disparities in higher education between working‐class students (i.e., students who are low income and/or do not have parents with four‐year college degrees) and middle‐class students (i.e., students who are high income and/or have at least one parent with a four year‐degree) are on the rise. There is an urgent need for interventions, or changes to universities' ideas and practices, to increase working‐class students' access to and performance in higher education. The current article identifies key factors that characterize successful interventions aimed at reducing social class disparities, and proposes additional interventions that have the potential to improve working‐class students' chances of college success. As we propose in the article, effective interventions must first address key individual and structural factors that can create barriers to students' college success. At the same time, interventions should also fortify school‐relevant selves, or increase students' sense that the pursuit of a college degree is central to “who I am.” When students experience this strong connection between their selves and what it means to attend and perform well in college, they will gain a sense that they fit in the academic environment and will be empowered to do what it takes to succeed there.
The Psychology of Charitable Donations to Disaster Victims and Beyond
Authors: Zagefka Hanna , James Trevor
Published: January 2015

This contribution summarizes the literature on the psychology of charitable donations to victims of disasters and other unfortunate circumstances. Four distinct research areas are reviewed. We begin with the literature on donations in general, and then move to the literature on donations to disaster victims specifically, which is what most of our own research has focused on. We then review the literature on intergroup prosociality, because many donations occur in some kind of intergroup context. We then cover some of the main insights from the literature on generic prosocial processes, which has generated insights that are generalizable to donations and have applied implications. Finally, we summarize some of the main recommendations for eliciting donations which can be generated from these literatures. An emphasis is placed on the translation of academic knowledge into practical steps which practitioners might find useful.
Lack of drug interaction between cyclosporine and telaprevir in a liver transplant recipient
Authors: Lemaitre F. , Jezequel C. , Verdier M.‐C. , Dermu M. , Boglione‐Kerrien C. , Boudjema K. , Bellissant E.
Published: January 2015

Telaprevir is a novel NS3A/4A protease inhibitor approved in combination with ribavirin and peg‐interferon alfa for the treatment of genotype‐1 chronic hepatitis C. This drug is also known to be a potent cytochrome P450 3A and drug efflux protein ATP‐binding cassette B1 (also called P‐glycoprotein) inhibitor, and could therefore interact with immunosuppressive drugs. For this reason, a decrease in cyclosporine (CsA) dosage has been proposed when combining this drug with telaprevir. We report herein the case of an unpredictable lack of interaction between CsA and telaprevir in a liver transplant recipient. The decrease in CsA dosage, conducted as recommended in the literature, did not result in stable CsA concentrations but decreased them. However, the decrease in CsA exposure could have been unseen without the measurement of CsA concentrations 2 h after the administration (C2) of the drug, because it mainly resulted from the decrease in CsA peak. The mechanism leading to this lack of drug interaction in this patient has not been fully elucidated yet, but is likely to affect the absorption phase. Therapeutic drug monitoring using only CsA trough concentrations could be falsely reassuring, and the addition of the measurement of the C2 may add useful information to adapt CsA dosage in patients co‐treated with telaprevir.
Normal bacterial conjunctival flora in theHuacaya alpaca (Vicugna pacos)
Authors: Storms Goedele , Meersschaert Carole , Farnir Frédéric , Grauwels Magda
Published: January 2015

Objective

To describe the bacterial flora of the normal conjunctiva ofHuacaya alpacas (Vicugna pacos) and to determine the effect of age and gender on this flora.

Animals studied

FiftyHuacaya alpacas.

Procedures

After a complete ophthalmic examination, conjunctival swabs were obtained from both eyes and cultured for aerobic and anaerobic bacteria. Logistic andPoisson regression analyses were used to evaluate the effect of age and gender on bacterial isolation.

Results

Four animals were excluded because of signs of external ocular disease. Of the remaining 46 alpacas, bacteria were recovered from 96.7% (89/92) of the eyes. A total of 190 bacterial isolates were cultured with a mean of 2.1 bacterial isolates per eye. The majority of isolates (70%) wereGram‐positive.Staphylococcus xylosus(44/190: 23.2%) predominated, followed by viridans streptococci (32/190: 16.8%) andPantoea agglomerans(24/190: 12.6%). Other frequently isolated bacteria includedRothia mucilaginosa(12/190: 6.3%),Staphylococcus equorum(12/190: 6.3%),Bacillusspecies (9/190: 4.7%),Moraxella ovis(9/190: 4.7%), andMoraxella catarrhalis(6/190: 3.2%). Statistical analysis showed that alpacas harboring viridans streptococci andMoraxellaspecies were significantly younger. Gender did not significantly affect type of bacterial isolation. There appeared to be no significant effect of age or gender on number of bacteria isolated.

Conclusions

Gram‐positive aerobes were most commonly cultured, withS. xylosusand viridans streptococci predominating. To the best of the authors' knowledge, this is the first report describing the presence ofMoraxellaspecies in the healthy conjunctival sac of alpacas. Alpacas harboring viridans streptococci andMoraxellaspecies were significantly younger.
Reinnervation following catheter‐based radio‐frequency renal denervation
Authors: Booth Lindsea C. , Nishi Erika E. , Yao Song T. , Ramchandra Rohit , Lambert Gavin W. , Schlaich Markus P. , May Clive N.
Published: January 2015

New Findings

What is the topic of this review?

Does catheter‐based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur?

What advances does it highlight?

Following catheter‐based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene‐related peptide were significantly reduced. By 11 months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation.

Renal denervation reduces blood pressure in animals with experimental hypertension and, recently, catheter‐based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. The randomized, sham‐controlled Symplicity HTN‐3 trial failed to meet its primary efficacy end‐point, but there is evidence that renal denervation was incomplete in many patients. Currently, there is little information regarding the effectiveness of catheter‐based renal denervation and the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5 and 11 months postdenervation. In anaesthetized, non‐denervated sheep, there was a high level of renal sympathetic nerve activity, and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, renal sympathetic nerve activity and the responses to electrical stimulation were absent, indicating effective denervation. By 11 months after denervation, renal sympathetic nerve activity was present and the responses to electrical stimulation were normal, indicating reinnervation. Anatomical measures of renal innervation by sympathetic efferent nerves (tissue noradrenaline and tyrosine hydroxylase) and afferent sensory nerves (calcitonin gene‐related peptide) demonstrated large decreases at 1 week postdenervation, but normal levels at 11 months postdenervation. In summary, catheter‐based renal denervation is effective, but reinnervation occurs. Studies of central and renal changes postdenervation are required to understand the causes of the prolonged hypotensive response to catheter‐based renal denervation in human hypertension.
Simulation Analysis and Material Optimization of an Aircraft Wing Leading Edge When Subjected to an Artificial Bird Strike
Authors: Srinivasan K. , Channankaiah  , Johnson George P.
Published: January 2015

Bird strike resistance is a strict certification requirement in aircraft industries, and the Federal Aviation Regulations specifically gives various specifications to be followed for certification of various parts of the aircraft. The primary objective of this research is to develop a methodology, which can be utilized to certify an aircraft for bird strike using computational methods, and the impact behavior of a 4-lb artificial bird impinging on the wing leading edge is performed using smooth particle hydrodynamics (SPH) method. The study is focused on the most-frequently used bird configuration in the literatures: namely, cylinder with hemispherical ends. The skin is modeled with an aluminum 2014 alloy, which is prominently used in aircraft industries, and aluminum 8090 alloy. The effects of impact on these materials are studied.
Architectural Synthesis and Analysis of Dual-Cellular Fluidic Flexible Matrix Composites for Multifunctional Metastructures
Authors: Li Suyi , Wang K. W.
Published: January 2015

Recently, a cellular structure concept based on fluidic flexible matrix composites (F2MCs) was investigated for its potential of concurrently achieving multiple adaptive functions. Such structure consists of two fluidically connected F2MC cells, and it has been proven capable of dynamic actuation with enhanced authority, variable stiffness, and vibration absorption. The purpose of the research presented in this paper is to develop comprehensive design and synthesis tools to exploit the rich functionality and versatility of this F2MC based system. To achieve this goal, two progressive research topics are addressed: The first is to survey unique architectures based on rigorous mathematical principles. Four generic types of architectures are identified for the dual-cellular structure based on fluidic and mechanical constraints between the two cells. The system governing equations of motion are derived and experimentally tested for these architectures, and it is found that the overall structural dynamics are related to the F2MC cell stiffness, internal pressure difference, and static flow volume between the two cells according to the architectural layout. The second research topic is to derive a comprehensive synthesis procedure to assign the F2MC designs so that the cellular structure can simultaneously reach a set of different performance targets. Synthesis case studies demonstrate the range of performance of the F2MC based cellular structure with respect to different architectures. The outcome of this investigation could provide valuable insights and design methodologies to foster the adoption of F2MC to advance the state of art of a variety of engineering applications. It also lays the foundation for a large-scale “metastructure,” where many pairs of fluidically connected F2MC can be employed as modules to achieve synergetic global performance.
Mixed Efficient Global Optimization for Time-Dependent Reliability Analysis
Authors: Hu Zhen , Du Xiaoping
Published: January 2015

Time-dependent reliability analysis requires the use of the extreme value of a response. The extreme value function is usually highly nonlinear, and traditional reliability methods, such as the first order reliability method (FORM), may produce large errors. The solution to this problem is using a surrogate model of the extreme response. The objective of this work is to improve the efficiency of building such a surrogate model. A mixed efficient global optimization (m-EGO) method is proposed. Different from the current EGO method, which draws samples of random variables and time independently, the m-EGO method draws samples for the two types of samples simultaneously. The m-EGO method employs the adaptive Kriging–Monte Carlo simulation (AK–MCS) so that high accuracy is also achieved. Then, Monte Carlo simulation (MCS) is applied to calculate the time-dependent reliability based on the surrogate model. Good accuracy and efficiency of the m-EGO method are demonstrated by three examples.
A Repetitive Learning Method Based on Sliding Mode for Robot Control With Actuator Saturation
Authors: Tian Huihui , Su Yuxin
Published: January 2015

This paper proposes a sliding mode based repetitive learning control method for high-precision tracking of robot manipulators with actuator saturation. Advantages of the proposed control include the absence of model parameter in the control law formulation and the ability to remove the possibility of actuator failure due to excessive torque input levels. Lyapunov's direct method is employed to prove semiglobal asymptotic tracking. Simulation results on a three degree-of-freedom (3DOF) robot illustrate the effectiveness and improved performance of the proposed scheme.
Performance enhancement of GaN metal–semiconductor–metal ultraviolet photodetectors by insertion of ultrathin interfacial HfO2 layer
Authors: Kumar Manoj , Tekcan Burak , Okyay Ali Kemal
Published: January 2015

The authors demonstrate improved device performance of GaN metal–semiconductor–metal ultraviolet (UV) photodetectors (PDs) by ultrathin HfO2 (UT-HfO2) layer on GaN. The UT-HfO2 interfacial layer is grown by atomic layer deposition. The dark current of the PDs with UT-HfO2 is significantly reduced by more than two orders of magnitude compared to those without HfO2 insertion. The photoresponsivity at 360 nm is as high as 1.42 A/W biased at 5 V. An excellent improvement in the performance of the devices is ascribed to allowed electron injection through UT-HfO2 on GaN interface under UV illumination, resulting in the photocurrent gain with fast response time.
Highly (001) oriented L1-CoPt/TiN multilayer films on glass substrates with perpendicular magnetic anisotropy
Authors: An Hongyu , Xie Qian , Wang Jian , Sannomiya Takumi , Muraishi Shinji , Zhang Zhengjun , Nakamura Yoshio , Shi Ji
Published: January 2015

To obtain strong perpendicular magnetic anisotropy (PMA) based on L10 structure for magnetic storage devices, costly single crystalline substrates are generally required to achieve (001) texture. Recently, various studies also have focused on depositing different kinds of seed layers on glass or other amorphous substrates to promote (001) preferred orientation of L10 CoPt and FePt. TiN is a very promising seed layer material because of its cubic crystalline structure (similar to MgO) and excellent diffusion barring property even at high temperatures. In the present work, highly (001) oriented L10-CoPt/TiN multilayer films have been successfully deposited on glass substrates. After annealing at 700 °C, the film exhibits PMA, and a strong (001) peak is detected from the x-ray diffraction profiles, indicating the ordering transformation of CoPt layers from fcc (A1) to L10 structure. It also is found that alternate deposition of cubic TiN and CoPt effectively improves the crystallinity and (001) preferred orientation of CoPt layers. This effect is verified by the substantial enhancement of (001) reflection and PMA with increasing the period number of the multilayer films.
Defining disease
Chronic Disease in the Twentieth Century A History
George Weisz
Johns Hopkins University Press, 2014. 325 pp.
Authors: Weindling Paul
Published: January 2015

Paul Weindling welcomes a historical approach to the concept of chronic illness
Laser fusion, with a difference
Authors: Clery Daniel
Published: January 2015

Europe's Laser Mégajoule project blazes its own trail toward nuclear ignition.
Draft Genome Sequence of the Extremely Halophilic Bacterium Halomonas salina Strain CIFRI1, Isolated from the East Coast of India
Authors: Behera Bijay Kumar , Das Priyanka , Maharana Jitendra , Paria Prasenjit , Mandal Shambhu Nath , Meena Dharmendra Kumar , Sharma Anil Prakash , Jayarajan Rijith , Dixit Vishal , Verma Ankit , Vellarikkal Shamsudheen Karuthedath , Scaria Vinod , Sivasubbu Sridhar , Rao Atmakuri Ramakrishna , Mohapatra Trilochan
Published: January 2015

Halomonas salina
strain CIFRI1 is an extremely salt-stress-tolerant bacterium isolated from the salt crystals of the east coast of India. Here we report the annotated 3.45-Mb draft genome sequence of strain CIFRI1 having 86 contigs with 3,139 protein coding loci, including 62 RNA genes.
Draft Genome Sequence of Bordetella trematum Strain HR18
Authors: Chang Dong-Ho , Jin Tae-Eun , Rhee Moon-Soo , Jeong Haeyoung , Kim Seil , Kim Byoung-Chan
Published: January 2015

The genus
Bordetella
is reportedly a human or animal pathogen and environmental microbe. We report the draft genome sequence of
Bordetella trematum
strain HR18, which was isolated from the rumen of Korean native cattle (Hanwoo;
Bos taurus
coreanae
). It is the first genome sequence of a
Bordetella
sp. isolated from the rumen of cattle.
Complete Genome Sequence of VpKK5, a Novel Vibrio parahaemolyticus Lytic Siphophage
Authors: Lal Tamrin M. , Ransangan Julian
Published: January 2015

This paper describes the complete sequence of a novel lytic marine siphophage, VpKK5, that is specific to Vibrio parahemolyticus.
Studying Bordetella pertussis Populations by Use of SNPeX, a Simple High-Throughput Single Nucleotide Polymorphism Typing Method
Authors: Zeddeman Anne , Witteveen Sandra , Bart Marieke J. , van Gent Marjolein , van der Heide Han G. J. , Heuvelman Kees J. , Schouls Leo M. , Mooi Frits R.
Published: January 2015

Large outbreaks of pertussis occur despite vaccination. A first step in the analyses of outbreaks is strain typing. However, the typing of
Bordetella pertussis
, the causative agent of pertussis, is problematic because the available assays are insufficiently discriminatory, not unequivocal, time-consuming, and/or costly. Here, we describe a single nucleotide primer extension assay for the study of
B. pertussis
populations, SNPeX (single nucleotide primer extension), which addresses these problems. The assay is based on the incorporation of fluorescently labeled dideoxynucleotides (ddNTPs) at the 3′ end of allele-specific poly(A)-tailed primers and subsequent analysis with a capillary DNA analyzer. Each single nucleotide polymorphism (SNP) primer has a specific length, and as a result, up to 20 SNPs can be determined in one SNPeX reaction. Importantly, PCR amplification of target DNA is not required. We selected 38 SNPeX targets from the whole-genome sequencing data of 74
B. pertussis
strains collected from across the world. The SNPeX-based phylogenetic trees preserved the general tree topology of
B. pertussis
populations based on whole-genome sequencing, with a minor loss of details. We envisage a strategy whereby SNP types (SnpTs) are quickly identified with the SNPeX assay during an outbreak, followed by whole-genome sequencing (WGS) of a limited number of isolates representing predominant SnpTs and the incorporation of novel SNPs in the SNPeX assay. The flexibility of the SNPeX assay allows the method to evolve along with the pathogen, making it a promising method for studying outbreaks of
B. pertussis
and other pathogens.
Validation of a New Aspergillus Real-Time PCR Assay for Direct Detection of Aspergillus and Azole Resistance of Aspergillus fumigatus on Bronchoalveolar Lavage Fluid
Authors: Chong Ga-Lai M. , van de Sande Wendy W. J. , Dingemans Gijs J. H. , Gaajetaan Giel R. , Vonk Alieke G. , Hayette Marie-Pierre , van Tegelen Dennis W. E. , Simons Guus F. M. , Rijnders Bart J. A.
Published: January 2015

Azole resistance in
Aspergillus fumigatus
is increasingly reported. Here, we describe the validation of the AsperGenius, a new multiplex real-time PCR assay consisting of two multiplex real-time PCRs, one that identifies the clinically relevant
Aspergillus
species, and one that detects the TR34, L98H, T289A, and Y121F mutations in CYP51A and differentiates susceptible from resistant
A. fumigatus
strains. The diagnostic performance of the AsperGenius assay was tested on 37 bronchoalveolar lavage (BAL) fluid samples from hematology patients and 40 BAL fluid samples from intensive care unit (ICU) patients using a BAL fluid galactomannan level of ≥1.0 or positive culture as the gold standard for detecting the presence of
Aspergillus
. In the hematology and ICU groups combined, there were 22 BAL fluid samples from patients with invasive aspergillosis (IA) (2 proven, 9 probable, and 11 nonclassifiable). Nineteen of the 22 BAL fluid samples were positive, according to the gold standard. The optimal cycle threshold value for the presence of
Aspergillus
was <36. Sixteen of the 19 BAL fluid samples had a positive PCR (2
Aspergillus
species and 14
A. fumigatus
samples). This resulted in a sensitivity, specificity, and positive and negative predictive values of 88.9%, 89.3%, 72.7%, and 96.2%, respectively, for the hematology group and 80.0%, 93.3%, 80.0%, and 93.3%, respectively, in the ICU group. The CYP51A real-time PCR confirmed 12 wild-type and 2 resistant strains (1 TR34-L98H and 1 TR46-Y121F-T289A mutant). Voriconazole therapy failed for both patients. The AsperGenius multiplex real-time PCR assay allows for sensitive and fast detection of
Aspergillus
species directly from BAL fluid samples. More importantly, this assay detects and differentiates wild-type from resistant strains, even if BAL fluid cultures remain negative.
Human Immunodeficiency Virus Type 1 Employs the Cellular Dynein Light Chain 1 Protein for Reverse Transcription through Interaction with Its Integrase Protein
Authors: Jayappa Kallesh Danappa , Ao Zhujun , Wang Xiaoxia , Mouland Andrew J. , Shekhar Sudhanshu , Yang Xi , Yao Xiaojian
Published: January 2015

In this study, we examined the requirement for host dynein adapter proteins such as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and p150
Glued
in early steps of human immunodeficiency virus type 1 (HIV-1) replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or p150
Glued
, resulted in significantly lower levels of HIV-1 reverse transcription in cells. Following an attempt to determine how DYNLL1 could impact HIV-1 reverse transcription, we detected the DYNLL1 interaction with HIV-1 integrase (IN) but not with capsid (CA), matrix (MA), or reverse transcriptase (RT) protein. Furthermore, by mutational analysis of putative DYNLL1 interaction motifs in IN, we identified the motifs
52
GQVD and
250
VIQD in IN as essential for DYNLL1 interaction. The DYNLL1 interaction-defective IN mutant HIV-1 (HIV-1IN
Q53A/Q252A
) exhibited impaired reverse transcription. Through further investigations, we have also detected relatively smaller amounts of particulate CA in DYNLL1-KD cells or in infections with HIV-1IN
Q53A/Q252A
mutant virus. Overall, our study demonstrates the novel interaction between HIV-1 IN and cellular DYNLL1 proteins and suggests the requirement of this virus-cell interaction for proper uncoating and efficient reverse transcription of HIV-1.

IMPORTANCE
Host cellular DYNLL1, DYNLT1, and p150
Glued
proteins have been implicated in the replication of several viruses. However, their roles in HIV-1 replication have not been investigated. For the first time, we demonstrated that during viral infection, HIV-1 IN interacts with DYNLL1, and their interaction was found to have a role in proper uncoating and efficient reverse transcription of HIV-1. Thus, interaction of IN and DYNLL1 may be a potential target for future anti-HIV therapy. Moreover, while our study has evaluated the involvement of IN in HIV-1 uncoating and reverse transcription, it also predicts a possible mechanism by which IN contributes to these early viral replication steps.
The Interface between Hepatitis B Virus Capsid Proteins Affects Self-Assembly, Pregenomic RNA Packaging, and Reverse Transcription
Authors: Tan Zhenning , Pionek Karolyn , Unchwaniwala Nuruddin , Maguire Megan L. , Loeb Daniel D. , Zlotnick Adam
Published: January 2015

Hepatitis B virus (HBV) capsid proteins (Cps) assemble around the pregenomic RNA (pgRNA) and viral reverse transcriptase (P). pgRNA is then reverse transcribed to double-stranded DNA (dsDNA) within the capsid. The Cp assembly domain, which forms the shell of the capsid, regulates assembly kinetics and capsid stability. The Cp, via its nucleic acid-binding C-terminal domain, also affects nucleic acid organization. We hypothesize that the structure of the capsid may also have a direct effect on nucleic acid processing. Using structure-guided design, we made a series of mutations at the interface between Cp subunits that change capsid assembly kinetics and thermodynamics in a predictable manner. Assembly in cell culture mirrored
in vitro
activity. However, all of these mutations led to defects in pgRNA packaging. The amount of first-strand DNA synthesized was roughly proportional to the amount of RNA packaged. However, the synthesis of second-strand DNA, which requires two template switches, was not supported by any of the substitutions. These data demonstrate that the HBV capsid is far more than an inert container, as mutations in the assembly domain, distant from packaged nucleic acid, affect reverse transcription. We suggest that capsid molecular motion plays a role in regulating genome replication.

IMPORTANCE
The hepatitis B virus (HBV) capsid plays a central role in the virus life cycle and has been studied as a potential antiviral target. The capsid protein (Cp) packages the viral pregenomic RNA (pgRNA) and polymerase to form the HBV core. The role of the capsid in subsequent nucleic acid metabolism is unknown. Here, guided by the structure of the capsid with bound antiviral molecules, we designed Cp mutants that enhanced or attenuated the assembly of purified Cp
in vitro
. In cell culture, assembly of mutants was consistent with their
in vitro
biophysical properties. However, all of these mutations inhibited HBV replication. Specifically, changing the biophysical chemistry of Cp caused defects in pgRNA packaging and synthesis of the second strand of DNA. These results suggest that the HBV Cp assembly domain potentially regulates reverse transcription, extending the activities of the capsid protein beyond its presumed role as an inert compartment.
Contribution of MxB Oligomerization to HIV-1 Capsid Binding and Restriction
Authors: Buffone Cindy , Schulte Bianca , Opp Silvana , Diaz-Griffero Felipe
Published: January 2015

The alpha interferon (IFN-α)-inducible restriction factor myxovirus B (MxB) blocks HIV-1 infection after reverse transcription but prior to integration. MxB binds to the HIV-1 core, which is composed of capsid protein, and this interaction leads to inhibition of the uncoating process of HIV-1. Previous studies suggested that HIV-1 restriction by MxB requires binding to capsid. This work tests the hypothesis that MxB oligomerization is important for the ability of MxB to bind to the HIV-1 core. For this purpose, we modeled the structure of MxB using the published tertiary structure of MxA. The modeled structure of MxB guided our mutagenic studies and led to the discovery of several MxB variants that lose the capacity to oligomerize. In agreement with our hypothesis, MxB variants that lost the oligomerization capacity also lost the ability to bind to the HIV-1 core. MxB variants deficient for oligomerization were not able to block HIV-1 infection. Overall, our work showed that oligomerization is required for the ability of MxB to bind to the HIV-1 core and block HIV-1 infection.

IMPORTANCE
MxB is a novel restriction factor that blocks infection of HIV-1. MxB is inducible by IFN-α, particularly in T cells. The current work studies the oligomerization determinants of MxB and carefully explores the contribution of oligomerization to capsid binding and restriction. This work takes advantage of the current structure of MxA and models the structure of MxB, which is used to guide structure-function studies. This work leads to the conclusion that MxB oligomerization is important for HIV-1 capsid binding and restriction.
Cretinism presenting as a pseudotumour
Authors: Mahesh D M , Jebasingh Felix K , Baruah Manash P , Thomas Nihal
Published: January 2015

A 43-year-old man from a remote part of India (over 1800 km from our institution), presented with a headache of 3 years duration. He was of short stature, had delayed puberty and was mentally retarded. On evaluation he was detected to have primary hypothyroidism with markedly elevated thyroid-stimulating hormone titres. A CT of the brain revealed a large sellar mass with suprasellar extension into the third ventricle causing obstructive hydrocephalus. Surgical intervention was deferred due to absence of visual impairment and the presence of gross hypothyroidism. The clinical diagnosis of congenital hypothyroidism was confirmed by the absence of radioiodine uptake in the thyroid bed. With thyroid hormone replacement therapy, the ‘tumour’ underwent significant reduction in size with the resolution of hydrocephalus thereby favouring a potential pituitary pseudotumour. This was an unusual situation of a giant pituitary pseudotumour detected in an adult with untreated congenital hypothyroidism.
Quetiapine-induced myocarditis presenting as acute STEMI
Authors: Wassef Nancy , Khan Nazish , Munir Shahzad
Published: January 2015

An 18-year-old man diagnosed with attention-deficit hyperactivity disorder was recently started on quetiapine in addition to regular methylphenidate, which he had been taking for a number of years. He presented with chest pain and inferolateral ST elevation, and underwent urgent coronary angiography, which showed normal coronary arteries. The initial troponin level was raised and an inpatient echocardiogram showed mild left ventricular systolic dysfunction with no evidence of regional wall motion abnormality. Cardiac MRI showed subepicardial late gadolinium enhancement, which was suggestive of myocarditis. Quetiapine and methylphenidate were discontinued and the patient was discharged home after 1 week. He was followed up within 8 weeks with complete recovery and no symptoms.
Breast pain in a patient on dialysis: a rare manifestation of calcific uraemic arteriolopathy
Authors: Buscher Konrad , Gabriëls Gert , Barth Peter , Pavenstädt Hermann
Published: January 2015

A 63-year-old woman presented with progredient bilateral breast pain. Her medical history included rheumatoid arthritis, AA amyloidosis and end-stage renal disease treated by peritoneal dialysis. Inflamed skin alterations of the breast and laboratory values suggested mastitis non-puerpuralis but antibiotics did not resolve the symptoms. Sonography and mammography showed severe vessel calcification suggesting calcific uraemic arteriolopathy (calciphylaxis) as a rare complication of chronic kidney disease. Treatment included intensified haemodialysis, thiosulfate application, analgaesia and wound management leading to significant improvement, however, without complete remission.
A matched-group study protocol to evaluate the implementation of an Integrated Care Pathway programme for chronic obstructive pulmonary disease in Singapore
Authors: Wu Christine Xia , Tan Woan Shin , See Ryan Chor Kian , Yu Weichang , Kwek Lynette Siang Lim , Toh Matthias Paul Han Sim , Chee Thong Gan , Chua Gerald Seng Wee
Published: January 2015

Introduction

The treatment of chronic obstructive pulmonary disease (COPD) involves different care providers across care sites. This fragmentation of care increases the morbidity and mortality burden, as well as acute health services use. The COPD-Integrated Care Pathway (ICP) was designed and implemented to integrate the care across different sites from primary care to acute hospital and home. It aims to reduce the prevalence of COPD among the population in the catchment, reduce risk of hospital admissions, delay or prevent the progression of the disease and reduce mortality rate by adopting a coordinated and multidisciplinary approach to the management of the patients’ medical conditions. This study on the COPD-ICP programme is undertaken to determine the impact on processes of care, clinical outcomes and acute care utilisation.

Methods and analysis

This will be a retrospective, pre-post, matched-groups study to evaluate the effectiveness of the COPD-ICP programme in improving clinical outcomes and reducing healthcare costs. Programme enrolees (intervention group) and non-enrolees (comparator group) will be matched using propensity scores. Administratively, we set 30% as our target for proportion admission difference between programme and non-programme patients. A sample size of 62 patients in each group will be needed for statistical comparisons to be made at 90% power. Adherence with recommended care elements will be measured at baseline and quarterly during 1-year follow-up. Risk of COPD-related hospitalisations as primary outcome, healthcare costs, disease progression and 1-year mortality during 1-year follow-up will be compared between the groups using generalised linear regression models.

Ethics and dissemination

This protocol describes the implementation and proposed evaluation of the COPD-ICP programme. The described study has received ethical approval from the NHG Domain Specific Review Board (DSRB Ref: 2013/01200). Results of the study will be reported through peer-review publications and presentations at healthcare conferences.
Increased utilisation of primary healthcare in persons exposed to severe stress in prenatal life: a national population-based study in Denmark
Authors: Li Jiong , Yang Hu , Guldin Mai-Britt , Vedsted Peter , Vestergaard Mogens
Published: January 2015

Objective

Recent studies have suggested that stress in a pregnant mother may affect the future health of the unborn child negatively. An excellent proxy for health problems is the use of healthcare resources. Using nationwide data, we examined whether persons born to mothers who lost a close relative during pregnancy have more contacts to general practice.

Design

Population-based cohort study.

Setting

Denmark.

Participants

We included all children born in Denmark from 1973 to 2002 (N=2 032 528). Exposure of prenatal stress was defined as maternal bereavement by the death of a close relative during the antenatal period. The outcome of interest was contact with general practice between 2003 and 2009 when the participants were between 1 and 35 years of age. Poisson regression was used to assess the association between exposure and outcome.

Outcome measures

Contacts to general practitioner.

Results

Overall, persons exposed to prenatal stress had 2% more GP contacts than those not exposed, primarily due to increased utilisation of healthcare services during late adolescence and early adulthood. The exposed persons born to mothers who had lost a spouse had a higher risk (relative risk (RR) 1.12, 95% CI 1.10 to 1.14) and so did those born to mothers who had lost a close relative due to unexpected death (RR 1.06, 95% CI 1.05 to 1.06). Exposed persons had more contacts to general practice in daytime and more psychometric tests, talk therapies and C reactive protein tests than unexposed persons.

Conclusions

Prenatal stress following maternal bereavement was associated with a slightly increased utilisation of primary healthcare, mainly due to increased healthcare needs related to mental health and infections. Understanding how stress during pregnancy influences the future health of the child is an important aspect of prenatal care.
An emerging evidence base for PET-CT in the management of childhood rhabdomyosarcoma: systematic review
Authors: Norman Gill , Fayter Debra , Lewis-Light Kate , Chisholm Julia , McHugh Kieran , Levine Daniel , Jenney Meriel , Mandeville Henry , Gatz Suzanne , Phillips Bob
Published: January 2015

Introduction

Rhabdomyosarcoma (RMS) management depends on risk stratification at diagnosis and treatment response. Assessment methods include CT, MRI, bone scintigraphy, histological analysis and bone marrow biopsy. Advanced functional imaging (FI) has potential to improve staging accuracy and management strategies.

Methods and analysis

We conducted a systematic review (PROSPERO 2013:CRD42013006128) of diagnostic accuracy and clinical effectiveness of FI in histologically proven paediatric RMS. PRISMA guidance was followed. We searched 10 databases to November 2013. Studies with ≥10 patients with RMS which compared positron emission tomography (PET), PET-CT or diffusion-weighted imaging (DWI) MRI to conventional imaging at any treatment stage were included. Study quality was assessed. Limited, heterogeneous effectiveness data required narrative synthesis, illustrated by plotting sensitivity and specificity in receiver operating curve (ROC) space.

Results

Eight studies (six PET-CT, two PET) with 272 RMS patients in total were included. No DWI-MRI studies met inclusion criteria. Pooled estimates were not calculated due to sparseness of data. Limited evidence indicated initial PET-CT results were predictive of survival. PET-CT changed management of 7/40 patients. Nodal involvement PET-CT: sensitivity ranged from 80% to 100%; specificity from 89% to 100%. Distant metastatic involvement: PET-CT sensitivity ranged from 95% to 100%; specificity from 80% to100%. Data on metastases in different sites were sparse. Limited data were found on outcome prediction by PET-CT response.

Dissemination and ethics

PET/PET-CT may increase initial staging accuracy in paediatric RMS, specifically in the detection of nodal involvement and distant metastatic spread. There is a need to further assess PET-CT for this population, ideally in a representative, unbiased and transparently selected cohort of patients.
Treatment approaches of palliative medicine specialists for depression in the palliative care setting: findings from a qualitative, in-depth interview study
Authors: Ng Felicity , Crawford Gregory B , Chur-Hansen Anna
Published: January 2015

Background

Treatment of depression in the palliative care setting is complicated by varied treatment preferences, a small body of research, and unique challenges associated with the end-of-life. Little is known about the treatment practices of medical practitioners in this setting.

Objective

This study aimed to investigate and characterise the treatment approaches of palliative medicine specialists for depression.

Design

Semistructured, in-depth interviews were conducted to explore explanatory models of depression from palliative medicine specialists, including a focus on treatment. Verbatim interview transcripts were analysed for themes.

Setting/participants

Palliative medicine specialists practising in Australia were recruited and purposively sampled. Nine participants were interviewed to reach data saturation.

Results

Five themes were identified in relation to treatment of depression: (1) guiding principles of treatment; (2) treatment approaches; (3) factors underpinning treatment decisions; (4) difficulties arising in treatment; and (5) interdisciplinary roles. Participants described five distinct treatment approaches, consisting of biological orientation, psychosocial orientation, combination approach, undifferentiated approach and ambivalence. Treatment decisions were contingent on patient, depression, clinician and sociocultural factors. Difficulties included discomfort with treating depression, being inadequately equipped and confronting therapeutic limitations. Treating depression was considered to require multidisciplinary team effort.

Conclusions

Palliative medicine specialists’ treatment approaches are linked to their concepts of and causal explanations for depression. Future treatment guidelines could aim to consider specific varieties of depression, be more differentiated in treatment modality and type, and consider decision-shaping factors. Continuing mental health education and the incorporation of psychiatry and psychology into palliative care services may have enduring benefits.
The challenges of conducting prehospital research: successes and lessons learnt from the Head Injury Transportation Straight to Neurosurgery (HITS-NS) trial
Authors: McClelland Graham , Pennington Elspeth , Byers Sonia , Russell Wanda , Lecky Fiona
Published: January 2015

Head Injury Transportation Straight to Neurosurgery was a cluster randomised trial studying suspected severe head injury treatment pathways conducted in the North East Ambulance Service NHS Foundation Trust and North West Ambulance Service NHS Trust between January 2012 and March 2013. This was the world's first large scale trial of any trauma bypass and was conducted as a feasibility study. This short report will describe some of the lessons learnt during this ground breaking and complex trial.
Effect of signs of oestrus, disease stressors and cow activity on pregnancy rate following artificial insemination
Authors: Bijker I. , Christley R. M. , Smith R. F. , Dobson H.
Published: January 2015

The objective was to examine (a) how pregnancy rate on one farm (500 cows) was affected by signs of oestrus and disease stressors and (b) whether pregnancy rate could be maximised by considering cow activity. The signs of oestrus and timings were recorded at artificial insemination (AI), and cow activity was monitored by neck collars. Pregnancy rate tended to be higher in animals that displayed standing oestrus (35 v 26 per cent; P=0.06) but was 10 per cent lower in those cows with an elevated somatic cell count (SCC; >200,000 cells/ml milk) within 0–4 or 4–8 weeks prior to AI (P=0.01 and 0.05, respectively), irrespective of the incidence of clinical mastitis prior to AI. Cow activity data were available for 525 inseminations (from a total of 1299). The mean interval from increased activity to AI in all cows (11 hours 32 minutes; 95 per cent CI 10 hours 40 minutes to 12 hours 24 minutes) was not different for cows that did or did not establish a pregnancy (P=0.90). The pregnancy rate improved to the average of unaffected cows if AI was delayed by about eight hours in animals with an elevated SCC 0–4 weeks prior to AI (P=0.025), indicating that, in cows with prior elevated SCC, AI could be repeated approximately eight hours later to achieve maximum pregnancy rates.
Additions to the Eocene Perissodactyla of the Margaret Formation, Eureka Sound Group, Ellesmere Island, Arctic Canada
Authors: Eberle Jaelyn J. , Eberth David A.
Published: January 2015

We describe early Eocene (Wasatchian) occurrences of the isectolophid Homogalax, tapiroids Heptodon posticus, Heptodon cf. H. posticus, and Heptodon sp., as well as early middle Eocene (Bridgerian) fossils of the brontothere Palaeosyops from localities in the Margaret Formation of the Eureka Sound Group on Ellesmere Island, Nunavut, Arctic Canada. Their occurrence on Ellesmere Island considerably extends the geographic range of these taxa, previously known from mid-latitude localities in British Columbia (only Heptodon), the Western Interior of the United States, and Asia (Homogalax, Heptodon, and Palaeosyops). We also place the fossil localities near Bay Fiord on central Ellesmere Island into a refined lithostratigraphic framework based upon data from three measured stratigraphic sections. Our stratigraphic data confirm the presence of two, stratigraphically distinct fossil assemblages — a late Wasatchian-aged lower assemblage and a Bridgerian-aged upper assemblage that were previously hypothesized by others based on faunal differences — that are separated by a 478 m thick stratigraphic gap that appears to lack fossil vertebrates. From a paleoenvironmental perspective, occurrence of the tapiroid Heptodon in the Eocene Arctic corroborates an hypothesis put forward by others that tapiroids are proxies for densely forested habitats, although they were adapted to a range of temperatures including near (or at) freezing temperatures of Eocene Arctic winters. Further, Arctic occurrences of tapiroids and brontotheres imply that these typical mid-latitude ungulate mammals were adapted to Arctic environments, thereby increasing the probability of Trans-Beringian dispersal during early and middle Eocene time.
Effects of predation on telemetry-based survival estimates: insights from a study on endangered Atlantic salmon smolts
Authors: Gibson A. Jamie F. , Halfyard Edmund A. , Bradford Rod G. , Stokesbury Michael J.W. , Redden Anna M.
Published: January 2015

Telemetry is increasingly being used to estimate population-level survival rates. However, these estimates may be affected by the detectability of telemetry tags and are reliant on the assumption that telemetry data represent the movements of the tagged fish. Predation on tagged fish has the potential to bias survival estimates, and unlike the issue of detectability, methods to correct for the resulting bias (termed “predation bias”) are not yet developed. In an acoustic telemetry study on inner Bay of Fundy Atlantic salmon (Salmo salar) smolts during 2008 and 2011, unusual tag detection patterns were indicative that some data may have been representative of the movements of predators rather than smolts. To incorporate predation effects into the resulting survival estimates, a suite of 11 summary migration metrics were compared between Atlantic salmon smolts and striped bass (Morone saxatilis). Cluster analyses revealed that 2.4% to 13.6% of tags implanted in smolts exhibited migration patterns more similar to striped bass than to other smolts, which was interpreted here as evidence of predation. Reassigning the fate of these tags as “depredated–died” reduced estimated survival from 43.5% to 41.1% in 2008 and from 32.6% to 19.0% in 2011 relative to a traditional mark–recapture model, illustrating the effect of predation bias in this case study.