bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of oral cyclosporine on canine T‐cell expression of IL‐2 and IFN‐gamma across a 12‐h dosing interval
Authors: Fellman C. L. , Archer T. M. , Stokes J. V. , Wills R. W. , Lunsford K. V. , Mackin A. J. 
Published: December 2015

The duration of immunosuppressive effects following oral cyclosporine in dogs is unknown. This study used flow cytometry and quantitative reverse transcription–polymerase chain reaction (qRT‐PCR) to evaluate the effects of high‐dose oral cyclosporine across a 12‐h dosing interval. Expression of interleukin‐2 (IL‐2) and interferon‐gamma (IFN‐γ) was compared before and after 8 days of cyclosporine at 10 mg/kg every 12 h in six healthy dogs. Samples were collected at 0, 2, 4, and 8 h postdosing for analysis of unactivated and activated T‐cell and whole blood cytokine expression using flow cytometry and qRT‐PCR, respectively, and at 0, 2, 4, 6, 8, and 10 h postdosing for measurement of cyclosporine concentrations. Flow cytometry and qRT‐PCR both demonstrated significant marked reductions in IL‐2 and IFN‐γ levels at 0, 2, 4, and 8 h after dosing compared to pretreatment levels (P < 0.05) for activated samples, with less consistent effects observed for unactivated samples. Both flow cytometry and qRT‐PCR are viable techniques for measuring cyclosporine pharmacodynamics in dogs, yielding comparable results with activated samples. Two hours postdrug administration is the preferred time for concurrent assessment of peak drug concentration and cytokine expression, and T‐cell activation is needed for optimal results.
Evidence from pyrosequencing indicates that natural variation in animal personality is associated with DRD4 DNA methylation
Authors: Verhulst Eveline C. , Mateman A. Christa , Zwier Mathijs V. , Caro Samuel P. , Verhoeven Koen J.F. , van Oers Kees 
Published: December 2015

AbstractPersonality traits are heritable and respond to natural selection, but are at the same time influenced by the ontogenetic environment. Epigenetic effects, such as DNA methylation, have been proposed as a key mechanism to control personality variation. However, to date little is known about the contribution of epigenetic effects to natural variation in behaviour. Here, we show that great tit (Parus major) lines artificially selected for divergent exploratory behaviour for four generations differ in their DNA methylation levels at the dopamine receptor D4 (DRD4) gene. This D4 receptor is statistically associated with personality traits in both humans and nonhuman animals, including the great tit. Previous work in this songbird failed to detect functional genetic polymorphisms within DRD4 that could account for the gene–trait association. However, our observation supports the idea that DRD4 is functionally involved in exploratory behaviour but that its effects are mediated by DNA methylation. While the exact mechanism underlying the transgenerational consistency of DRD4 methylation remains to be elucidated, this study shows that epigenetic mechanisms are involved in shaping natural variation in personality traits. We outline how this first finding provides a basis for investigating the epigenetic contribution to personality traits in natural systems and its subsequent role for understanding the ecology and evolution of behavioural consistency.
Prevalence, clinical presentation, prognosis, and outcome of 17 dogs with spinal shock and acute thoracolumbar spinal cord disease
Authors: Full Amanda M. , Heller Heidi L. Barnes , Mercier Miyu 
Published: December 2015

AbstractObjectiveTo describe the prevalence, signalment, clinical features, etiology, and outcome in dogs with acute thoracolumbar disease and suspected spinal shock.DesignRetrospective clinical case study (2005–2010).SettingPrivate specialty practice.AnimalsMedical records of 263 dogs with thoracolumbar spinal magnetic resonance imaging were reviewed. If decreased or absent withdrawal reflexes were present in 1 or both pelvic limbs, in the absence of a spinal lesion in the lumbosacral intumescence, dogs were diagnosed with spinal shock. Dogs with suspected or confirmed spinal neoplasia, myelomalacia, or meningomyelitis were excluded. Seventeen of 263 dogs (6%) met inclusion criteria.InterventionsNone.Measurements and Main ResultsThoracic lesions were significantly more likely to result in spinal shock when compared to lumbar lesions (P = 0.03). Fibrocartilaginous embolism was the most commonly diagnosed etiology (7 of 17 dogs), and was more common in the thoracic spine compared to in the lumbar spine (P = 0.10). Six of 17 dogs (35%) were diagnosed with intervertebral disk herniation; 4 of 17 dogs (24%) with suspected acute noncompressive nucleus pulposus extrusion. Two dogs were lost to follow‐up. Fourteen of 15 (93%) dogs had improved or normal reflexes by 60 days post injury.ConclusionsAlthough the prevalence of spinal shock was low, it should be considered in any dog presenting with an acute history of thoracolumbar spinal injury with reduced or absent reflexes in the pelvic limbs. The presence of spinal shock should not dissuade a veterinarian from pursuing appropriate diagnostic testing and therapy for the underlying etiology.
The effect of burst patterning of preganglionic input on the efficacy of transmission at the cat stellate ganglion
Authors: Birks R. I. , Laskey W. , Polosa C. 
Published: December 2015

1. The effect of burst patterned preganglionic stimulation on the efficacy of transmission at the cat stellate ganglion in vivo was studied to determine whether the increase in acetylcholine (ACh) release that occurs at preganglionic terminals with similar stimulation is synaptically active.2. Stimulation of the whole or a portion of the thoracic sympathetic trunk between rami T4 and T5 with recording of evoked compound action potentials in the inferior cardiac nerve yielded a preparation with a subliminal fringe with a mean value 2·5 times the size of the discharge zone.3. Preganglionic stimulation with 0·5 s bursts at 10, 20 and 40 Hz with 10 s interburst intervals caused an increase with time in the area of the compound action potential evoked by a single interburst test stimulus. The increase reached 70‐75% of the final value after the first burst, 75‐90% after 5 bursts and was virtually complete after 5 min. It was then maintained without attenuation as stimulation was continued.4. On cessation of burst patterned stimulation test compound action potentials returned to control levels with a half‐time of 5 min.5. The increase in area of test compound action potentials with 40 Hz intraburst frequency was always as great as the increase following tetanization of the pathway. The increases with 20 and 10 Hz bursts were less.6. There was no increase in area of compound action potentials when equally spaced pulses at 2 Hz or less were applied preganglionically, nor was there any increase when 40 Hz burst patterns were delivered directly to the inferior cardiac nerve.7. It is concluded that burst patterned preganglionic activity at frequencies similar to those observed in vivo can recruit rapidly into the discharge zone all of the ganglionic neurones that were originally in the subliminal fringe. It is proposed that this effect is related directly to the increase in ACh release at ganglionic synapses that such activity has been shown to induce.
Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency
Authors: Alfson Kendra J. , Worwa Gabriella , Carrion Ricardo , Griffiths Anthony 
Published: December 2015

ABSTRACTEbola virus (EBOV) is an RNA virus that can cause hemorrhagic fever with high fatality rates, and there are no approved vaccines or therapies. Typically, RNA viruses have high spontaneous mutation rates, which permit rapid adaptation to selection pressures and have other important biological consequences. However, it is unknown if filoviruses exhibit high mutation frequencies. Ultradeep sequencing and a recombinant EBOV that carries the gene encoding green fluorescent protein were used to determine the spontaneous mutation frequency of EBOV. The effects of the guanosine analogue ribavirin during EBOV infections were also assessed. Ultradeep sequencing revealed that the mutation frequency for EBOV was high and similar to those of other RNA viruses. Interestingly, significant genetic diversity was not observed in viable viruses, implying that changes were not well tolerated. We hypothesized that this could be exploited therapeutically.In vitro, the presence of ribavirin increased the error rate, and the 50% inhibitory concentration (IC50) was 27 μM. In a mouse model of ribavirin therapy given pre-EBOV exposure, ribavirin treatment corresponded with a significant delay in time to death and up to 75% survival. In mouse and monkey models of therapy given post-EBOV exposure, ribavirin treatment also delayed the time to death and increased survival. These results demonstrate that EBOV has a spontaneous mutation frequency similar to those of other RNA viruses. These data also suggest a potential for therapeutic use of ribavirin for human EBOV infections.IMPORTANCEEbola virus (EBOV) causes a severe hemorrhagic disease with high case fatality rates; there are no approved vaccines or therapies. We determined the spontaneous mutation frequency of EBOV, which is relevant to understanding the potential for the virus to adapt. The frequency was similar to those of other RNA viruses. Significant genetic diversity was not observed in viable viruses, implying that changes were not well tolerated. We hypothesized that this could be exploited therapeutically. Ribavirin is a viral mutagen approved for treatment of several virus infections; it is also cheap and readily available. In cell culture, we showed that ribavirin was effective at reducing production of infectious EBOV. In mouse and monkey models of therapy given post-EBOV exposure, ribavirin treatment delayed the time to death and increased survival. These data provide a better understanding of EBOV spontaneous mutation and suggest that ribavirin may have great value in the context of human disease.
Early Activation of Primary Brain Microvascular Endothelial Cells by Nipah Virus Glycoprotein-Containing Particles
Authors: Freitag Tanja C. , Maisner Andrea 
Published: December 2015

ABSTRACT
Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes pronounced infection of brain endothelia and central nervous system (CNS) inflammation. Using primary porcine brain microvascular endothelial cells, we showed that upregulation of E-selectin precedes cytokine induction and is induced not only by infectious NiV but also by NiV-glycoprotein-containing virus-like particles. This demonstrates that very early events in NiV brain endothelial infection do not depend on NiV replication but can be triggered by the NiV glycoproteins alone.
VITALITY trial: protocol for a randomised controlled trial to establish the role of postnatal vitamin D supplementation in infant immune health
Authors: Allen Katrina J , Panjari Mary , Koplin Jennifer J , Ponsonby Anne-Louise , Vuillermin Peter , Gurrin Lyle C , Greaves Ronda , Carvalho Natalie , Dalziel Kim , Tang Mimi L K , Lee Katherine J , Wake Melissa , Curtis Nigel , Dharmage Shyamali C 
Published: December 2015

IntroductionPostnatal vitamin D supplementation may be associated with a reduction in IgE-mediated food allergy, lower respiratory tract infections and improved bone health. Countries in the Northern hemisphere recommend universal infant vitamin D supplementation to optimise early vitamin D levels, despite the absence of large trials proving safety or efficacy for any disease outcome. With the aim of determining the clinical and cost-effectiveness of daily vitamin D supplementation in breastfed infants from age 6–8 weeks to 12 months of age, we have started a double-blind, randomised, placebo-controlled trial of daily 400 IU vitamin D supplementation during the first year of life, VITALITY.Methods nd analysisInfants (n=3012) who are fully breastfed and not receiving vitamin D supplementation will be recruited at the time of their first immunisation, from council-led immunisation clinics throughout metropolitan Melbourne, Australia. The primary outcome is challenge-proven food allergy at 12 months of age. Secondary outcomes are food sensitisation (positive skin prick test), number of lower respiratory infections (through hospital linkage), moderately-severe and persistent eczema (by history and examination) and vitamin D deficiency (serum vitamin D <50 nmol/L) at age 12 months. The trial is underway and the first 130 participants have been recruited.Ethics and disseminationThe VITALITY study is approved by the Royal Children's Hospital (RCH) Human Research Ethics Committee (#34168). Outcomes will be disseminated through publication and will be presented at scientific conferences.Trial registration numbersANZCTR12614000334606 andNCT02112734; pre-results.
Survey of the capacity for essential surgery and anaesthesia services in Papua New Guinea
Authors: Martin Janet , Tau Goa , Cherian Meena Nathan , Vergel de Dios Jennifer , Mills David , Fitzpatrick Jane , Adu-Krow William , Cheng Davy 
Published: December 2015

ObjectiveTo assess capacity to provide essential surgical services including emergency, obstetric and anaesthesia care in Papua New Guinea (PNG) in order to support planning for relevant post-2015 sustainable development goals for PNG.DesignCross-sectional survey.SettingHospitals and health facilities in PNG.Participants21 facilities including 3 national/provincial hospitals, 11 district/rural hospitals, and 7 health centres.Outcome measuresThe WHO Situational Analysis Tool to Assess Emergency and Essential Surgical Care (WHO-SAT) was used to measure each participating facility's capacity to deliver essential surgery and anaesthesia services, including 108 items related to relevant infrastructure, human resources, interventions and equipment.ResultsWhile major surgical procedures were provided at each hospital, fewer than 30% had uninterrupted access to oxygen, and 57% had uninterrupted access to resuscitation bag and mask. Most hospitals reported capacity to provide general anaesthesia, though few hospitals reported having at least one certified surgeon, obstetrician and anaesthesiologist. Access to anaesthetic machines, pulse oximetry and blood bank was severely limited. Many non-hospital health centres providing basic surgical procedures, but almost none had uninterrupted access to electricity, running water, oxygen and basic supplies for resuscitation, airway management and obstetric services.ConclusionsCapacity for essential surgery and anaesthesia services is severely limited in PNG due to shortfalls in physical infrastructure, human resources, and basic equipment and supplies. Achieving post-2015 sustainable development goals, including universal healthcare, will require significant investment in surgery and anaesthesia capacity in PNG.
Therapeutic management of complex anal fistulas by installing a nitinol closure clip: study protocol of a multicentric randomised controlled trial—FISCLOSE
Authors: Dubois Anne , Carrier Guillaume , Pereira Bruno , Gillet Brigitte , Faucheron Jean-Luc , Pezet Denis , Balayssac David 
Published: December 2015

IntroductionComplex anal fistulas are responsible for pain, faecal incontinence and impaired quality of life. The rectal mucosa advancement flap (RMAF) procedure to cover the internal opening of the fistula remains a strategy of choice. However, a new procedure for closing anal fistulas is now available with the use of a nitinol closure clip (OTSC Proctology, OVESCO), which should ensure a better healing rate. This procedure is currently becoming more widespread, though without robust scientific validation, and it is therefore essential to carry out a prospective evaluation in order to determine the efficacy and safety of this new medical device for complex anal fistulas.Methods and analysisThe FISCLOSE trial is aimed at evaluating the efficacy and safety of a nitinol closure clip compared to the RMAF procedure for the management of complex anal fistulas. This trial is a prospective, randomised, controlled, single-blind, bicentre and interventional study. Patients (n=46 per group) will be randomly assigned for management with either a closure clip or RMAF. The main objectives are to improve the healing rate of the anal fistula, lessen the postoperative pain and faecal incontinency, enhance the quality of life, and lower the number of reinterventions and therapeutic management costs. The primary outcome is the proportion of patients with a healed fistula at 3 months. The secondary outcomes are anal fistula healing (6 and 12 months), proctological pain (visual analogue scale), the faecal incontinence score (Jorge and Wexner questionnaire), digestive disorders and quality of life (Gastrointestinal Quality of Life Index and Euroqol EQ5D-3 L) up to 1 year.Ethics and disseminationThe study was approved by an independent medical ethics committee 1 (IRB00008526, CPP Sud-Est 6, Clermont-Ferrand, France) and registered by the competent French authority (ANSM, Saint Denis, France). The results will be disseminated in a peer-reviewed journal and presented at international congresses.Trial registration numberNCT02336867; pre-result.
Use of a high-precision gravity survey to understand the formation of oceanic crust and the role of melt at the southern Red Sea rift in Afar, Ethiopia
Authors: Lewi E. , Keir D. , Birhanu Y. , Blundy J. , Stuart G. , Wright T. , Calais E. 
Published: December 2015

Abstract
The Red Sea arm of the triple junction in northeastern Ethiopia provides an opportunity to investigate rift-forming processes at divergent boundaries. In an attempt to study the subsurface, especially the distribution and role of melt in the rifting process, we carried out a high-precision gravity survey with a mean-square error of 0.011 mgal, assisted by differential global positioning system measurements. The profile is 162 km long and strikes ENE–WSW across the southern part of the Red Sea rift at a latitude of approximately 11.75° N. Modelling of the Bouguer anomaly, constrained by a priori information, showed detailed in-rift variations in the crustal structure and the distribution of melt beneath the rift axis. Our interpretation suggested that the process of continental break-up is governed by crustal stretching and rifting accompanied by the emplacement of melt into the lower crust above a lower density upper mantle. In addition, we interpreted the thickness of the crust beneath this part of the rift axis to be 25 km. The subsurface distribution of density beneath the profile shows that the south-central part of the Red Sea rift has modified thinned crust, intruded by high-density material, which resembles the crust formed during seafloor spreading.
Synergistic use of satellite thermal detection and science: a decadal perspective using ASTER
Authors: Ramsey Michael S. 
Published: December 2015

Abstract
Many volcanoes around the world are poorly monitored and new eruptions increase the need for rapid ground-based monitoring, which is not always available in a timely manner. Initial observations therefore are commonly provided by orbital remote sensing instruments at different temporal, spatial and wavelength scales. Even at well-monitored volcanoes, satellite data still play an important role. The ASTER (Advanced Spaceborne Thermal Emission Radiometer) orbital sensor provides moderately high spatial resolution images in multiple wavelength regions; however, because ASTER is a scheduled instrument, the data are not acquired over specific targets every orbit. Therefore, in an attempt to improve the temporal frequency of ASTER specifically for volcano observations and to have the images integrate synergistically with high temporal resolution data, the Urgent Request Protocol (URP) system was developed in 2004. Now integrated with both the AVHRR (Advanced Very High Resolution Radiometer) and MODIS (Moderate Resolution Imaging Spectroradiometer) hotspot monitoring programmes, the URP acquires an average of 24 volcanic datasets every month and planned improvements will allow this number to increase in the future. New URP data are sent directly to investigators responding to the ongoing eruption, and the large archive is also being used for retrospective science and operational studies for future instruments. The URP Program has been very successful over the past decade and will continue until at least 2017 or as long as the ASTER sensor is operational. Several volcanic science examples are given here that highlight the various stages of the URP development. However, not all are strictly focused on effusive eruptions. Rather, these examples were chosen to demonstrate the wide range of applications, as well as the general usefulness of the higher resolution, multispectral data of ASTER.
Archosaur footprints (cf.
Brachychirotherium
) with unusual morphology from the Upper Triassic Fleming Fjord Formation (Norian–Rhaetian) of East Greenland
Authors: Klein Hendrik , Milàn Jesper , Clemmensen Lars B. , Frobøse Nicolaj , Mateus Octávio , Klein Nicole , Adolfssen Jan S. , Estrup Eliza J. , Wings Oliver 
Published: December 2015

Abstract

The Ørsted Dal Member of the Upper Triassic Fleming Fjord Formation in East Greenland is well known for its rich vertebrate fauna, represented by numerous specimens of both body and ichnofossils. In particular, the footprints of theropod dinosaurs have been described. Recently, an international expedition discovered several slabs with 100 small chirotheriid pes and manus imprints (pes length 4–4.5 cm) in siliciclastic deposits of this unit. They show strong similarities with
Brachychirotherium
, a characteristic Upper Triassic ichnogenus with a global distribution. A peculiar feature in the Fleming Fjord specimens is the lack of a fifth digit, even in more deeply impressed imprints. Therefore, the specimens are assigned here tentatively to cf.
Brachychirotherium
. Possibly, this characteristic is related to the extremely small size and early ontogenetic stage of the trackmaker. The record from Greenland is the first evidence of this morphotype from the Fleming Fjord Formation. Candidate trackmakers are crocodylian stem group archosaurs; however, a distinct correlation with known osteological taxa from this unit is not currently possible. While the occurrence of sauropodomorph plateosaurs in the bone record links the Greenland assemblage more closer to that from the Germanic Basin of central Europe, here the described footprints suggest a Pangaea-wide exchange.

Supplementary material:

Three-dimensional model of cf.
Brachychirotherium
pes–manus set (from MGUH 31233b) from the Upper Triassic Fleming Fjord Formation (Norian–Rhaetian) of East Greenland as pdf, ply and jpg files (3D model created by Oliver Wings; photographs taken by Jesper Milàn) is available at
https://doi.org/10.6084/m9.figshare.c.2133546