bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies and Resources for Increasing the PhD Pipeline and Producing Independent Nurse Scientists
Authors: Stanfill Ansley Grimes , Aycock Dawn , Dionne‐Odom J. Nicholas , Rosa William E.
Published: November 2019

Nurse scientists play an indispensable role in developing new knowledge to advance the health of patients, families, and communities. Yet PhD nurse enrollment has significantly dropped, and many later career nurse scientists are nearing retirement. The purpose of this article is to outline potential strategies to enhance the PhD nurse pipeline. Potential strategies are identified at three distinct time points along the PhD trajectory: (a) prior to a PhD program (increasing the pipeline), (b) during a PhD program (enhancing graduation rates and transitioning into research‐focused careers), and (c) in the postdoctoral or early career period (establishing scholarly independence and an active program of research). Talented students should be approached early on in their education to ascertain interest in a scientific research‐based career, and all students could be engaged in research opportunities while in undergraduate programs. During a PhD program, supportive mentors are a key component for student success and may provide assistance in obtaining ongoing funding and scholarship support. Throughout doctoral study and into early career, less structured opportunities can be influential, including conference support, online and face‐to‐face training, and ongoing funding and scholarship support for postdoctoral study or fellowships. At each career stage, there should be a focus on designing scientifically sound nursing research that will impact outcomes in measurable and sustainable ways. We must not focus our attention only on student recruitment. Public messaging efforts are needed to raise awareness of the role of nurse researchers. In addition, several stakeholders play a role in increasing the PhD pipeline and producing independent nurse scientists, and they should be acknowledged in these efforts. The strategies described may be beneficial for any nurse contemplating a research career as well as for those who may serve as mentors to these individuals. More broadly, these strategies may be employed by colleges and universities, funding bodies, professional nursing societies, and healthcare organizations in the United States and abroad. Increasing the PhD pipeline, and fostering a more robust field of independent nurse scientists, will translate into improved patient outcomes.
MRI Findings in Pediatric Abusive Head Trauma: A Review
Authors: Orman Gunes , Kralik Stephen F. , Meoded Avner , Desai Nilesh , Risen Sarah , Huisman Thierry A.G.M.
Published: November 2019

Trauma is the most common cause of death and significant morbidity in childhood; abusive head trauma (AHT) is a prominent cause of significant morbidity and mortality in children younger than 2 years old. Correctly diagnosing AHT is challenging both clinically and radiologically. The primary diagnostic challenges are that the abused children are usually too young to provide an adequate history, perpetrators are unlikely to provide truthful account of trauma, and clinicians may be biased in their assessment of potentially abused children. The main radiological challenge is that there is no single imaging finding that is independently specific for or diagnostic of AHT. The radiological evaluation should be based on the multiplicity and severity of findings and an inconsistency with the provided mechanism of trauma. While the most common neuroimaging finding in AHT is subdural hemorrhage, other less well‐known magnetic resonance imaging (MRI) findings such as the “lollipop sign” or “tadpole sign,” parenchymal or cortical lacerations, subpial hemorrhage, cranio‐cervical junction injuries including retroclival hematomas, as well as diffuse hypoxic brain injury have been identified and described in the recent literature. While AHT is ultimately a clinical diagnosis combining history, exam, and neuroimaging, familiarity with the typical as well as the less‐well known MRI findings will improve recognition of AHT by radiologists.
Changes in heart rate related to rhythmic masticatory muscle activities and limb movements in patients with sleep bruxism
Authors: Zhong Zhijun , Xu Miao , Zou Xueliang , Ouyang Qian , Zhang Ling , Yu Bin , Wang Kelun , Yao Dongyuan
Published: November 2019

Most sleep bruxism (SB) episodes are accompanied by an increase in sympathetic tone and heart rate (HR). To characterise heart rate (HR) changes in relation to rhythmic masticatory muscle activities (RMMAs) in SB patients, polysomnographic recordings were performed on 10 SB patients and 11 normal controls. The duration of movement events, amplitude and duration of HR increases, and time to reach HR peak associated with RMMAs and limb movements (LMs) were determined, and the relationships of the parameters of HR increases with types of movements and RMMAs were analysed. All of the parameters of HR increases associated with three types of movements (RMMAs, RMMAs + LMs and LMs) and masseter activities (phasic, tonic and mixed) were significantly different (two‐way ANOVA, P < .001 for all) in both SB patients and controls. The duration of RMMAs/LMs was positively correlated with the parameters (SB patients: R2 = .24‐.85, P < .0001; controls: R2 = .23‐.68, P < .0001). The amplitude of HR increases was also positively correlated with respiration changes in the SB patients (R2 = .3258, P < .0001) and controls (R2 = .09469, P < .05). The proportions of phasic RMMAs associated with awakenings, microarousals and no cortical arousals were significantly different and so were the proportions of tonic and mixed RMMAs (Friedman's tests, P < .05‐.001). The HR increases associated with RMMAs may be intrinsic to the cortical arousal response and autonomic activation, and differences in HR increases associated with different types of movements and RMMAs might be related to the changes in respiration and differences in cortical arousal levels.
Bond Strength of Denture Teeth to Heat‐Cured, CAD/CAM and 3D Printed Denture Acrylics
Authors: Choi Joanne Jung Eun , Uy Caira Ellyse , Plaksina Polina , Ramani Rishi Sanjay , Ganjigatti Ritu , Waddell John Neil
Published: November 2019

Purpose

To establish the fracture toughness (K1C) and flexural bond strength of commercially available denture teeth to heat cured, CAD/CAM and 3D printed denture‐based resins (DBRs).

Materials and Methods

Three types of DBRs (Heat cure, CAD‐milled and 3D printed) and four different types of commercial denture teeth (Unfilled PMMA, double cross‐linked PMMA, PMMA with nanofillers and 3D printed resin teeth) were investigated. DBR and epoxy embedded denture teeth (n = 30 per group) specimen beams (25 × 4 × 3 mm) were fabricated. The testing ends of all the specimens were surface treated, bonded and processed according to manufacturer's instructions. Twenty specimens were thermal cycled to simulate the effects of 6 and 12 months intraorally. A 4‐point bend test, using the chevron‐notched beam method was done and K1C (MPa ·m1/2) and flexure bond strength (MPa) were calculated. All specimens were analysed for the mode of failure under the light microscope and selected specimens under scanning electron microscope. Results were statistically analysed using ANOVA (SPSS Ver 24).

Results

The mean K1C was the highest for the teeth bonded to the heat‐cured DBR group (1.09 ± 0.24), followed by CAD/CAM (0.43 ± 0.05) and 3D printed groups (0.17 ± 0.01). Differences were statistically significant (p < 0.01). Within each group, aging showed statistically significantly lower values but no statistical significance between the mean K1C and flexural bond strength (p = 0.36). The dominant mode of failure was cohesive in the CAD/CAM groups and adhesive in the heat‐cured and 3D printed groups.

Conclusion

Teeth bonded to heat‐cured DBRs produced the highest K1C.The bond strength decreased significantly with aging. Teeth bonded to CAD/CAM and 3D printed DBRs showed significantly lower bond strength, with no significant influence of aging.
Genetic innovations: Transposable element recruitment and de novo formation lead to the birth of orphan genes in the rice genome
Authors: Jin Gui‐Hua , Zhou Yan‐Li , Yang Hong , Hu Yan‐Ting , Shi Yong , Li Ling , Siddique Abu N. , Liu Chang‐Ning , Zhu An‐Dan , Zhang Cheng‐Jun , Li De‐Zhu
Published: November 2019

Orphan genes are genetic innovations that lack homologs in other lineages. Orphan genes can rapidly originate and become substantially functional, yet the mechanisms underlying their origins are still largely unknown in plants. Here, we investigated the origin of orphan genes in the Oryza sativa ssp. japonica “Nipponbare” genome using genome‐wide comparisons with 10 closely related Oryza species. We identified a total of 37 orphan genes in the Nipponbare genome that show short sequence lengths, elevated GC content, and absence of introns. Interestingly, half of the identified orphan genes originated by way of a distinctive mechanism that involved the generation of new coding sequences through independent and rapid divergence within the inserted transposable element. Our results provide valuable insight into genetic innovations in the model rice genome that formed on a very short timescale.
Climatic vulnerabilities and ecological preferences of soil invertebrates across biomes
Authors: Bastida Felipe , Eldridge David J. , Abades Sebastián , Alfaro Fernando D. , Gallardo Antonio , García‐Velázquez Laura , García Carlos , Hart Stephen C. , Pérez Cecilia A. , Santos Fernanda , Trivedi Pankaj , Williams Mark A. , Delgado‐Baquerizo Manuel
Published: November 2019

Unlike plants and vertebrates, the ecological preferences, and potential vulnerabilities of soil invertebrates to environmental change, remain poorly understood in terrestrial ecosystems globally. We conducted a cross‐biome survey including 83 locations across six continents to advance our understanding of the ecological preferences and vulnerabilities of the diversity of dominant and functionally important soil invertebrate taxa, including nematodes, arachnids and rotifers. The diversity of invertebrates was analyzed through amplicon sequencing. Vegetation and climate drove the diversity and dominant taxa of soil invertebrates. Our results suggest that declines in forest cover and plant diversity, and reductions in plant production associated with increases in aridity, can result in reductions of the diversity of soil invertebrates in a drier and more managed world. We further developed global atlases of the diversity of these important soil invertebrates, which were cross‐validated using an independent database. Our study advances the current knowledge of the ecological preferences and vulnerabilities of the diversity and presence of functionally important soil invertebrates in soils from across the globe. This information is fundamental for improving and prioritizing conservation efforts of soil genetic resources and management policies.
Communication and indifference
Authors: Abreu Zavaleta Martín
Published: November 2019

The propositional view of communication states that every literal assertoric utterance of an indicative sentence expresses a proposition, and the audience understands those utterances only if she entertains the proposition(s) the speaker expressed. According to an important objection due to Ray Buchanan, the propositional view is ill‐equipped to handle meaning underdeterminacy. Using resources from situation semantics and MacFarlane's nonindexical contextualism, this article develops a view of literal communication close to the propositional view which overcomes Buchanan's underdeterminacy considerations while accounting for the kind of indifference that typically characterizes speakers' intentions.
Historical changes in the stomatal limitation of photosynthesis: empirical support for an optimality principle
Authors: Lavergne Aliénor , Voelker Steve , Csank Adam , Graven Heather , de Boer Hugo J. , Daux Valérie , Robertson Iain , Dorado‐Liñán Isabel , Martínez‐Sancho Elisabet , Battipaglia Giovanna , Bloomfield Keith J. , Still Christopher J. , Meinzer Frederick C. , Dawson Todd E. , Julio Camarero J. , Clisby Rory , Fang Yunting , Menzel Annette , Keen Rachel M. , Roden John S. , Prentice I. Colin
Published: November 2019

The ratio of leaf internal (ci) to ambient (ca) partial pressure of CO2, defined here as χ, is an index of adjustments in both leaf stomatal conductance and photosynthetic rate to environmental conditions. Measurements and proxies of this ratio can be used to constrain vegetation model uncertainties for predicting terrestrial carbon uptake and water use.

We test a theory based on the least‐cost optimality hypothesis for modelling historical changes in χ over the 1951–2014 period, across different tree species and environmental conditions, as reconstructed from stable carbon isotopic measurements across a global network of 103 absolutely dated tree‐ring chronologies. The theory predicts optimal χ as a function of air temperature, vapour pressure deficit, ca and atmospheric pressure.

The theoretical model predicts 39% of the variance in χ values across sites and years, but underestimates the intersite variability in the reconstructed χ trends, resulting in only 8% of the variance in χ trends across years explained by the model.

Overall, our results support theoretical predictions that variations in χ are tightly regulated by the four environmental drivers. They also suggest that explicitly accounting for the effects of plant‐available soil water and other site‐specific characteristics might improve the predictions.
Liver stiffness correlates with serum osteopontin and TAZ expression in human liver cirrhosis
Authors: Khajehahmadi Zohreh , Mohagheghi Sina , Nikeghbalian Saman , Geramizadeh Bita , Khodadadi Iraj , Karimi Jamshid , Tavilani Heidar
Published: November 2019

The pivotal role of the extracellular matrix (ECM) as both a cause and consequence of liver fibrosis is striking. However, mechanotransducer molecules and profibrogenic factors induced by liver stiffness are still unclear. The current study aimed to investigate liver stiffness and its correlation with the expression of the transcriptional coactivator with PDZ‐binding motif (TAZ) and serum osteopontin (OPN) in human cirrhosis. In this case−control study, liver tissue stiffness was determined using atomic force microscopy in cirrhotic livers (n = 38) of different etiologies and in controls (n = 10). Immunohistochemical and qRT‐PCR analyses were performed to analyze TAZ expression. Besides, western blotting and ELISA were performed to assess liver Indian hedgehog and serum OPN levels, respectively. Liver stiffness, TAZ expression, and hepatic gene expression and serum protein levels of OPN were significantly increased in patients with cirrhosis compared with the control groups (all P < 0.001), specifically in autoimmune‐ and alcohol‐related cirrhosis. In cirrhotic patients, liver stiffness was significantly associated with the expression of nuclear TAZ and OPN. The correlation between matrix stiffness as a mechanical property, TAZ as a potential mechanotransducer, and OPN as a matricellular factor suggests possible effects of mechanical features of the ECM on the expression of the aforementioned profibrogenic markers, which is predominant in autoimmune‐ and alcohol‐related cirrhosis.
Visual and non‐visual properties of filters manipulating short‐wavelength light
Authors: Spitschan Manuel , Lazar Rafael , Cajochen Christian
Published: November 2019

Purpose

Optical filters and tints manipulating short‐wavelength light (sometimes called ‘blue‐blocking’ or ‘blue‐attenuating’ filters) are used in the management of a range of ocular, retinal, neurological and psychiatric disorders. In many cases, the only available quantification of the optical effects of a given optical filter is the spectral transmittance, which specifies the amount of light transmitted as a function of wavelength.

Methods

We propose a novel physiologically relevant and retinally referenced framework for quantifying the visual and non‐visual effects of these filters, incorporating the attenuation of luminance (luminous transmittance), the attenuation of melanopsin activation (melanopsin transmittance), the colour shift, and the reduction of the colour gamut (gamut reduction). Using these criteria, we examined a novel database of spectral transmittance functions of optical filters (n = 121) which were digitally extracted from a variety of sources.

Results

We find a large diversity in the alteration of visual and non‐visual properties. The spectral transmittance properties of the examined filters vary widely, in terms of shapes and cut‐off wavelengths. All filters show relatively more melanopsin attenuation than luminance attenuation (lower melanopsin transmittance than luminous transmittance). Across the data set, we find that melanopsin transmittance and luminous transmittance are correlated.

Conclusions

We suggest that future studies and examinations of the physiological effects of optical filters quantify the visual and non‐visual effects of the filters beyond the spectral transmittance, which will eventually aid in developing a mechanistic understanding of how different filters affect physiology. We strongly discourage comparing the downstream effects of different filters on, e.g. sleep or circadian responses, without considering their effects on the retinal stimulus.
Acetaminophen use in pregnancy: Examining prevalence, timing, and indication of use in a prospective birth cohort
Authors: Bandoli Gretchen , Palmsten Kristin , Chambers Christina
Published: November 2019

Background

Previous studies of prenatal acetaminophen use have not addressed what indications and maternal co‐factors describe acetaminophen use.

Objective

The objective of this study was to describe these parameters in a well‐characterised, prospective birth cohort.

Methods

Data were drawn from the MotherToBaby study of pregnant women enrolled from 2004 to 2018. Daily acetaminophen diaries were calculated for all exposed women with complete dose and duration information. Descriptive statistics were used to assess maternal characteristics associated with acetaminophen use. Prevalence by 2‐year interval was described, and linear regression was used to test for trend. Indication of use and dose per indication were summarised.

Results

Of 2441 subjects, 1515 (62%) reported use of acetaminophen. Over the 15‐year period, there was a decline in use of 2.5% for each 2‐year period (test for trend = 0.001) with 58% reporting acetaminophen use in 2017‐2018. Among women with acetaminophen use in pregnancy (n = 1515), 58% reported <10 days of use, 13% reported 10‐19 days of use, 9% reported 20‐44 days of use, and 9% reported 45 or more days of use. Twelve per cent had undefined duration of use. Increasing duration of exposure was associated with tobacco use, obesity, self‐reported depression or anxiety, and antidepressant use. The most frequently reported indication was headache, however, indication varied by duration of use, with more women reporting use for sleep or pain/injury in the categories with the longest duration of use. Median dose per exposed day was highest among those reporting use for sleep, and higher doses were more frequently reported for arthritis, injury, and pain.

Conclusion

Acetaminophen is used by the majority of pregnant women, and some continue to use for many weeks in pregnancy. Given the heterogeneity in duration of use, indication, and dose, studies that estimate the risk of adverse outcomes associated with acetaminophen must carefully consider these factors.
Dietary protein requirements of fish – a meta‐analysis
Authors: Teles Aires Oliva , Couto Ana , Enes Paula , Peres Helena
Published: November 2019

There are hundreds of fish reared in aquaculture, but nutrient requirements of the different species are still scarcely studied. Dietary protein is usually one of the first nutrients to be evaluated when considering the nutritional requirements of a novel species for aquaculture. Data on dietary protein requirement are already available for a large number of species, and this study aims to review the available data, enhancing eventual differences due to species, feeding habits, fish size, rearing temperature and water salinity. Overall, dietary protein requirements in the different studies ranged between 24 and 70% of the diet, depending on species and life stanzas. Dietary protein requirements were directly related to fish trophic level and water salinity, and inversely related to rearing temperature. Dietary protein intake was linearly related to weight gain, while protein retention was not affected, averaging 187 g protein kg−1 weight gain. On average, fish require a protein intake of 624 g kg−1 weight gain and dietary protein retention efficiency is close to 32%.
The Hot Hand in Professional Darts
Authors: Ötting Marius , Langrock Roland , Deutscher Christian , Leos-Barajas Vianey
Published: November 2019

We investigate the hot hand hypothesis in professional darts in a nearly ideal setting with minimal to no interaction between players. Considering almost 1 year of tournament data, corresponding to 167492 dart throws in total, we use state space models to investigate serial dependence in throwing performance. In our models, a latent state process serves as a proxy for a player's underlying form, and we use auto-regressive processes to model how this process evolves over time. Our results regarding the persistence of the latent process indicate a weak hot hand effect, but the evidence is inconclusive.
Quantifying the HIV treatment cascade in a South African health sub‐district by gender: retrospective cohort study
Authors: Lurie Mark N. , Kirwa Kipruto , Callaway Julia , Cornell Morna , Boulle Andrew , Bengtson Angela M. , Smith Mariette , Leon Natalie , Colvin Christopher
Published: November 2019

Objectives

To quantify the HIV care cascade in a Cape Town sub‐district to understand rates of linkage to and engagement in HIV care.

Methods

We used routinely collected data to reconstruct the treatment cascade for 8382 infected individuals who tested HIV + in 2012/2013. We obtained data on patient gender, year of initial HIV‐positive test, age at testing and initial CD4 cell count and defined five stages of the HIV care cascade. We quantified attrition across cascade stages.

Results

Two‐thirds of the sample (5646) were women. Men were older at time of first testing (36.5 vs. 31.3 years) and had more advanced HIV disease at diagnosis (298 vs. 404 CD4 cells/µL for women). The median duration of follow‐up was 818 days. Among women, 90.5% attended an initial HIV care visit, 54.6% became eligible for antiretroviral therapy under local guidelines during follow‐up, 49.3% initiated ART and 45.6% achieved a therapeutic response. Among men, 88.0% attended an initial HIV care visit, 67.4% became ART eligible during follow‐up, 48.0% initiated ART and 42.4% achieved a therapeutic response. Approximately 3% of women and 5% of men died during follow‐up.

Conclusions

We were able to reconstruct the HIV treatment cascade using routinely collected data. In this setting, rates of engagement in care differ by gender in key stages of the cascade, with men faring worse than women at each cascade point. This highlights the need for interventions aimed at encouraging earlier testing, linkage, ART initiation and retention among men.
Development of a mercury‐free ultraviolet high‐pressure plasma discharge for disinfection
Authors: Mayor‐Smith Ian , Templeton Michael R.
Published: November 2019

Ultraviolet (UV) disinfection is a critical and growing application for the disinfection of water. Current UV systems for disinfection applications are designed around the use of Low‐Pressure and High‐Pressure mercury‐based lamps. Increasing demand to reduce and ideally remove the use of mercury requires innovative adaptations and novel approaches to current technology. A potential alternative technology could be Light Emitting Diodes (LEDs), with current low efficiencies, high costs and low operating powers, a development gap for a high‐power mercury source has been identified. A mercury‐free tellurium‐based high‐pressure plasma was developed and assessed. Though relatively low efficiencies were measured compared to current mercury‐based technology rapid improvements are likely obtainable. Such an approach enables a novel adaptation to current technology utilising established: manufacturing facilities, approaches of UV system design and validation protocols. As a consequence, it offers the potential for a rapid low‐cost transition to mercury‐free UV disinfection where no alternative is currently available.
Terahertz optical properties of polymethacrylates after thermal annealing
Authors: Park Serang , Li Yanzeng , Fullager Daniel B. , Lata Marc , Kühne Philipp , Darakchieva Vanya , Hofmann T.
Published: November 2019

Polymer-based stereolithographic additive manufacturing has been established for the rapid and low-cost fabrication of terahertz (THz) optical components due to its ability to construct complex 3D geometries with high resolution. For polymer-based or integrated optics, thermal annealing processes are often used to optimize material properties. However, despite the growing interest in THz optics fabricated using stereolithography, the effects of thermal annealing on the THz dielectric properties of polymethacrylates compatible with stereolithography have not yet been studied. In this paper, the authors report on the THz ellipsometric response of thermally annealed polymethacrylates prepared using UV polymerization. The findings indicate that the investigated polymethacrylates maintain a stable optical response in the THz spectral range from 650 to 950 GHz after thermal annealing at temperatures up to 70°C for several hours.
Ankle and Midfoot Power During Single-Limb Heel Rise in Healthy Adults
Authors: DiLiberto Frank E. , Nawoczenski Deborah A.
Published: November 2019

Although the midfoot is recognized to have an important role in the successful performance of a single-limb heel rise, healthy heel rise performance remains primarily characterized by ankle function. The purpose of this study was to examine the contribution of midfoot region power to single-limb heel rise in healthy adults. Participants (N = 12) performed 20 single-limb heel rises. An electromagnetic motion capture system and a force plate were used to record 3-segment foot motion and ground reaction forces. Inverse dynamic calculations were performed to obtain ankle and midfoot region powers. These data were evaluated with descriptive statistics. A correlation was performed to evaluate the contribution of midfoot region power to heel height, as heel height is a clinical measure of heel-rise performance. The midfoot contributed power during single-limb heel rise (peak positive power: 0.5 [0.2] W·kg−1). Furthermore, midfoot peak power accounted for 36% of the variance in heel height (P = .04). As energy generating internal mechanisms, such as muscle activity, are attributed to power generation, midfoot tissue loading and muscle performance should be considered during clinical and modeling applications of the heel-rise task.
Identification of DHODH as a therapeutic target in small cell lung cancer
Authors: Li Leanne , Ng Sheng Rong , Colón Caterina I. , Drapkin Benjamin J. , Hsu Peggy P. , Li Zhaoqi , Nabel Christopher S. , Lewis Caroline A. , Romero Rodrigo , Mercer Kim L. , Bhutkar Arjun , Phat Sarah , Myers David T. , Muzumdar Mandar Deepak , Westcott Peter M. K. , Beytagh Mary Clare , Farago Anna F. , Vander Heiden Matthew G. , Dyson Nicholas J. , Jacks Tyler
Published: November 2019

Small cell lung cancer tumors are sensitive to DHODH inhibition, highlighting a potential treatment strategy for this disease.
Platelet regulation of myeloid suppressor of cytokine signaling 3 accelerates atherosclerosis
Authors: Barrett Tessa J. , Schlegel Martin , Zhou Felix , Gorenchtein Mike , Bolstorff Jennifer , Moore Kathryn J. , Fisher Edward A. , Berger Jeffrey S.
Published: November 2019

Platelet-induced myeloid
Socs3
expression in humans and mice contributes to unresolved atherosclerosis inflammation and sustained plaque growth.
In Vitro
Activity of Plazomicin Compared to Amikacin, Gentamicin, and Tobramycin against Multidrug-Resistant Aerobic Gram-Negative Bacilli
Authors: Fleischmann Wim A. , Greenwood-Quaintance Kerryl E. , Patel Robin
Published: November 2019

The worldwide spread of multidrug-resistant
Enterobacterales
is a serious threat to public health. Here, we compared the MICs of plazomicin, amikacin, gentamicin, and tobramycin against 303 multinational multidrug-resistant Gram-negative bacilli. We followed Clinical and Laboratory Standards Institute (CLSI) guidelines and applied CLSI breakpoints as well as those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for amikacin, gentamicin, and tobramycin and of the U.S.
Genetic Diversity of Collaborative Cross Mice Controls Viral Replication, Clinical Severity, and Brain Pathology Induced by Zika Virus Infection, Independently of
Oas1b
Authors: Manet Caroline , Simon-Lorière Etienne , Jouvion Grégory , Hardy David , Prot Matthieu , Conquet Laurine , Flamand Marie , Panthier Jean-Jacques , Sakuntabhai Anavaj , Montagutelli Xavier
Published: November 2019

In recent outbreaks, ZIKV has infected millions of people and induced rare but potentially severe complications, including Guillain-Barré syndrome and encephalitis in adults. While several viral sequence variants were proposed to enhance the pathogenicity of ZIKV, the influence of host genetic variants in mediating the clinical heterogeneity remains mostly unexplored. We addressed this question using a mouse panel which models the genetic diversity of the human population and a ZIKV strain from a recent clinical isolate. Through a combination of
in vitro
and
in vivo
approaches, we demonstrate that multiple host genetic variants determine viral replication in infected cells and the clinical severity, the kinetics of blood viral load, and brain pathology in mice. We describe new mouse models expressing high degrees of susceptibility or resistance to ZIKV and to other flaviviruses. These models will facilitate the identification and mechanistic characterization of host genes that influence ZIKV pathogenesis.
The Capsid Protein of Semliki Forest Virus Antagonizes RNA Interference in Mammalian Cells
Authors: Qian Qi , Zhou Hui , Shu Ting , Mu Jingfang , Fang Yuan , Xu Jiuyue , Li Tao , Kong Jing , Qiu Yang , Zhou Xi
Published: November 2019

Alphaviruses are a genus of positive-stranded RNA viruses and include numerous important human pathogens, such as Chikungunya virus, Ross River virus, Western equine encephalitis virus, etc., which create the emerging and reemerging public health threat worldwide. RNA interference (RNAi) is one of the most important antiviral mechanisms in plants and insects. Accumulating evidence has provided strong support for the existence of antiviral RNAi in mammals. In response to antiviral RNAi, viruses have evolved to encode viral suppressors of RNAi (VSRs) to antagonize the RNAi pathway. It is unclear whether alphaviruses encode VSRs that can suppress antiviral RNAi during their infection in mammals. In this study, we first uncovered that capsid protein encoded by Semliki Forest virus (SFV), a prototypic alphavirus, had a potent VSR activity that can antagonize antiviral RNAi in the context of SFV infection in mammalian cells, and this mechanism is probably used by other alphaviruses.
Experimental Evolution Generates Novel Oncolytic Vesicular Stomatitis Viruses with Improved Replication in Virus-Resistant Pancreatic Cancer Cells
Authors: Seegers Sara L. , Frasier Connor , Greene Sarah , Nesmelova Irina V. , Grdzelishvili Valery Z.
Published: November 2019

Vesicular stomatitis virus (VSV)-based oncolytic viruses are promising agents against pancreatic ductal adenocarcinoma (PDAC). However, some PDAC cell lines are resistant to VSV. Here, using a directed viral evolution approach, we generated novel oncolytic VSVs with an improved ability to replicate in virus-resistant PDAC cell lines, while remaining highly attenuated in nonmalignant cells. Two independently evolved VSVs obtained 2 identical VSV glycoprotein mutations, K174E and E238K. Additional experiments indicated that these acquired G mutations improved VSV replication, at least in part due to improved virus attachment to SUIT-2 cells. Importantly, no deletions or mutations were found in the virus-carried transgenes in any of the passaged viruses. Our findings demonstrate long-term genomic stability of complex VSV recombinants carrying large transgenes and support further clinical development of oncolytic VSV recombinants as safe therapeutics for cancer.
Geologic controls on up-dip and along-strike propagation of slip during subduction zone earthquakes from a high-resolution seismic reflection survey across the northern limit of slip during the 2010 Mw 8.8 Maule earthquake, offshore Chile
Authors: Tréhu Anne M. , Hass Bridget , de Moor Alexander , Maksymowicz Andrei , Contreras-Reyes Eduardo , Vera Emilio , Tryon Michael D.
Published: November 2019

A grid of closely spaced, high-resolution multichannel seismic (MCS) reflection profiles was acquired in May 2012 over the outer accretionary prism up dip from the patch of greatest slip during the 2010 Mw 8.8 Maule earthquake (offshore Chile) to complement a natural-source seismic experiment designed to monitor the post-earthquake response of the outer accretionary prism. We describe the MCS data and discuss the implications for the response of the accretionary prism during the earthquake and for the long-term evolution of the margin. The most notable observation from the seismic reflection survey is a rapid north-to-south shift over a short distance from nearly total frontal accretion of the trench sediments to nearly total underthrusting of undeformed trench sediments that occurs near the northern edge of slip in the 2010 earthquake. Integrating our structural observations with other geological and geophysical observations, we conclude that sediment subduction beneath a shallow décollement is associated with propagation of slip to the trench during great earthquakes in this region. The lack of resolvable compressive deformation in the trench sediment along this segment of the margin indicates that the plate boundary here is very weak, which allowed the outer prism to shift seaward during the earthquake, driven by large slip down dip. The abrupt shift from sediment subduction to frontal accretion indicates a stepdown in the plate boundary fault, similar to the stepovers that commonly arrest slip propagation in strike-slip faults. We do not detect any variation along strike in the thickness or reflective character of the trench sediments adjacent to the change in deformation front structure. This change, however, is correlated with variations in the morphology and structure of the accretionary prism that extend as far as 40 km landward of the deformation front. We speculate that forearc structural heterogeneity is the result of subduction of an anomalously shallow or rough portion of plate that interacted with and deformed the overlying plate and is now deeply buried. This study highlights need for three-dimensional structural images to understand the interaction between geology and slip during subduction zone earthquakes.
mHealth tool to improve community health agent performance for child development: study protocol for a cluster-randomised controlled trial in Peru
Authors: Westgard Christopher Michael , Rivadeneyra Natalia , Mechael Patricia
Published: November 2019

Introduction

Cultivating child health and development creates long-term impact on the well-being of the individual and society. The Amazon of Peru has high levels of many risk factors that are associated with poor child development. The use of ‘community health agents’ (CHAs) has been shown to be a potential solution to improve child development outcomes. Additionally, mobile information and communication technology (ICT) can potentially increase the performance and impact of CHAs. However, there is a knowledge gap in how mobile ICT can be deployed to improve child development in low resource settings.

Methods and analysis

The current study will evaluate the implementation and impact of a tablet-based application that intends to improve the performance of CHAs, thus improving the child-rearing practices of caregivers and ultimately child health and development indicators. The CHAs will use the app during their home visits to record child health indicators and present information, images and videos to teach key health messages. The impact will be evaluated through an experimental cluster randomised controlled trial. The clusters will be assigned to the intervention or control group based on a covariate-constrained randomisation method. The impact on child development scores, anaemia and chronic malnutrition will be assessed with an analysis of covariance. The secondary outcomes include knowledge of healthy child-rearing practices by caregivers, performance of CHAs and use of health services. The process evaluation will report on implementation outcomes. The study will be implemented in the Amazon region of Peru with children under 4. The results of the study will provide evidence on the potential of a mHealth tool to improve child health and development indicators in the region.

Ethics and dissemination

The study received approval from National Hospital ‘San Bartolome’ Institutional Ethics Committee on 8 November 2018 (IRB Approval #15463–18) and will be disseminated via peer-reviewed publications.

Trial registration number

ISRCTN43591826.
Contribution of serum lipids as effect modifiers to a relationship between mean arterial pressure and coronary heart disease in Chinese rural population: the Henan Rural Cohort Study
Authors: Zhang Xia , Li Yuqian , Wang Yanhua , Hu Kai , Tu Runqi , Zhang Haiqing , Tian Zhongyan , Qiao Dou , Zhang Gongyuan , Wang Chongjian
Published: November 2019

Objectives

The aim of this study was to evaluate the relationship between mean arterial pressure (MAP) and coronary heart disease (CHD) in Chinese rural population. In addition, we hypothesised that this relationship might be mediated by some degree of serum lipids.

Design

This is a cross-sectional study.

Setting

The participants were from the Henan Rural Cohort Study, initiated in five rural areas (Tongxu county of Kaifeng city, Yima county of Sanmenxia city, Suiping county of Zhumadian city, Xinxiang county of Xinxiang city and Yuzhou county of Xuchang city) in Henan Province, China, during July 2015 and September 2017.

Participants

The study included 39 020 subjects aged 18–79 years as current research population.

Outcome measures

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using an electronic sphygmomanometer. MAP was calculated by one-third SBP plus two-thirds DBP. The study used restricted cubic splines and logistic regression models to evaluate the ORs and 95% CIs. Mediation analysis using bootstrap was performed to examine the contribution of serum lipids to MAP-related CHD.

Results

The adjusted OR (95% CI) for the highest MAP quartile with the risk of CHD was 1.45 (1.24 to 1.69) compared with the lowest quartile. Simultaneously, each 1-SD increment in MAP was significantly associated with a 12% increased risk of CHD. A linear dose–response relationship between MAP and CHD was found (p value for non-linear=0.1169) in the fully adjusted model. We further reported that 36.07% of proportion explained risk of CHD was mediated through serum lipids.

Conclusions

Increased MAP was a significant marker of CHD in Chinese rural population. Meanwhile, the relationship was mediated by some degree of serum lipids, and triglyceride was the strongest mediator.

Trial registration number

Henan Rural Cohort study has been registered at Chinese Clinical Trial Register (ChiCTR-OOC-15006699) and the stage it relates to is Post-results.
Optical coherence tomography (OCT) in unconscious and systemically unwell patients using a mobile OCT device: a pilot study
Authors: Liu Xiaoxuan , Kale Aditya Uday , Capewell Nicholas , Talbot Nicholas , Ahmed Sumiya , Keane Pearse A , Mollan Susan , Belli Antonio , Blanch Richard J , Veenith Tonny , Denniston Alastair K
Published: November 2019

Objective

This study aims to evaluate the feasibility of retinal imaging in critical care using a novel mobile optical coherence tomography (OCT) device. The Heidelberg SPECTRALIS FLEX module (Heidelberg Engineering, Heidelberg, Germany) is an OCT unit with a boom arm, enabling ocular OCT assessment in less mobile patients.

Design

We undertook an evaluation of the feasibility of using the SPECTRALIS FLEX for undertaking ocular OCT images in unconscious and critically ill patients.

Setting

This study was conducted in the critical care unit of a large tertiary referral unit in the United Kingdom.

Participants

13 systemically unwell patients admitted to the critical care unit were purposively sampled to enable evaluation in patients with a range of clinical states.

Outcome measures

The primary outcome was the feasibility of acquiring clinically interpretable OCT scans on a consecutive series of patients. The standardised scanning protocol included macula-focused OCT, OCT optic nerve head (ONH), OCT angiography (OCTA) of the macula and ONH OCTA.

Results

OCT images from 13 patients were attempted. The success rates of each scan type are 84% for OCT macula, 76% for OCT ONH, 56% for OCTA macula and 36% for OCTA ONH. The overall mean success rate of scans per patient was 64% (95% CI 46% to 81%). Clinicians reported clinical value in 100% scans which were successfully obtained, including both ruling in and ruling out relevant ocular complications such as corneal thinning, macular oedema and optic disc swelling. The most common causes of failure to achieve clinically interpretable scans were inadequately sustained OCT alignment in delirious patients and a compromised ocular surface due to corneal exposure.

Conclusions

This prospective evaluation indicates the feasibility and potential clinical value of the SPECTRALIS FLEX OCT system on the critical care unit. Portable OCT systems have the potential to bring instrument-based ophthalmic assessment to critically ill patients, enabling detection and micron-level monitoring of ocular complications.
Usefulness of applying research reporting guidelines as Writing Aid software: a crossover randomised controlled trial
Authors: Hawwash Dana , Sharp Melissa K , Argaw Alemayehu , Kolsteren Patrick , Lachat Carl
Published: November 2019

Objectives

To assess the intention of using a Writing Aid software, which integrates four research reporting guidelines (Consolidated Standards of Reporting Trials, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Strengthening the Reporting of Observational Studies in Epidemiology and STrengthening the Reporting of Observational Studies in Epidemiology-nutritional epidemiology) and their Elaboration & Explanation (E&E) documents during the write-up of research in Microsoft Word compared with current practices.

Design

Two-arms crossover randomised controlled trial with no blinding and no washout period.

Setting

Face-to-face or online sessions.

Participants

54 (28 in arm 1 and 26 in arm 2) doctoral and postdoctoral researchers.

Interventions

Reporting guidelines and their E&E document were randomly administered as Writing Aid or as Word documents in a single 30 min to 1 hour session, with a short break before crossing over to the other study intervention.

Primary and secondary outcomes

Using the Technology Acceptance Model, we assessed the primary outcome: the difference in the mean of intention of use; and secondary outcomes: the difference in mean perceived ease of use and perceived usefulness. The three outcomes were measured using questions with a 7-point Likert-scale. Secondary analysis using structural equation modelling (SEM) was applied to explore the relationships between the outcomes.

Results

No significant difference in reported intention of use (mean difference and 95% CI 0.25 (–0.05 to 0.55), p=0.10), and perceived usefulness (mean difference and 95% CI 0.19 (–0.04 to 0.41), p=0.10). The Writing Aid performed significantly better than the word document on researchers’ perceived ease of use (mean difference and 95% CI 0.59 (0.29 to 0.89), p<0.001). In the SEM analysis, participants’ intention of using the tools was indirectly affected by perceived ease of use (beta 0.53 p=0.002).

Conclusions

Despite no significant difference in the intention of use between the tools, administering reporting guidelines as Writing Aid is perceived as easier to use, offering a possibility to further explore its applicability to enhance reporting adherence.
CRISTAL: protocol for a cluster randomised, crossover, non-inferiority trial of aspirin compared to low molecular weight heparin for venous thromboembolism prophylaxis in hip or knee arthroplasty, a registry nested study
Authors: Sidhu Verinder Singh , Graves Steven E , Buchbinder Rachelle , Naylor Justine Maree , Pratt Nicole L , de Steiger Richard S , Chong Beng H , Ackerman Ilana N , Adie Sam , Harris Anthony , Hansen Amber , Cripps Maggie , Lorimer Michelle , Webb Steve , Clavisi Ornella , Griffith Elizabeth C , Anandan Durga , O'Donohue Grace , Kelly Thu-Lan , Harris Ian A
Published: November 2019

Introduction

Venous thromboembolism (VTE) is a serious complication following hip arthroplasty (HA) and knee arthroplasty (KA). This study aims to determine whether aspirin is non-inferior to low molecular weight heparin (LMWH) in preventing symptomatic VTE following HA and KA.

Methods and analysis

This is a cluster randomised, crossover, non-inferiority, trial nested within the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). The clusters will consist of Australian hospitals performing at least 250 HA and/or KA procedures per annum. All adult patients undergoing HA or KA will be included. The intervention will be aspirin, orally, 85–150 mg daily. The comparator will be LMWH (enoxaparin) 40 mg, subcutaneously, daily. Both drugs will commence within 24 hours postoperatively and continue for 35 days after HA and 14 days after KA. Each hospital will be randomised to commence with aspirin or LMWH and then crossover to the alternative treatment after meeting the recruitment target. Data will be collected through the AOANJRR via patient-reported surveys. The primary outcome is symptomatic VTE within 90 days post surgery, verified by AOANJRR staff. The primary analysis will include only patients undergoing elective primary total hip arthroplasty and total knee arthroplasty for osteoarthritis. Secondary outcomes will include symptomatic VTE for all HA and KA (including partial and revision) within 90 days, readmission, reoperation, major bleeding and death within 90 days and reoperation, death and patient-reported pain, function and health status at 6 months. If aspirin is found to be inferior, a cost-effectiveness analysis will be conducted. The study will aim to recruit 15 562 patients from 31 hospitals.

Ethics and dissemination

Ethics approval has been granted. Trial results will be submitted for publication. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001879257, pre-results) and is endorsed by the Australia and New Zealand Musculoskeletal Clinical Trials Network.