bluuebunny/crossref_metadata_2025 huggingface dataset:
A quantitative systems pharmacology analysis of KRAS G12C covalent inhibitors
Authors: Stites Edward C. , Shaw Andrey S.
Published: June 2017

The KRAS oncogene is the most common, activating, oncogenic mutation in human cancer. KRAS has proven difficult to target effectively. Two different strategies have recently been described for covalently targeting the most common activating KRAS mutant in lung cancer, KRAS G12C. Previously, we have developed a computational model of the processes that regulate Ras activation and this model has proven useful for understanding the complex behaviors of Ras signaling. Here, we use this model to perform a computational systems pharmacology analysis of KRAS G12C targeted covalent inhibitors. After updating our model to include Ras protein turnover, we verified the validity of our model for problems in this domain by comparing model behaviors with experimental behaviors. The model naturally reproduces previous experimental data, including several experimental observations that were interpreted as being contrary to conventional wisdom. Overall, this suggests that our model describes the Ras system well, including those areas where conventional wisdom struggles. We then used the model to investigate possible strategies to improve the ability of KRAS G12C inhibitors to inhibit Ras pathway signaling. We identify one, as of yet unexplored mechanism, that, if optimized, could improve the effectiveness of one class of KRAS inhibitor. We also simulated resistance to targeted therapies and found that resistance promoting mutations may reverse which class of KRAS G12C inhibitor inhibits the system better, suggesting that there may be value to pursuing both types of KRAS G12C inhibitors. Overall, this work demonstrates that systems biology approaches can provide insights that inform the drug development process.
Diffusion MRI of white matter microstructure development in childhood and adolescence: Methods, challenges and progress
Authors: Tamnes Christian K. , Roalf David R. , Goddings Anne-Lise , Lebel Catherine
Published: June 2017

Diffusion magnetic resonance imaging (dMRI) continues to grow in popularity as a useful neuroimaging method to study brain development, and longitudinal studies that track the same individuals over time are emerging. Over the last decade, seminal work using dMRI has provided new insights into the development of brain white matter (WM) microstructure, connections and networks throughout childhood and adolescence. This review provides an introduction to dMRI, both diffusion tensor imaging (DTI) and other dMRI models, as well as common acquisition and analysis approaches. We highlight the difficulties associated with ascribing these imaging measurements and their changes over time to specific underlying cellular and molecular events. We also discuss selected methodological challenges that are of particular relevance for studies of development, including critical choices related to image acquisition, image analysis, quality control assessment, and the within-subject and longitudinal reliability of dMRI measurements. Next, we review the exciting progress in the characterization and understanding of brain development that has resulted from dMRI studies in childhood and adolescence, including brief overviews and discussions of studies focusing on sex and individual differences. Finally, we outline future directions that will be beneficial to the field.
Quantum Calculations Of A Large Section Of The Voltage Sensing Domain Of The Kv1.2 Channel Show That Proton Transfer, Not S4 Motion, Provides The Gating Current
Authors: Kariev Alisher M. , Green Michael E.
Published: June 2017

Quantum calculations on much of the voltage sensing domain (VSD) of the Kv1.2 potassium channel (pdb: 3Lut) have been carried out on a 904 atom subset of the VSD, plus 24 water molecules (total, 976 atoms). Those side chains that point away from the center of the VSD were truncated; in all calculations, S1,S2,S3 end atoms were fixed; in some calculations, S4 end atoms were also fixed, while in other calculations they were free. After optimization at Hartree-Fock level, single point calculations of energy were carried out using DFT (B3LYP/6-31G**), allowing accurate energies of different cases to be compared. Open conformations (i.e.,zero or positive membrane potentials) are consistent with the known X-ray structure of the open state when the salt bridges in the VSD are not ionized (H+on the acid), whether S4 end atoms were fixed or free (closer fixed than free). Based on these calculations, the backbone of the S4 segment, free or not, moves no more than 2.5 Å upon switching from positive to negative membrane potential, and the movement is in the wrong direction for closing the channel. This leaves H+motion as the principal component of gating current. Groups of 3-5 side chains are important for proton transport, based on the calculations. Our calculations point to a pair of steps in which a proton transfers from a tyrosine, Y266, through arginine (R300), to a glutamate (E183); this would account for approximately 20-25% of the gating charge. The calculated charges on each arginine and glutamate are appreciably less than one. Groupings of five amino acids appear to exchange a proton; the group is bounded by the conserved aromatic F233. Dipole rotations appear to also contribute. Alternate interpretations of experiments usually understood in terms of the standard model are shown to be plausible.
Elevated ozone reduces photosynthetic carbon gain by accelerating leaf senescence of inbred and hybrid maize in a genotype-specific manner
Authors: Yendrek Craig R. , Erice Gorka , Montes Christopher M. , Tomaz Tiago , Sorgini Crystal A. , Brown Patrick J. , McIntyre Lauren M. , Leakey Andrew D.B. , Ainsworth Elizabeth A.
Published: June 2017

Exposure to elevated tropospheric ozone concentration ([O3]) accelerates leaf senescence in many C3crops. However, the effects of elevated [O3] on C4crops including maize (Zea maysL.) are poorly understood in terms of physiological mechanism and genetic variation in sensitivity. Using Free Air gas Concentration Enrichment (FACE), we investigated the photosynthetic response of 18 diverse maize inbred and hybrid lines to season-long exposure to elevated [O3] (~100 nL L−1) in the field. Gas exchange was measured on the leaf subtending the ear throughout the grain filling period. On average over the lifetime of the leaf, elevated [O3] led to reductions in photosynthetic CO2assimilation of both inbred (-22%) and hybrid (-33%) genotypes. There was significant variation among both inbred and hybrid lines in the sensitivity of photosynthesis to elevated [O3], with some lines showing no change in photosynthesis at elevated [O3]. Based on analysis of inbred line B73, the reduced CO2assimilation at elevated [O3] was associated with accelerated senescence decreasing photosynthetic capacity, and not altered stomatal limitation. These findings across diverse maize genotypes could advance the development of more ozone tolerant maize, and provide experimental data for parameterization and validation of studies modeling how O3impacts crop performance.
CoralSymbiodiniumcommunity composition across the Belize Mesoamerican Barrier Reef System is influenced by host species and thermal variability
Authors: Baumann JH , Davies SW , Aichelman HE , Castillo KD
Published: June 2017

Reef-building corals maintain a symbiotic relationship with dinoflagellate algae of the genusSymbiodiniumand this symbiosis is vital for the survival of the coral holobiont.Symbiodiniumcommunity composition within the coral host has been shown to influence a coral’s ability to resist and recover from stress. A multitude of stressors including ocean warming, ocean acidification, and eutrophication have been linked to global scale decline in coral health and cover in recent decades. Three distinct thermal regimes (highTP, modTP, and lowTP) following an inshore-offshore gradient of declining average temperatures and thermal variation were identified on the Belize Mesoamerican Barrier Reef System (MBRS). Quantitative metabarcoding of the ITS-2 locus was employed to investigate differences and similarities inSymbiodiniumgenetic diversity of the Caribbean coralsSiderastrea siderea,S. radians, andPseudodiploria strigosabetween the three thermal regimes. A total of tenSymbiodinium lineageswere identified across the three coral host species.Siderastrea sidereaassociated with distinctSymbiodiniumcommunities, howeverSymbiodiniumcommunities of its congener,S. radians, andP. strigosa, were more similar to one another. Thermal regime played a role in definingSymbiodiniumcommunities in S. siderea but notS. radiansorP. strigosa. Against expectations,Symbiodinium trenchii, a symbiont known to confer thermal tolerance, was dominant only inS. sidereaat one sampled offshore site and was rare inshore, suggesting that coral thermal tolerance in more thermally variable inshore habitats is achieved through alternative mechanisms. Overall, thermal parameters alone were likely not the only primary drivers ofSymbiodiniumcommunity composition, suggesting that environmental variables unrelated to temperature (i.e., light availability, or nutrients) may play key roles in structuring coral-algal communities in Belize and that the relative importance of these environmental variables may vary by coral host species.
Fluid administration rate for uncontrolled intraabdominal hemorrhage in pigs
Authors: Yanala Ujwal R. , Johanning Jason M. , Pipinos Iraklis I. , High Robin R. , Larsen Gustavo , Velander William H. , Carlson Mark A.
Published: June 2017

Background

We hypothesized that slow crystalloid resuscitation would improve blood loss and hemoglobin compared to a rapid resuscitation during uncontrolled hemorrhage.

Methods

Anesthetized, splenectomized domestic swine underwent hepatic lobar hemitransection. Lactated Ringers was given at 150 or 20 mL/min IV (rapidvs.slow, respectively, N = 12 per group; limit of 100 mL/kg). Vital sign monitoring and serum testing was done for up to 180 min, followed by necropsy.

Results

Survival was 7vs.8 out of 12 subjects, rapid vs. slow respectively (p>0.05). The slow group had a less blood loss (1.6 vs. 2.7 L, respectively) and a higher final hemoglobin concentration (6.0 vs. 3.4 g/dL).

Conclusions

Using a fixed volume of crystalloid resuscitation in this porcine model of uncontrolled intraabdominal hemorrhage, a slow IV infusion rate produced less blood loss and a higher hemoglobin level compared to rapid infusion.
Natural selection shaped the rise and fall of passenger pigeon genomic diversity
Authors: Murray Gemma G. R. , Soares André E. R. , Novak Ben J. , Schaefer Nathan K. , Cahill James A. , Baker Allan J. , Demboski John R. , Doll Andrew , Da Fonseca Rute R. , Fulton Tara L. , Gilbert M. Thomas P. , Heintzman Peter D. , Letts Brandon , McIntosh George , O’Connell Brendan L. , Peck Mark , Pipes Marie-Lorraine , Rice Edward S. , Santos Kathryn M. , Sohrweide A. Gregory , Vohr Samuel H. , Corbett-Detig Russell B. , Green Richard E. , Shapiro Beth
Published: June 2017

The extinct passenger pigeon was once the most abundant bird in North America, and possibly the world. While theory predicts that large populations will be more genetically diverse and respond more efficiently to selection, passenger pigeon genetic diversity was surprisingly low. To investigate this we analysed 41 mitochondrial and 4 nuclear genomes from passenger pigeons, and 2 genomes from band-tailed pigeons, passenger pigeons’ closest living relatives. We find that passenger pigeons’ large population size allowed for faster adaptive evolution and removal of harmful mutations, but that this drove a huge loss in neutral genetic diversity. These results demonstrate how great an impact selection can have on a vertebrate genome, and invalidate previous results that suggested population instability contributed to this species’ surprisingly rapid extinction.
Interplay between mitochondria and diet mediates pathogen and stress resistance inC. elegans
Authors: Revtovich Alexey V. , Lee Ryan , Kirienko Natalia V.
Published: June 2017

Diet is a crucial determinant of organismal biology. Here we demonstrate the dramatic impact of a subtle shift in diet on the ability ofCaenorhabditis elegansto survive pathogenic or abiotic stress. Interestingly, this shift occurs independently of canonical host defense pathways, arising instead from improvements in mitochondrial health. Using a variety of assays, we reveal that the most commonC. elegansfood source (E. coliOP50) results in a vitamin B12 deficiency that compromises mitochondrial homeostasis. Increasing B12 supply by feeding onE. coliHT115 or by supplementing bacterial media with methylcobalamin restored mitochondrial function, even if the bacteria were dead. B12 supplementation also efficiently increased host health without adversely affecting lifespan. Our study forges a molecular link between a dietary deficiency (nutrition/microbiota) and a physiological consequence (host sensitivity), using the host-microbiota-diet framework. The ubiquity of B12 deficiency (~10-40% of US adults) highlights the importance of our findings.
Corrigendum and follow-up: Whole genome sequencing of multiple CRISPR-edited mouse lines suggests no excess mutations
Authors: Schaefer Kellie A. , Darbro Benjamin W , Colgan Diana F. , Tsang Stephen H. , Bassuk Alexander G. , Mahajan Vinit B.
Published: June 2017

Our previous publication suggested CRISPR-Cas9 editing at the zygotic stage might unexpectedly introduce a multitude of subtle but unintended mutations, an interpretation that not surprisingly raised numerous questions. The key issue is that since parental lines were not available, might the reported variants have been inherited? To expand upon the limited available whole genome data on whether CRISPR-edited mice show more genetic variation, whole-genome sequencing was performed on two other mouse lines that had undergone a CRISPR-editing procedure. Again, parents were not available for either the Capn5 nor Fblim1 CRISPR-edited mouse lines, so strain controls were examined. Additionally, we also include verification of variants detected in the initial mouse line. Taken together, these whole-genome-sequencing-level results support the idea that in specific cases, CRISPR-Cas9 editing can precisely edit the genome at the organismal level and may not introduce numerous, unintended, off-target mutations.
Insm1a regulates motor neuron development in zebrafish
Authors: Gong Jie , Wang Xin , Zhu Chenwen , Dong Xiaohua , Zhang Qinxin , Wang Xiaoning , Duan Xuchu , Qian Fuping , Gao Yu , Zhao Qingshun , Chai Renjie , Liu Dong
Published: June 2017

Insulinoma-associated1a (Insm1a) is a zinc-finger transcription factor playing a series of functions in cell formation and differentiation of vertebrate central and peripheral nervous systems and neuroendocrine system. However, its roles on the development of motor neuron have still remained uncovered. Here, we provided evidences thatinsmlawas a vital regulator of motor neuron development and provide a mechanistic understanding of how it contributes to this process. Firstly, we showed the localization ofinsmlain spinal cord and primary motor neurons (PMNs) of zebrafish embryos byin situhybridization and imaging analysis of transgenic reporter lineTg(insmla: mCherry)ntu805. Then we demonstrated that the deficiency ofinsmlain zebrafish larvae lead to the defects of PMNs development, including the reduction of caudal primary motor neurons (CaP) and middle primary motor neurons (MiP), the excessive branching of motor axons, and the disorganized distance between adjacent CaPs. Additionally, knockout ofinsm1impaired motor neuron differentiation in the spinal cord. Locomotion analysis showed thatinsmla-null zebrafish significantly reduced the swimming activity. Furthermore, we proved that theinsmlaloss of function significantly decreased the transcripts levels of botholig2andnkx6.1. Microinjection ofolig2andnkx6.1mRNA rescued the motor neuron defects ininsmladeficient embryos. Taken together, these data indicate thatinsmlaregulates the motor neuron development, at least in part, through modulation of the expressions ofolig2andnkx6.1.
Mammal extinctions and the increasing isolation of humans on the tree of life
Authors: Pavoine Sandrine , Bonsall Michael B. , Davies T. Jonathan , Masi Shelly
Published: June 2017

A sixth great mass extinction is ongoing due to the direct and indirect effects of human pressures. However, not all lineages are impacted equally. As humans, we frequently believe that we hold a unique place on Earth. Here, we show that our current impacts on the natural world risk to heighten that expectation. Evolutionary proximity toHomo sapiensemerges as a powerful predictor of extinction risk among mammals. Our analysis shows that the species most closely related toH. sapiensare exposed to a large variety of threat types and that they may also have greater intrinsic sensitivity to threats. Pruning back the tree of life around us will lead to our species being among those with the fewest close relatives. We will erase our evolutionary history, forcing its uniqueness. If no action is taken, we will lose crucial biodiversity for the preservation of Earth ecosystems, and a key reference to what makes us human.
Welfare of zebra finches used in research
Authors: Yamahachi Homare , Zai Anja T. , Tachibana Ryosuke O. , Stepien Anna E. , Rodrigues Diana I. , Cavé-Lopez Sophie , Narula Gagan , Lee Juneseung , Huang Ziqiang , Hörster Heiko , Düring Daniel , Hahnloser Richard H. R.
Published: June 2017

Over the past 50 years, songbirds have become a valuable model organism for scientists studying vocal communication from its behavioral, hormonal, neuronal, and genetic perspectives. Many advances in our understanding of vocal learning result from research using the zebra finch, a close-ended vocal learner. We review some of the manipulations used in zebra finch research, such as isolate housing, transient/irreversible impairment of hearing/vocal organs, implantation of small devices for chronic electrophysiology, head fixation for imaging, aversive song conditioning using sound playback, and mounting of miniature backpacks for behavioral monitoring. We highlight the use of these manipulations in scientific research, and estimate their impact on animal welfare, based on the literature and on data from our past and ongoing work. The assessment of harm-benefits tradeoffs is a legal prerequisite for animal research in Switzerland. We conclude that a diverse set of known stressors reliably lead to suppressed singing rate, and that by contraposition, increased singing rate may be a useful indicator of welfare. We hope that our study can contribute to answering some of the most burning questions about zebra finch welfare in research on vocal behaviors.
Ludicrous Speed Linear Mixed Models for Genome-Wide Association Studies
Authors: Kadie Carl , Heckerman David
Published: June 2017

We have developed Ludicrous Speed Linear Mixed Models, a version of FaST-LMM optimized for the cloud. The approach can perform a genome-wide association analysis on a dataset of one million SNPs across one million individuals at a cost of about 868 CPU days with an elapsed time on the order of two weeks. A Python implementation is available athttps://fastlmm.github.io/.

Significance

Identifying SNP-phenotype correlations using GWAS is difficult because effect sizes are so small for common, complex diseases. To address this issue, institutions are creating extremely large cohorts with sample sizes on the order of one million. Unfortunately, such cohorts are likely to contain confounding factors such as population structure and family/cryptic relatedness. The linear mixed model (LMM) can often correct for such confounding factors, but is too slow to use even with algebraic speedups known as FaST-LMM. We present a cloud implementation of FaST-LMM, called Ludicrous Speed LMM, that can process one million samples and one million test SNPs in a reasonable amount of time and at a reasonable cost.
Draft genome of the Reindeer (Rangifer tarandus)
Authors: Li Zhipeng , Lin Zeshan , Chen Lei , Ba Hengxing , Yang Yongzhi , Wang Kun , Wang Wen , Qiang Qiu , Li Guangyu
Published: June 2017

Abstract

Background

Reindeer (Rangifer tarandus) is the only fully domesticated species in the Cervidae family, and is the only cervid with a circumpolar distribution. Unlike all other cervids, female reindeer regularly grow cranial appendages (antlers, the defining characteristics of cervids), as well as males. Moreover, reindeer milk contains more protein and less lactose than bovids’ milk. A high quality reference genome of this specie will assist efforts to elucidate these and other important features in the reindeer.

Findings

We obtained 723.2 Gb (Gigabase) of raw reads by an Illumina Hiseq 4000 platform, and a 2.64 Gb final assembly, representing 95.7% of the estimated genome (2.76 Gb according to k-mer analysis), including 92.6% of expected genes according to BUSCO analysis. The contig N50 and scaffold N50 sizes were 89.7 kilo base (kb) and 0.94 mega base (Mb), respectively. We annotated 21,555 protein-coding genes and 1.07 Gb of repetitive sequences by de novo and homology-based prediction. Homology-based searches detected 159 rRNA, 547 miRNA, 1,339 snRNA and 863 tRNA sequences in the genome of R. tarandus. The divergence time between R. tarandus, and ancestors of Bos taurus and Capra hircus, is estimated to be 29.55 million years ago (Mya).

Conclusions

Our results provide the first high-quality reference genome for the reindeer, and a valuable resource for studying evolution, domestication and other unusual characteristics of the reindeer.
Tolloid cleavage activates latent GDF8 by priming the pro-complex for dissociation
Authors: Le Viet Q. , Iacob Roxana E. , Tian Yuan , McConaughy William , Jackson Justin , Su Yang , Zhao Bo , Engen John R. , Pirruccello-Straub Michelle , Springer Timothy A.
Published: June 2017

Growth differentiation factor 8 (GDF8)/Myostatin is a latent TGF­β family member that potently inhibits skeletal muscle growth. Here, we compared the conformation and dynamics of precursor, latent, and Tolloid­cleaved GDF8 pro­complexes to understand structural mechanisms underlying latency and activation of GDF8. Negative stain electron microscopy (EM) of precursor and latent pro­complexes reveals a V­shaped conformation that is unaltered by furin cleavage and sharply contrasts with the ring­like, cross­armed conformation of latent TGF­β1. Surprisingly, Tolloid­cleaved GDF8 does not immediately dissociate, but in EM exhibits structural heterogeneity consistent with partial dissociation. Hydrogen–deuterium exchange was not affected by furin cleavage. In contrast, Tolloid cleavage, in the absence of prodomain–growth factor dissociation, increased exchange in regions that correspond in pro-TGF-β1 to the α1-helix, latency lasso, and β1 strand in the prodomain and to the β6’–7’ strands in the growth factor. Thus, these regions are important in maintaining GDF8 latency. Our results show that Tolloid cleavage activates latent GDF8 by destabilizing specific prodomain–growth factor interfaces and primes the growth factor for release from the prodomain.
Spectrin is a mechanoresponsive protein shaping the architecture of intercellular invasion
Authors: Duan Rui , Kim Ji Hoon , Shilagardi Khurts , Schiffhauer Eric , Son Sungmin , Lee Donghoon , Li Shuo , Thomas Graham , Luo Tianzhi , Fletcher Daniel A. , Robinson Douglas N. , Chen Elizabeth H.
Published: June 2017

Spectrin is a membrane skeletal protein best known for its structural role in maintaining cell shape and protecting cells from mechanical damage1-3. Here, we report that spectrin dynamically accumulates and dissolves at the fusogenic synapse, where an attacking fusion partner mechanically invades its receiving partner with actin-propelled protrusions to promote cell-cell fusion4-7. Using genetics, cell biology, biophysics and mathematical modeling, we demonstrate that unlike myosin II that responds to dilation deformation, spectrin exhibits a mechanosensitive accumulation in response to shear deformation, which is highly elevated at the fusogenic synapse. The accumulated spectrin forms an uneven network, which functions as a “sieve” to constrict the invasive fingerlike protrusions, thus putting the fusogenic synapse under high mechanical tension to promote cell membrane fusion. Taken together, our study has revealed a previously unrecognized function of spectrin as a dynamic mechanoresponsive protein that shapes the architecture of intercellular invasion. These findings have general implications for understanding spectrin function in other dynamic cellular processes beyond cell-cell fusion.
Elections, news cycles, and attention to disasters
Authors: Bright Candace Forbes , Bagley Braden
Published: June 2017

Purpose

Political elections, especially presidential elections, have a tendency to overshadow other events, including disasters. Response to disasters during elections, such as Hurricane Matthew and the Baton Rouge flooding in 2016, are often dependent on attention given to them from the media, as well as prominent political figures and political candidates candidates. The purpose of this paper is to explore how election cycles affect government response to disasters and ultimately demonstrate the dependency of crisis communication on media agenda-setting for presenting saliency of disaster risk and needs.

Design/methodology/approach

Responses from presidential candidates Donald Trump and Hillary Clinton, as well as President Barack Obama, in regards to the Baton Rouge flooding and Hurricane Matthew, were observed using media reports and social media accounts. These results were matched with key events from the presidential election timeline.

Findings

There is a positive relationship between news exposure and attention, and also between attention and civic response. In regards to the 2016 presidential election, news coverage of the release of the Donald Trump-Billy Bush tape distracted national attention from the approach, landfall, and recovery of Hurricane Matthew. Information subsidies provided by the candidates directed the media agenda away from the needs of the communities and individuals impacted by these disasters.

Originality/value

Disasters are often assumed to be value-free because they are “blind to politics.” Here, it is argued that this was not the case in relation to these two disasters. Thus, the authors encouraged more research be conducted to clarify the impact that political elections have on strategic news coverage of disasters and ultimately on disaster response.
Understanding framings and perceptions of spillover
Authors: Lawson Elaine Tweneboah , Ohemeng Fidelia , Ayivor Jesse , Leach Melissa , Waldman Linda , Ntiamoa-Baidu Yaa
Published: June 2017

Purpose

Bats provide many ecosystem services and have intrinsic value. They also act as host reservoirs for some viruses. Several studies have linked zoonotic diseases to bats, raising questions about the risks bats pose, especially to people living close to bat roosts. Through a series of case studies undertaken in three communities, the purpose of this paper is to explore the various ways in which framings and perceptions of bats can influence a potential spillover of bat-borne viruses to humans in Ghana. It assesses the social, cultural and economic factors that drive human-bat interactions and posits that understanding the socio-economic contexts in which human-bat interactions occur is key to the success of future communication strategies.

Design/methodology/approach

Primary data collection methods included participatory landscape mappings, transect walks, focus group discussions and questionnaire surveys.

Findings

Perceptions of bats vary and are influenced by personal beliefs, the perceived economic benefits derived from bats and the location of bat roosts. Activities that put people at risk include bat hunting, butchering and consumption of poorly prepared bat meat. Those who live and work close to bat roosts, and bat hunters, for example, are more at risk of bat-borne zoonotic disease spillover. Disease risk perceptions were generally low, with high levels of uncertainty, indicating the need for clearer information about personal protective practices.

Originality/value

The results of the study may well inform future risk communication strategies as well as help in developing effective responses to zoonotic disease risk, disease outbreaks and the conservation of bats in communities.
Boldness predicts an individual's position along an exploration–exploitation foraging trade‐off
Authors: Patrick Samantha C. , Pinaud David , Weimerskirch Henri
Published: June 2017

Individuals do not have complete information about the environment and therefore they face a trade‐off between gathering information (exploration) and gathering resources (exploitation). Studies have shown individual differences in components of this trade‐off but how stable these strategies are in a population and the intrinsic drivers of these differences is not well understood.

Top marine predators are expected to experience a particularly strong trade‐off as many species have large foraging ranges and their prey often have a patchy distribution. This environment leads these species to exhibit pronounced exploration and exploitation phases but differences between individuals are poorly resolved. Personality differences are known to be important in foraging behaviour but also in the trade‐off between exploration and exploitation. Here we test whether personality predicts an individual exploration–exploitation strategy using wide ranging wandering albatrosses (Diomedea exulans) as a model system.

Using GPS tracking data from 276 wandering albatrosses, we extract foraging parameters indicative of exploration (searching) and exploitation (foraging) and show that foraging effort, time in patch and size of patch are strongly correlated, demonstrating these are indicative of an exploration–exploitation (EE) strategy. Furthermore, we show these are consistent within individuals and appear stable in the population, with no reproductive advantage.

The searching and foraging behaviour of bolder birds placed them towards the exploration end of the trade‐off, whereas shy birds showed greater exploitation. This result provides a mechanism through which individual foraging strategies may emerge. Age and sex affected components of the trade‐off, but not the trade‐off itself, suggesting these factors may drive behavioural compensation to maintain resource acquisition and this was supported by the evidence that there were no fitness consequence of any EE trait nor the trade‐off itself.

These results demonstrate a clear trade‐off between information gathering and exploitation of prey patches, and reveals for the first time that boldness may drive these differences. This provides a mechanism through which widely reported links between personality and foraging may emerge.
Cost‐benefit Analysis and the Controversial Reinvestment Assumption in IRR and NPV Estimates: Some New Evidence Against Reinvestment Assumption
Authors: Arjunan Kannapiran C. , Kannapiran Karthi
Published: June 2017

The reliability of CBA and the capital investment analysis is often questioned because of the controversy surrounding the assumption of reinvestment. The validity of this assumption is evaluated using new approaches and the results are summarised in this paper. These results provide sufficient evidence that there is no reinvestment of intermediate income in the internal rate of return (IRR) or net present value (NPV) estimates. The results are consistent under both normal and non‐normal cash flow projects. Obviously, text books dealing with capital investment analysis should move away from such an assumption. The CBA and the capital investment analysis using the IRR and NPV is, therefore, reliable.
Quantifying apart what belongs together: A multi‐state species distribution modelling framework for species using distinct habitats
Authors: Frans Veronica F. , Augé Amélie A. , Edelhoff Hendrik , Erasmi Stefan , Balkenhol Niko , Engler Jan O.
Published: June 2017

Species distribution models (SDMs) have been used to inform scientists and conservationists about the status and change in occurrence patterns in threatened species. Many mobile species use multiple functionally distinct habitats, and cannot occupy one habitat type without the other being within a reachable distance. For such species, classical applications of SDMs might lead to erroneous representations of habitat suitability, as the complex relationships between predictors are lost when merging occurrence information across multiple habitats. To better account for the spatial arrangement of complementary—yet mandatory—habitat types, it is important to implement modelling strategies that partition occurrence information according to habitat use in a spatial context. Here, we address this issue by introducing a multi‐state SDM framework.

The multi‐state SDM framework stratifies occurrences according to the temporal or behavioural use of distinct habitat types, referred to as “states.” Multiple SDMs are then run for each state and statistical thresholds of presence are used to combine these separate predictions. To identify suitable sites that account for distance between habitats, two optional modules are proposed where the thresholded output is aggregated and filtered by minimum area size, or through moving windows across maximum reachable distances.

We illustrate the full use of this framework by modelling the dynamic terrestrial breeding habitat preferences of the New Zealand sea lion (NZSL) (Phocarctos hookeri), using Maxent and trialling both modules to identify suitable sites for possible recolonization.

The Maxent predictions showed excellent performance, and the multi‐state SDM framework highlighted 36–77 potential suitable breeding sites in the study area.

This framework can be applied to inform management when defining habitat suitability for species with complex changes in habitat use. It accounts for temporal and behavioural changes in distribution, maintains the individuality of each partitioned SDM, and considers distance between distinct habitat types. It also yields one final, easy‐to‐understand output for stakeholders and managers.
Neurology Concepts: Young Women and Ischemic Stroke—Evaluation and Management in the Emergency Department
Authors: Chang Bernard P. , Wira Charles , Miller Joseph , Akhter Murtaza , Barth Bradley E. , Willey Joshua , Nentwich Lauren , Madsen Tracy
Published: June 2017

Objective

Ischemic stroke is a leading cause of morbidity and mortality worldwide. While the incidence of ischemic stroke is highest in older populations, incidence of ischemic stroke in adults has been rising particularly rapidly among young (e.g., premenopausal) women. The evaluation and timely diagnosis of ischemic stroke in young women presents a challenging situation in the emergency department, due to a range of sex‐specific risk factors and to broad differentials. The goals of this concepts paper are to summarize existing knowledge regarding the evaluation and management of young women with ischemic stroke in the acute setting.

Methods

A panel of six board‐certified emergency physicians, one with fellowship training in stroke and one with training in sex‐ and sex‐based medicine, along with one vascular neurologist were coauthors involved in the paper. Each author used various search strategies (e.g., PubMed, PsycINFO, and Google Scholar) for primary research and reviewed articles related to their section. The references were reviewed and evaluated for relevancy and included based on review by the lead authors.

Results

Estimates on the incidence of ischemic stroke in premenopausal women range from 3.65 to 8.9 per 100,000 in the United States. Several risk factors for ischemic stroke exist for young women including oral contraceptive (OCP) use and migraine with aura. Pregnancy and the postpartum period (up to 12 weeks) is also an important transient state during which risks for both ischemic stroke and cerebral hemorrhage are elevated, accounting for 18% of strokes in women under 35. Current evidence regarding the management of acute ischemic stroke in young women is also summarized including use of thrombolytic agents (e.g., tissue plasminogen activator) in both pregnant and nonpregnant individuals.

Conclusion

Unique challenges exist in the evaluation and diagnosis of ischemic stroke in young women. There are still many opportunities for future research aimed at improving detection and treatment of this population.
Randomized Controlled Double‐blind Trial Comparing Haloperidol Combined With Conventional Therapy to Conventional Therapy Alone in Patients With Symptomatic Gastroparesis
Authors: Roldan Carlos J. , Chambers Kimberly A. , Paniagua Linda , Patel Sonali , Cardenas‐Turanzas Marylou , Chathampally Yashwant
Published: June 2017

Objective

Gastroparesis is a debilitating condition that causes nausea, vomiting, and abdominal pain. Management includes analgesics and antiemetics, but symptoms are often refractory. Haloperidol has been utilized in the palliative care setting for similar symptoms. The study objective was to determine whether haloperidol as an adjunct to conventional therapy would improve symptoms in gastroparesis patients presenting to the emergency department (ED).

Study Design and Methods

This was a randomized, double‐blind, placebo‐controlled trial of adult ED patients with acute exacerbation of previously diagnosed gastroparesis. The treatment group received 5 mg of haloperidol plus conventional therapy (determined by the treating physician). The control group received a placebo plus conventional therapy. The severity of each subject's abdominal pain and nausea were assessed before intervention and every 15 minutes thereafter for 1 hour using a 10‐point scale for pain and a 5‐point scale for nausea. Primary outcomes were decreased pain and nausea 1 hour after treatment.

Results

Of the 33 study patients, 15 were randomized to receive haloperidol. Before treatment, the mean intensity of pain was 8.5 in the haloperidol group and 8.28 in the placebo group; mean pretreatment nausea scores were 4.53 and 4.11, respectively. One hour after therapy, the mean pain and nausea scores in the haloperidol group were 3.13 and 1.83 compared to 7.17 and 3.39 in the placebo group. The reduction in mean pain intensity therapy was 5.37 in the haloperidol group (p ≤ 0.001) compared to 1.11 in the placebo group (p = 0.11). The reduction in mean nausea score was 2.70 in the haloperidol group (p ≤ 0.001) and 0.72 in the placebo group (p = 0.05). Therefore, the reductions in symptom scores were statistically significant in the haloperidol group but not in the placebo group. No adverse events were reported.

Conclusions

Haloperidol as an adjunctive therapy is superior to placebo for acute gastroparesis symptoms.
Prehospital Advanced Cardiac Life Support for Out‐of‐hospital Cardiac Arrest: A Cohort Study
Authors: Cournoyer Alexis , Notebaert Éric , Iseppon Massimiliano , Cossette Sylvie , Londei‐Leduc Luc , Lamarche Yoan , Morris Judy , Piette Éric , Daoust Raoul , Chauny Jean‐Marc , Sokoloff Catalina , Cavayas Yiorgos Alexandros , Paquet Jean , Denault André
Published: June 2017

Objectives

Out‐of‐hospital advanced cardiac life support (ACLS) has not consistently shown a positive impact on survival. Extracorporeal cardiopulmonary resuscitation (E‐CPR) could render prolonged on‐site resuscitation (ACLS or basic cardiac life support [BCLS]) undesirable in selected cases. The objectives of this study were to evaluate, in patients suffering from out‐of‐hospital cardiac arrest (OHCA) and in a subgroup of potential E‐CPR candidates, the association between the addition of prehospital ACLS to BCLS and survival to hospital discharge, prehospital return of spontaneous circulation (ROSC), and delay from call to hospital arrival.

Methods

This cohort study targets adult patients treated for OHCA between April 2010 and December 2015 in the city of Montreal, Canada. We defined potential E‐CPR candidates using clinical criteria previously described in the literature (65 years of age or younger, initial shockable rhythm, absence of ROSC after 15 minutes of prehospital resuscitation, and emergency medical services–witnessed collapse or witnessed collapse with bystander cardiopulmonary resuscitation). Associations were evaluated using multivariate regression models.

Results

A total of 7,134 patients with OHCA were included, 761 (10.7%) of whom survived to discharge. No independent association between survival to hospital discharge and the addition of prehospital ACLS to BCLS was found in either the entire cohort (adjusted odds ratio [AOR] = 1.05 [95% confidence interval {CI} = 0.84–1.32], p = 0.68) or among the 246 potential E‐CPR candidates (AOR = 0.82 [95% CI = 0.36–1.84], p = 0.63). The addition of prehospital ACLS to BCLS was associated with a significant increase in the rate of prehospital ROSC in all patients experiencing OHCA (AOR = 3.92 [95% CI = 3.38–4.55], p < 0.001) and in potential E‐CPR candidates (AOR = 3.48 [95% CI = 1. 76–6.88], p < 0.001) compared to isolated prehospital BCLS. Delay from call to hospital arrival was longer in the ACLS group than in the BCLS group (difference = 16 minutes [95% CI = 15–16 minutes], p < 0.001).

Conclusions

In a tiered‐response urban emergency medical service setting, prehospital ACLS is not associated with an improvement in survival to hospital discharge in patients suffering from OHCA and in potential E‐CPR candidates, but with an improvement in prehospital ROSC and with longer delay to hospital arrival.
The course and distribution of the buccal nerve: clinical relevance in dentistry
Authors: Takezawa K , Ghabriel M , Townsend G
Published: June 2017

Background

The buccal branch of the mandibular division of the trigeminal nerve is commonly anaesthetized for dental procedures and may be damaged during surgery. Descriptions of the distribution of the buccal nerve (BN) in anatomical texts are generally lacking in detail and do not provide information about the extent of its variation between individuals. There are also commonly‐held clinical beliefs about the BN that lack support from anatomical dissections.

Methods

Detailed dissections of the course and distribution of the BN were performed in a sample of 12 hemi‐heads from 11 edentulous and partially dentate human adult cadavers.

Results

A broader distribution of the BN was found than described previously, with innervation extending to the lips in all cases. Approximately half of the lateral sides of the lips were innervated by the BN in two cases and approximately one‐third of their lateral sides in the other 10 cases. Distribution of the BN to the lower lips was wider than to the upper lips.

Conclusions

Our findings provide a stronger anatomical basis to underpin clinical procedures involving the BN and indicate that some commonly‐held clinical views about this nerve are not supported by anatomical evidence.
The Challenges of Transitioning from Opposition to Government: Liberal Party Planning for Government 1983 – 1996
Authors: Taflaga Marija
Published: June 2017

Studies examining opposition transition to government processes and planning usually emphasise the responsibility of oppositions as a legislative institution and the role of party leaders. However, such approaches place too much emphasis on notions of responsible opposition and party leaders. They de‐emphasise the importance of partisan considerations that shape transition planning or how party organisations have attempted to assert control over parliamentary parties. Drawing on archival materials, policy documents, and elite interviews, this study examines both public and internal transition to government strategies undertaken by the Liberal Party of Australia during their opposition years (1983–1996). The paper finds that while party leaders became more important over time, the party organisation's involvement remained significant. The Liberal Party transition planning focused primarily on cabinet processes, Australian Public Service (APS) organisation, particularly the senior bureaucratic level, and selecting political staff. In so doing, the Liberal Party anticipated many of the Hawke government's 1987 reforms to the APS. The Liberal Party was motivated by its desire to restructure the machinery and culture of government and to allocate sufficient political staff resources to government. Its aim was to better equip the party to achieve its political and ideological goals when next in government.
Croatian Anti‐Fascism in the Second World War: An Australian Perspective
Authors: Drapac Vesna
Published: June 2017

The historiography of the Second World War in Yugoslavia rests on the dichotomous resistance/collaboration paradigm pitting “Yugoslav” resisters against extreme nationalist collaborators. This historiography also presents us with a Balkanist interpretation of the war as exceptionally savage and brutal. The collapse of Yugoslavia led to the collapse of the Partisan Epic. It also led to the rise of nationalist historiographies of the war and the rehabilitation of collaborators, notably the Serbian Chetniks. A corrective to the exceptionalism of many standard studies of the war in Yugosalvia may be found in an analysis of the experiences of Australian Yugoslavs and their perceptions of resistance and collaboration. Based almost entirely on hitherto underutilised archival sources, this article traces the differences between two rival Yugoslav groups in Australia: (mostly Serbian) royalist supporters of the Chetniks and the old centralist regime, and Croatian supporters of Tito's Partisans and the idea of a new, federative Yugoslavia. It demonstrates that both groups were adept at mobilising opinion and actively engaging in the political process to advance their cause. However, the Croats and their organisational structures had a wider reach. Furthermore, they were able to demonstrate that they were contributing more to the Allied cause — which was their own — than their rivals. This had an impact on their standing in Australian society and on attitudes towards Yugoslavs and Yugoslavia. Finally, this article sheds new light on the Australian home‐front, revealing the generally civil and tolerant attitude of state and commonwealth governments towards “friendly aliens” in their desire both to be connected to their country of birth and integrated into their adopted homeland.