bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Indocyanine Green on Hepatic Gd-EOB-DTPA Uptake
Authors: Akai Hiroyuki , Yasaka Koichiro , Nojima Masanori , Inoue Yusuke , Ohtomo Kuni , Kiryu Shigeru
Published: February 2017

Objectives

The aim of this study was to explore the influence of indocyanine green (ICG) on hepatic uptake of gadolinium ethoxybenzyldiethylenetriaminepenta-acetic acid (Gd-EOB-DTPA).

Materials and Methods

Groups of 6 female C57BL6 mice were injected with 5 mg/kg ICG, 20 mg/kg ICG, or phosphate-buffered saline (control group) 10 minutes before the injection of Gd-EOB-DTPA; identical 3-dimensional gradient echo T1-weighted images were subsequently obtained to create time-intensity curves and to measure the peak contrast ratios (CRs) of liver parenchyma. We studied both hypothermic and normothermic mice. Peak CRs for all experimental conditions were evaluated, and among-group differences were assessed using 2-way factorial analysis of variance with Bonferroni post hoc testing.

Results

In hypothermic mice, the time-intensity curves of the 3 groups gradually increased from 5 to 30 minutes and almost plateaued after 30 minutes. The peak CR decreased as the amount of injected ICG increased (control group, 5 mg/kg ICG, 20 mg/kg ICG: 1.66 ± 0.09, 1.37 ± 0.18, 1.25 ± 0.24, respectively). In normothermic animals, the time-intensity curves of the control and ICG 5 mg/kg groups peaked 10 to 15 minutes after injection, the peak CRs were very similar (control group, 5 mg/kg ICG: 2.01 ± 0.16, 1.95 ± 0.14, respectively), and the intensities thereof then gradually fell until 60 minutes. Compared with these groups, the ICG 20 mg/kg group exhibited lower peak CR (1.48 ± 0.14) and a weaker decrease in intensity to 60 minutes. Both the amount of ICG injected (P < 0.001) and the experimental temperature (P < 0.001) significantly affected the measurements.

Conclusions

Indocyanine green inhibits the hepatic uptake of Gd-EOB-DTPA and affects the signal intensity upon Gd-EOB-DTPA–enhanced magnetic resonance imaging. Such inhibition was more obvious in hypothermic mice.
Single-cell transcriptomics of malaria parasites
Authors: Reid Adam J. , Talman Arthur M. , Bennett Hayley M. , Gomes Ana R. , Sanders Mandy J. , Illingworth Christopher J. R. , Billker Oliver , Berriman Matthew , Lawniczak Mara K. N.
Published: February 2017

Single-cell RNA-sequencing is revolutionising our understanding of seemingly homogeneous cell populations, but has not yet been applied to single cell organisms. Here, we established a method to successfully investigate transcriptional variation across individual malaria parasites. We discover an unexpected, discontinuous program of transcription during asexual growth previously masked by bulk analyses, and uncover novel variation among sexual stage parasites in their expression of gene families important in host-parasite interactions.
High-Throughput Controlled Mechanical Stimulation and Functional ImagingIn Vivo
Authors: Cho Yongmin , Porto Daniel A. , Hwang Hyundoo , Grundy Laura J. , Schafer William R. , Lu Hang
Published: February 2017

Understanding mechanosensation and other sensory behavior in genetic model systems such asC. elegansis relevant to many human diseases. These studies conventionally require immobilization by glue and manual delivery of stimuli, leading to low experimental throughput and high variability. Here we present a microfluidic platform that delivers precise mechanical stimuli robustly. The system can be easily used in conjunction with functional imaging and optical interrogation techniques, as well as other capabilities such as sorting or more sophisticated fluid delivery schemes. The platform is fully automated, thereby greatly enhancing the throughput and robustness of experiments. We show that behavior of the well-known gentle and harsh touch neurons and their receptive fields can be recapitulated in our system. Using calcium dynamics as a readout, we demonstrate the ability to perform a drug screenin vivo. Furthermore, using an integrated chip platform that can deliver both mechanical and chemical stimuli, we examine sensory integration in interneurons in response to multimodal sensory inputs. We envision that this system will be able to greatly accelerate the discovery of genes and molecules involved in mechanosensation and multimodal sensory behavior, as well as the discovery of therapeutics for related diseases.
Single-Neuron Gene Expression Analysis Using the Maxwell® 16 LEV System in the Neural Systems and Behavior Course
Authors: Harris Rayna M. , Otopalik Adriane G. , Smith Colin J. , Bucher Dirk , Golowasch Jorge , Hofmann Hans A.
Published: February 2017

Gene expression analysis from single cells has become increasingly prominent across biological disciplines; thus, it is important to train students in these approaches. Here, we present an experimental and analysis pipeline that we developed for the Neural Systems & Behavior (NS&B) course at Marine Biological Laboratory. Our approach used the Maxwell®16 LEV simplyRNA Tissue Kit and GoTaq®2-Step RT-qPCR System for gene expression analysis from single neurons of the crustacean stomatogastric ganglion, a model system to study the generation of rhythmic motor patterns. We used double-stranded RNA to knockdown expression of a putative neuromodulator-activated sodium channel. We then examined the electrophysiological responses to known neuromodulators and confirmed that the response was reduced. Finally, we measured how mRNA levels of several ion channel genes changed in response. Our results provide new insights into the neural mechanisms underlying the generation and modulation of rhythmic motor patterns.
Epidemic network analysis for mitigation of invasive pathogens in seed systems: Potato in Ecuador
Authors: Buddenhagen C. E. , Hernandez Nopsa J. F. , Andersen K. F. , Andrade-Piedra J. , Forbes G. A. , Kromann P. , Thomas-Sharma S. , Useche P. , Garrett K. A.
Published: February 2017

Seed systems have an important role in the distribution of high quality seed and improved varieties. The structure of seed networks also helps to determine the epidemiological risk for seedborne disease. We present a new method for evaluating the epidemiological role of nodes in seed networks, and apply it to a regional potato farmer consortium (CONPAPA) in Ecuador. We surveyed farmers to estimate the structure of networks of farmer seed tuber and ware potato transactions, and farmer information sources about pest and disease management. Then we simulated pathogen spread through seed transaction networks to identify priority nodes for disease detection. The likelihood of pathogen establishment was weighted based on the quality and/or quantity of information sources about disease management. CONPAPA staff and facilities, a market, and certain farms are priorities for disease management interventions, such as training, monitoring and variety dissemination. Advice from agrochemical store staff was common but assessed as significantly less reliable. Farmer access to information (reported number and quality of sources) was similar for both genders. Women had a smaller amount of the market share for seed-tubers and ware potato, however. Understanding seed system networks provides input for scenario analyses to evaluate potential system improvements.
Quiescent Body as a Reversible Subcellular Structure Formed in Non-growing Bacterial Cells
Authors: Yu Jiayu , Liu Yang , Yin Huijia , Chang Zengyi
Published: February 2017

Bacterial cells take a variable lag time and maintain a multi-drug tolerant non-growing state before resuming growth when encountering growth-supportive conditions. Some of them exhibit an extraordinarily long lag, as pathogenic persisters do. It remains unknown on what determines lag time duration. Here, we unveiled a subcellular structure, termed quiescent body, that is formed in bacterial cells entering non-growing state and sequesters selected proteins essential for cell growth. Their formation occurs progressively in each cell and heterogeneously among individual cells. They only dissolve in re-growing cells to release proteins for immediate re-functioning when conditions become fit. Quiescent body, whose degree of formation is highly correlated with duration of lag time or level of antibiotic tolerance, apparently functions as a biological timer for bacterial growth resumption. Further, suppressing their formation, which directly relies on cellular respiration complexes, or promoting their dissolution might be a viable strategy to eradicate persisters.
Stratified Linkage Disequilibrium Score Regression reveals enrichment of eQTL effects on complex traits is not tissue specific
Authors: Ip Hill F. , Jansen Rick , Abdellaoui Abdel , Bartels Meike ,   UK Brain Expression Consortium, Boomsma Dorret I. , Nivard Michel G.
Published: February 2017

Both gene expression levels and eQTLs (expression quantitative trait loci) are partially tissue-specific, complicating the detection of eQTLs in tissues with limited sample availability, such as the brain. However, eQTL overlap between tissues might be non-trivial, allowing for inference of eQTL functioning in the brain via eQTLs measured in readily accessible tissues, e.g. whole blood. Using Stratified Linkage Disequilibrium Score Regression (SLDSR), we quantify the enrichment in GWAS signal of blood and brain eQTLs in genome-wide association study (GWAS) on 11 complex traits (schizophrenia, BMI, educational attainment, Crohn’s disease, rheumatoid arthritis, ulcerative colitis, age at menarche, coronary artery disease, height, LDL levels, and smoking behavior). Our analyses established significant enrichment of blood and brain eQTLs in their effects across all traits. As we do not know the true number of causal eQTLs, it is difficult to determine the precise magnitude of enrichment. We found no evidence for tissue-specific enrichment in GWAS signal for either eQTLs uniquely seen in the brain or whole blood. To follow up on our findings, we tested tissue-specific enrichment of eQTLs discovered in 44 tissues by the Genotype-Tissue Expression (GTEx) consortium, and, again, found no tissue-specific eQTL effects. We further integrated the GTEx eQTLs with SNPs associated with tissue-specific histone modifiers, and interrogate its effect on rheumatoid arthritis and schizophrenia. We observed substantially enriched effects on schizophrenia, though again not tissue-specific. Finally, we extracted eQTLs in tissue-specific differentially expressed genes, and determined their effects on rheumatoid arthritis and schizophrenia. We conclude that, while eQTLs are strongly enriched in GWAS signal, the enrichment is not specific to the tissue used in eQTL discovery. Therefore, working with relatively accessible tissues, such as whole blood, as proxy for eQTL discovery is sensible; and restricting lookups for GWAS hits to a specific tissue might not be advisable.
Genomic contingencies and beak shape variation in a hybrid species
Authors: Runemark Anna , Fernández Laura Piñeiro , Eroukhmanoff Fabrice , Sætre GlennPeter
Published: February 2017

Hybridization is increasingly recognized as a potent evolutionary force. Though additive genetic variation and novel combinations of parental genes theoretically increase the potential for hybrid species to adapt, few empirical studies have investigated the adaptive potential within a hybrid species. Here, we investigate factors promoting phenotypic divergence using genomically diverged island populations of the homoploid hybrid Italian sparrowPasser italiaefrom Crete, Corsica, and Sicily. We address whether genomic contingencies, adaptation to climate or diet best explain divergence in beak morphology. Populations vary significantly in beak morphology, both between and within islands of origin. Temperature seasonality best explains population divergence in beak size. Interestingly, beak shape along all significant dimensions of variation was best explained by annual precipitation, genomic composition and their interaction, suggesting a role for contingencies. Moreover, beak shape similarity to a parent species correlates with proportion of the genome inherited from that species, consistent with the presence of contingencies. In conclusion, adaptation to local conditions and genomic contingencies arising from putatively independent hybridization events jointly explain beak morphology in the Italian sparrow. Hence, hybridization may induce contingencies and restrict evolution in certain directions dependent on the genetic background.
Variation and constraints in hybrid genome formation
Authors: Runemark Anna , Trier Cassandra N. , Eroukhmanoff Fabrice , Hermansen Jo S. , Matschiner Michael , Ravinet Mark , Elgvin Tore O. , Sætre Glenn-Peter
Published: February 2017

Recent genomic investigations have revealed hybridization to be an important source of variation, the working material of natural selection1,2. Hybridization can spur adaptive radiations3, transfer adaptive variation across species boundaries4, and generate species with novel niches5. Yet, the limits to viable hybrid genome formation are poorly understood. Here we investigated to what extent hybrid genomes are free to evolve or whether they are restricted to a specific combination of parental alleles by sequencing the genomes of four isolated island populations of the homoploid hybrid Italian sparrowPasser italiae6,7. Based on 61 Italian sparrow genomes from Crete, Corsica, Sicily and Malta, and 10 genomes of each of the parent speciesP. domesticusandP. hispaniolensis,we report that a variety of novel and fully functional hybrid genomic combinations have arisen on the different islands, with differentiation in candidate genes for beak shape and plumage colour. There are limits to successful genome fusion, however, as certain genomic regions are invariably inherited from the same parent species. These regions are overrepresented on the Z-chromosome and harbour candidate incompatibility loci, including DNA-repair and mito-nuclear genes; loci that may drive the general reduction of introgression on sex chromosomes8. Our findings demonstrate that hybridization is a potent process for generating novel variation, but variation is limited by DNA-repair and mito-nuclear genes, which play an important role in reproductive isolation and thus contribute to speciation.
Stochastic satisficing account of confidence in uncertain value-based decisions
Authors: Hertz Uri , Bahrami Bahador , Keramati Mehdi
Published: February 2017

Every day we make choices under uncertainty; choosing what route to work or which queue in a supermarket to take, for example. It is unclear how outcome variance, e.g. uncertainty about waiting time in a queue, affects decisions and confidence when outcome is stochastic and continuous. How does one evaluate and choose between an option with unreliable but high expected reward, and an option with more certain but lower expected reward? Here we used an experimental design where two choices’ payoffs took continuous values, to examine the effect of outcome variance on decision and confidence. We found that our participants’ probability of choosing the good (high expected reward) option decreased when the good or the bad options’ payoffs were more variable. Their confidence ratings were affected by outcome variability, but only when choosing the good option. Unlike perceptual detection tasks, confidence ratings correlated only weakly with decisions’ time, but correlated with the consistency of trial-by-trial choices. Inspired by the satisficing heuristic, we propose a “stochastic satisficing” (SSAT) model for evaluating options with continuous uncertain outcomes. In this model, options are evaluated by their probability of exceeding an acceptability threshold, and confidence reports scale with the chosen option’s thus-defined satisficing probability. Participants’ decisions were best explained by an expected reward model, while the SSAT model provided the best prediction of decision confidence. We further tested and verified the predictions of this model in a second experiment. Our model and experimental results generalize the models of metacognition from perceptual detection tasks to continuous-value based decisions. Finally, we discuss how the stochastic satisficing account of decision confidence serves psychological and social purposes associated with the evaluation, communication and justification of decision-making.

Author Summary

Every day we make several choices under uncertainty, like choosing a queue in a supermarket. However, the computational mechanisms underlying such decisions remain unknown. For example, how does one choose between an option with unreliable high expected reward, like the volatile express queue, and an option with more certain but lower expected reward in the standard queue? Inspired by bounded rationality and the notion of ‘satisficing’, i.e. settling for a good enough option, we propose that such decisions are made by comparing the likelihood of different actions to surpass an acceptability threshold. When facing uncertain decisions, our participants’ confidence ratings were not consistent with the expected outcome’s rewards, but instead followed the satisficing heuristic proposed here. Using an acceptability threshold may be especially useful when evaluating and justifying decisions under uncertainty.
Viscoelastic dissipation stabilizes cell shape changes during tissue morphogenesis
Authors: Clément R , Collinet C. , Dehapiot B. , Lecuit T. , Lenne P.-F.
Published: February 2017

Tissue morphogenesis relies on the production of active cellular forces. Understanding how such forces are mechanically converted into cell shape changes is essential to our understanding of morphogenesis. Here we use Myosin II pulsatile activity duringDrosophilaembryogenesis to study how transient forces generate irreversible cell shape changes. Analyzing the dynamics of junction shortening and elongation resulting from Myosin II pulses, we find that long pulses yield less reversible deformations, typically a signature of dissipative mechanics. This is consistent with a simple viscoelastic description, which we use to model individual shortening and elongation events. The model predicts that dissipation typically occurs on the minute timescale, a timescale commensurate with that of force generation by Myosin II pulses. We test this estimate by applying time-controlled forces on junctions with optical tweezers. Our results argue that active junctional deformation is stabilized by dissipation. Hence, tissue morphogenesis requires coordination between force generation and dissipation.
Wild tobacco genomes reveal the evolution of nicotine biosynthesis
Authors: Xu Shuqing , Brockmöller Thomas , Navarro-Quezada Aura , Kuhl Heiner , Gase Klaus , Ling Zhihao , Zhou Wenwu , Kreitzer Christoph , Stanke Mario , Tang Haibao , Lyons Eric , Pandey Priyanka , Pandey Shree P. , Timmermann Bernd , Gaquerel Emmanuel , Baldwin Ian T.
Published: February 2017

Nicotine, the signature alkaloid ofNicotianaspecies responsible for the addictive properties of human tobacco smoking, functions as a defensive neurotoxin against attacking herbivores. However, the evolution of the genetic features that contributed to the assembly of the nicotine biosynthetic pathway remains unknown. We sequenced and assembled genomes of two wild tobaccos,Nicotiana attenuata(2.5 Gb) andN. obtusifolia(1.5 Gb), two ecological models for investigating adaptive traits in nature. We show that after the Solanaceae whole genome triplication event, a repertoire of rapidly expanding transposable elements (TEs) bloated theseNicotianagenomes, promoted expression divergences among duplicated genes and contributed to the evolution of herbivory-induced signaling and defenses, including nicotine biosynthesis. The biosynthetic machinery that allows for nicotine synthesis in the roots evolved from the stepwise duplications of two ancient primary metabolic pathways: the polyamine and nicotinic acid dinucleotide (NAD) pathways. While the duplication of the former is shared among several Solanaceous genera which produce polyamine-derived tropane alkaloids, the innovation and efficient production of nicotine in the genusNicotianarequired lineage-specific duplications within the NAD pathway and the evolution of root-specific expression of the duplicated Solanaceae-specific ethylene response factor (ERF) that activates the expression of all nicotine biosynthetic genes. Furthermore, TE insertions that incorporated transcription factor binding motifs also likely contributed to the coordinated metabolic flux of the nicotine biosynthetic pathway. Together, these results provide evidence that TEs and gene duplications facilitated the emergence of a key metabolic innovation relevant to plant fitness.
Multidimensional encoding of brain connectomes
Authors: Caiafa Cesar F. , Pestilli Franco
Published: February 2017

The ability to map brain networks at the macroscale in living individuals is fundamental in efforts to chart the relation between human behavior, health and disease. We present a framework to encode structural brain connectomes and diffusion-weighted magnetic resonance data into multidimensional arrays (tensors). The framework overcomes current limitations in building connectomes; it prevents information loss by integrating the relation between connectome nodes, edges, fascicles and diffusion data. We demonstrate the utility of the framework forin vivowhite matter mapping and anatomical computing. The framework reduces dramatically storage requirements for connectome evaluation methods, with up to 40x compression factors. We apply the framework to evaluate 1,980 connectomes, thirteen tractography methods, and three data sets. We describe a general equation to predicts connectome resolution (number of fascicles) given data quality and tractography model parameters. Finally, we provide open-source software implementing the method and data to reproduce the results.
Multi-tissue polygenic models for transcriptome-wide association studies
Authors: Park Yongjin , Sarkar Abhishek , Bhutani Kunal , Kellis Manolis
Published: February 2017

I.

Transcriptome-wide association studies (TWAS) have proven to be a powerful tool to identify genes associated with human diseases by aggregating cis-regulatory effects on gene expression. However, TWAS relies on building predictive models of gene expression, which are sensitive to the sample size and tissue on which they are trained. The Gene Tissue Expression Project has produced reference transcriptomes across 53 human tissues and cell types; however, the data is highly sparse, making it difficult to build polygenic models in relevant tissues for TWAS. Here, we propose fQTL, a multi-tissue, multivariate model for mapping expression quantitative trait loci and predicting gene expression. Our model decomposes eQTL effects into SNP-specific and tissue-specific components, pooling information across relevant tissues to effectively boost sample sizes. In simulation, we demonstrate that our multi-tissue approach outperforms single-tissue approaches in identifying causal eQTLs and tissues of action. Using our method, we fit polygenic models for 13,461 genes, characterized the tissue-specificity of the learnedcis-eQTLs, and performed TWAS for Alzheimer’s disease and schizophrenia, identifying 107 and 382 associated genes, respectively.
Field-based species identification in eukaryotes using real-time nanopore sequencing
Authors: Parker Joe , Helmstetter Andrew J. , Devey Dion , Papadopulos Alexander S.T.
Published: February 2017

Advances in DNA sequencing and informatics have revolutionised biology over the past four decades, but technological limitations have left many applications unexplored1,2. Recently, portable, real-time, nanopore sequencing (RTnS) has become available. This offers opportunities to rapidly collect and analyse genomic data anywhere3–5. However, the generation of datasets from large, complex genomes has been constrained to laboratories6,7. The portability and long DNA sequences of RTnS offer great potential for field-based species identification, but the feasibility and accuracy of these technologies for this purpose have not been assessed. Here, we show that a field-based RTnS analysis of closely-related plant species (Arabidopsis spp.)8has many advantages over laboratory-based high-throughput sequencing (HTS) methods for species level identification-by-sequencing andde novophylogenomics. Samples were collected and sequenced in a single day by RTnS using a portable,“al fresco”laboratory. Our analyses demonstrate that correctly identifying unknown reads from matches to a reference database with RTnS reads enables rapid and confident species identification. Individually annotated RTnS reads can be used to infer the evolutionary relationships ofA. thaliana. Furthermore, hybrid genome assembly with RTnS and HTS reads substantially improved upon a genome assembled from HTS reads alone. Field-based RTnS makes real-time, rapid specimen identification and genome wide analyses possible. These technological advances are set to revolutionise research in the biological sciences9and have broad implications for conservation, taxonomy, border agencies and citizen science.
Targeted sequencing of venom genes from cone snail genomes reveals coupling between dietary breadth and conotoxin diversity
Authors: Phuong Mark A , Mahardika Gusti N
Published: February 2017

Although venomous taxa provide an attractive system to study the genetic basis of adaptation and speciation, the slow pace of toxin gene discovery through traditional laboratory techniques (e.g., cDNA cloning) have limited their utility in the study of ecology and evolution. Here, we applied targeted sequencing techniques to selectively recover venom gene superfamilies and non-toxin loci from the genomes of 32 species of cone snails (family, Conidae), a hyper diverse group of carnivorous marine gastropods that capture their prey using a cocktail of neurotoxic proteins (conotoxins). We were able to successfully recover conotoxin gene superfamilies across all species sequenced in this study with high confidence (> 100X coverage). We found that conotoxin gene superfamilies are composed of 1-6 exons and adjacent noncoding regions are not enriched for simple repetitive elements. Additionally, we provided further evidence for several genetic factors shaping venom composition in cone snails, including positive selection, extensive gene turnover, expression regulation, and potentially, presence-absence variation. Using comparative phylogenetic methods, we found that while diet specificity did not predict patterns of conotoxin gene superfamily size evolution, dietary breadth was positively correlated with total conotoxin gene diversity. These results continue to emphasize the importance of dietary breadth in shaping venom evolution, an underappreciated ecological correlate in venom biology. Finally, the targeted sequencing technique demonstrated here has the potential to radically increase the pace at which venom gene families are sequenced and studied, reshaping our ability to understand the impact of genetic changes on ecologically relevant phenotypes and subsequent diversification.
SUPERMANprevents stamen formation and promotes stem cell termination in the fourth whorl of the Arabidopsis flower
Authors: Prunet Nathanaël , Yang Weibing , Das Pradeep , Meyerowitz Elliot M. , Jack Thomas P.
Published: February 2017

The molecular and genetic networks underlying the determination of floral organ identity are well studied, but much less is known about how the flower is partitioned into four developmentally distinct whorls. TheSUPERMANgene is required for proper specification of the boundary between stamens in whorl 3 and carpels in whorl 4, assupermanmutants exhibit supernumerary stamens but usually lack carpels. However, it has remained unclear whether extra stamens insupermanmutants originate from an organ identity change in whorl 4 or the overproliferation of whorl 3. Using live confocal imaging, we show that the extra stamens insupermanmutants arise from cells in whorl 4, which change their fate from female to male, while floral stem cells proliferate longer, allowing for the production of additional stamens.
Inferring intracellular signal transduction circuitry from molecular perturbation experiments
Authors: Wynn Michelle L. , Egbert Megan , Consul Nikita , Chang Jungsoo , Wu Zhi-Fen , Meravjer Sofia D. , Schnell Santiago
Published: February 2017

The development of network inference methodologies that accurately predict connectivity in dysregulated pathways may enable the rational selection of patient therapies. Accurately inferring an intracellular network from data remains a very challenging problem in molecular systems biology. Living cells integrate extremely robust circuits that exhibit significant heterogeneity, but still respond to external stimuli in predictable ways. This phenomenon allows us to introduce a network inference methodology that integrates measurements of protein activation from perturbation experiments. The methodology relies on logic-based networks to provide a predictive approximation of the transfer of signals in a network. The approach presented was validatedin silicowith a set of test networks and applied to investigate the epidermal growth factor receptor signaling of a breast epithelial cell line, MFC10A. In our analysis, we predict the potential signaling circuitry most likely responsible for the experimental readouts of several proteins in the mitogen activated protein kinase and phosphatidylinositol-3 kinase pathways. The approach can also be used to identify additional necessary perturbation experiments to distinguish between a set of possible candidate networks.
Why Performance Management Should Not Be Like Dieting*
Authors: Blackman Deborah , Buick Fiona , O'Donnell Michael
Published: February 2017

Globally, organisations have long been preoccupied with using employee performance management to enhance organisational performance. However, due to the compliance‐based way in which it is often implemented, success has been limited. This paper proposes lessons can be learnt from adopting the analogy of ‘dieting’. Short‐term weight‐loss practices can lead to a cyclical pattern that generates weight gain, rather than loss, in longer term. This occurs due to dieters following fads focused on short‐term loss, rather than habitual modifications necessary for long‐term weight change. This may explain why despite organisations pursuing the perfect employee performance management system (akin to dieting fads), they remain ineffective. We argue that compliance‐based approaches encourage a short‐term focus on completing the process (known pejoratively as ‘tick‐and‐flick’). However, where performance management is considered core business, more sustainable practices emerge. Similar to weight loss, these represent the habitual modifications necessary for enabling high performance over the longer term.
Lack of incremental effect of histamine receptor antagonists over proton pump inhibitors on the risk of neoplastic progression in patients with Barrett's esophagus: a cohort study
Authors: Thota Prashanthi N , Hajifathalian Kaveh , Benjamin Tanmayee , Runkana Ashok , Lopez Rocio , Sanaka Madhusudhan R
Published: February 2017

OBJECTIVE

Long‐term acid suppression reduces the risk of progression to esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). Given recent reports about the harmful effects of using chronic proton pump inhibitors (PPI) there is renewed interest in alternative methods of acid suppression. Hence, we studied the effect of H2 receptor antagonists (H2RA) on the risk of progression to neoplasia in our BE cohort.

METHODS

This is a retrospective analysis of prospectively collected data of patients in our BE registry from 2002 to 2015. Patients' characteristics, endoscopic findings, such as the length of BE, hiatal hernia size and histological findings and patients' use of medications such as PPI, aspirin, H2RA, metformin and antihyperlipidemic agents were studied.

RESULTS

The cohort consisted of 1466 patients with a mean age of 61 ± 13 years. The patients had a predominance of male sex (76.7% [1118/1457]) and Caucasian race (96.6% [1209/1252]). After excluding prevalent high‐grade dysplasia (HGD) or EAC, 1025 patients had a median follow up of 43.6 months during which 57 patients progressed to HGD or EAC. PPI use (56% in progressors vs 69% in non‐progressors; P = 0.007) but not H2RA use (12% progressors vs 19% in non‐progressors P = 0.162) was associated with lower risk of neoplastic progression. On multivariate analysis, there was no synergistic effect of addition of H2RA to PPI on risk of neoplastic progression to HGD or EAC (relative risk 0.33; confidence intervals 0.05–2.29, P = 0.262).

CONCLUSION

H2RA do not seem to have a chemopreventive role in patients with BE.
Split‐dose bowel preparation with polyethylene glycol for colonoscopy performed under propofol sedation. Is there an optimal timing?
Authors: Alghamry Alaa , Ponnuswamy Sureshkumar K , Agarwal Aditya , Moattar Hadi , Yerkovich Stephanie T , Vandeleur Ann E ,   Endoscopy Nurses Collaborative (ENC), Thomas James , Croese John , Rahman Tony , Hodgson Ruth
Published: February 2017

OBJECTIVE

Aspiration risk, especially with propofol sedation, remains a concern after split‐dose bowel preparation of up to 1 L polyethylene glycol for the procedure. We aimed to identify the ideal timing of bowel preparation to achieve optimal colon cleansing with no increased risk of aspiration.

METHODS

A total of 892 consecutive patients undergoing simultaneous esophagogastroduodenoscopy (EGD) and colonoscopy were prospectively recruited. Residual gastric volume (RGV) and pH of gastric contents were measured at EGD, and patients' characteristics, runway time (duration between completion of the final liter of bowel preparation and colonoscopy commencement), and cleansing quality were recorded.

RESULTS

A shorter runway time resulted in better colon cleansing (r = −0.124, P < 0.001). No correlation between runway time and RGV or pH was found (r = −0.017, P = 0.62 and r = −0.030, P = 0.47, respectively). RGV and pH did not differ significantly with runway time of 4 or 5 h. RGV with runway time ≤3 h was 35.9 ± 11.8 mL and 17.4 ± 0.6 mL after runway time >3 h (P < 0.001). No aspiration pneumonia occurred. The only factors independently related to higher RGV were younger age and male sex.

CONCLUSIONS

The consumption of bowel preparation agent within 3–4 h before propofol sedation resulted in a similar RGV and pH as those achieved by more prolonged fasting, with no increased risk of aspiration even in patients perceived to be at high risk.
Emotion processing and psychosocial functioning in euthymic bipolar disorder
Authors: Aparicio A. , Santos J. L. , Jiménez‐López E. , Bagney A. , Rodríguez‐Jiménez R. , Sánchez‐Morla E. M.
Published: February 2017

Objective

To examine emotion processing in euthymic bipolar patients (EBP) compared to healthy controls. In addition, to determine whether or not there is an association between emotion processing and psychosocial functioning.

Material and methods

A sample of 60 EBP and 60 healthy controls matched for age, gender, education level, and premorbid intelligence were studied. All subjects were assessed using the MATRICS Consensus Cognitive Battery (MCCB) and two additional executive function measures: the Trail Making Test‐Part B and the Stroop Test. Emotion processing was examined using the Mayer‐Salovey‐Caruso Emotional Intelligence Test (MSCEIT). Psychosocial functioning was assessed using the Functional Assessment Short Test (FAST).

Results

Euthymic bipolar patients obtained lower scores than controls in all MSCEIT measures except for the using emotions branch. Likewise, EBP obtained a worse performance than healthy controls in all neurocognitive domains. Correlation between MSCEIT strategic area measures and FAST total score was found (r = −0.311; P < 0.016). Regression analysis showed that residual depressive symptomatology explains a 9.1% of the variance in functional outcome. MSCEIT strategic area score explained an additional 8.6%. Neurocognition did not increase the percentage of the variance explained by emotion processing.

Conclusions

Euthymic bipolar patients exhibit deficits in emotion processing. Emotion processing is associated with social functioning in these patients.
Knowledge, attitude and practises of dentists towards oral health care during pregnancy: A cross sectional survey in New South Wales, Australia
Authors: George A , Ajwani S , Bhole S , Dahlen HG , Reath J , Korda A , Ng Chok H , Miranda C , Villarosa A , Johnson M
Published: February 2017

Background

Studies internationally show a lack of consensus among dentists regarding perinatal oral health yet no study in Australia has explored the perceptions of dentists in this area. This study aims to determine the knowledge, perceptions and practises of dentists in New South Wales (NSW), Australia, about perinatal oral health.

Methods

An online survey was distributed to 1357 members of the Australian Dental Association (NSW) and 185 (13.4%) completed surveys were returned.

Results

Most dentists (99%) stated that pregnant women should receive a dental check, yet only 20% agreed that there was a good understanding among health professionals on this topic. Dentists were aware of safe dental practises during pregnancy but had limited knowledge about the association between periodontal disease and birth outcomes. Dentists were more likely to advise pregnant women to delay dental visits when there was a perceived lack of knowledge of the risks involved (odds ratio, 2.157) or were concerned about providing treatment without consent from their general practitioner (odds ratio, 2.449). Most dentists (95.7%) stated that they wanted further information about dental care during pregnancy.

Conclusions

Findings suggest a need for continuing education for dentists and practise guidelines on perinatal oral health. Further research with a national sample is recommended to confirm these findings.
The analgesic efficacy of pre‐operative bilateral erector spinae plane (ESP) blocks in patients having ventral hernia repair
Authors: Chin K. J. , Adhikary S. , Sarwani N. , Forero M.
Published: February 2017

Laparoscopic ventral hernia repair is an operation associated with significant postoperative pain, and regional anaesthetic techniques are of potential benefit. The erector spinae plane (ESP) block performed at the level of the T5 transverse process has recently been described for thoracic surgery, and we hypothesised that performing the ESP block at a lower vertebral level would provide effective abdominal analgesia. We performed pre‐operative bilateral ESP blocks with 20–30 ml ropivacaine 0.5% at the level of the T7 transverse process in four patients undergoing laparoscopic ventral hernia repair. Median (range) 24‐h opioid consumption was 18.7 mg (0.0–43.0 mg) oral morphine. The highest and lowest median (range) pain scores in the first 24 h were 3.5 (3.0–5.0) and 2.5 (0.0–3.0) on an 11‐point numerical rating scale. We also performed the block in a fresh cadaver and assessed the extent of injectate spread using computerised tomography. There was radiographic evidence of spread extending cranially to the upper thoracic levels and caudally as far as the L2–L3 transverse processes. We conclude that the ESP block is a promising regional anaesthetic technique for laparoscopic ventral hernia repair and other abdominal surgery when performed at the level of the T7 transverse process. Its advantages are the ability to block both supra‐umbilical and infra‐umbilical dermatomes with a single‐level injection and its relative simplicity.
Idiopathic epicardial ventricular tachycardia from the coronary venous system: From electrocardiographic recognition to appropriate therapy
Authors: Boulé Stéphane , Federspiel Claire , Verbrugge Eric , Klug Didier
Published: February 2017

Idiopathic epicardial ventricular tachycardias (VTs) account for 9% of idiopathic VTs. The recognition of this entity is important, as a minimally invasive ablation procedure performed exclusively through the coronary sinus branches may be considered, avoiding the potential risks associated with access to the left ventricular endocardium, the aortic root, and the pericardial space. The electrocardiographic features and therapeutic management of this rare form of tachycardia are discussed.
A Substance Exchanger‐Based Bioreactor Culture of Pig Discs for Studying the Immature Nucleus Pulposus
Authors: Li Pei , Gan Yibo , Wang Haoming , Xu Yuan , Song Lei , Wang Liyuan , Ouyang Bin , Zhou Qiang
Published: February 2017

Various research models have been developed to study the biology of disc cells. Recently, the adult disc nucleus pulposus (NP) has been well studied. However, the immature NP is underinvestigated due to a lack of a suitable model. This study aimed to establish an organ culture of immature porcine disc by optimizing culture conditions and using a self‐developed substance exchanger‐based bioreactor. Immature porcine discs were first cultured in the bioreactor for 7 days at various levels of glucose (low, medium, high), osmolarity (hypo‐, iso‐, hyper‐) and serum (5, 10, 20%) to determine the respective optimal level. The porcine discs were then cultured under the optimized conditions in the novel bioreactor, and were compared with fresh discs at day 14. For high‐glucose, iso‐osmolarity, or 10% serum, cell viability, the gene expression profile (for anabolic genes and catabolic genes), and glycosaminoglycan (GAG) and hydroxyproline (HYP) contents were more favorable than for other levels of glucose, osmolarity, and serum. When the immature discs were cultured under the optimized conditions using the novel bioreactor for 14 days, the viability of the immature NP was maintained based on histology, cell viability, GAG and HYP contents, and matrix molecule expression. In conclusion, the viability of the immature NP in organ culture could be maintained under the optimized culture conditions (high‐glucose, iso‐osmolarity, and 10% serum) in the substance exchanger‐based bioreactor.
Objectification of people and thoughts: An attitude change perspective
Authors: Briñol Pablo , Petty Richard E. , Belding Jennifer
Published: February 2017

Many objectification phenomena can be understood from a mind–body dualism perspective in which the more people focus on their bodies, the less they focus on their minds. Instead of viewing mind and body in opposition to each other, we advocate for a more reciprocal view in which mind and body work in conjunction. Consistent with an integrated mind–body approach, we begin our review by describing research on embodied persuasion revealing that focusing on our own body can reduce but also increase thinking (elaboration), as well as affecting the use of thoughts in forming evaluations (validation). Next, we extend our integrated view to a new domain and suggest that physical objects can influence thoughts and that one's thoughts can also be objectified. The first portion of this section focuses on research on enclothed cognition revealing that wearing physical objects can operate through the same processes of elaboration (increasing and decreasing thinking) and validation (increasing and decreasing thought usage) as the body. The second portion reveals that thoughts can be understood and treated as if they were physical objects affecting evaluative processes by influencing elaboration and validation processes. The final section provides some practical guidance relevant to campaigns designed to reduce the objectification of women and the infrahumanization of stigmatized groups.
Stereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial
Authors: Siva Shankar , Pham Daniel , Kron Tomas , Bressel Mathias , Lam Jacqueline , Tan Teng Han , Chesson Brent , Shaw Mark , Chander Sarat , Gill Suki , Brook Nicholas R. , Lawrentschuk Nathan , Murphy Declan G. , Foroudi Farshad
Published: February 2017

Objective

To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes.

Materials and Methods

This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time‐to‐event outcomes were described using the Kaplan–Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size.

Results

Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow‐up was 24 months. Treatment‐related grade 1–2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4–5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001).

Conclusion

The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune‐mediated response and warrants further investigation.
The composition of municipal associations and policy requests to provincial governments: Selected cases
Authors: Shott Alison
Published: February 2017

Municipal associations lobby senior levels of government for legislative changes. This article tests how the composition and size of municipal associations affects such policy requests for provincial programs or funding transfers by examining four Canadian associations in BC, Nova Scotia and two in Alberta between 1999 and 2013. The findings suggest that associations with more homogeneous member populations lobby primarily for provincial programs; those with more heterogeneous member populations are more likely to lobby for funds to enact municipal programs. This suggests that the collective intergovernmental lobbying of local government associations is influenced by the internal composition of members as well as the political norms and the external environment.