bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Ventilation, Weaning Practices, and Decision Making in European PICUs*
Authors: Tume Lyvonne N. , Kneyber Martin C. J. , Blackwood Bronagh , Rose Louise
Published: February 2017

Objectives:

This survey had three key objectives: 1) To describe responsibility for key ventilation and weaning decisions in European PICUs and explore variations across Europe; 2) To describe the use of protocols, spontaneous breathing trials, noninvasive ventilation, high-flow nasal cannula use, and automated weaning systems; and 3) To describe nurse-to-patient staffing ratios and perceived nursing autonomy and influence over ventilation decision making.

Design:

Cross-sectional electronic survey.

Setting:

European PICUs.

Participants:

Senior ICU nurse and physician from participating PICUs.

Interventions:

None.

Measurements and Main Results:

Response rate was 64% (65/102) representing 19 European countries. Determination of weaning failure was most commonly based on collaborative decision making (81% PICUs; 95% CI, 70–89%). Compared to this decision, selection of initial ventilator settings and weaning method was least likely to be collaborative (relative risk, 0.30; 95% CI, 0.20–0.47 and relative risk, 0.45; 95% CI, 0.32–0.45). Most PICUs (> 75%) enabled physicians in registrar (fellow) positions to have responsibility for key ventilation decisions. Availability of written guidelines/protocols for ventilation (31%), weaning (22%), and noninvasive ventilation (33%) was uncommon, whereas sedation protocols (66%) and sedation assessment tools (76%) were common. Availability of protocols was similar across European regions (all p > 0.05). High-flow nasal cannula (53%), noninvasive ventilation (52%) to avoid intubation, and spontaneous breathing trials (44%) were used in approximately half the PICUs greater than 50% of the time. A nurse-to-patient ratio of 1:2 was most frequent for invasively (50%) and noninvasively (70%) ventilated patients. Perceived nursing autonomy (median [interquartile range], 4 [2–6]) and influence (median [interquartile range], 7 [5–8]) for ventilation and weaning decisions varied across Europe (p = 0.007 and p = 0.01, respectively) and were highest in Northern European countries.

Conclusions:

We found variability across European PICUs in interprofessional team involvement for ventilation decision making, nurse staffing, and perceived nursing autonomy and influence over decisions. Patterns of adoption of tools/adjuncts for weaning and sedation were similar.
Correlation between Facial Nerve Axonal Load and Age and Its Relevance to Facial Reanimation
Authors: Hembd Austin , Nagarkar Purushottam , Perez Justin , Gassman Andrew , Tolley Philip , Reisch Joan , White Charles L. , Rozen Shai M.
Published: February 2017

Background:

Two-stage facial reanimation procedures with a cross-facial nerve graft often have unsatisfactory results in the older patient. Although the cause of result variability is likely multifactorial, some studies suggest that increased donor nerve axonal load improves function of a free muscle transfer after a cross-facial nerve graft. This study attempts to characterize the relationship between age and facial nerve axonal load.

Methods:

Sixty-three fresh cadaveric heads were dissected to expose the facial nerve. For each hemiface, two facial nerve samples were taken: one proximal as the nerve exits the stylomastoid foramen, and one distal at the buccal branch (at a point 1 cm proximal to the anterior parotid border). Nerve samples were stained and quantified. Correlation analysis was completed using a Pearson correlation coefficient.

Results:

Thirty-six female and 27 male cadavers were dissected; their average age was 71 years (range, 22 to 97 years). At the proximal (r = −0.26; p < 0.01; n = 104) and distal (r = −0.45; p < 0.0001; n = 114) sampling points, there was a significant negative correlation between age and axonal load.

Conclusions:

As age increases, the axonal load of the facial nerve decreases at the buccal and zygomatic branches approximately 1 cm proximal to the anterior parotid border. The authors previously suggested this location as significant for cross-facial nerve coaptation. These results propose that decreasing axonal load can be a factor in the unsatisfactory outcomes of cross-facial grafting in the aging population. Moreover, this underscores the importance of recruiting more donor axons in attempting to improve facial reanimation in the older patient.
Advances in multicellular spheroids formation
Authors: Cui X. , Hartanto Y. , Zhang H.
Published: February 2017

Three-dimensional multicellular spheroids (MCSs) have a complex architectural structure, dynamic cell–cell/cell–matrix interactions and bio-mimickingin vivomicroenvironment. As a fundamental building block for tissue reconstruction, MCSs have emerged as a powerful tool to narrow down the gap between thein vitroandin vivomodel. In this review paper, we discussed the structure and biology of MCSs and detailed fabricating methods. Among these methods, the approach in microfluidics with hydrogel support for MCS formation is promising because it allows essential cell–cell/cell–matrix interactions in a confined space.
Workshop on reconstruction schemes for magnetic resonance data: summary of findings and recommendations
Authors: Ozturk-Isik Esin , Marshall Ian , Filipiak Patryk , Benjamin Arnold J. V. , Ones Valia Guerra , Ramón Rafael Ortiz , Valdés Hernández Maria del C.
Published: February 2017

The high-fidelity reconstruction of compressed and low-resolution magnetic resonance (MR) data is essential for simultaneously improving patient care, accuracy in diagnosis and quality in clinical research. Sponsored by the Royal Society through the Newton Mobility Grant Scheme, we held a half-day workshop on reconstruction schemes for MR data on 17 August 2016 to discuss new ideas from related research fields that could be useful to overcome the shortcomings of the conventional reconstruction methods that have been evaluated to date. Participants were 21 university students, computer scientists, image analysts, engineers and physicists from institutions from six different countries. The discussion evolved around exploring new avenues to achieve high resolution, high quality and fast acquisition of MR imaging. In this article, we summarize the topics covered throughout the workshop and make recommendations for ongoing and future works.
Rachis morphology cannot accurately predict the mechanical performance of primary feathers in extant (and therefore fossil) feathered flyers
Authors: Lees John , Garner Terence , Cooper Glen , Nudds Robert
Published: February 2017

It was previously suggested that the flight ability of feathered fossils could be hypothesized from the diameter of their feather rachises. Central to the idea is the unvalidated assumption that the strength of a primary flight feather (i.e. its material and structural properties) may be consistently calculated from the external diameter of the feather rachis, which is the only dimension that is likely to relate to structural properties available from fossils. Here, using three-point bending tests, the relationship between feather structural properties (maximum bending moment,Mmaxand Young's modulus,Ebend) and external morphological parameters (primary feather rachis length, diameter and second moment of area at the calamus) in 180 primary feathers from four species of bird of differing flight style was investigated. Intraspecifically, bothEbendandMmaxwere strongly correlated with morphology, decreasing and increasing, respectively, with all three morphological measures. Without accounting for species, however, external morphology was a poor predictor of rachis structural properties, meaning that precise determination of aerial performance in extinct, feathered species from external rachis dimensions alone is not possible. Even if it were possible to calculate the second moment of area of the rachis, our data suggest that feather strength could still not be reliably estimated.
Field patterns: a new mathematical object
Authors: Milton Graeme W. , Mattei Ornella
Published: February 2017

Field patterns occur in space–time microstructures such that a disturbance propagating along a characteristic line does not evolve into a cascade of disturbances, but rather concentrates on a pattern of characteristic lines. This pattern is the field pattern. In one spatial direction plus time, the field patterns occur when the slope of the characteristics is, in a sense, commensurate with the space–time microstructure. Field patterns with different spatial shifts do not generally interact, but rather evolve as if they live in separate dimensions, as many dimensions as the number of field patterns. Alternatively one can view a collection as a multi-component potential, with as many components as the number of field patterns. Presumably, if one added a tiny nonlinear term to the wave equation one would then see interactions between these field patterns in the multi-dimensional space that one can consider them to live, or between the different field components of the multi-component potential if one views them that way. As a result of

P
T

-symmetry many of the complex eigenvalues of an appropriately defined transfer matrix have unit norm and hence the corresponding eigenvectors correspond to propagating modes. There are also modes that blow up exponentially with time.
The genetics of mate preferences in hybrids between two young and sympatric Lake Victoria cichlid species
Authors: Svensson Ola , Woodhouse Katie , van Oosterhout Cock , Smith Alan , Turner George F. , Seehausen Ole
Published: February 2017

The genetic architecture of mate preferences is likely to affect significant evolutionary processes, including speciation and hybridization. Here, we investigate laboratory hybrids between a pair of sympatric Lake Victoria cichlid fish species that appear to have recently evolved from a hybrid population between similar predecessor species. The species demonstrate strong assortative mating in the laboratory, associated with divergent male breeding coloration (red dorsum versus blue). We show in a common garden experiment, using DNA-based paternity testing, that the strong female mate preferences among males of the two species are fully recovered in a large fraction of their F2 hybrid generation. Individual hybrid females often demonstrated consistent preferences in multiple mate choice trials (more than or equal to five) across a year or more. This result suggests that female mate preference is influenced by relatively few major genes or genomic regions. These preferences were not changed by experience of a successful spawning event with a male of the non-preferred species in a no-choice single-male trial. We found no evidence for imprinting in the F2 hybrids, although the F1 hybrid females may have been imprinted on their mothers. We discuss this nearly Mendelian inheritance of consistent innate mate preferences in the context of speciation theory.
Mammal body size evolution in North America and Europe over 20 Myr: similar trends generated by different processes
Authors: Huang Shan , Eronen Jussi T. , Janis Christine M. , Saarinen Juha J. , Silvestro Daniele , Fritz Susanne A.
Published: February 2017

Because body size interacts with many fundamental biological properties of a species, body size evolution can be an essential component of the generation and maintenance of biodiversity. Here we investigate how body size evolution can be linked to the clade-specific diversification dynamics in different geographical regions. We analyse an extensive body size dataset of Neogene large herbivores (covering approx. 50% of the 970 species in the orders Artiodactyla and Perissodactyla) in Europe and North America in a Bayesian framework. We reconstruct the temporal patterns of body size in each order on each continent independently, and find significant increases of minimum size in three of the continental assemblages (except European perissodactyls), suggesting an active selection for larger bodies. Assessment of trait-correlated birth-death models indicates that the common trend of body size increase is generated by different processes in different clades and regions. Larger-bodied artiodactyl species on both continents tend to have higher origination rates, and both clades in North America show strong links between large bodies and low extinction rate. Collectively, our results suggest a strong role of species selection and perhaps of higher-taxon sorting in driving body size evolution, and highlight the value of investigating evolutionary processes in a biogeographic context.
Small birds, big effects: the little auk (Alle alle) transforms high Arctic ecosystems
Authors: González-Bergonzoni Ivan , Johansen Kasper L. , Mosbech Anders , Landkildehus Frank , Jeppesen Erik , Davidson Thomas A.
Published: February 2017

In some arctic areas, marine-derived nutrients (MDN) resulting from fish migrations fuel freshwater and terrestrial ecosystems, increasing primary production and biodiversity. Less is known, however, about the role of seabird-MDN in shaping ecosystems. Here, we examine how the most abundant seabird in the North Atlantic, the little auk (Alle alle), alters freshwater and terrestrial ecosystems around the North Water Polynya (NOW) in Greenland. We compare stable isotope ratios (δ15N andδ13C) of freshwater and terrestrial biota, terrestrial vegetation indices and physical–chemical properties, productivity and community structure of fresh waters in catchments with and without little auk colonies. The presence of colonies profoundly alters freshwater and terrestrial ecosystems by providing nutrients and massively enhancing primary production. Based on elevatedδ15N in MDN, we estimate that MDN fuels more than 85% of terrestrial and aquatic biomass in bird influenced systems. Furthermore, by using different proxies of bird impact (colony distance, algalδ15N) it is possible to identify a gradient in ecosystem response to increasing bird impact. Little auk impact acidifies the freshwater systems, reducing taxonomic richness of macroinvertebrates and truncating food webs. These results demonstrate that the little auk acts as an ecosystem engineer, transforming ecosystems across a vast region of Northwest Greenland.
Three-dimensional trajectories and network analyses of group behaviour within chimney swift flocks during approaches to the roost
Authors: Evangelista Dennis J. , Ray Dylan D. , Raja Sathish K. , Hedrick Tyson L.
Published: February 2017

Chimney swifts (
Chaetura pelagica
) are highly manoeuvrable birds notable for roosting overnight in chimneys, in groups of hundreds or thousands of birds, before and during their autumn migration. At dusk, birds gather in large numbers from surrounding areas near a roost site. The whole flock then employs an orderly, but dynamic, circling approach pattern before rapidly entering a small aperture
en masse
. We recorded the three-dimensional trajectories of ≈1 800 individual birds during a 30 min period encompassing flock formation, circling, and landing, and used these trajectories to test several hypotheses relating to flock or group behaviour. Specifically, we investigated whether the swifts use local interaction rules based on topological distance (e.g. the
n
nearest neighbours, regardless of their distance) rather than physical distance (e.g. neighbours within
x
m, regardless of number) to guide interactions, whether the chimney entry zone is more or less cooperative than the surrounding flock, and whether the characteristic subgroup size is constant or varies with flock density. We found that the swift flock is structured around local rules based on physical distance, that subgroup size increases with density, and that there exist regions of the flock that are less cooperative than others, in particular the chimney entry zone.
Female fecundity variation affects reproducibility of experiments on host plant preference and acceptance in a phytophagous insect
Authors: Schäpers Alexander , Petrén Hampus , Wheat Christopher W. , Wiklund Christer , Friberg Magne
Published: February 2017

Reproducibility is a scientific cornerstone. Many recent studies, however, describe a reproducibility crisis and call for assessments of reproducibility across scientific domains. Here, we explore the reproducibility of a classic ecological experiment—that of assessing female host plant preference and acceptance in phytophagous insects, a group in which host specialization is a key driver of diversification. We exposed multiple cohorts of
Pieris napi
butterflies from the same population to traditional host acceptance and preference tests on three Brassicaceae host species. Whereas the host plant rank order was highly reproducible, the propensity to oviposit on low-ranked hosts varied significantly even among cohorts exposed to similar conditions. Much variation could be attributed to among-cohort variation in female fecundity, a trait strongly correlated both to female size and to the size of the nuptial gift a female receives during mating. Small males provide small spermatophores, and in our experiment small females that mated with small males had a disproportionally low propensity to oviposit on low-ranked hosts. Hence, our results provide empirical support to the theoretical prediction that female host utilization is strongly affected by non-genetic, environmental variation, and that such variation can affect the reproducibility of ecological experiments even under seemingly identical conditions.
Repli-seq: genome-wide analysis of replication timing by next-generation sequencing
Authors: Marchal Claire , Sasaki Takayo , Vera Daniel , Wilson Korey , Sima Jiao , Rivera-Mulia Juan Carlos , Trevilla García Claudia , Nogues Coralin , Nafie Ebtesam , Gilbert David M.
Published: February 2017

Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early and late replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and sub-nuclear position. Moreover, RT is regulated during development and is altered in disease. Exploring mechanisms linking RT to other cellular processes in normal and diseased cells will be facilitated by rapid and robust methods with which to measure RT genome wide. Here, we describe a rapid, robust and relatively inexpensive protocol to analyze genome-wide RT by next-generation sequencing (NGS). This protocol yields highly reproducible results across laboratories and platforms. We also provide computational pipelines for analysis, parsing phased genomes using single nucleotide polymorphisms (SNP) for analyzing RT allelic asynchrony, and for direct comparison to Repli-chip data obtained by analyzing nascent DNA by microarrays.
microCT-Based Phenomics in the Zebrafish Skeleton Reveals Virtues of Deep Phenotyping in a Distributed Organ System
Authors: Hur Matthew , Gistelinck Charlotte A. , Huber Philippe , Lee Jane , Thompson Marjorie H. , Monstad-Rios Adrian T. , Watson Claire J. , McMenamin Sarah K. , Willaert Andy , Parichy David M , Coucke Paul , Kwon Ronald Y.
Published: February 2017

Phenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds of measures comprised of morphological and densitometric traits from a large number sites in the axial skeleton of adult zebrafish. We show the potential for vertebral patterns to confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared to analyzing individual vertebrae in isolation. We identify phenotypes associated with human brittle bone disease and thyroid stimulating hormone receptor hyperactivity. Finally, we develop allometric models and show their potential to aid in the discrimination of mutant phenotypes masked by alterations in growth. Our studies demonstrate virtues of deep phenotyping in a spatially distributed organ. Analyzing phenotypic patterns may increase productivity in genetic screens, and could facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.
Individual nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) to determine protein-RNA interactions
Authors: Sibley Christopher R.
Published: February 2017

RNA-binding proteins (RBPs) interact with and determine the fate of many cellular RNA transcripts. In doing so they help direct many essential roles in cellular physiology, whilst their perturbed activity can contribute to disease aetiology. In this chapter we detail a functional genomics approach, termed individual nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP), that can determine the interactions of RBPs with their RNA targets in high throughput and at nucleotide resolution. iCLIP achieves this by exploiting UV-induced covalent crosslinks formed between RBPs and their target RNAs to both purify the RBP-RNA complexes under stringent conditions, and to cause reverse transcription stalling that then identifies the direct crosslink sites in the high throughput sequenced cDNA libraries.
A rareIL2RAhaplotype identifies SNP rs61839660 as causal for autoimmunity
Authors: Rainbow Daniel B. , Pekalski Marcin , Cutler Antony J. , Burren Oliver , Walker Neil , Todd John A. , Wallace Chris , Wicker Linda S.
Published: February 2017

IL2RAis associated with multiple autoimmune diseases including type 1 diabetes (T1D). Higher expression ofIL2RAmRNA and its protein product CD25 in T lymphocytes is associated with a T1D-protective haplotype. Here we show that a rare variation of this haplotype that loses the protective allele at a single SNP, rs61839660, reducesIL2RAexpression and T1D protection, identifying it as the causal factor in disease.
Oestrogenic vascular effects are diminished by ageing
Authors: Nicholson Christopher J. , Sweeney Michèle , Robson Stephen C. , Taggart Michael J.
Published: February 2017

The beneficial role of oestrogen in the vascular system may be due, in part, through reduction of peripheral vascular resistance. The use of oestrogen therapy to prevent cardiovascular disease in post-menopausal women remains contentious. This study investigated the influence of the menopause and ageing on the acute vasodilatory effects of oestrogen inex vivouterine resistance arteries.

Vessels were obtained from young (2.9 ± 0.1 months) and aged (24.2 ± 0.1 and 28.9 ± 0.3 months) female mice and pre-(42.3 ± 0.5 years) and post-menopausal (61.9 ± 0.9 years) women. Ageing was associated with profound structural alterations of murine uterine arteries, including the occurrence of outward hypertrophic remodelling and increased stiffness. Endothelial and smooth muscle function were diminished in uterine (and tail) arteries from aged mice and post-menopausal women. The acute vasodilatory effects of 17β-oestradiol (non-specific oestrogen receptor (ER) agonist), PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) on resistance arteries were attenuated by ageing and the menopause. However, the impairment of oestrogenic relaxation was evident after the occurrence of age-related endothelial dysfunction and diminished distensibility. The data indicate, therefore, that adverse resistance arterial ageing is a dominant factor leading to weakened vasodilatory action of oestrogenic compounds.
Modeling prediction error improves power of transcriptome-wide association studies
Authors: Bhutani Kunal , Sarkar Abhishek , Park Yongjin , Kellis Manolis , Schork Nicholas J.
Published: February 2017

1

Transcriptome-wide association studies (TWAS) test for associations between imputed gene expression levels and phenotypes in GWAS cohorts using models of transcriptional regulation learned from reference transcriptomes. However, current methods for TWAS only use point estimates of imputed expression and ignore uncertainty in the prediction. We develop a novel two-stage Bayesian regression method which incorporates uncertainty in imputed gene expression and achieves higher power to detect TWAS genes than existing TWAS methods as well as standard methods based on missing value and measurement error theory. We apply our method to GTEx whole blood transcriptomes and GWAS cohorts for seven diseases from the Wellcome Trust Case Control Consortium and find 45 TWAS genes, of which 17 do not overlap previously reported case-control GWAS or differential expression associations. Surprisingly, we replicate only 2 of 40 previously reported TWAS genes after accounting for uncertainty in the prediction.
Cardiac events after macrolides or fluoroquinolones in patients hospitalized for community-acquired pneumonia: post-hoc analysis of a cluster-randomized trial
Authors: Postma D.F. , Spitoni C. , van Werkhoven C.H. , van Elden L.J.R. , Oosterheert J.J. , Bonten M.J.M.
Published: February 2017

Background

Guidelines recommend macrolides and fluoroquinolones in patients hospitalized with community-acquired pneumonia (CAP), but their use has been associated with cardiac events.

Objective

To quantify associations between macrolide and fluoroquinolone use and cardiac events in patients hospitalized with CAP in non-ICU wards.

Design

Post-hoc analysis of a cluster-randomized trial

Setting

Six hospitals in the Netherlands

Patients

CAP patients admitted to non-ICU wards and without a cardiac event on admission

Measurements

Cause-specific hazard ratio’s (HR’s) were calculated for effects of time-dependent macrolide and fluoroquinolone exposure on cardiac events, defined as occurrence of new or worsening heart failure, arrhythmia, or myocardial ischemia during hospitalization.

Results

Cardiac events occurred in 146 (6.9%) of 2,107 patients and included episodes of heart failure (n=101, 4.8%), arrhythmia (n=53, 2.5%), and myocardial ischemia (n=14, 0.7%). Cardiac events occurred in 11 of 207 (5.3%), 18 of 250 (7.2%), and 31 of 277 (11.2%) patients exposed to azithromycin, clarithromycin, and erythromycin for at least one day, respectively, and in 9 of 234 (3.8%), 5 of 194 (2.6%), and 23 of 566 (4.1%) patients exposed to ciprofloxacin, levofloxacin, and moxifloxacin, respectively. Hazard ratios for any cardiac event, adjusted for confounding, were 0.89 (95% confidence interval (CI) 0.48 to 1.67), 1.06 (95% CI 0.61 to 1.83) and 1.68 (95% CI 1.07 to 2.62) for azithromycin, clarithromycin, and erythromycin, respectively, and adjusted hazard ratios were 0.86 (95% CI 0.47 to 1.57), 0.42 (95% CI 0.18 to 0.96) and 0.62 (95% CI 0.39 to 0.99) for ciprofloxacin, levofloxacin, and moxifloxacin, respectively. Erythromycin was associated with an adjusted hazard ratio of 2.08 (95% CI 1.25 to 3.46) for heart failure.

Limitations

Possibility of confounding by indication and observational bias

Conclusions

Among patients with CAP hospitalized to non-ICU wards, erythromycin use was associated with a 68% increased risk of hospital-acquired cardiac events, mainly heart failure. Levofloxacin and moxifloxacin were associated with a lower risk of heart failure.

Registration

The original trial was registered under ClinicalTrials.gov IdentifierNCT01660204

Funding Source

The Netherlands Organization for Health Research and Development (ZONmw, Health care efficiency research, project id: 171202002).
Neutrophil elastase inhibitor sivelestat ameliorates gefitinib-naphthalene-induced acute pneumonitis in mice
Authors: Mikumo Hironori , Yanagihara Toyoshi , Hamada Naoki , Harada Eiji , Ogata-Suetsugu Saiko , Ikeda-Harada Chika , Arimura-Omori Masako , Suziki Kunihiro , Yokoyama Tetsuya , Nakanishi Yoichi
Published: February 2017

Background and objective

Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective therapeutic agent for non-small cell lung cancer with EGFR mutations. It can cause severe acute pneumonitis in some patients. We previously demonstrated that mice with naphthalene-induced airway epithelial injury developed severe gefitinib-induced pneumonitis and that neutrophils played important roles in the development of the disease. This study aimed to investigate the effects of the neutrophil elastase inhibitor sivelestat on gefitinib-induced pneumonitis in mice.

Methods

C57BL/6J mice received naphthalene (200 mg/kg) intraperitoneally on day 0. Gefitinib (250 or 300 mg/kg) was orally administered to mice from day −1 until day 13. Sivelestat (150 mg/kg) was administered intraperitoneally from day 1 until day 13. Bronchoalveolar lavage fluid (BALF) and lung tissues were sampled on day 14.

Results

Sivelestat treatment significantly reduced the protein level, neutrophil count, neutrophil elastase activity in BALF, and severity of histopathologic findings on day 14 for mice administered with 250 mg/kg of gefitinib. Moreover, sivelestat treatment significantly improved the survival of mice administered with 300 mg/kg of gefitinib. Conclusions: These results indicate that sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.

Summary statement

Neutrophil elastase inhibitor sivelestat is a promising therapeutic agent for severe acute pneumonitis caused by gefitinib.
The regulation of tDNA transcription during the directed differentiation of stem cells
Authors: Woolnough J. L , Schneider D. A. , Giles K.E.
Published: February 2017

The human genome consists of 625 tDNA copies that encode 51 distinct isoacceptor families. Recent studies demonstrated that changes in chromatin structure during cellular differentiation can alter the expression of these tDNA. However, the mechanism by which tDNA can be differentially regulated remains unclear. Here we used the directed differentiation of pluripotent human embryonic stem cells (hESCs) towards the endoderm lineage as a model system to study the developmental regulation of individual tDNA. We demonstrated a significant change in the Pol III occupancy at 49 tDNA (22 reduced and 27 increased). The regulation of tDNA did not correlate with changes in TFIIIB or TFIIIC occupancy, H3K4me3, or H3K27me3 levels. However, tDNA that had an increase in Pol III binding were preferentially found within strong CTCF-COHESIN chromatin loops. The knockdown of either Ctcf or Rad21 in mouse tail tip fibroblasts had similar effects on changes in tRNA levels. We identified 7 isoacceptors that were differentially expressed during the directed differentiation of hESCs. The open reading frames of the ribosomal protein genes, which are translationally repressed during hESC differentiation, are enriched for codons that are decoded by these downregulated isoacceptors. Thus, translation efficiency during cellular differentiation may be affected by changes in tDNA regulation.
A generator of morphological clones for plant species
Authors: Potapov Ilya , Järvenpää Marko , Åkerblom Markku , Raumonen Pasi , Kaasalainen Mikko
Published: February 2017

Detailed and realistic tree form generators have numerous applications in ecology and forestry. Here, we present an algorithm for generating morphological tree “clones” based on the detailed reconstruction of the laser scanning data, statistical measure of similarity, and a plant growth algorithm with simple stochastic rules. The algorithm is designed to produce tree forms, i.e. morphological clones, similar as a whole (coarse-grain scale), but varying in minute details of organization (fine-grain scale). We present a general procedure for obtaining these morphological clones. Although we opted for certain choices in our algorithm, its various parts may vary depending on the application. Namely, we have shown that specific multi-purpose procedural stochastic growth model can be algorithmically adjusted to produce the morphological clones replicated from the target experimentally measured tree. For this, we have developed a statistical measure of similarity (structural distance) between any given pair of trees, which allows for the comprehensive comparing of the tree morphologies in question by means of empirical distributions describing geometrical and topological features of a tree. Our algorithm can be used in variety of applications and contexts for exploration of the morphological potential of the growth models, arising in all sectors of plant science research.

Summary Statement

We present an algorithmic framework, based on the Bayesian inference, for generating morphological tree clones using a combination of stochastic growth models and experimentally derived tree structures.
Unmet Needs for Analyzing Biological Big Data: A Survey of 704 NSF Principal Investigators
Authors: Barone Lindsay , Williams Jason , Micklos David
Published: February 2017

In a 2016 survey of 704 National Science Foundation (NSF) Biological Sciences Directorate principal investigators (BIO PIs), nearly 90% indicated they are currently or will soon be analyzing large data sets. BIO PIs considered a range of computational needs important to their work—including high performance computing (HPC), bioinformatics support, multi-step workflows, updated analysis software, and the ability to store, share, and publish data. Previous studies in the United States and Canada emphasized infrastructure needs. However, BIO PIs said the most pressing unmet needs are training in data integration, data management, and scaling analyses for HPC—acknowledging that data science skills will be required to build a deeper understanding of life. This portends a growing data knowledge gap in biology and challenges institutions and funding agencies to redouble their support for computational training in biology.
mixOmics: an R package for ‘omics feature selection and multiple data integration
Authors: Rohart Florian , Gautier Benoît , Singh Amrit , Lê Cao Kim-Anh
Published: February 2017

The advent of high throughput technologies has led to a wealth of publicly available ‘omics data coming from different sources, such as transcriptomics, proteomics, metabolomics. Combining such large-scale biological data sets can lead to the discovery of important biological insights, provided that relevant information can be extracted in a holistic manner. Current statistical approaches have been focusing on identifying small subsets of molecules (a ‘molecular signature’) to explain or predict biological conditions, but mainly for a single type of ‘omics. In addition, commonly used methods are univariate and consider each biological feature independently.

We introducemixOmics, an R package dedicated to the multivariate analysis of biological data sets with a specific focus on data exploration, dimension reduction and visualisation. By adopting a system biology approach, the toolkit provides a wide range of methods that statistically integrate several data sets at once to probe relationships between heterogeneous ‘omics data sets. Our recent methods extend Projection to Latent Structure (PLS) models for discriminant analysis, for data integration across multiple ‘omics data or across independent studies, and for the identification of molecular signatures. We illustrate our latestmixOmicsintegrative frameworks for the multivariate analyses of ‘omics data available from the package.
Evaluation of anticancer and anti-mitotic properties of quinazoline and quinazolino-benzothiadiazine derivatives
Authors: Shaik Thoukhir B. , Malik M. Shaheer , Seddigid Zaki S. , Routhu Sunitha R , Kamal Ahmed
Published: February 2017

Cancer is one of the major health and social-economic problems despite considerable progress in its early diagnosis and treatment. Owing to the emergence and increase of multi drug resistance to various conventional drugs, and the continuing importance on health-care expenditure, many researchers have focused to develop novel and effective anticancer compounds. In the present study, a series of in-house synthesized quinazoline and quinazolino-benzothiadiazine derivatives were investigated for their anticancer efficacy against a panel of five cancer (DU145, MCF7, HepG2, SKOV3 and MDA-MB-231) and one normal (MRC5) cell lines. Among all the tested compounds, fifteen of them exhibited promising growth-inhibitory effect (0.15 - 5.0 μM) and induced cell cycle arrest in G2/M phase. In addition, the selected compounds inhibited the microtubule assembly; altered mitochondrial membrane potential and enhanced the levels of caspase-9 in MCF-7 cells. Furthermore, the active compound with combination of drugs showed synergistic effect at lower concentrations and the drug uptake was mediated through clathrin mediated endocytic pathway. Our results indicated that quinazoline and quinazolino-benzothiadiazine conjugates could serve as potential leads in the development of personalized cancer therapeutics.

The present study describes the exploration of small molecules based on heterocyclic scaffolds for tubulin target based development of anticancer agents.
Inferring demographic history using two-locus statistics
Authors: Ragsdale Aaron P. , Gutenkunst Ryan N.
Published: February 2017

Population demographic history may be learned from contemporary genetic variation data. Methods based on aggregating the statistics of many single loci into an allele frequency spectrum (AFS) have proven powerful, but such methods ignore potentially informative patterns of linkage disequilibrium (LD) between neighboring loci. To leverage such patterns, we developed a composite-likelihood framework for inferring demographic history from aggregated statistics of pairs of loci. Using this framework, we show that two-locus statistics are indeed more sensitive to demographic history than single-locus statistics such as the AFS. In particular, two-locus statistics escape the notorious confounding of depth and duration of a bottleneck, and they provide a means to estimate effective population size based on the recombination rather than mutation rate. We applied our approach to a Zambian population ofDrosophila melanogaster. Notably, using both single– and two-locus statistics, we found substantially lower estimates of effective population size than previous works. Together, our results demonstrate the broad potential for two-locus statistics to enable powerful population genetic inference.
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
Authors: Gupte Rebecca , Liu Ziying , Kraus W. Lee
Published: February 2017

The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates. Supporting these advances is a host of methodological approaches from chemical biology, proteomics, genomics, cell biology, and genetics that have propelled new discoveries in the field. New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer. These studies have begun to reveal the promising ways in which PARPs may be targeted therapeutically for the treatment of disease. In this review, we discuss these topics and relate them to the future directions of the field.
Consumers’ switching motivations and intention in the case of bank mergers: a cross-cultural study
Authors: Farah Maya F.
Published: February 2017

Purpose

The purpose of this paper is to analyze consumer switching behavior, which in the retail banking sector is of outmost importance, particularly during financial crises and in their ensuing consolidation pressures. Moreover, research indicates that cultural values play a critical role in determining a customer’s likelihood to switch the service provider. The theory of planned behavior offers a comprehensive theoretical framework for an understanding of this behavior. Its application implies that switching is influenced not only by one’s attitudes toward changing banking service providers, but also by the merger situation at hand, the influence of significant others, and whether the switching decision is under one’s behavioral control.

Design/methodology/approach

This paper scrutinizes the merger between Lloyds TSB and Halifax Bank of Scotland in the Spanish market, with a focus on the differences between British and Spanish consumers. In all, 30 face-to-face exploratory interviews were conducted with a sample of customers from both nationalities selected through a purposive sampling technique.

Findings

The results indicate that the switching behavior within the banking sector is largely determined by one’s cultural background. While individualistic consumers are more prone to switch banks, collectivist consumers are highly risk averse and are unwilling to lose the established relations with a bank’s personnel. These particular characteristics make them unlikely to switch banks irrespective of a merger and its related consequences.

Originality/value

This paper examines the impact of cross-cultural differences on consumer switching motivations and intentions in the particular case of a real-life banks’ merger.
Exploring the antecedents of loyalty in the context of multi-channel banking
Authors: Bapat Dhananjay
Published: February 2017

Purpose

The purpose of this paper is to assess the antecedent of satisfaction and loyalty in the context of a multi-channel banking environment. Multi-channel banking involves both branch and electronic banking channels through which the customers interact with the bank.

Design/methodology/approach

The study involved a customer survey of 229 respondents, which used a convenience sampling approach through intercepts and interviews held at bank branches. A structured questionnaire was used, and data were analyzed using structural equation modeling.

Findings

While examining factors such as perceived ease of use, branch service quality evaluation, satisfaction, and loyalty, it is observed, using structural equation modeling, that perceived ease of use and branch service quality are antecedents to satisfaction and satisfaction positively affects the loyalty.

Originality/value

Although it is realized that digital banking will positively influence loyalty, the role of branch service quality cannot be ignored. The role played by the ease of use is higher than branch service quality evaluations.
Local governance, corruption, and public service quality: evidence from a national survey in Vietnam
Authors: Nguyen Thang V. , Bach Thang N. , Le Thanh Q. , Le Canh Q.
Published: February 2017

Purpose

The purpose of this paper is to examine whether higher levels of transparency, accountability, and participation have a statistically significant association with corruption, and whether corruption is highly correlated with lower public service quality in the context of Vietnam’s transition economy.

Design/methodology/approach

Using individual-level survey data from Vietnam Provincial Governance and Public Administration Performance Index, the research employs an ordered probit model to test whether greater transparency, accountability, and participation is associated with lower levels of corruption. Moreover, district-level data are used to test the relationship between corruption and quality of public services particularly in healthcare and primary education.

Findings

Results show that a higher level of transparency, participation, and accountability is associated with a lower level of corruption, and that corruption is negatively associated with public service quality.

Research limitations/implications

The use of cross-sectional data does not allow the establishment of causal relationships among variables.

Practical implications

The research suggests that fostering accountability to citizens and non-state sectors and promotion of genuine participation from these actors are critical for the future anti-corruption agenda.

Originality/value

In developing countries, whether corruption enhances efficiency of service provision is highly debatable. This research contributes to this debate by suggesting that corruption significantly decreases the quality of public service, and that improving local governance helps reduce corruption.
Use of methodology of “underdevelopment whirlpools” with analysis of problems and perspectives of economic growth in Asian countries
Authors: Popkova Elena G.
Published: February 2017

Purpose

This paper aims to solve the problem of reduction of disproportions of the global economy and overcoming the underrun of Asian countries from Europe. The author offers a hypothesis that the reason of such underrun is the existence of “underdevelopment whirlpools” in Asian countries. The purpose of this paper is to verify this hypothesis and to determine problems and perspectives of economic growth in Asian countries.

Design/methodology/approach

As tools for verification of this hypothesis, the author uses the methodology of analysis of “underdevelopment whirlpools”, aimed at the determination of problems and perspectives of economic growth in countries of Asia; methodology of strengths, weaknesses, opportunities, threats (SWOT) analysis for determination of key factors of economic growth in countries of Asia; instrumentarium of theory of games for the evaluation of effectiveness of the use of various strategies of economic development of Asian countries.

Findings

As a result of the research, the author proves the offered hypothesis and offers – as a solution to the problem of the existence of “underdevelopment whirlpools” in Asian countries – the use of new models of economic development in view of specifics of Asian countries, aimed at transition to new quality of economic growth.

Research limitations/implications

A certain limitation of the conducted research is primarily theoretical substantiation of the necessity for overcoming the “underdevelopment whirlpools” in Asian countries and framework character of the offered recommendations. Therefore, during further research in this sphere, it is expedient to focus the efforts on the development of the system of practical measures for achievement of this purpose.

Practical implications

Practical significance of the author’s conclusions and recommendations consists in the possibility for their use during the development of state economic policy in Asian countries in the interests of overcoming the “underdevelopment whirlpools” and transition to the new quality of economic growth.

Originality/value

At the time of preparation of this paper, the concept “underdevelopment whirlpool” is rather new, and application of methodology of their calculation by the example of Asian countries in the context of analysis of problems and perspectives of economic grows constitutes the basis for originality, scientific value and novelty of the performed research.