bluuebunny/crossref_metadata_2025 huggingface dataset:
Substructured population growth in the Ashkenazi Jews inferred with Approximate Bayesian Computation
Authors: Gladstein Ariella L. , Hammer Michael F.
Published: November 2018

The Ashkenazi Jews (AJ) are a population isolate that have resided in Central Europe since at least the 10th century and share ancestry with both European and Middle Eastern populations. Between the 11th and 16th centuries, AJ expanded eastward leading to two culturally distinct communities, one in central Europe and one in eastern Europe. Our aim was to determine if there are genetically distinct AJ subpopulations that reflect the cultural groups, and if so, what demographic events contributed to the population differentiation. We used Approximate Bayesian Computation (ABC) to choose among models of AJ history and infer demographic parameter values, including divergence times, effective population size, and gene flow. For the ABC analysis we used allele frequency spectrum and identical by descent based statistics to capture information on a wide timescale. We also mitigated the effects of ascertainment bias when performing ABC on SNP array data by jointly modeling and inferring the SNP discovery. We found that the most likely model was population differentiation between the Eastern and Western AJ ~400 years ago. The differentiation between the Eastern and Western AJ could be attributed to more extreme population growth in the Eastern AJ (0.25 per generation) than the Western AJ (0.069 per generation).
Phylogenomics, biogeography, and evolution in the American palm genusBrahea
Authors: Barrett Craig F. , Sinn Brandon T. , King Loren T. , Medina Jesus C. , Bacon Christine D. , Lahmeyer Sean C. , Hodel Donald R.
Published: November 2018

Background and Aims

Slow rates of molecular evolution at low taxonomic levels hamper studies of relationships among species, and subsequent biogeographic and evolutionary analyses. An example is the genusBrahea, which is among the most poorly understood lineages of American palms and is characterized by a wide variety of growth forms and intermediate morphological features.

Methods

We generated approximately 400 kb of genome-scale data from all three genomes for the 11 currently described species ofBraheato infer phylogenetic relationships, reconstruct ancestral growth form, estimate ancestral geographic ranges, and test for niche equivalency among closely related species with geographic overlap.

Key Results

Relationships receive strong support, and conform to previous subgeneric assignments, except for placement of the dwarf speciesB. mooreiwithin subgenusErythea.Our robust phylogenetic hypothesis reveals trends in growth form including an overall increase in height in theB. armataclade, and independent evolution of dwarf forms from taller ancestors in theB. pimoandB. dulcisclades. Ancestral range estimation reveals roles of dispersal (e.g.B. edulison Guadalupe Island) and sympatric speciation in some cases (e.g. in theB. armataclade), but is equivocal in others (e.g. in theB. pimo clade). We find evidence of niche non-equivalency among species within theB. armataclade in northwestern Mexico, and some evidence of niche non-equivalency betweenB. berlandieriandB. dulcis, the former of which is synonymized underB. dulcis.

Conclusions

Our findings have implications for the complex biogeographic history in Central America and Mexico, suggesting that sympatric speciation and dispersal are the predominant processes of species diversification. Future studies should include population-level sampling across the genus, along with morphological and ecological information, to assess distinctness among species and, particularly, levels of gene flow, in an integrative fashion.
Core components of endosomal mRNA transport are evolutionarily conserved in fungi
Authors: Müller Jessica , Pohlmann Thomas , Feldbrügge Michael
Published: November 2018

Active movement of mRNAs by sophisticated transport machineries determines precise spatiotemporal expression of encoded proteins. A prominent example discovered in fungi is microtubule-dependent transport via endosomes. This mode of transport was thought to be only operational in the basidiomycete Ustilago maydis. Here, we report that distinct core components are evolutionarily conserved in fungal species of distantly related phyla like Mucoromycota. Interestingly, orthologues of the key RNA-binding protein Rrm4 from the higher basidiomycete Coprinopsis cinerea and the mucoromycete Rhizophagus irregularis shuttle on endosomes in hyphae of U. maydis. Thus, endosomal mRNA transport appears to be more wide-spread than initially anticipated.

Highlights

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Core transport components Upa1 and Rrm4 are conserved in different fungal phyla

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Components of the Rrm4 machinery were most likely secondarily lost in ascomycetes

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Upa1 from Microbotryum lychnidis-dioicae is functional in U. maydis

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Rrm4 orthologues from Basidio- and Mucoromycota shuttle in hyphae of U. maydis
Towards feedback control of the cell-cycle across a population of yeast cells
Authors: Perrino Giansimone , Fiore Davide , Napolitano Sara , di Bernardo Mario , di Bernardo Diego
Published: November 2018

Cells are defined by their unique ability to selfreplicate through cell division. This periodic process is known as the cell-cycle and it happens with a defined period in each cell. The budding yeast divides asymmetrically with a mother cell generating multiple daughter cells. Within the cell population each cell divides with the same period but asynchronously. Here, we investigate the problem of synchronising the cell-cycle across a population of yeast cells through a microfluidics-based feedback control platform. We propose a theoretical and experimental approach for cell-cycle control by considering a yeast strain that can be forced to start the cell-cycle by changing growth medium. The duration of the cell-cycle is strictly linked to the cell volume growth, hence a hard constraint in the controller design is to prevent excessive volume growth. We experimentally characterised the yeast strain and derived a simplified phase-oscillator model of the cell-cycle. We then designed and implemented three impulsive control strategies to achieve maximal synchronisation across the population and assessed their control performance by numerical simulations. The first two controllers are based on event-triggered strategies, while the third uses a model predictive control (MPC) algorithm to select the sequence of control impulses while satisfying built-in constraints on volume growth. We compared the three strategies by computing two cost functions: one quantifying the level of synchronisation across the cell population and the other volume growth during the process. We demonstrated that the proposed control approaches can effectively achieve an acceptable trade-off between two conflicting control objectives: (i) obtaining maximal synchronisation of the cell cycle across the population while (ii) minimizing volume growth. The results can be used to implement effective strategies to unfold the biological mechanisms controlling cell cycle and volume growth in yeast cells.
Inter-generational Consequences for Growing C.elegans in Liquid
Authors: Lev Itamar , Bril Roberta , Liu Yunan , Ceré Lucila Inés , Rechavi Oded
Published: November 2018

In recent years, studies in Caenorhabditis elegans nematodes have shown that different stresses can generate multigenerational changes. Here we show that worms that grow in liquid media, and also their plate-grown progeny, are different from worms whose ancestors were grown on plates. It has been suggested that C.elegans might encounter liquid environments in nature, although actual observations in the wild are few and far between. In contrast, in the lab, growing worms in liquid is commonplace, and often used as an alternative to growing worms on agar plates, to control the composition of the worms’ diet, to starve (and synchronize) worms, or to grow large populations for biochemical assays. We found that plate-grown descendants of M9 liquid media-grown worms were longer than control worms, and the heritable effects were apparent already very early in development. We tested for the involvement of different known epigenetic inheritance mechanisms, but could not find a single mutant in which these intergenerational effects are canceled. While we found that growing in liquid always leads to inter-generational changes in the worms’ size, trans-generational effects were found to be variable, and in some cases the effects were gone after 1 -2 generations. These results demonstrate that standard cultivation conditions in early life can dramatically change the worms’ physiology in adulthood, and can also affect the next generations.
FishResp: R Package and GUI Application for Analysis of Aquatic Respirometry Data
Authors: Morozov Sergey , McCairns R. J. Scott , Merilä Juha
Published: November 2018

Intermittent-flow respirometry is widely used to measure oxygen uptake rates and subsequently estimate aerobic metabolic rates of aquatic animals. However, the lack of a standard quality-control software to detect technical problems represents a potential impediment to comparisons across studies. Here, we introduce ‘FishResp’, a versatile R package and its graphical implementation for quality-control and filtering of raw respirometry data. Our goal is to provide a straightforward, cross-platform and free software to help improve the quality and comparability of metabolic rate estimates for reducing methodological fragmentation in the field of aquatic respirometry. FishResp accepts data from various respirometry systems, allows users to detect potential mechanical problems which can occur during oxygen uptake measurements (e.g. chamber leaking, poor water circulation), and offers six options to correct raw data for microbial oxygen consumption. The software performs filtering of raw data based on user criteria, and produces accurate and unbiased estimates of absolute and mass-specific metabolic rates. Using data from three-spined sticklebacks (Gasterosteus aculeatus) and Trinidadian guppies (Poecilia reticulata), we demonstrate the virtues of FishResp, highlighting the importance of detecting mechanical problems and correcting measurements for background respiration.

Lay summary

FishResp is a user-friendly tool for calculating oxygen uptake of aquatic organisms. The aim of the software is to improve the quality of metabolic rate estimates based on a straightforward pipeline: background respiration correction, detection of mechanical problems, conduction of QC tests, and filtration based on user-defined criteria.
Predicting trait regulators by identifying co-localization of DNA binding and GWAS variants in regulatory regions
Authors: Quon Gerald , Feizi Soheil , Marbach Daniel , Claussnitzer Melina , Kellis Manolis
Published: November 2018

Genomic regions associated with complex traits and diseases are primarily located in non-coding regions of the genome and have unknown mechanism of action. A critical step to understanding the genetics of complex traits is to fine-map each associated locus; that is, to find the causal variant(s) that underlie genetic associations with a trait. Fine-mapping approaches are currently focused on identifying genomic annotations, such as transcription factor binding sites, which are enriched in direct overlap with candidate causal variants. We introduce CONVERGE, the first computational tool to search for co-localization of GWAS causal variants with transcription factor binding sites in the same regulatory regions, without requiring direct overlap. As a proof of principle, we demonstrate that CONVERGE is able to identify five novel regulators of type 2 diabetes which subsequently validated in knockdown experiments in pancreatic beta cells, while existing fine-mapping methods were unable to find any statistically significant regulators. CONVERGE also recovers more established regulators for total cholesterol compared to other fine-mapping methods. CONVERGE is therefore unique and complementary to existing fine-mapping methods and is useful for exploring the regulatory architecture of complex traits.
Gradients of connectivity distance in the cerebral cortex of the macaque monkey
Authors: Oligschläger Sabine , Xu Ting , Baczkowski Blazej M. , Falkiewicz Marcel , Falchier Arnaud , Linn Gary , Margulies Daniel S.
Published: November 2018

Cortical connectivity conforms to a series of organizing principles that are common across species. Spatial proximity, similar cortical type, and similar connectional profile all constitute factors for determining the connectivity between cortical regions. We previously demonstrated another principle of connectivity that is closely related to the spatial layout of the cerebral cortex. Using functional connectivity from resting-state fMRI in the human cortex, we found that the further a region is located from primary cortex, the more distant are its functional connections with other areas of the cortex. However, it remains unknown whether this relationship between cortical layout and connectivity extends to other primate species. Here, we investigated this relationship using both resting-state functional connectivity as well as gold-standard tract-tracing connectivity in the macaque monkey cortex. For both measures of connectivity, we found a gradient of connectivity distance extending between primary and frontoparietal regions. As in the human cortex, the further a region is located from primary areas, the stronger its connections to distant portions of the cortex, with connectivity distance highest in frontal and parietal regions. The similarity between the human and macaque findings provide evidence for a phylogenetically conserved relationship between the spatial layout of cortical areas and connectivity.
Lineage tracing on transcriptional landscapes links state to fate during differentiation
Authors: Weinreb Caleb , Rodriguez-Fraticelli Alejo , Camargo Fernando , Klein Allon M
Published: November 2018

A challenge in stem cell biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Though the development of single cell assays allows for the capture of progenitor cell states in great detail, these assays cannot definitively link cell states to their long-term fate. Here, we use expressed DNA barcodes to clonally trace single cell transcriptomes dynamically during differentiation and apply this approach to the study of hematopoiesis. Our analysis identifies functional boundaries of cell potential early in the hematopoietic hierarchy and locates them on a continuous transcriptional landscape. We reconstruct a developmental hierarchy showing separate ontogenies for granulocytic subtypes and two routes to monocyte differentiation that leave a persistent imprint on mature cells. Finally, we use our approach to benchmark methods of dynamic inference from single-cell snapshots, and provide evidence of strong early fate biases dependent on cellular properties hidden from single-cell RNA sequencing.
An atlas of polygenic risk score associations to highlight putative causal relationships across the human phenome
Authors: Richardson Tom G. , Harrison Sean , Hemani Gibran , Smith George Davey
Published: November 2018

The age of large-scale genome-wide association studies (GWAS) has provided us with an unprecedented opportunity to evaluate the genetic liability of complex disease using polygenic risk scores (PRS). In this study, we have analysed 162 PRS (P<5×l005) derived from GWAS and 551 heritable traits from the UK Biobank study (N=334,398). Findings can be investigated using a web application (http://mrcieu.mrsoftware.org/PRS_atlas/), which we envisage will help uncover both known and novel mechanisms which contribute towards disease susceptibility.

To demonstrate this, we have investigated the results from a phenome-wide evaluation of schizophrenia genetic liability. Amongst findings were inverse associations with measures of cognitive function which extensive follow-up analyses using Mendelian randomization (MR) provided evidence of a causal relationship. We have also investigated the effect of multiple risk factors on disease using mediation and multivariable MR frameworks. Our atlas provides a resource for future endeavours seeking to unravel the causal determinants of complex disease.
A simple method to co-purify genomic DNA, RNA, and proteins for functional studies
Authors: Jiang Jian , Ma Junfei , Liu Bin , Wang Ying
Published: November 2018

Understanding the regulation of gene expression, from the epigenetic modifications on genomes to posttranscriptional and translational controls, are critical for elucidating molecular mechanisms underlying distinct phenotypes in biology. With the rapid development of Multi-Omics analyses, it is desirable to minimize sample variations by using DNA, RNA, and proteins co-purified from the same samples. Currently, most of the co-purification protocols rely on Tri Reagent (Trizol as a common representative) and require protein precipitation and dissolving steps, which render difficulties in experimental handling and high-throughput analyses. Here, we established a simple and robust method to minimize the precipitation steps and yield ready-to-use RNA and protein in solutions. This method can be applied to samples in small quantity, such as protoplasts. We demonstrated that the protoplast system equipped with this method may facilitate studies on viroid biogenesis. Given the ease and the robustness of this new method, it will have broad applications for plant research and other disciplines in molecular biology.
Discover Stable Expression Hot Spot in Genome of Chinese Hamster Ovary Cells Using Lentivirus based Random Integration Method
Authors: Zhou Songtao , Ding Xuefeng , Yang Lei , Chen Yun , Gong Xiaohai , Jin Jian , Li Huazhong
Published: November 2018

Traditional construction method for stable expression cell line was mainly achieved by using random integration method. However, target gene might be integrated into heterochromatin region or unstable region of chromatin by using this method, and thus required multiple rounds of selection to obtain desirable expression cell lines with stable expression level of target proteins. Rational cell line construction method can overcome this shortcoming by integrating transgenes into stable hot spot within genome specifically. Thus, to discover novel effective hot spot would be critical for this new cell line construction method. Here we reported one practical method to discover new stable hot spot by using lentivirus infection and random integration. One such hot spot located at NW_006880285.1 was thoroughly investigated in this article. The expression stability of this hot spot was verified by detecting Zsgreen1 reporter gene expression for over 50 passages. When cells were adapted to suspension culture, they successfully kept expressing Zsgreen1 reporter gene. In addition, this suspension cell line could keep expressing reporter gene stably for another 50 passages. In summary, this research offered an easy new method for researchers to identify their own stable hot spots within CHO genome, and would contribute to the development of site-specific integration study in the future.
Cryo-EM structure of the receptor-activated TRPC5 ion channel at 2.9 angstrom resolution
Authors: Duan Jingjing , Li Jian , Chen Gui-Lan , Zeng Bo , Xie Kechen , Peng Xiaogang , Zhou Wei , Zhong Jianing , Zhang Yixing , Xu Jie , Xue Changhu , Zhu Lan , Liu Wei , Tian Xiao-Li , Wang Jianbin , Clapham David E. , Li Zongli , Zhang Jin
Published: November 2018

The transient receptor potential canonical subfamily member 5 (TRPC5) is a non-selective calcium-permeant cation channel. As a depolarizing channel, its function is studied in the central nervous system and kidney. TRPC5 forms heteromultimers with TRPC1, but also forms homomultimers. It can be activated by reducing agents through reduction of the extracellular disulfide bond. Here we present the 2.9 Å resolution electron cryo-microscopy (cryo-EM) structure of TRPC5. The structure of TRPC5 in its apo state is partially open, which may be related to the weak activation of TRPC5 in response to extracellular pH. We also report the conserved negatively charged residues of the cation binding site located in the hydrophilic pocket between S2 and S3. Comparison of the TRPC5 structure to previously determined structures of other TRPC and TRP channels reveals differences in the extracellular pore domain and in the length of the S3 helix. Together, these results shed light on the structural features that contribute to the specific activation mechanism of the receptor-activated TRPC5.
ImmuneRegulation: A web-based tool for identifying human immune regulatory elements
Authors: Kalayci Selim , Selvan Myvizhi Esai , Ramos Irene , Cotsapas Chris , Montgomery Ruth R. , Poland Gregory , Pulendran Bali , Tsang John , Klein Robert J. , Gümüş Zeynep H.
Published: November 2018

Humans can vary considerably in their healthy immune phenotypes and in their immune responses to various stimuli. We have developed an interactive web-based tool, ImmuneRegulation, to enable discovery of human regulatory elements that drive some of the phenotypic differences observed in gene expression profiles. ImmuneRegulation currently provides the largest centrally integrated resource available in the literature on transcriptome regulation in whole blood and blood cell types, including genotype data from 23,040 individuals, with associated gene expression data from 30,562 experiments, that provide genetic variant-gene expression associations on ∼200 million eQTLs. In addition, it includes 14 million transcription factor (TF) binding region hits extracted from 1945 TF ChIP-seq peaks and the latest GWAS catalog of 67,230 published SNP-trait associations. Users can interactively explore ImmuneRegulation to visualize and discover associations between their gene(s) of interest and their regulators (genetic variants or transcription factors) across multiple cohorts and studies. These regulators can explain cohort or cell type dependent gene expression variations and may be critical in selecting the ideal cohorts or cell types for follow-up studies. Overall, ImmuneRegulation aims to contribute to our understanding of the effects of eQTLs and TFs on heterogeneous transcriptional responses reported in studies on the blood; in the development of molecular signatures of immune response; and facilitate their future application in patient management. ImmuneRegulation is freely available at http://icahn.mssm.edu/immuneregulation.
Matrix linear models for high-throughput chemical genetic screens
Authors: Liang Jane W. , Nichols Robert J. , Sen Śaunak
Published: November 2018

We develop a flexible and computationally efficient approach for analysing high throughput chemical genetic screens. In such screens, a library of genetic mutants is phenotyped in a large number of stresses. The goal is to detect interactions between genes and stresses. Typically, this is achieved by grouping the mutants and stresses into categories, and performing modified t-tests for each combination. This approach does not have a natural extension if mutants or stresses have quantitative or non-overlapping annotations (eg. if conditions have doses, or a mutant falls into more than one category simultaneously). We develop a matrix linear model framework that allows us to model relationships between mutants and conditions in a simple, yet flexible multivariate framework. It encodes both categorical and continuous relationships to enhance detection of associations. To handle large datasets, we develop a fast estimation approach that takes advantage of the structure of matrix linear models. We evaluate our method’s performance in simulations and in an E. coli chemical genetic screen, comparing it with an existing univariate approach based on modified t-tests. We show that matrix linear models perform slightly better than the univariate approach when mutants and conditions are classified in non-overlapping categories, and substantially better when conditions can be ordered in dosage categories. Our approach is much faster computationally and is scalable to larger datasets. It is an attractive alternative to current methods, and provides a natural framework extensible to larger, and more complex chemical genetic screens. A Julia implementation of matrix linear models and the code used for the analysis in this paper can be found at https://bitbucket.org/jwliang/mlm_packages and https://bitbucket.org/jwliang/mlm_gs_supplement, respectively.
Composition of the Survival Motor Neuron (SMN) complex in Drosophila melanogaster
Authors: Matera A. Gregory , Raimer Amanda C. , Schmidt Casey A. , Kelly Jo A. , Droby Gaith N. , Baillat David , ten Have Sara , Lamond Angus I. , Wagner Eric J. , Gray Kelsey M.
Published: November 2018

Spinal Muscular Atrophy (SMA) is caused by homozygous mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. SMN is part of an oligomeric complex with core binding partners, collectively called Gemins. Biochemical and cell biological studies demonstrate that certain Gemins are required for proper snRNP assembly and transport. However, the precise functions of most Gemins are unknown. To gain a deeper understanding of the SMN complex in the context of metazoan evolution, we investigated the composition of the SMN complex in Drosophila melanogaster. Using a stable transgenic line that exclusively expresses Flag-tagged SMN from its native promoter, we previously found that Gemin2, Gemin3, Gemin5, and all nine classical Sm proteins, including Lsm10 and Lsm11, co-purify with SMN. Here, we show that CG2941 is also highly enriched in the pulldown. Reciprocal co-immunoprecipitation reveals that epitope-tagged CG2941 interacts with endogenous SMN in Schneider2 cells. Bioinformatic comparisons show that CG2941 shares sequence and structural similarity with metazoan Gemin4. Additional analysis shows that three other genes (CG14164, CG31950 and CG2371) are not orthologous to Gemins 6-7-8, respectively, as previously suggested. In D.melanogaster, CG2941 is located within an evolutionarily recent genomic triplication with two other nearly identical paralogous genes (CG32783 and CG32786). RNAi-mediated knockdown of CG2941 and its two close paralogs reveals that Gemin4 is essential for organismal viability.
Information sharing, operations capabilities, market intelligence responsiveness and firm performance
Authors: Song Moxi , Liao Yuanhong
Published: November 2018

Purpose

The purpose of this paper is to offer an alternative explanation for inconclusive results in the existing literature on the information sharing-firm performance link by examining a moderated mediation model in which operations capabilities mediate the interactive effects of information sharing and market intelligence responsiveness on firm performance within a supply chain context. Drawing on the indirect view of dynamic capability theory, the authors propose that information sharing redeploys and reconfigures operations capabilities, thus leading to superior firm performance, even with a high level of market intelligence responsiveness.

Design/methodology/approach

The hypotheses were tested using hierarchical regression and bootstrapping methods with a sample of 154 Chinese manufacturing firms. A survey-based, two-informant design was used to collect data.

Findings

The results revealed that operations capabilities fully mediate the relationship between information sharing and firm performance. The information sharing-operations capabilities link is positively moderated by market intelligence responsiveness. Moreover, operations capabilities positively mediate the interactive effects of information sharing and responsiveness on performance.

Originality/value

The study shifts the research focus from the moderating effect of market intelligence responsiveness in the information sharing-performance link to the interactive effects between information sharing and responsiveness on performance via operations capabilities, thus offering a finer-grained picture of the essential information sharing-performance link. To the best of our knowledge, this study is among the first to advocate and substantiate the theoretical claim that even with a high level of responsiveness, a firm’s performance relies on its operations capabilities, which are renewed and enhanced by information sharing, rather than on information sharing itself.
Comparison of algorithms for road surface temperature prediction
Authors: Liu Bo , Shen Libin , You Huanling , Dong Yan , Li Jianqiang , Li Yong
Published: November 2018

Purpose

The influence of road surface temperature (RST) on vehicles is becoming more and more obvious. Accurate predication of RST is distinctly meaningful. At present, however, the prediction accuracy of RST is not satisfied with physical methods or statistical learning methods. To find an effective prediction method, this paper selects five representative algorithms to predict the road surface temperature separately.

Design/methodology/approach

Multiple linear regressions, least absolute shrinkage and selection operator, random forest and gradient boosting regression tree (GBRT) and neural network are chosen to be representative predictors.

Findings

The experimental results show that for temperature data set of this experiment, the prediction effect of GBRT in the ensemble algorithm is the best compared with the other four algorithms.

Originality/value

This paper compares different kinds of machine learning algorithms, observes the road surface temperature data from different angles, and finds the most suitable prediction method.
Heart Valve Disease Predict Mortality in Hemodialysis Patients: A Single Center Experience
Authors: Ozelsancak Ruya , Tekkarismaz Nihan , Torun Dilek , Micozkadioglu Hasan
Published: November 2018

Our aim is to investigate the clinical and laboratory findings affecting the mortality of the patients in 3 years follow‐up who underwent hemodialysis at our center. In this retrospective, observational cohort study, 432 patients who underwent hemodialysis at our center for at least 5 months were included. The first recorded data and subsequent clinical findings of patients who died and survived were compared. Two hundred and ninety patients survived, 142 patients died. The mean age of the patients who died was higher (63.4 ± 12.3 years, vs. 52 ± 16.1 years, P = 0.0001), 60.5% of them had coronary artery disease (P = 0.0001), 93.7% of them had a heart valve disease. Duration of hemodialysis (survived 57 [21–260] months; died 44 [5–183] months, P = 0.000) was lower in patients who died. Serum potassium level before dialysis (5.1 ± 0.6; 4.9 ± 0.7 mEq/L, P = 0.030), parathyroid hormone (435 [4–3054]; 304 [1–3145] pg/mL, P = 0.0001), albumin (3.9 ± 0.4; 3.8 ± 0.4 mg/dL, P = 0.0001) and Kt/V (1.48 ± 0.3; 1.40 ± 0.3, P = 0.019) levels were lower, C‐reactive protein (5[1–208]; 8.7[2–256] mg/L, P = 0.000) levels were higher in patients who died. Logistic regression analysis showed age (OR = 1.1), coronary artery disease (OR = 1.7) and more than one heart valve disease (OR = 2.4) are independent risk factors for mortality. Potassium level before dialysis (OR = 0.60), parathyroid hormone (OR = 0.99), and higher Kt/V (OR = 0.28) were found to be an advantage for survival. Age, coronary artery disease and especially pathology in more than one heart valve are risk factors for mortality. Heart valve problems might develop because of malnutrition and inflammation caused by the chronic renal failure.
Case–control study found that primary language disorders were associated with screen exposure
Authors: Collet M , Gagnière B , Rousseau C , Chapron A , Fiquet L , Certain C
Published: November 2018

Aim

We explored the associations between childhood exposure to screens, including televisions, computers, game consoles, tablets and smartphones and primary language disorders.

Methods

This multi‐centre case–control study comprised 167 children aged 3.5–6.5 years, who were born in 2010–2012 and diagnosed with primary language disorders, and 109 matched controls without language disorders. Questionnaires were completed by their parents who were recruited by 16 family doctors and 27 speech and language therapists in the Ille‐et‐Vilaine region of France. The data were analysed using a multivariate logistic regression model and presented as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI).

Results

We found that cases (44.3%) and controls (22.0%) exposed to screens in the morning before nursery or primary school were three times more likely to develop primary language disorders (aOR 3.40, 95% CI 1.60–7.23). When this risk was combined with rarely or never discussing screen content with their parents (aOR 2.14, 95% CI 1.01–4.54) they were six times more likely to have language problems (aOR 5.86, 95% CI 1.44–23.95).

Conclusion

Being exposed to screens in the morning before school, and rarely or never discussing screen content with parents, meant children were six times more likely to develop primary language disorders.
Traffic‐related air pollution induces non‐allergic eosinophilic airway inflammation and cough hypersensitivity in guinea‐pigs
Authors: Fang Zhangfu , Huang Chuqin , Zhang Junfeng (Jim) , Xie Jiaxing , Dai Shouhui , Ge Erjia , Xiang Juan , Yao Hongmei , Huang Rongquan , Bi Xinhui , Wang Boguang , Zhong Nanshan , Lai Kefang
Published: November 2018

Background

The pathogenesis and pathophysiology of eosinophilia‐related chronic cough such as non‐asthmatic eosinophilic bronchitis and cough variant asthma are still not clear.

Objective

This study is to examine the potential role of traffic‐related air pollution (TRAP) in eosinophilic inflammation and cough responses.

Methods

Non‐sensitized guinea‐pigs were exposed to TRAP in an urban traffic tunnel or kept in a filtered air environment for 7 or 14 days. Reflexive cough was measured using citric acid and allyl isothiocyanate (AITC) challenges, respectively. Spontaneous cough counting was determined using audio recording and a waveform analysis. Airway inflammation was evaluated using differential cells in bronchoalveolar lavage fluid (BALF) and lung histopathology. To further elucidate the relationship between airway inflammation and cough hypersensitivity, a subgroup of those exposed for 14 days received a dexamethasone treatment.

Results

Compared to reflexive cough count (mean (95% confidence interval) in 10 minutes) provoked by the AITC challenge for the unexposed animals (3.1 (1.7‐4.5)), those were increased significantly following both the 7‐day (12.0 (6.8‐17.2), P < 0.01) and the 14‐day (12.0 (6.4‐17.6), P < 0.01) TRAP exposure. The effect provoked by the citric acid challenge was more profound following the 14‐day exposure (26.0 (19.5‐32.5) vs 3.8 (1.5‐6.0) for the control, P < 0.001). TRAP exposures enhanced spontaneous cough events, caused a significant increase of eosinophils and neutrophils in BALF and resulted in a dramatic eosinophilic infiltration in submucosal layer of trachea and bronchus, which can be inhibited significantly by dexamethasone treatment.

Conclusions & Clinical Relevance

TRAP exposures induced cough hypersensitivity and non‐allergic eosinophilic inflammation of airways in guinea‐pigs. This study highlights the potential mechanisms of eosinophilia‐related chronic cough that can be induced by traffic‐related air pollution.
Antihistamine‐resistant chronic spontaneous urticaria: 1‐year data from the AWARE study
Authors: Maurer Marcus , Raap Ulrike , Staubach Petra , Richter‐Huhn Grit , Bauer Andrea , Oppel Eva M. , Hillen Uwe , Baeumer Daniel , Reinhardt Maximilian , Chapman‐Rothe Nadine
Published: November 2018

Background

Previous reports indicate that patients with chronic spontaneous urticaria (CSU) are undertreated and that physicians show poor adherence to guideline recommendations. Awareness of CSU has improved in recent years, but it remains unclear if this has improved the management of these patients in clinical practice.

Objective

To describe disease burden, quality of life (QoL), and treatment patterns of patients with H1‐antihistamine‐refractory CSU in Germany.

Method

A World‐wide Antihistamine‐Refractory chronic urticaria (CU) patient Evaluation (AWARE) is a global prospective, non‐interventional study of CU in the real‐world setting, supported by the manufacturer of omalizumab. Patients (18‐75 years) were included who had H1‐antihistamine‐refractory CSU for ≥2 months. Disease characteristics, pharmacological treatments, and QoL (dermatology life quality index [DLQI], CU‐QoL questionnaire, and angioedema QoL questionnaire) are reported for patients enrolled in Germany.

Results

After 1 year in AWARE, CSU remained uncontrolled (urticaria control test [UCT] score <12) in 432 of 1032 (42.2%) patients. QoL impairment remained high after 1 year, with 28.2% of patients reporting that CSU had a moderate/very large/extremely large effect on the DLQI. Most patients did not receive guideline‐recommended treatments at the end of the 1‐year observation period. Changes in treatments were most evident at the first patient visit, with an increase in patients receiving omalizumab vs prior therapy from 8.5% to 21.4%, and a decrease in those receiving no treatment from 29.9% to 12.8%. These changes were associated with reduced hives, angioedema, UCT scores, and QoL scores at Month 3, but only modest improvements thereafter. Of 528 patients with uncontrolled CSU and who were eligible for treatment escalation, only 3% received up‐dosing of H1‐antihistamines and only 5% were initiated on omalizumab during 1 year of treatment.

Conclusions & Clinical Relevance

This study highlights a significant discrepancy between recommendations for managing CSU in international guidelines, and in real‐world clinical practice in Germany.
Variability of blood eosinophils in patients in a clinic for severe asthma
Authors: Rakowski Ewa , Zhao Sibo , Liu Mengling , Ahuja Shilpi , Durmus Nedim , Grunig Gabriele , Curotto de Lafaille Maria , Wu Yinxiang , Reibman Joan
Published: November 2018

Background

Blood eosinophils are used to determine eligibility for agents targeting IL‐5 in patients with uncontrolled asthma. However, little is known about the variability of blood eosinophil measures in these patients before treatment initiation.

Objective

To characterize variability and patterns of variability of blood eosinophil levels in a real‐world clinic for severe asthmatics.

Methods

Retrospective review of blood eosinophils measured over a 5‐year period in patients enrolled in an urban clinic. Repeated measures of blood eosinophil levels in individuals were evaluated, and cluster analysis was performed to characterize patients by eosinophil patterns. Clinical characteristics associated with eosinophil levels and patterns of variability were analysed.

Results

Patients treated in the Bellevue Hospital Asthma Clinic within a 3‐month period were identified (n = 219). Blood eosinophil measures were obtained over the previous 5 years. Only 6% (n = 13) of patients had levels that were consistently above 300 cells/μL. Nearly 50% (n = 104) had eosinophil levels that traversed the threshold of 300 cells/μL. In contrast, 102 (46%) had levels that never reached the threshold of 300 cells/μL. Cluster analyses revealed three clusters with differing patterns of levels and variability. There was a suggestion of decreased clinical control and increased atopy in the cluster with the greatest variability in blood eosinophil measures.

Conclusion

In an urban clinic for patients referred for uncontrolled asthma, blood measures of eosinophils were variable and showed differing patterns of variability. These data reinforce the need to perform repeated eosinophil blood measures for appropriate designation for therapeutic intervention.
Dividing neutrophils in subsets reveals a significant role for activated neutrophils in the development of airway hyperreactivity
Authors: Ekstedt Sandra , Säfholm Jesper , Georén Susanna Kumlien , Cardell Lars Olaf
Published: November 2018

Background

Previous research has emphasized the importance of eosinophils in allergic asthma, while paying less attention to neutrophils. The known functionality of neutrophils in the inflammatory process has recently changed and knowledge about subsets of neutrophils, as characterized by their expression of CD16 and CD62L, has surfaced. Their specific roles in asthma are still unknown.

Objective

To study the functional differences between subsets of neutrophils by characterizing the impact of individual subsets on airway smooth muscle reactivity.

Methods

The direct effect of neutrophils on airway hyperresponsiveness was assessed by co‐culturing different subsets of neutrophils (produced by LPS in vitro stimulation) with human isolated small airways or murine tracheae with subsequent evaluation of smooth muscle reactivity to bradykinin in myographs. Supernatants and tissue were saved for ELISA and immunohistochemistry.

Results

The CD16high CD62Ldim neutrophils were found to enhance the response to bradykinin in both human isolated small airways and murine tracheae. No such effects were obtained for the other subsets. The response is due to an upregulation of bradykinin receptor 2 through release of TNFα from the neutrophil.

Conclusions and Clinical Relevance

The present study introduces a new concept regarding the role of neutrophils and defines a novel direct link between a specific activated neutrophil subset and airway smooth muscle, establishing neutrophils as important players in the development of asthmatic airway hyperactivity.
Individual shark profiling: An innovative and environmentally responsible approach for selectively managing human fatalities
Authors: Clua Eric E. G. , Linnell John D. C.
Published: November 2018

Most shark‐induced human fatalities are followed by widespread and unselective culling campaigns that have limited effectiveness and may have high ecological costs for threatened species. The blanket culling strategy implicitly assumes that incident risk is directly correlated with shark density, an assumption that has yet to be demonstrated. We present the alternative hypothesis that incidents are more likely to be caused by behavioral variability among individual sharks than due to shark density. Throughout their ontogenetic development, large species of sharks opportunistically establish a diet that is rarely, if ever, inclusive of humans as a food source. We propose that, some animals with specific behaviors (including boldness) may potentially pose a higher risk than conspecifics. Under this scenario, the risk of a shark attack in a given area would relate to the presence of a limited number of high‐risk individuals rather than shark density.

In terms of management of human fatalities, such a hypothesis would favor abandoning general culling campaigns and replacing them with approaches that profile and selectively remove the potential problem individuals, as is done in the terrestrial realm when managing predators that attack humans or livestock.
Lung cancer after lung transplantation: An analysis of 25 years of experience in a single institution
Authors: Chatron Eva , Dégot Tristan , Salvaterra Elena , Dumazet Antoine , Porzio Michele , Hirschi Sandrine , Schuller Armelle , Massard Gilbert , Renaud‐Picard Benjamin , Kessler Romain
Published: November 2018

Background

The aim of our study was to describe the lung cancer characteristics in lung transplant recipients at our institution.

Methods

Between January 1, 1992, and August 15, 2017, 463 patients underwent lung transplantation.

Results

We found a total of 19 lung cancers (4.10%). Eight patients had lung cancer in the explanted lung, 8 in the native remaining lung, and 3 in the transplanted lung. Histopathological findings were: adenocarcinoma in 10, SCC in 8 patients, and 1 was undetermined. Among lung cancers in the explanted lungs, there were 6 stage I, 1 stage III, 1 stage IV. Among patients with a lung cancer in the remaining native lung, 3 had early stage disease and 5 had stage IV disease. Among lung cancers in the transplanted lung, there were: 1 stage I, 1 stage II and 1 stage IV. Overall median survival in lung transplant recipients without lung cancer was 8.77 ± 0.74 years compared to 6.19 ± 1.4 years in recipients with lung cancer.

Conclusion

Lung cancer following lung transplantation was uncommon. Early stage lung cancer discovered in the explanted lungs had no impact on survival. Lung cancer occurring in the transplanted or in the native remaining lung had a poor prognosis.
The role of sensorimotor experience in the development of mimicry in infancy
Authors: de Klerk Carina C. J. M. , Lamy‐Yang Iona , Southgate Victoria
Published: November 2018

During social interactions we often have an automatic and unconscious tendency to copy or ‘mimic’ others’ actions. The dominant view on the neural basis of mimicry appeals to an automatic coupling between perception and action. It has been suggested that this coupling is formed through associative learning during correlated sensorimotor experience. Although studies with adult participants have provided support for this hypothesis, little is known about the role of sensorimotor experience in supporting the development of perceptual‐motor couplings, and consequently mimicry behaviour, in infancy. Here we investigated whether the extent to which an observed action elicits mimicry depends on the opportunity an infant has had to develop perceptual‐motor couplings for this action through correlated sensorimotor experience. We found that mothers’ tendency to imitate their 4‐month‐olds’ facial expressions during a parent‐child interaction session was related to infants’ facial mimicry as measured by electromyography. Maternal facial imitation was not related to infants’ mimicry of hand actions, and instead we found preliminary evidence that infants’ tendency to look at their own hands may be related to their tendency to mimic hand actions. These results are consistent with the idea that mimicry is supported by perceptual‐motor couplings that are formed through correlated sensorimotor experience obtained by observing one's own actions and imitative social partners.
The effect of stricter capital regulation on banks’ risk‐taking: Theory and evidence
Authors: Lundtofte Frederik , Nielsen Caren Yinxia
Published: November 2018

A simple portfolio choice model shows that, when a bank's capital is constrained by regulation, regulatory cost (risk weightings) alters the risk and value calculations for the bank's assets. In particular, we find that banks may respond to stricter regulation by increasing the share of high‐risk assets. Our empirical results show that US banks responded to the implementation of the stricter Basel II regulations by increasing the share of high‐risk assets in the risky part of their portfolios.