bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing surface stabilization of CH3NH3PbI3 perovskite by Cl and Br doping: First-principles study
Authors: Pramchu Sittichain , Cheiwchanchamnangij Tawinan , Laosiritaworn Yongyut , Jaroenjittichai Atchara Punya
Published: March 2019

In this study, the effects of Cl and Br surface doping on the surfaces' structural stability of CH3NH3PbI3 (MAPbI3) perovskite have been investigated using the density functional theory. Its aim is to pursue how to stabilize a flat surfaces structure (no vacancy) of the MAPbI3 perovskite in overcoming its chemical instability. In this calculation, the (001) texture of the MAPbI3 perovskite surface was modeled as a prototype. The 216-atom and 264-atom supercells were employed to imitate the Lead Iodide (PbI2)- and Methylammonium Iodine (MAI)-terminated surfaces, respectively. It was found that doping of either Cl or Br atoms on perovskite surfaces enhances the energies required for releasing PbI2 and MAI molecules from the surfaces, causing vacancies on the surfaces. This is owed to the binding energies between the Cl and Br dopants and their surrounding atoms on the surfaces being stronger than those created by the Iodine atom. This implies that the formation of surface vacancies—which causes perovskite's degradation—can be prevented by Cl and Br surface doping. The obtained results elucidate the capability of Cl and Br dopants on surface stabilization, describing why one should incorporate Cl/Br into MAPbI3 to overcome instability issues and enhance the efficiency of the MAPbI3-based perovskite solar cell.
Repulsively coupled Kuramoto-Sakaguchi phase oscillators ensemble subject to common noise
Authors: Gong Chen Chris , Zheng Chunming , Toenjes Ralf , Pikovsky Arkady
Published: March 2019

We consider the Kuramoto-Sakaguchi model of identical coupled phase oscillators with a common noisy forcing. While common noise always tends to synchronize the oscillators, a strong repulsive coupling prevents the fully synchronous state and leads to a nontrivial distribution of oscillator phases. In previous numerical simulations, the formation of stable multicluster states has been observed in this regime. However, we argue here that because identical phase oscillators in the Kuramoto-Sakaguchi model form a partially integrable system according to the Watanabe-Strogatz theory, the formation of clusters is impossible. Integrating with various time steps reveals that clustering is a numerical artifact, explained by the existence of higher order Fourier terms in the errors of the employed numerical integration schemes. By monitoring the induced change in certain integrals of motion, we quantify these errors. We support these observations by showing, on the basis of the analysis of the corresponding Fokker-Planck equation, that two-cluster states are non-attractive. On the other hand, in ensembles of general limit cycle oscillators, such as Van der Pol oscillators, due to an anharmonic phase response function as well as additional amplitude dynamics, multiclusters can occur naturally.
Bandgap narrowing and Mott transition in Si-doped Al0.7Ga0.3N
Authors: Bharadwaj Shyam , Islam S. M. , Nomoto Kazuki , Protasenko Vladimir , Chaney Alexander , Xing Huili (Grace) , Jena Debdeep
Published: March 2019

Deep ultraviolet light-emitting diodes (LEDs) composed of III-Nitride semiconductors need layers of heavy doping (>1 × 1019 cm−3) to overcome large dopant activation energies and maintain high electrical conductivity. This work reports that at doping densities of [Si] ∼1.5 × 1019/cm3 for n-Al0.7Ga0.3N, Burstein-Moss and bandgap renormalization effects result in a net reduction of the bandgap of ∼70 meV. At these doping levels, a transition to a metallic conductivity state is observed, with a vanishing of the effective dopant activation energy. The sheet and contact resistivities of Rsh,n = 0.045 Ω cm and ρc,n = 1.13 × 10−6 Ω cm2 are achieved, with uniform conductivity in the vertical direction. The results show that when heavily doped n-AlGaN cladding regions are used for high efficiency deep-UV LEDs or lasers, the accompanying bandgap narrowing reduces the window of optical transparency at the lowest wavelengths that can take advantage of high conductivity.
Computational analysis for residue-specific CDK2-inhibitor bindings
Authors: Yang Yun-peng , He Li-ping , Bao Jing-xiao , Qi Yi-fei , Zhang John Z. H.
Published: March 2019

Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, leukemia, and lymphomas. Quantitative characterization of the interactions between CDK2 and its inhibitors at atomic level may provide a deep understanding of protein-inhibitor interactions and clues for more effective drug discovery. In this study, we have used the computational alanine scanning approach in combination with an efficient interaction entropy method to study the microscopic mechanism of binding between CDK2 and its 13 inhibitors. The total binding free energy from the method shows a correlation of 0.76−0.83 with the experimental values. The free energy component reveals two binding mode in the 13 complexes, namely van der Waals dominant, and electrostatic dominant. Decomposition of the total energy to per-residue contribution allows us to identify five hydrophobic residues as hot spots during the binding. Residues that are responsible for determining the strength of the binding were also analyzed.
PTEN arginine methylation by PRMT6 suppresses PI3K–AKT signaling and modulates pre-mRNA splicing
Authors: Feng Jiawen , Dang Yaping , Zhang Weiqi , Zhao Xuyang , Zhang Cong , Hou Zhiyuan , Jin Yan , McNutt Michael A. , Marks Andrew R. , Yin Yuxin
Published: March 2019

Significance

Based on the Sanger COSMIC (Catalogue of Somatic Mutations in Cancer) database, >30% of missense mutations of the
PTEN
gene result in disruption of arginine residues. We identified arginine methylation of PTEN using mass-spectrometry analysis and found that PRMT6 methylates PTEN on R159, resulting in suppression of the PI3K–AKT cascade. PTEN R159 is highly conserved, and R159 mutations have been found in cancer-susceptibility syndromes and in sporadic cancers. Disruption of PRMT6 or PTEN methylation leads to activation of PI3K–AKT signaling. Moreover, transcriptome analysis revealed that PTEN methylation influences mature mRNA transcripts through modulation of pre-mRNA alternative splicing, which may influence multiple cellular processes.
Female choice for related males in wild red-backed toadlets (Pseudophryne coriacea)
Authors: O’Brien Daniel M , Keogh J Scott , Silla Aimee J , Byrne Phillip G
Published: March 2019

Mate choice for genetic benefits is assumed to be widespread in nature, yet very few studies have comprehensively examined relationships between female mate choice and male genetic quality in wild populations. Here, we use exhaustive sampling and single nucleotide polymorphisms to provide a partial test of the “good genes as heterozygosity” hypothesis and the “genetic compatibility” hypothesis in an entire population of terrestrial breeding red-backed toadlets, Pseudophryne coriacea. We found that successful males did not display higher heterozygosity, despite a positive relationship between male heterozygosity and offspring heterozygosity. Rather, in the larger of 2 breeding events, we found that successful males were more genetically similar to their mate than expected under random mating, indicating that females can use pre- or post-copulatory mate choice mechanisms to bias paternity toward more related males. These findings provide no support for the good genes as heterozygosity hypothesis but lend support to the genetic compatibility hypothesis. A complete test of this hypothesis will now require evaluating how parental genetic similarity impacts offspring fitness. Terrestrial toadlets show a high degree of site fidelity, high levels of genetic structuring between populations, and frequently hybridize with sister species. As such, female mate choice for related males may be an adaptive strategy to reduce outbreeding depression. Our findings provide the first population-wide evidence for non-random preferential inbreeding in a wild amphibian. We argue that such reproductive patterns may be common in amphibians because extreme genetic differentiation within meta-populations creates an inherently high risk of outbreeding depression.
ERVcaller: identifying polymorphic endogenous retrovirus and other transposable element insertions using whole-genome sequencing data
Authors: Chen Xun , Li Dawei
Published: March 2019

Motivation

Approximately 8% of the human genome is derived from endogenous retroviruses (ERVs). In recent years, an increasing number of human diseases have been found to be associated with ERVs. However, it remains challenging to accurately detect the full spectrum of polymorphic (unfixed) ERVs using whole-genome sequencing (WGS) data.

Results

We designed a new tool, ERVcaller, to detect and genotype transposable element (TE) insertions, including ERVs, in the human genome. We evaluated ERVcaller using both simulated and real benchmark WGS datasets. Compared to existing tools, ERVcaller consistently obtained both the highest sensitivity and precision for detecting simulated ERV and other TE insertions derived from real polymorphic TE sequences. For the WGS data from the 1000 Genomes Project, ERVcaller detected the largest number of TE insertions per sample based on consensus TE loci. By analyzing the experimentally verified TE insertions, ERVcaller had 94.0% TE detection sensitivity and 96.6% genotyping accuracy. Polymerase chain reaction and Sanger sequencing in a small sample set verified 86.7% of examined insertion statuses and 100% of examined genotypes. In conclusion, ERVcaller is capable of detecting and genotyping TE insertions using WGS data with both high sensitivity and precision. This tool can be applied broadly to other species.

Availability and implementation

http://www.uvm.edu/genomics/software/ERVcaller.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
FLAS: fast and high-throughput algorithm for PacBio long-read self-correction
Authors: Bao Ergude , Xie Fei , Song Changjin , Song Dandan
Published: March 2019

Motivation

The third generation PacBio long reads have greatly facilitated sequencing projects with very large read lengths, but they contain about 15% sequencing errors and need error correction. For the projects with long reads only, it is challenging to make correction with fast speed, and also challenging to correct a sufficient amount of read bases, i.e. to achieve high-throughput self-correction. MECAT is currently among the fastest self-correction algorithms, but its throughput is relatively small (Xiao et al., 2017).

Results

Here, we introduce FLAS, a wrapper algorithm of MECAT, to achieve high-throughput long-read self-correction while keeping MECAT’s fast speed. FLAS finds additional alignments from MECAT prealigned long reads to improve the correction throughput, and removes misalignments for accuracy. In addition, FLAS also uses the corrected long-read regions to correct the uncorrected ones to further improve the throughput. In our performance tests on Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana and human long reads, FLAS can achieve 22.0–50.6% larger throughput than MECAT. FLAS is 2–13× faster compared to the self-correction algorithms other than MECAT, and its throughput is also 9.8–281.8% larger. The FLAS corrected long reads can be assembled into contigs of 13.1–29.8% larger N50 sizes than MECAT.

Availability and implementation

The FLAS software can be downloaded for free from this site: https://github.com/baoe/flas.

Supplementary information

Supplementary data are available at Bioinformatics online.
The Contemporary Repertoire of Contentious Identity Politics and Religious Conflicts in France
Authors: D’Appollonia Ariane Chebel
Published: March 2019

This paper analyses the framing and meaning of contentious politics in contemporary France. Building on the work of Charles Tilly and Sidney Tarrow, this study of contention involves two interrelated dimensions. The first one relates to inherited, historical forms of collective action (repertoires). Here, contentious politics varies in connection with political power, institutional regimes, and the dominant culture. In early modern history, such forms of contention were linked to a traditional repertoire of grievances (about bread, belief, or land) and concerns about the purity of the religious community. A new repertoire emerged in the 18th century, as well as new forms of contention. Yet, key components of contentious politics remained, such as concerns about the purity of the nation, and grievances fuelled by the threat posed by “Others.” As a result, there are significant similarities between past conflicts about religion, and the current debate over the alleged threats to French secularism.
Solitary Day, Solitary Activities, and Associations With Well-Being Among Older Adults
Authors: Lam Jack , García-Román Joan
Published: March 2019

Objectives

Drawing on activity theory of aging, we examined whether solitary activities may be associated with negative well-being, as they may reflect social isolation. Using American Time Use Surveys, with information on “with whom” individuals engaged in activities over a 24 hr period, we created measures capturing solitary days and solitary activities to understand their prevalence and associations with well-being.

Methods

At the daily level, we examined associations between solitary days and proportion of the day in solitary activities with life satisfaction. At the activity level, we examined associations between engaging in an activity alone versus with others and emotional state during the activity.

Results

Solitary days and higher proportion of the day spent in solitary activities were associated with lower life satisfaction. These associations were attenuated controlling for individual covariates. Engagement in activities alone was associated with lower levels of happiness and higher levels of sadness and pain during the activity, and association with happiness remained even adjusting for covariates.

Discussion

A sizable proportion of older adults reported solitary days, and proportion of the day spent in solitary activities increases by age. Examining lived experiences of older adults and presence of others during activities could contribute to research on social isolation.
Tissue regulatory T cells and neural repair
Authors: Ito Minako , Komai Kyoko , Nakamura Toshihiro , Srirat Tanakorn , Yoshimura Akihiko
Published: March 2019

Inflammation and immune responses after tissue injury play pivotal roles in the pathology, resolution of inflammation, tissue recovery, fibrosis and remodeling. Regulatory T cells (Tregs) are the cells responsible for suppressing immune responses and can be activated in secondary lymphatic tissues, where they subsequently regulate effector T cell and dendritic cell activation. Recently, Tregs that reside in non-lymphoid tissues, called tissue Tregs, have been shown to exhibit tissue-specific functions that contribute to the maintenance of tissue homeostasis and repair. Unlike other tissue Tregs, the role of Tregs in the brain has not been well elucidated because the number of brain Tregs is very small under normal conditions. However, we found that Tregs accumulate in the brain at the chronic phase of ischemic brain injury and control astrogliosis through secretion of a cytokine, amphiregulin (Areg). Brain Tregs resemble other tissue Tregs in many ways but, unlike the other tissue Tregs, brain Tregs express neural-cell-specific genes such as the serotonin receptor (Htr7) and respond to serotonin. Administering serotonin or selective serotonin reuptake inhibitors (SSRIs) in an experimental mouse model of stroke increases the number of brain Tregs and ameliorates neurological symptoms. Knowledge of brain Tregs will contribute to the understanding of various types of neuroinflammation.
‘Warning: allergic to penicillin’: association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes
Authors: West R M , Smith C J , Pavitt S H , Butler C C , Howard P , Bates C , Savic S , Wright J M , Hewison J , Sandoe J A T
Published: March 2019

Background

The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging.

Objectives

To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care.

Methods

We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection.

Results

PenA prevalence was 5.9% (IQR = 3.8%–8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records.

Conclusions

PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes.
An electronic health record–based interoperable eReferral system to enhance smoking Quitline treatment in primary care
Authors: Fiore Michael , Adsit Rob , Zehner Mark , McCarthy Danielle , Lundsten Susan , Hartlaub Paul , Mahr Todd , Gorrilla Allison , Skora Amy , Baker Timothy
Published: March 2019

Objective

The study sought to determine whether interoperable, electronic health record–based referral (eReferral) produces higher rates of referral and connection to a state tobacco quitline than does fax-based referral, thus addressing low rates of smoking treatment delivery in health care.

Materials and Methods

Twenty-three primary care clinics from 2 healthcare systems (A and B) in Wisconsin were randomized, unblinded, over 2016-2017, to 2 smoking treatment referral methods: paper-based fax-to-quit (system A =6, system B = 6) or electronic (eReferral; system A = 5, system B = 6). Both methods referred adult patients who smoked to the Wisconsin Tobacco Quitline. A total of 14 636 smokers were seen in the 2 systems (system A: 54.5% women, mean age 48.2 years; system B: 53.8% women, mean age 50.2 years).

Results

Clinics with eReferral, vs fax-to-quit, referred a higher percentage of adult smokers to the quitline: system A clinic referral rate = 17.9% (95% confidence interval [CI], 17.2%-18.5%) vs 3.8% (95% CI, 3.5%-4.2%) (P < .001); system B clinic referral rate = 18.9% (95% CI, 18.3%-19.6%) vs 5.2% (95% CI, 4.9%-5.6%) (P < .001). Average rates of quitline connection were higher in eReferral than F2Q clinics: system A = 5.4% (95% CI, 5.0%-5.8%) vs 1.3% (95% CI, 1.1%-1.5%) (P < .001); system B = 5.3% (95% CI, 5.0%-5.7%) vs 2.0% (95% CI, 1.8%-2.2%) (P < .001).

Discussion

Electronic health record–based eReferral provided an effective, closed-loop, interoperable means of referring patients who smoke to telephone quitline services, producing referral rates 3-4 times higher than the current standard of care (fax referral), including especially high rates of referral of underserved individuals.

Conclusions

eReferral may help address the challenge of providing smokers with treatment for tobacco use during busy primary care visits.

ClinicalTrials.gov; No. NCT02735382.
Early experiences with patient generated health data: health system and patient perspectives
Authors: Adler-Milstein Julia , Nong Paige
Published: March 2019

Objective

Although patient generated health data (PGHD) has stimulated excitement about its potential to increase patient engagement and to offer clinicians new insights into patient health status, we know little about these efforts at scale and whether they align with patient preferences. This study sought to characterize provider-led PGHD approaches, assess whether they aligned with patient preferences, and identify challenges to scale and impact.

Materials and Methods

We interviewed leaders from a geographically diverse set of health systems (n = 6), leaders from large electronic health record vendors (n = 3), and leaders from vendors providing PGHD solutions to health systems (n = 3). Next, we interviewed patients with 1 or more chronic conditions (n = 10), half of whom had PGHD experience. We conducted content analysis to characterize health system PGHD approaches, assess alignment with patient preferences, and identify challenges.

Results

In this study, 3 primary approaches were identified, and each was designed to support collection of a different type of PGHD: 1) health history, 2) validated questionnaires and surveys, and 3) biometric and health activity. Whereas patient preferences aligned with health system approaches, patients raised concerns about data security and the value of reporting. Health systems cited challenges related to lack of reimbursement, data quality, and clinical usefulness of PGHD.

Discussion

Despite a federal policy focus on PGHD, it is not yet being pursued at scale. Whereas many barriers contribute to this narrow pursuit, uncertainty around the value of PGHD, from both patients and providers, is a primary inhibitor.

Conclusion

Our results reveal a fairly narrow set of approaches to PGHD currently pursued by health systems at scale.
Developments of human adrenomedullin-IgG1 Fc fusion proteins
Authors: Nagata Sayaka , Yamasaki Motoo , Kawano Aya , Kitamura Kazuo
Published: March 2019

Human adrenomedullin (hAM) is a hypotensive peptide hormone that exerts powerful anti-inflammatory effects. However, treatment required continuous administration of hAM, as the half-life of native hAM is quite short in blood. To resolve this problem, we designed two kinds of human IgG1 Fc fusion proteins containing either full-length hAM (IgG1-AM) or hAM residues 6–52 [IgG1-AM (6–52)]. A DNA construct was constructed by connecting DNA sequences encoding hAM and the IgG1 Fc region with a DNA sequence encoding a (GGGGS)3 linker. The molecular weights of IgG1-AM and IgG1-AM (6–52) were determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and gel filtration chromatography. By protein sequencing, the N-terminal sequence of both recombinant AM-Fc fusions showed the expected human IgG1 sequence. Sufficient concentrations of both AM-Fc fusions were observed in blood 2 days after a single subcutaneous administration. IgG1-AM and IgG1-AM (6–52) stimulated cAMP production in human embryonic kidney-293 cells stably expressing the AM1 receptor. The activity of IgG1-AM (6–52) was higher than that of IgG1-AM. Treatment with IgG1-AM (6–52) inhibited blood pressure increase in spontaneously hypertensive rats. In addition, IgG1-AM (6–52) reduced total inflammation scores in the dextran sulfate sodium colitis model. Therefore, AM-IgG1 Fc fusions represent potential novel therapeutic agents.
First-Line Systemic Treatments for Stage IV Non-Small Cell Lung Cancer in California: Patterns of Care and Outcomes in a Real-World Setting
Authors: Maguire Frances B , Morris Cyllene R , Parikh-Patel Arti , Cress Rosemary D , Keegan Theresa H M , Li Chin-Shang , Lin Patrick S , Kizer Kenneth W
Published: March 2019

Background

Multiple systemic treatments have been developed for stage IV non-small cell lung cancer (NSCLC), but their use and effect on outcomes at the population level are unknown. This study describes the utilization of first-line systemic treatments among stage IV NSCLC patients in California and compares survival among treatment groups.

Methods

Data on 17 254 patients diagnosed with stage IV NSCLC from 2012 to 2014 were obtained from the California Cancer Registry. Systemic treatments were classified into six groups. The Kaplan-Meier method and multivariable Cox proportional hazards models were used to compare survival between treatment groups.

Results

Fifty-one percent of patients were known to have received systemic treatment. For patients with nonsquamous histology, pemetrexed regimens were the most common treatment (14.8%) followed by tyrosine kinase inhibitors (11.9%) and platinum doublets (11.5%). Few patients received pemetrexed/bevacizumab combinations (4.5%), bevacizumab combinations (3.6%), or single agents (1.7%). There was statistically significantly better overall survival for those on pemetrexed regimens (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.80 to 0.92), bevacizumab regimens (HR = 0.73, 95% CI = 0.65 to 0.81), pemetrexed/bevacizumab regimens (HR = 0.68, 95% CI = 0.61 to 0.76), or tyrosine kinase inhibitors (HR = 0.62, 95% CI = 0.57 to 0.67) compared with platinum doublets. The odds of receiving most systemic treatments decreased with decreasing socioeconomic status. For patients with squamous histology, platinum doublets were predominant (33.7%) and were not found to have statistically significantly different overall survival from single agents.

Conclusions

These population-level findings indicate low utilization of systemic treatments, survival differences between treatment groups, and evident treatment disparities by socioeconomic status.
Correlation between mass segregation and structural concentration in relaxed stellar clusters
Authors: de Vita Ruggero , Trenti Michele , MacLeod Morgan
Published: March 2019

The level of mass segregation in the core of globular clusters has been previously proposed as a potential indicator of the dynamical constituents of the system, such as presence of a significant population of stellar-mass black holes (BHs), or even a central intermediate-mass black hole (IMBH). However, its measurement is limited to clusters with high-quality Hubble Space Telescope data. Thanks to a set of state-of-the-art direct N-body simulations with up to 200k particles inclusive of stellar evolution, primordial binaries, and varying BH/neutron stars, we highlight for the first time the existence of a clear and tight linear relation between the degree of mass segregation and the cluster structural concentration index. The latter is defined as the ratio of the radii containing 5 per cent and 50 per cent of the integrated light (R5/R50), making it robustly measurable without the need to individually resolve low-mass stars. Our simulations indicate that given R5/R50, the mass segregation Δm (defined as the difference in main-sequence median mass between centre and half-light radius) is expressed as Δm/M⊙ = −1.166R5/R50 + 0.3246, with a root-mean-square error of 0.0148. In addition, we can explain its physical origin and the values of the fitted parameters through basic analytical modelling. Such correlation is remarkably robust against a variety of initial conditions (including presence of primordial binaries and IMBHs) and cluster ages, with a slight dependence in best-fitting parameters on the prescriptions used to measure the quantities involved. Therefore, this study highlights the potential to develop a new observational tool to gain insight on the dynamical status of globular clusters and on its dark remnants.
Abundant serendipitous emission line sources with JWST/NIRSpec
Authors: Maseda Michael V , Franx Marijn , Chevallard Jacopo , Curtis-Lake Emma
Published: March 2019

The James Webb Space Telescope will provide observational capabilities that far exceed those of current ground- or space-based instrumentation. In particular, the Near-Infrared Spectrograph (NIRSpec) instrument will take highly sensitive spectroscopic data for hundreds of objects simultaneously from 0.6 to 5.3 $\mu$m. Current photometric observations suggest a large and increasing number of faint (MUV > −16) galaxies at high redshift, with increasing evidence that galaxies at these redshifts have optical emission lines with extremely high equivalent widths. A simple model of their emission line fluxes and number density evolution with redshift is used to predict the number of galaxies that NIRSpec will serendipitously observe during normal observations with the microshutter array. At exposure times of ≈20 h in the low-resolution prism mode, the model predicts that, on average, every open 1 × 3 ‘microslit’ will contain an un-targeted galaxy with a detectable [O iii] and/or H α emission line; while most of these detections are predicted to be of [O iii], H α detections alone would still number 0.56 per open ‘microslit’ for this exposure time. Many of these objects are spectroscopically detectable even when they are fainter than current photometric limits and/or their flux centroids lie outside of the open microshutter area. The predicted number counts for such galaxies match z ∼ 2 observations of [O iii] emitters from slitless grism spectroscopic surveys, as well as theoretical predictions based on sophisticated modelling of galaxy spectral energy distributions. These serendipitous detections could provide the largest numbers of z > 6 spectroscopic confirmations in the deepest NIRSpec surveys.
Gene Expression Does Not Support the Developmental Hourglass Model in Three Animals with Spiralian Development
Authors: Wu Longjun , Ferger Kailey E , Lambert J David
Published: March 2019

It has been proposed that animals have a pattern of developmental evolution resembling an hourglass because the most conserved development stage—often called the phylotypic stage—is always in midembryonic development. Although the topic has been debated for decades, recent studies using molecular data such as RNA-seq gene expression data sets have largely supported the existence of periods of relative evolutionary conservation in middevelopment, consistent with the phylotypic stage and the hourglass concepts. However, so far this approach has only been applied to a limited number of taxa across the tree of life. Here, using established phylotranscriptomic approaches, we found a surprising reverse hourglass pattern in two molluscs and a polychaete annelid, representatives of the Spiralia, an understudied group that contains a large fraction of metazoan body plan diversity. These results suggest that spiralians have a divergent midembryonic stage, with more conserved early and late development, which is the inverse of the pattern seen in almost all other organisms where these phylotranscriptomic approaches have been reported. We discuss our findings in light of proposed reasons for the phylotypic stage and hourglass model in other systems.
River Valleys Shaped the Maternal Genetic Landscape of Han Chinese
Authors: Li Yu-Chun , Ye Wei-Jian , Jiang Chuan-Gui , Zeng Zhen , Tian Jiao-Yang , Yang Li-Qin , Liu Kai-Jun , Kong Qing-Peng
Published: March 2019

A general south-north genetic divergence has been observed among Han Chinese in previous studies. However, these studies, especially those on mitochondrial DNA (mtDNA), are based either on partial mtDNA sequences or on limited samples. Given that Han Chinese comprise the world’s largest population and reside around the whole China, whether the north-south divergence can be observed after all regional populations are considered remains unknown. Moreover, factors involved in shaping the genetic landscape of Han Chinese need further investigation. In this study, we dissected the matrilineal landscape of Han Chinese by studying 4,004 mtDNA haplogroup-defining variants in 21,668 Han samples from virtually all provinces in China. Our results confirmed the genetic divergence between southern and northern Han populations. However, we found a significant genetic divergence among populations from the three main river systems, that is, the Yangtze, the Yellow, and the Zhujiang (Pearl) rivers, which largely attributed to the prevalent distribution of haplogroups D4, B4, and M7 in these river valleys. Further analyses based on 4,986 mitogenomes, including 218 newly generated sequences, indicated that this divergence was already established during the early Holocene and may have resulted from population expansion facilitated by ancient agricultures along these rivers. These results imply that the maternal gene pools of the contemporary Han populations have retained the genetic imprint of early Neolithic farmers from different river basins, or that river valleys represented relative migration barriers that facilitated genetic differentiation, thus highlighting the importance of the three ancient agricultures in shaping the genetic landscape of the Han Chinese.
Genome-Wide Analysis of Long Intergenic Noncoding RNAs Responding to Low-Nutrient Conditions in Arabidopsis thaliana: Possible Involvement of Trans-Acting siRNA3 in Response to Low Nitrogen
Authors: Fukuda Makiha , Nishida Sho , Kakei Yusuke , Shimada Yukihisa , Fujiwara Toru
Published: March 2019

Long intergenic noncoding RNAs (lincRNAs) play critical roles in transcriptional and post-transcriptional regulation of gene expression in a wide variety of organisms. Thousands of lincRNAs have been identified in plant genomes, although their functions remain mostly uncharacterized. Here, we report a genome-wide survey of lincRNAs involved in the response to low-nutrient conditions in Arabidopsis thaliana. We used RNA sequencing data derived from A. thaliana roots exposed to low levels of 12 different nutrients. Using bioinformatics approaches, 60 differentially expressed lincRNAs were identified that were significantly upregulated or downregulated under deficiency of at least one nutrient. To clarify their roles in nutrient response, correlations of expression patterns between lincRNAs and reference genes were examined across the 13 conditions (12 low-nutrient conditions and control). This analysis allowed us to identify lincRNA-RNA pairs with highly positive or negative correlations. In addition, calculating interaction energies of those pairs showed lincRNAs that may act as regulatory interactors; e.g. small interfering RNAs (siRNAs). Among them, trans-acting siRNA3 (TAS3), which is known to promote lateral root development by producing siRNA against Auxin response factor 2, 3, and 4, was revealed as a nitrogen (N)-responsive lincRNA. Furthermore, nitrate transporter 2 was identified as a potential target of TAS3-derived siRNA, suggesting that TAS3 participates in multiple pathways by regulating N transport and root development under low-N conditions. This study provides the first resource for candidate lincRNAs involved in multiple nutrient responses in plants.
Influenza in carehome residents: applying a conceptual framework to describe barriers to the implementation of guidance on treatment and prophylaxis
Authors: Phipps Emily , Watson Conall , Mearkle Rachel , Lock Sarah
Published: March 2019

Background

The European Centre for Disease Prevention and Control, National Institute for Health and Care Excellence and Public Health England have all endorsed the use of antivirals for the treatment and prophylaxis of influenza for care home residents. However, implementing these guidelines in practice is often challenging. This article aims to explore what factors impact the management of care home flu outbreaks in England according to national guidelines and highlight opportunities for change.

Methods

Qualitative data from notified outbreaks between September 2017 to April 2018 in the South East of England were analyzed, applying the Greenhalgh framework for barriers to guideline implementation. Summary statistics on outbreak characteristics were generated. Stakeholders were mapped out using Eden and Ackermann’s grid of interest and influence. A process map was developed to describe operational pathways.

Results

There was often a delay in notifying potential outbreaks to Public Health England. Clinicians cited a lack of robust evidence for the use of antivirals and the available guidelines being too unwieldy as reasons for not implementing prescribing guidance. Many high interests and high influence stakeholders are involved in the sometimes complex care pathway, requiring coordinated work and agreement before antivirals can be prescribed.

Conclusions

Our findings highlight points in the care pathway that stakeholders can target to improve quality of care and increase the likelihood of national guidance being implemented. The principles described in this article can also be applied to other challenges of translating evidence into practice and cross-organisational working.
ESTIMATION OF THE ANISOTROPY EMISSION OF LPN/CIEMAT NEUTRON SOURCES: EFFECT OF HEAVY CAPSULE HOLDERS
Authors: Villafañe Roberto Mendez , de Sousa Lacerda Marco Aurélio , Blanco Xandra Campo , Sánchez Francisco González , Vega-Carrillo Héctor René
Published: March 2019

In order to estimate the anisotropy emission of 241Am-Be and 252Cf neutron sources from the Spanish Neutron Standards Laboratory (LPN/CIEMAT) detailed models of sources capsules and capsule holders were designed with the MCNPX code. Simulations of the sources inside the capsules without the capsule holders were done to validate the MC model by comparison with experimental results provided by other authors. After that, the capsule holders were incorporated to the simulation. In general, a good agreement has been found between measurements and our calculations. Results show the additional encapsulations have significant influence on anisotropy factors, energy spectra and dose rates.
Multiplex End-Point PCR for the Detection of Three Species of Ophiosphaerella Causing Spring Dead Spot of Bermudagrass
Authors: Iturralde Martinez J. Francisco , Flores Francisco J. , Koch Alma R. , Garzón Carla D. , Walker Nathan R.
Published: March 2019

A multiplex end-point polymerase chain reaction (PCR) assay was developed for identifying the three-fungal species in the genus Ophiosphaerella that cause spring dead spot (SDS), a devastating disease of bermudagrass. These fungi are difficult to identify by morphology because they seldom produce pseudothecia. To achieve species-specific diagnosis, three pairs of primers were designed to identify fungal isolates and detect the pathogen in infected roots. The internal transcribed spacer region, the translation elongation factor 1-α, and the RNA polymerase II second-largest subunit were selected as targets and served as templates for the design of each primer pair. To achieve uniform melting temperatures, three to five random nucleotide extensions (flaps) were added to the 5′ terminus of some of the designed specific primers. Temperature cycling conditions and PCR components were standardized to optimize specificity and sensitivity of the multiplex reaction. Primers were tested in multiplex on DNA extracted from axenic fungal cultures and from field-collected infected and uninfected roots. A distinct amplicon was produced for each Ophiosphaerella sp. tested. The DNA from Ophiosphaerella close relatives and other common bermudagrass pathogens did not amplify during the multiplex assay. Metagenomic DNA from infected bermudagrass produced species-specific amplicons while DNA extracted from noninfected roots did not. This multiplex end-point PCR approach is a sensitive and specific molecular technique that allows for correct identification of SDS-associated Ophiosphaerella spp. from field-collected roots.
Randomized Trial of an Innovative Electronic Screening and Brief Intervention for Reducing Drinking Among Women of Childbearing Age
Authors: Nayak Madhabika B. , Kaskutas Lee A. , Mericle Amy A.
Published: March 2019

Objectives:

To evaluate the efficacy of an innovative, self-administered, electronic Screening and Brief Intervention (e-SBI) in English and Spanish, “DrinkWise,” for reducing drinking among nonpregnant women of childbearing age.

Methods:

A parallel design, phase 1 trial included 185 nonpregnant women reporting risky drinking (8 or more drinks in a week or 3 or more drinks in a day) who were recruited from 2 publicly funded Nutritional Assistance for Women, Infants and Children (WIC) program sites in the United States from 2016 to 2017. Participants were 18 to 44 years in age, 75% of Hispanic ethnicity, 44% Spanish speakers, 30% had not completed high school, and 15% were currently breastfeeding. Participants were randomized to receive (intervention condition, n = 99) or not receive (control condition, no intervention, n = 86) DrinkWise and followed at 3 and 6 months.

Results:

Women receiving DrinkWise had greater reductions in the odds of self-reported weekly alcohol use (odds ratio [OR] = 0.22, SE = 0.12, P < 0.01) and heavy alcohol use (OR = 0.23, SE = 0.14, P < 0.05) at 6-month follow-up than controls, with no group differences at 3-month follow-up. Compared with heavy drinking controls, heavy drinkers receiving DrinkWise showed a trend (P = 0.06) for greater reductions in drink (pour) size from 3- to 6-month follow-up.

Conclusions:

DrinkWise may be efficacious in reducing drinking among low-income women of childbearing age and provides a low-cost tool for increasing access to recommended SBI among childbearing-age women. Studies should continue to build DrinkWise's evidence base.

Trial registration: :

ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02337361
The Association of Preoperative Anemia and the Postoperative Course and Oncological Outcome in Patients Undergoing Rectal Cancer Surgery: A Multicenter Snapshot Study
Authors: Bruns Emma R.J. , Borstlap Wernard A. , van Duijvendijk Peter , van der Zaag-Loonen Hester J. , Buskens Christianne J. , van Munster Barbara C. , Bemelman Willem A. , Tanis Pieter J.
Published: March 2019

BACKGROUND:

There is still controversy about the relationship between preoperative anemia and outcomes after rectal cancer surgery.

OBJECTIVE:

The aim of this study was to analyze the association between preoperative anemia and postoperative complications and the survival of patients undergoing surgery for rectal cancer in the era of laparoscopic surgery and modern perioperative care.

DESIGN:

This was a cohort study.

SETTINGS:

Data were gathered from 71 hospitals in The Netherlands.

PATIENTS:

Patients who underwent resection for rectal cancer in 2011, for whom preoperative hemoglobin level was registered, were included.

INTERVENTIONS(s):

There were no interventions.

MAIN OUTCOME MEASURES:

Short-term outcome parameters were any postoperative complication or mortality within 30 days postoperatively, and pelvic infectious complications defined as anastomotic leakage and presacral abscess. Long-term outcomes were chronic sinus diagnosed at any time during 3-year follow-up, 3-year local and distant recurrence rates, and 3-year overall survival.

RESULTS:

Of 2095 patients, 1857 had a registered preoperative hemoglobin level; 576 (31%) of these patients anemic and 1281 (69%) were nonanemic. Preoperative anemia was not independently associated with postoperative complications (HR, 1.1; 95% CI, 0.9–1.4; p = 0·24) or 30-day mortality (HR, 1.4, 95% CI, 0.7–2.8; p = 0·29). Preoperative anemia was associated with 3-year overall survival (HR, 2.1; 95% CI, 1.7–2.5; p < 0.0001), after multivariable analysis (HR, 1.4; 95% CI, 1.1–1.8; p = 0·008), and with local recurrence rate (HR, 1.6; 95% CI, 1.1–2.4; p = 0.026), but not with distant recurrence rate (HR, 1.2; 95% CI, 1.0–1.5; p = 0.054).

LIMITATIONS:

Preoperative anemia appeared to have only limited association with postoperative and disease-specific outcome after rectal cancer surgery in contrast to published meta-analysis of small historical series.

CONCLUSIONS:

Anemia is associated with overall survival. It might be considered as one of the warning signs in identifying high-risk patients. See Video Abstract at http://links.lww.com/DCR/A913.
Combined Ab Externo Cyclopexy and Cryopexy in Cyclodialysis Cleft Repair
Authors: Liu Xiongfei , Thung Elaine G. , Caprioli Joseph , Law Simon K.
Published: March 2019

Purpose:

To evaluate outcomes of an ab externo surgical technique combining cyclopexy with partial-thickness scleral flap dissection and suture reattachment of ciliary muscle and cryopexy through partial-scleral bed for cyclodialysis cleft repair.

Materials and Methods:

Consecutive patients in a tertiary academic practice with cyclodialysis cleft confirmed by gonioscopy or ultrasound biomicroscopy and had received the combined procedure were reviewed. Primary outcomes included differences between the preoperative and postoperative best-corrected visual acuity (BCVA) and intraocular pressure (IOP). Secondary outcomes included complications and additional surgeries.

Results:

Six consecutive patients (eyes) from October 2006 to November 2012 (6 y) were enrolled. No patient had received prior laser or surgical treatment for cyclodialysis cleft. Patient’s age ranged from 14 to 81 years (median=37 y). Follow-up ranged from 1 to 72 months (median=12 mo). The cyclodialysis clefts of 3 patients (50%) were caused by blunt injuries and the other 3 (50%) from complicated intraocular surgery. Preoperative BCVA ranged from 20/40 to counting fingers with mean IOP of 2.3±2.1 mm Hg (range, 0 to 6 mm Hg). Final postoperative BCVA ranged from 20/20 to hand motions with mean IOP of 11.3±5.7 mm Hg (range, 3 to 18 mm Hg). Five patients (83%) had an increase in IOP and recovery of vision to 20/50 or better at the final visit (including further surgeries). No complication was noted and no additional cyclopexy was required.

Conclusions:

Combined ab externo cyclopexy with partial-thickness scleral flap dissection and suture reattachment of the ciliary muscle and cryopexy delivered on the partial-thickness scleral bed is safe and effective as primary surgical repair for cyclodialysis cleft.
Assistant Independent Self-retaining Truncated Gonioscopy Contact Lens for Minimally Invasive Glaucoma Surgery
Authors: Chalam Kakarla V. , Ng Caleb
Published: March 2019

A new assistant independent self-retaining surgical goniolens provide panoramic view of angle during ocular surgery by means of new optical system that consists of 2 fused elements. First element comprises of a concave lens that mirror corneal curvature with 3 stabilizing feet for retention and stability on corneal surface during surgery. Second element comprise of a fused biconvex lens with prism that direct images of the angle through prism into surgical microscope. This surgical lens can be used for visualization of angle during all glaucoma procedures and especially helpful for performing minimally invasive glaucoma surgery.