bluuebunny/crossref_metadata_2025 huggingface dataset:
New objective measurements of semen wave motion are associated with fertility in sheep
Authors: David I. , Kohnke P. , Fehrenbach J. , Lopes Simoes A. R. , Debreuve E. , Descombes X. , Plouraboue F. , Degond P. , Druart X.
Published: March 2018

In sheep, wave motion in semen is currently used by AI centres to select ejaculates for insemination. Despite its low cost, convenience and established ability to predict fertility, the subjectivity of this assessment is a limiting factor for its applicability. The aims of the present study were to establish an objective method for the analysis of wave motion and to assess the associations of objective parameters with fertility after cervical insemination. Collective sperm motion in undiluted semen was observed by phase contrast microscopy at low magnification in a 100-µm deep glass chamber. Images of moving dark waves over a grey background were recorded and analysed by the optic flow method, producing several velocity-related parameters. Turbulence was assessed from the motion of fluorescent polystyrene beads. Among objective parameters, optical flow entropy and the average speed of beads were both able to discriminate ejaculates suitable for insemination. Two synthetic variables of optic flow and bead motion and a global objective variable were computed from linear combinations of individual parameters and compared with the subjective motion score for their predictive value. These were as efficient as the wave motion score for assessing fertility and can be proposed for the assessment of ram semen in routine AI procedures.
Frequencies, probabilities, and association measures in usage-/exemplar-based linguistics
Authors: Gries Stefan Th.
Published: March 2018

In the last few years, a particular quantitative approach to the syntax-lexis interface has been developed: collostructional analysis (CA). This approach is an application of association measures to co-occurrence data from corpora, from a usage-based/cognitive-linguistic perspective. In spite of some popularity, this approach has come under criticism in Bybee (2010), who criticizes the method for several perceived shortcomings and advocates the use of raw frequencies/percentages instead. This chapter has two main objectives. The first is to refute Bybee’s criticism on theoretical and empirical grounds; the second and further-reaching one is to outline, on the basis of what frequency data really look like, a cline of analytical approaches and, ultimately, a new perspective on the notion of construction based on this cline.
Maskin, maski, masque… in the Spanish and Portuguese creoles of Asia
Authors: Vázquez Veiga Nancy , Fernández Mauro A.
Published: March 2018

While much of the scholarship on the subject of Ibero-Asian pidgins and creoles does contain some mention of the maski/maskin/masque particle, so far no detailed study has been made of the contrasting uses of the form in the different varieties. The prevailing wisdom holds that the particle originated solely from Portuguese mas que, based on the mistaken belief that the same construction in Spanish had no concessive value. In this paper, we will examine the significant variations in the meaning of this particle in the different Portuguese and Spanish creole languages of Asia. Building on that analysis, we will challenge the notion of a common Portuguese origin and show instead how the differences in meaning between Spanish-Philippine creoles and the other varieties in the region came about as a result of the contact that took place between Spanish and the indigenous languages of the Philippines.
Microstructure and properties of laser clad high-entropy alloy coating on aluminium
Authors: Shi Yan , Ni Cong , Liu Jia , Huang Genzhe
Published: March 2018

An AlCrFeNiCuCo high-entropy alloy (HEA) coating was synthesised on an aluminium substrate by laser cladding. Samples were characterised using an optical microscope, X-ray diffraction, scanning electron microscopy with energy-dispersive spectroscopy, a microhardness tester, and an electrochemical workstation. The results showed that the interface between the cladding layer and matrix was sound, while the HEA coating consisted of BCC and FCC solid solutions and an Al-rich phase resulting from substrate dilution. The microstructure of the clad layer comprised both columnar and equiaxed grains. The average microhardness of the coating was 550 HV0.2, and it exhibited better corrosion resistance than the aluminium matrix in a 1 mol L−1 H2SO4 solution. The typical corrosion characteristic of the coating was pitting and localised corrosion.
Using Twitter to Study Public Discourse in the Wake of Judicial Decisions
Authors: Clark Tom S. , Staton Jeffrey K. , Wang Yu , Agichtein Eugene
Published: March 2018

At the intersection of behavioral and institutional studies of policy making lie a series of questions about how elite choices affect mass public opinion. Scholars have considered how judicial decisions—especially US Supreme Court decisions—affect individuals’ support for specific policy positions. These studies yield a series of competing findings. Whereas past research uses opinion surveys to assess how individuals’ opinions are shaped, we believe that modern techniques for analyzing social media provide analytic leverage that traditional approaches do not offer. We present a framework for employing Twitter data to study mass opinion discourse. We find that the Supreme Court’s decisions relating to same-sex marriage in 2013 had significant effects on how the public discussed same-sex marriage and had a polarizing effect on mass opinion. We conclude by connecting these findings and our analyses to larger problems and debates in the area of democratic deliberation and big-data analysis.
Court Leadership, Agenda Transformation, and Judicial Dissent
Authors: Bentsen Henrik Litleré
Published: March 2018

The previous literature debates whether rising rates of dissent are best explained by changes in court leadership and the composition of justices or by greater judicial discretion and changes in agenda. This article examines the influential hypotheses derived from the literature in the relevant and testable European case of the Supreme Court of Norway. It shows that the rising rate of dissent in the Court in the 1990s was mainly catalyzed by fundamental changes to the Court’s discretionary power and by its newfound agenda to work more actively with the development of the law and the protection of human rights.
Gender and Judicial Replacement
Authors: Arrington Nancy B.
Published: March 2018

Employing a matching design on US state supreme court vacancies and replacements from 1970 to 2016, I demonstrate that patterns of judicial replacement are gendered. Vacancies made by women are filled by women at a greater rate than vacancies made by men, and vacancies made by men are filled by men at a greater rate than vacancies made by women. To examine whether these patterns of replacement have systematically suppressed or advantaged the selection of women judges, I compare judicial selections to the gender composition of lawyers. Women are selected to state supreme courts at rates that parallel the gender diversity of lawyers over time, which suggests that gendered patterns of replacement have neither advantaged nor excluded women from state supreme courts in the aggregate.
Testing Legislative Deferral
Authors: Parent Jonathan F.
Published: March 2018

The legislative deferral hypothesis posits that elected policy makers, anxious to avoid the political repercussions of taking clear positions on controversial issues, will actively seek to involve the judiciary in resolving these disputes. This study seeks to further test the legislative deferral theory by considering its applicability to the state level. What is revealed from an examination of the development of abortion policy in New York is that, despite the controversial nature of the issue, lawmakers did not seem to attempt to involve the courts in its resolution, and virtually no policy was created by the state’s judicial branch. I propose an alternative explanation for judicial noninvolvement, borrowing from path-dependence theory, that emphasizes the importance of the initial location of policy change and the issue frames that first took hold around this issue.
A novel computational approach for drug repurposing using systems biology
Authors: Peyvandipour Azam , Saberian Nafiseh , Shafi Adib , Donato Michele , Draghici Sorin
Published: March 2018

Motivation

Identification of novel therapeutic effects for existing US Food and Drug Administration (FDA)-approved drugs, drug repurposing, is an approach aimed to dramatically shorten the drug discovery process, which is costly, slow and risky. Several computational approaches use transcriptional data to find potential repurposing candidates. The main hypothesis of such approaches is that if gene expression signature of a particular drug is opposite to the gene expression signature of a disease, that drug may have a potential therapeutic effect on the disease. However, this may not be optimal since it fails to consider the different roles of genes and their dependencies at the system level.

Results

We propose a systems biology approach to discover novel therapeutic roles for established drugs that addresses some of the issues in the current approaches. To do so, we use publicly available drug and disease data to build a drug-disease network by considering all interactions between drug targets and disease-related genes in the context of all known signaling pathways. This network is integrated with gene-expression measurements to identify drugs with new desired therapeutic effects based on a system-level analysis method. We compare the proposed approach with the drug repurposing approach proposed by Sirota et al. on four human diseases: idiopathic pulmonary fibrosis, non-small cell lung cancer, prostate cancer and breast cancer. We evaluate the proposed approach based on its ability to re-discover drugs that are already FDA-approved for a given disease.

Availability and implementation

The R package DrugDiseaseNet is under review for publication in Bioconductor and is available at https://github.com/azampvd/DrugDiseaseNet.

Supplementary information

Supplementary data are available at Bioinformatics online.
ddPCRclust: an R package and Shiny app for automated analysis of multiplexed ddPCR data
Authors: Brink Benedikt G , Meskas Justin , Brinkman Ryan R
Published: March 2018

Motivation

Droplet digital PCR (ddPCR) is an emerging technology for quantifying DNA. By partitioning the target DNA into ∼20 000 droplets, each serving as its own PCR reaction compartment, a very high sensitivity of DNA quantification can be achieved. However, manual analysis of the data is time consuming and algorithms for automated analysis of non-orthogonal, multiplexed ddPCR data are unavailable, presenting a major bottleneck for the advancement of ddPCR transitioning from low-throughput to high-throughput.

Results

ddPCRclust is an R package for automated analysis of data from Bio-Rad’s droplet digital PCR systems (QX100 and QX200). It can automatically analyze and visualize multiplexed ddPCR experiments with up to four targets per reaction. Results are on par with manual analysis, but only take minutes to compute instead of hours. The accompanying Shiny app ddPCRvis provides easy access to the functionalities of ddPCRclust through a web-browser based GUI.

Availability and implementation

R package: https://github.com/bgbrink/ddPCRclust; Interface: https://github.com/bgbrink/ddPCRvis/; Web: https://bibiserv.cebitec.uni-bielefeld.de/ddPCRvis/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Exploiting and assessing multi-source data for supervised biomedical named entity recognition
Authors: Galea Dieter , Laponogov Ivan , Veselkov Kirill
Published: March 2018

Motivation

Recognition of biomedical entities from scientific text is a critical component of natural language processing and automated information extraction platforms. Modern named entity recognition approaches rely heavily on supervised machine learning techniques, which are critically dependent on annotated training corpora. These approaches have been shown to perform well when trained and tested on the same source. However, in such scenario, the performance and evaluation of these models may be optimistic, as such models may not necessarily generalize to independent corpora, resulting in potential non-optimal entity recognition for large-scale tagging of widely diverse articles in databases such as PubMed.

Results

Here we aggregated published corpora for the recognition of biomolecular entities (such as genes, RNA, proteins, variants, drugs and metabolites), identified entity class overlap and performed leave-corpus-out cross validation strategy to test the efficiency of existing models. We demonstrate that accuracies of models trained on individual corpora decrease substantially for recognition of the same biomolecular entity classes in independent corpora. This behavior is possibly due to limited generalizability of entity-class-related features captured by individual corpora (model ‘overtraining’) which we investigated further at the orthographic level, as well as potential annotation standard differences. We show that the combined use of multi-source training corpora results in overall more generalizable models for named entity recognition, while achieving comparable individual performance. By performing learning-curve-based power analysis we further identified that performance is often not limited by the quantity of the annotated data.

Availability and implementation

Compiled primary and secondary sources of the aggregated corpora are available on: https://github.com/dterg/biomedical_corpora/wiki and https://bitbucket.org/iAnalytica/bioner.

Supplementary information

Supplementary data are available at Bioinformatics online.
Homoeolog-specific activation of genes for heat acclimation in the allopolyploid grass Brachypodium hybridum
Authors: Takahagi Kotaro , Inoue Komaki , Shimizu Minami , Uehara-Yamaguchi Yukiko , Onda Yoshihiko , Mochida Keiichi
Published: March 2018

Background

Allopolyploid plants often show wider environmental tolerances than their ancestors; this is expected to be due to the merger of multiple distinct genomes with a fixed heterozygosity. The complex homoeologous gene expression could have been evolutionarily advantageous for the adaptation of allopolyploid plants. Despite multiple previous studies reporting homoeolog-specific gene expression in allopolyploid species, there are no clear examples of homoeolog-specific function in acclimation to a long-term stress condition.

Results

We found that the allopolyploid grass Brachypodium hybridum and its ancestor Brachypodium stacei show long-term heat stress tolerance, unlike its other ancestor, Brachypodium distachyon. To understand the physiological traits of B. hybridum, we compared the transcriptome of the 3 Brachypodium species grown under normal and heat stress conditions. We found that the expression patterns of approximately 26% and approximately 38% of the homoeolog groups in B. hybridum changed toward nonadditive expression and nonancestral expression, respectively, under normal condition. Moreover, we found that B. distachyon showed similar expression patterns between normal and heat stress conditions, whereas B. hybridum and B. stacei significantly altered their transcriptome in response to heat after 3 days of stress exposure, and homoeologs that were inherited from B. stacei may have contributed to the transcriptional stress response to heat in B. hybridum. After 15 days of heat exposure, B. hybridum and B. stacei maintained transcriptional states similar to those under normal conditions. These results suggest that an earlier response to heat that was specific to homoeologs originating from B. stacei contributed to cellular homeostasis under long-term heat stress in B. hybridum.

Conclusions

Our results provide insights into different regulatory events of the homoeo-transcriptome that are associated with stress acclimation in allopolyploid plants.
Manipulation of successive crystalline transformations to control electron transfer and switchable functions
Authors: Jiao Cheng-Qi , Jiang Wen-Jing , Meng Yin-Shan , Wen Wen , Zhao Liang , Wang Jun-Li , Hu Ji-Xiang , Gurzadyan Gagik G , Duan Chun-Ying , Liu Tao
Published: March 2018

Electron transfer in solid is crucial to switchable magnetic, electrical, optical and mechanical properties. However, it is a formidable challenge to control electron-transfer behaviors via manipulation of crystalline phases, especially through dynamic crystalline transformation. Herein, three crystalline phases of an {Fe2Co2} compound were obtained via enhancement of intermolecular π···π interactions inducing successive single-crystal-to-single-crystal transformations, from solvated 1·2CH3OH·4H2O, to desolvated 1 and its polymorph 1a accompanying electron transfer. 1·2CH3OH·4H2O showed thermally induced reversible intermetallic electron transfer in mother liquor. No electron-transfer behavior was observed in 1. 1a showed reversible intermetallic electron transfer upon thermal treatment or alternative irradiation with 808- and 532-nm lasers at cryogenic temperatures. The electron-transfer behaviors significantly change the magnetic and optical properties, providing a strategy to realize different electron-transfer behaviors and switchable functions via π···π interactions manipulated dynamic crystalline transformation.
Integrative taxonomy resolves three new cryptic species of small southern African horseshoe bats (Rhinolophus)
Authors: Taylor Peter J , Macdonald Angus , Goodman Steven M , Kearney Teresa , Cotterill Fenton P D , Stoffberg Sam , Monadjem Ara , Schoeman M Corrie , Guyton Jennifer , Naskrecki Piotr , Richards Leigh R
Published: March 2018

Examination of historical and recent collections of small Rhinolophus bats revealed cryptic taxonomic diversity within southern African populations previously referred to as R. swinnyi Gough, 1908 and R. landeri Martin, 1832. Specimens from Mozambique morphologically referable to R. swinnyi were phylogenetically unrelated to topotypic R. swinnyi from the Eastern Cape Province of South Africa based on cytochrome b sequences and showed distinctive echolocation, baculum and noseleaf characters. Due to their genetic similarity to a previously reported molecular operational taxonomic unit (OTU) from north-eastern South Africa, Zimbabwe and Zambia, we recognize the available synonym (R. rhodesiae Roberts, 1946) to denote this distinct evolutionary species. This new taxon is genetically identical to R. simulator K. Andersen, 1904 based on mtDNA and nuclear DNA sequences but can easily be distinguished on morphological and acoustic grounds. We attribute this genetic similarity to historical introgression, a frequently documented phenomenon in bats. An additional genetically distinct and diminutive taxon in the swinnyi s.l. group (named herein, R. gorongosae sp. nov.) is described from Gorongosa National Park, central Mozambique. Specimens from Mozambique referable based on morphology to R. landeri were distinct from topotypic landeri from West Africa based on mtDNA sequences, and acoustic, noseleaf and baculum characters. This Mozambique population is assigned to the available synonym R. lobatus Peters, 1952.
Inoculation Method, Temperature, and Relative Humidity Affect Leaf and Neck Anthracnose, a New Onion Disease in Michigan
Authors: Rodriguez-Salamanca Lina M. , Naegele Rachel P. , Quesada-Ocampo Lina M. , Hausbeck Mary K.
Published: March 2018

Leaf and neck anthracnose caused by Colletotrichum coccodes is a new disease of onion in Michigan. To test the effect of inoculation method, Prince onion seedlings were grown in the greenhouse and inoculated with either a conidial suspension of C. coccodes (alone or with an abrasive agent) or infested millet seed (dry or wet, 2 or 5 g). Foliar disease severity was greater when a conidial suspension (>39%) was used compared with infested millet seed (≤24.3%). Growth chamber studies were conducted using Infinity onion seedlings that were inoculated with a conidial suspension spray to determine the effects of temperature (15, 20, 25, or 30°C) and duration (0, 12, 24, 48, or 72 h) of high (95 ± 5%) relative humidity (RH) on disease severity (percentage of leaf area with C. coccodes lesions). Significant differences and interactions among temperature and RH were observed. The combination of high temperature (≥25°C) and extended (≥24 h) high RH resulted in >20% disease severity 28 days postinoculation. Results suggest that onion leaf and neck anthracnose symptoms are likely to be more severe when the environmental conditions are ≥25°C with ≥24 h of high RH.
Fusarium oxysporum f. sp. dianthi virus 1 Accumulation Is Correlated with Changes in Virulence and Other Phenotypic Traits of Its Fungal Host
Authors: Lemus-Minor Carlos Germán , Cañizares M. Carmen , García-Pedrajas María Dolores , Pérez-Artés Encarnación
Published: March 2018

Fusarium oxysporum f. sp. dianthi virus 1 (FodV1) was detected in isolate 116 (116V+) of Fusarium oxysporum f. sp. dianthi, reaching such a high accumulation level that it was clearly visible after agarose gel electrophoresis of total DNA extracts. FodV1 consists of four double-stranded RNA segments that correspond to a new mycovirus in the Chrysoviridae family. We obtained an isolate of F. oxysporum f. sp. dianthi 116 (116V−) with only a residual level of FodV1 RNA accumulation by single-conidia selection. Compared with 116V−, isolate 116V+ showed significant phenotypic alterations in vegetative growth and virulence. Thus, the presence of a high titer of mycovirus FodV1 was associated with a modified morphology and a reduced growth of the colonies on solid medium, and with a diminished conidiation in liquid medium. Inoculation of four susceptible carnation cultivars with either 116V− or 116V+ showed that the presence of a high titer of FodV1 was also correlated with a significantly reduced virulence of its fungal host. All of the results suggest that FodV1 could be associated with hypovirulence, identifying it as a potential biocontrol agent for Fusarium wilt of carnation. This is the first report of a mycovirus potentially associated with the induction of hypovirulence in the species F. oxysporum.
Simulation-Based Assessment of Critical Care “Front-Line” Providers*
Authors: Boyle Walter A. , Murray David J. , Beyatte Mary Beth , Knittel Justin G. , Kerby Paul W. , Woodhouse Julie , Boulet John R.
Published: March 2018

Objectives:

Develop a standardized simulation method to assess clinical skills of ICU providers.

Design:

Simulation assessment.

Setting:

Simulation laboratory.

Subjects:

Residents, Critical Care Medicine fellows, acute care nurse practitioner students.

Interventions:

Performance scoring in scenarios from multiple Critical Care Medicine competency domains.

Measurements and Main Results:

Three-hundred eighty-four performances by 48 participants were scored using checklists (% correct) and holistic “global” ratings (1 [unprepared] to 9 [expert]). One-hundred eighty were scored by two raters. Mean checklist and global scores (± sd) ranged from 65.0% (± 16.3%) to 84.5% (± 17.3%) and 4.7 (± 1.4) to 7.2 (± 1.2). Checklist and global scores for Critical Care Medicine fellows and senior acute care nurse practitioner students (Experienced group, n = 26) were significantly higher than those for the Novice acute care nurse practitioner students (Novice group, n = 14) (75.6% ± 15.6% vs 68.8% ± 21.0% and 6.1 ± 1.6 vs 5.4 ± 1.5, respectively; p < 0.05). Residents (Intermediate group, n = 8) scored between the two (75.4% ± 18.3% and 5.7 ± 1.7). 38.5% of the Experienced group scored in the top quartile for mean global score, compared with 12.5% of the Intermediate and 7.1% of the Novice groups. Conversely, 50% of the Novice group scored in the lower quartile (< 5.3), compared with 37.5% of the Intermediate and 11.5% of the Experienced groups. Psychometric analyses yielded discrimination values greater than 0.3 for most scenarios and reliability for the eight-scenario assessments of 0.51 and 0.60, with interrater reliability of 0.71 and 0.75, for checklist and global scoring, respectively.

Conclusions:

The simulation assessments yielded reasonably reliable measures of Critical Care Medicine decision-making skills. Despite a wide range of performance, those with more ICU training and experience performed better, providing evidence to support the validity of the scores. Simulation-based assessments may ultimately prove useful to determine readiness to assume decision-making roles in the ICU.
Comparison of Antivenom Dosing Strategies for Rattlesnake Envenomation
Authors: Spyres Meghan B. , Skolnik Aaron B. , Moore Elizabeth C. , Gerkin Richard D. , Padilla-Jones Angela , Ruha Anne-Michelle
Published: March 2018

Objectives:

This study compares maintenance with clinical- and laboratory-triggered (as-needed [PRN]) antivenom dosing strategies with regard to patient-centered outcomes after rattlesnake envenomation.

Design:

This is a retrospective cohort study of adult rattlesnake envenomations treated at a regional toxicology center. Data on demographics, envenomation details, antivenom administration, length of stay, and laboratory and clinical outcomes were compared between the PRN and maintenance groups. Primary outcomes were hospital length of stay and total antivenom used, with a hypothesis of no difference between the two dosing strategies.

Setting:

A single regional toxicology center

Patients:

Three-hundred ten adult patients envenomated by rattlesnakes between 2007 and 2014 were included. Patients were excluded if no antivenom was administered or for receiving an antivenom other than Crofab (BTG International, West Conshohocken, PA).

Interventions:

This is a retrospective study of rattlesnake envenomations treated with and without maintenance antivenom dosing.

Main Results:

One-hundred forty-eight in the maintenance group and 162 in the PRN group were included. There was no difference in demographics or baseline envenomation severity or hemotoxicity (32.7% vs 40.5%; respectively; p = 0.158) between the two groups. Comparing the PRN with the maintenance group, less antivenom was used (8 [interquartile range, 6–12] vs 16 [interquartile range, 12–18] vials, respectively; p < 0.001), and hospital length of stay was shorter (27 hr [interquartile range, 20–44 hr] vs 34 hr [interquartile range, 24–43 hr], respectively; p = 0.014). There were no differences in follow-up outcomes of readmission, retreatment, or bleeding and surgical complications.

Conclusions:

Hospital length of stay was shorter, and less antivenom was used in patients receiving a PRN antivenom dosing strategy after rattlesnake envenomation.
Understanding Patients’ Experiences of Diagnosis and Treatment of Advanced Colorectal Cancer in a Safety-Net Hospital System: A Qualitative Study
Authors: Leal Isabel M. , Kao Lillian S. , Karanjawala Burzeen , Escamilla Richard J. , Ko Tien C. , Millas Stefanos G.
Published: March 2018

BACKGROUND:

Greater understanding of barriers to screening of colorectal cancer among lower socioeconomic, particularly Hispanic, patients is needed to improve disparities in care.

OBJECTIVE:

This study aimed to explore patients’ perceptions and experiences of care seeking for colorectal cancer to identify barriers to early diagnosis and treatment.

DESIGN:

This explorative qualitative study was conducted as a focused ethnography of patients diagnosed with advanced-stage colorectal cancer.

SETTINGS:

This study was conducted at an urban safety-net hospital.

PARTICIPANTS:

Thirty lower-income, primarily minority, patients diagnosed with stage III and IV colorectal cancer without prior colorectal cancer screening were selected.

MAIN OUTCOME MEASURES:

The primary outcomes measured were participants’ perceptions and experiences of colorectal cancer and barriers they faced in seeking diagnosis and treatment

RESULTS:

Data analysis yielded 4 themes consistently influencing participants’ decisions to seek diagnosis and treatment: 1) limited resources for accessing care (structural barriers, including economic, health care and health educational resources); 2) (mis)understanding of symptoms by patients; misdiagnosis of symptoms, by physicians; 3) beliefs about illness and health, such as relying on faith, or self-care when symptoms developed; and 4) reactions to illness, including maintenance of masculinity, confusing interactions with physicians, embarrassment, and fear. These 4 themes describe factors on the structural, health care system, provider and patient level, that interact to make engaging in prevention foreign among this population, thus limiting early detection and treatment of colorectal cancer.

LIMITATIONS:

This study was limited by selection bias and the lack of generalizability.

CONCLUSION:

Improving screening rates among lower-income populations requires addressing barriers across the multiple levels, structural, personal, health care system, that patients encounter in seeking care for colorectal cancer. Acknowledging the complex, multilevel influences impacting patient health care choices and behaviors allows for the development of culturally tailored interventions, and educational, financial, and community resources to decrease disparities in cancer screening and care and improve outcomes for these at-risk patients. See Video Abstract at http://links.lww.com/DCR/A473.
Biological Effects From Low Doses and Dose Rates of Ionizing Radiation: Science in the Service of Protecting Humans, a Synopsis
Authors: Feinendegen Ludwig E. , Cuttler Jerry M.
Published: March 2018

There is considerable controversy regarding risk of health detriment after low-level exposure to ionizing radiation. This stems in part from a sort of distance between radiation biologists, epidemiologists, and radiation protection professionals, as well as regulatory institutions. Also, there is a lack of overview of the relevant data and their origins regarding health risks at low doses of ionizing radiation. This feeds seriously into a somewhat hazy fear of ionizing radiation that besets large portions of the public. The current synopsis aims at presenting a holistic view in a concise yet comprehensive manner in order to help people understand the full extent of inputs into attempting to relate low-dose radiation exposure to health risk. It emerges again that different approaches must be found for optimal radiation protection replacing the use of the linear no-threshold (LNT) model.
Factors Associated With Poor Child Motor Vehicle Restraint on the USA–Mexico Border
Authors: Schrodt Alexander , Huynh Tam , Fitzgerald Tamara N.
Published: March 2018

Motor vehicle collisions (MVCs) are a significant cause of pediatric morbidity, particularly in low- to middle-income countries. We describe car seat use in children on the USA–Mexico border. A retrospective review was conducted for children 0–9 years old, admitted to the region's only Level I trauma center. Simultaneously, data were obtained from the SAFE KIDS database, a program that encourages car seat use through city checkpoints. There were 250 MVC admissions and nine fatalities in children 0–9 years old from 2010 to 2015. Nine percent of MVCs occurred in Mexico and 49% in El Paso, TX. Comparing trauma admissions to SAFE KIDS, there was some correlation between the location of MVCs and screening checkpoints (r = .50). There was a weaker correlation between injured children's neighborhoods and screening locations (r = .32). Only 37% of parents knew the crash history of the car seat and 3% were using a car seat previously involved in an MVC. While 96% of inspected children were placed appropriately in the backseat, 80% of children were found to be inappropriately restrained. Younger children more likely to be restrained (p < .05). Children from New Mexico and Mexico had the lowest rates of proper restraint and the highest injury severity scores. Proper use of car seats is a public health concern on the USA–Mexico border, and children are not properly restrained. Screening may be improved by focusing where at-risk children live and where most accidents occur. Restraint education is needed, particularly in New Mexico and Mexico.
Update in Therapeutics: Prophylactic Antibiotics in Open Fractures
Authors: Samai Kathryn , Vilella Antonia
Published: March 2018

Acute management of open fractures is associated with high morbidity and mortality. Recommended antibiotic regimens for all Gustilo–Anderson fracture grades include first-, second-, and third-generation cephalosporins. Expanded gram-negative coverage is recommended for Grade II and III fractures if a first- or second-generation cephalosporin is selected, and additional anaerobic coverage is required if the open fracture is contaminated with organic or farm-related material. Open fractures endure a high rate of bacterial contamination, and antibiotics have demonstrated effectiveness at reducing infection rates when initiated early. Provided that the expected microbial spectrum is covered, antibiotics should be selected on the basis of patient-specific factors and hospital protocols.
Continuing Trauma Care After Discharge, the Experience of Outpatient Trauma Clinics in British Columbia
Authors: Tuyp Benjamin , Hassani Kasra , Thurston Cynthia , Fyvie Kathleen , Constable Lisa
Published: March 2018

The recovery process from traumatic injuries, and the potential for complications, extends beyond the time of hospital discharge. In 2014, the Fraser Health Trauma Network established outpatient clinics to provide follow-up care for trauma patients after discharge from hospital. The following research questions were asked: Which services were commonly performed by our trauma clinics and how satisfied were patients with the care they received at our clinics? A survey was distributed to patients after their clinic visit to assess overall satisfaction and areas for improvement. A retrospective medical record review was performed to illustrate and quantify the interventions provided during clinic visits. During the first 22 months of clinic operation, a total of 412 appointments were scheduled and the attendance rate was 88%. The provided services included obtaining additional imaging (41% of visits), providing wound and brace care (16%), and initiating referrals to specialists (12%). Seventy-seven patient satisfaction surveys were returned during the study period, 34 in 2014 and 43 in 2015. Seventy-four percent of respondents strongly agreed, and 21% agreed that they were satisfied with the care they received in the clinic. Ninety percent found their visit helpful, and only 10% reported having additional medical issues that were not addressed during the appointment. At trauma clinic follow-up, discharged patients have ongoing care requirements, including a need for further investigation, specialist referral, and wound or brace issues that are likely to benefit from specialist trauma care. Patients were satisfied with the care provided by a postdischarge trauma clinic.
pathfindR: An R Package for Pathway Enrichment Analysis Utilizing Active Subnetworks
Authors: Ulgen Ege , Ozisik Ozan , Sezerman Osman Ugur
Published: March 2018

PathfindR is a tool for pathway enrichment analysis utilizing active subnetworks. It identifies gene sets that form active subnetworks in a protein-protein interaction network using a list of genes provided by the user. It then performs pathway enrichment analyses on the identified gene sets. Further, using the R package pathview, it maps the user data on the enriched pathways and renders pathway diagrams with the mapped genes. Because many of the enriched pathways are usually biologically related, pathfindR also offers functionality to cluster these pathways and identify representative pathways in the clusters. PathfindR is built as a stand-alone package but it can easily be integrated with other tools, such as differential expression/methylation analysis tools, for building fully automated pipelines. In this article, an overview of pathfindR is provided and an example application on a rheumatoid arthritis dataset is presented and discussed.

Availability

The package is freely available under MIT license at:https://github.com/egeulgen/pathfindR
Genome-wide measurement of local nucleosome array regularity and spacing by nanopore sequencing
Authors: Baldi Sandro , Krebs Stefan , Blum Helmut , Becker Peter B.
Published: March 2018

The nature of chromatin as regular succession of nucleosomes has gained iconic status. However, since most nucleosomes in metazoans are poorly positioned it is unknown to which extent the bulk genomic nucleosome repeat length (NRL) reflects the regularity and spacing of nucleosome arrays at individual loci. We describe a new approach to map nucleosome array regularity and spacing through sequencing oligonucleosome-derived DNA by Illumina sequencing as well as emergent nanopore-technology. This revealed modulation of array regularity and NRL depending on functional chromatin states independently of nucleosome phasing and even in unmappable regions. We also found that nucleosome arrays downstream of silent promoters are considerably more regular than those downstream of highly expressed ones, despite more extensive nucleosome phasing of the latter. Our approach is generally applicable and provides an important parameter of chromatin organisation that so far had been missing.
Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood
Authors: Qi Ting , Wu Yang , Zeng Jian , Zhang Futao , Xue Angli , Jiang Longda , Zhu Zhihong , Kemper Kathryn , Yengo Loic , Zheng Zhili ,   eQTLGen Consortium, Marioni Riccardo E. , Montgomery Grant W. , Deary Ian J. , Wray Naomi R. , Visscher Peter M. , McRae Allan F. , Yang Jian
Published: March 2018

Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes associated with brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top associated cis-expression (cis-eQTLs or cis-mQTLs) between brain and blood for genes expressed (or CpG sites methylated) in both tissues, while accounting for errors in their estimated effects (rb). Using publicly available data (n = 72 to l,366), we find that the genetic effects of cis-eQTLs (PeQTL < 5×10−8) or mQTLs (PmQTL < 1×10−10) are highly correlated between independent brain and blood samples ( with SE = 0.015 for cis-eQTL and with SE = 0.006 for cis-mQTLs). Using meta-analyzed brain eQTL/mQTL data (n = 526 to 1,194), we identify 61 genes and 167 DNA methylation (DNAm) sites associated with 4 brain-related traits and disorders. Most of these associations are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = l,980 to 14,115). We further find that cis-eQTLs with tissue-specific effects are approximately uniformly distributed across all the functional annotation categories, and that mean difference in gene expression level between brain and blood is almost independent of the difference in the corresponding cis-eQTL effect. Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL or cis-mQTL data with large sample sizes.
The importance of semantic network brain regions in integrating prior knowledge with an ongoing dialogue
Authors: Raykov Petar P. , Keidel James L. , Oakhill Jane , Bird Chris M.
Published: March 2018

To understand a dialogue we need to know the specific topics that are being discussed. This enables us to integrate our knowledge of what was said previously, in order to interpret the current dialogue. Here, we selectively manipulated knowledge about the narrative content of dialogues between two people, presented in short videos. The videos were clips taken from television situation comedies and the speech in the first-half of the clip could either be presented normally (high context) or spectrally rotated in order to render it unintelligible (low context). Knowledge of the preceding narrative boosted memory for the following dialogues as well as increased the inter-subject semantic similarity of recalled descriptions of the dialogues. Sharing knowledge of the preceding narrative across participants had two effects on fMRI markers of neural processing: (1) it strengthened temporal inter-subject correlations in regions including the left angular (AG) and inferior frontal gyri (IFG), and (2) it increased spatial inter-subject pattern similarity in the bilateral anterior temporal lobes (ATL). We argue that these brain regions, which are known to be involved in semantic processing, support the activation and integration of prior knowledge, which helps people to better understand and remember dialogues as they unfold.
High-throughput inference of pairwise coalescence times identifies signals of selection and enriched disease heritability
Authors: Palamara Pier Francesco , Terhorst Jonathan , Song Yun S. , Price Alkes L.
Published: March 2018

Interest in reconstructing demographic histories has motivated the development of methods to estimate locus-specific pairwise coalescence times from whole-genome sequence data. We developed a new method, ASMC, that can estimate coalescence times using only SNP array data, and is 2-4 orders of magnitude faster than previous methods when sequencing data are available. We were thus able to apply ASMC to 113,851 phased British samples from the UK Biobank, aiming to detect recent positive selection by identifying loci with unusually high density of very recent coalescence times. We detected 12 genome-wide significant signals, including 6 loci with previous evidence of positive selection and 6 novel loci, consistent with coalescent simulations showing that our approach is well-powered to detect recent positive selection. We also applied ASMC to sequencing data from 498 Dutch individuals (Genome of the Netherlands data set) to detect background selection at deeper time scales. We observed highly significant correlations between average coalescence time inferred by ASMC and other measures of background selection. We investigated whether this signal translated into an enrichment in disease and complex trait heritability by analyzing summary association statistics from 20 independent diseases and complex traits (averageN=86k) using stratified LD score regression. Our background selection annotation based on average coalescence time was strongly enriched for heritability (p = 7×10−153) in a joint analysis conditioned on a broad set of functional annotations (including other background selection annotations), meta-analyzed across traits; SNPs in the top 20% of our annotation were 3.8x enriched for heritability compared to the bottom 20%. These results underscore the widespread effects of background selection on disease and complex trait heritability.
Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control
Authors: Chilloux Julien , Brial Francois , Everard Amandine , Smyth David , Andrikopoulos Petros , Zhang Liyong , Plovier Hubert , Myridakis Antonis , Hoyles Lesley , Moreno-Navarrete José Maria , Luque Jèssica Latorre , Casagrande Viviana , Menghini Rosella , Ahmetaj-Shala Blerina , Blancher Christine , Martinez-Gili Laura , Gencer Selin , Fearnside Jane F. , Barton Richard H. , Neves Ana Luisa , Rothwell Alice R. , Gérard Christelle , Calderari Sophie , Williamson Mark J. , Fuchs Julian E. , Govada Lata , Boulangé Claire L. , Patel Saroor , Scott James , Thursz Mark , Chayen Naomi , Glen Robert C. , Gooderham Nigel J. , Nicholson Jeremy K. , Federici Massimo , Fernández-Real José-Manuel , Gauguier Dominique , Liu Peter P. , Cani Patrice D. , Dumas Marc-Emmanuel
Published: March 2018

The global type 2 diabetes epidemic is a major health crisis and there is a critical need for innovative strategies to fight it. Although the microbiome plays important roles in the onset of insulin resistance (IR) and low-grade inflammation, the microbial compounds regulating these phenomena remain to be discovered. Here, we reveal that the microbiome inhibits a central kinase, eliciting immune and metabolic benefits. Through a series ofin vivoexperiments based on choline supplementation, blocking trimethylamine (TMA) production then administering TMA, we demonstrate that TMA decouples inflammation and IR from obesity in the context of high-fat diet (HFD) feeding. Throughin vitrokinome screens, we reveal TMA specifically inhibits Interleukin-1 Receptor-associated Kinase 4 (IRAK4), a central kinase integrating signals from various toll-like receptors and cytokine receptors. TMA blunts TLR4 signalling in primary human hepatocytes and peripheral blood monocytic cells, and improves mouse survival after a lipopolysaccharide-induced septic shock. Consistent with this, genetic deletion and chemical inhibition of IRAK4 result in similar metabolic and immune improvements in HFD. In summary, TMA appears to be a key microbial compound inhibiting IRAK4 and mediating metabolic and immune effects with benefits upon HFD. Thereby we highlight the critical contribution of the microbial signalling metabolome in homeostatic regulation of host disease and the emerging role of the kinome in microbial–mammalian chemical crosstalk.
The effect of strain level diversity on robust inference of virus-induced mortality
Authors: Beckett Stephen J. , Weitz Joshua S.
Published: March 2018

Infection and lysis of phytoplankton by viruses affects population dynamics and nutrient cycles within oceanic microbial communities. However, estimating the quantitative rates of viral-induced lysis remains challenging in situ. The modified dilution method is the most commonly utilised empirical approach to estimate virus-induced killing rates of phytoplankton. The lysis rate estimates of the modified dilution method are based on models of virus-host interactions involving only a single virus and a single host population. Here, using modelling approaches, we examine the robustness of the modified dilution method in multi-strain, complex communities. We assume that strains differ in their life history traits, including growth rates (of hosts) and lysis rates (by viruses). We show that trait differences affect resulting experimental dynamics such that lysis rates measured using the modified dilution method may be driven by the fastest replicating strains; which are not necessarily the most abundant in situ. We discuss the implications of using the modified dilution method and alternative dilution-based approaches for estimating viral-induced lysis rates in marine microbial communities.
Layer 3 dynamically coordinates columnar activity according to spatial context
Authors: Plomp Gijs , Larderet Ivan , Fiorini Matilde , Busse Laura
Published: March 2018

Spatial integration is a fundamental, context-dependent neural operation that involves extensive neural circuits across cortical layers of V1. To better understand how spatial integration is dynamically coordinated across layers we recorded single- and multi-unit activity and local field potentials across V1 layers of awake mice, and used dynamic Bayesian model comparisons to identify when laminar activity and inter-laminar functional interactions showed surround suppression, the hallmark of spatial integration. We found that surround suppression is strongest in layer 3 (L3) and L4 activity, showing rapidly sharpening receptive fields and increasing suppression strength. Importantly, we also found that specific directed functional connections were strongest for intermediate stimulus sizes and suppressed for larger ones, particularly for the L3->L5 and L3->L1 connections. Taken together, the results shed light on the different functional roles of cortical layers in spatial integration and show how L3 dynamically coordinates activity across a cortical column depending on spatial context.