bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Specimen Collection Technology in the Reduction of Collection Turnaround Time and Mislabeled Specimens in Emergency, Medical-Surgical, Critical Care, and Maternal Child Health Departments
Authors: Saathoff April M. , MacDonald Ryan , Krenzischek Erundina
Published: November 2017

The objective of this study was to evaluate the impact of specimen collection technology implementation featuring computerized provider order entry, positive patient identification, bedside specimen label printing, and barcode scanning on the reduction of mislabeled specimens and collection turnaround times in the emergency, medical-surgical, critical care, and maternal child health departments at a community teaching hospital. A quantitative analysis of a nonrandomized, pre-post intervention study design evaluated the statistical significance of reduction of mislabeled specimen percentages and collection turnaround times affected by the implementation of specimen collection technology. Mislabeled specimen percentages in all areas decreased from an average of 0.020% preimplementation to an average of 0.003% postimplementation, with a P < .001. Collection turnaround times longer than 60 minutes decreased after the implementation of specimen collection technology by an average of 27%, with a P < .001. Specimen collection and identification errors are a significant problem in healthcare, contributing to incorrect diagnoses, delayed care, lack of essential treatments, and patient injury or death. Collection errors can also contribute to an increased length of stay, increased healthcare costs, and decreased patient satisfaction. Specimen collection technology has structures in place to prevent collection errors and improve the overall efficiency of the specimen collection process.
Parvalbumin-containing GABA cells and schizophrenia: experimental model based on targeted gene delivery through adeno-associated viruses
Authors: Woloszynowska-Fraser Marta U. , Wulff Peer , Riedel Gernot
Published: November 2017

Understanding the contribution of transmitter systems in behavioural pharmacology has a long tradition. Multiple techniques such as transmitter-specific lesions, and also localized administration of pharmacological toxins including agonists and antagonists of selected receptors have been applied. More recently, modern genetic tools have permitted cell-type selective interferences, for example by expression of light-sensitive channels followed by optogenetic stimulation in behaviourally meaningful settings or by engineered channels termed DREADDS that respond to peripherally administered drugs. We here took a similar approach and employed a Cre recombinase-dependent viral delivery system (adeno-associated virus) to express tetanus toxin light chain (TeLc) and thus, block neural transmission specifically in parvalbumin-positive (PV+) neurons of the limbic and infralimbic prefrontal circuitry. PV-TeLc cohorts presented with normal circadian activity as recorded in PhenoTyper home cages, but a reproducible increase in anxiety was extracted in both the open field and light–dark box. Interestingly, working memory assessed in a spontaneous alternation Y-maze task was impaired in PV-TeLc mice. We also recorded local field potentials from a separate cohort and found no global changes in brain activity, but found a behaviourally relevant lack of modulation in the gamma spectral band. These anomalies are reminiscent of endophenotypes of schizophrenia and appear to be critically dependent on GABAergic signalling through PV neurones. At the same time, these observations validate the use of viral vector delivery and its expression in Cre-lines as a useful tool for understanding the role of selective components of the brain in behaviour and the underpinning physiology.
Clinicians’ ability, motivation, and opportunity to acquire and transfer knowledge: An age-driven perspective
Authors: Profili Silvia , Sammarra Alessia , Dandi Roberto , Mascia Daniele
Published: November 2017

Background:

Many countries are seeing a dramatic increase in the average age of their clinicians. The literature often highlights the challenges of high replacement costs and the need for strategies to retain older personnel. Less discussed are the potential pitfalls of knowledge acquisition and transfer that accompany this aging issue.

Purpose:

We propose a conceptual framework for understanding how clinicians' age interact with ability, motivation, and opportunity to predict clinical knowledge transfer and acquisition in health care organizations.

Approach:

This study integrates life-span development perspectives with the ability–motivation–opportunity framework to develop a number of testable propositions on the interaction between age and clinicians’ ability, motivation, and opportunity to acquire and transfer clinical knowledge.

Results:

We posit that the interaction between ability (the knowledge and skills to acquire knowledge), motivation (the willingness to acquire and transfer knowledge), and opportunity (resources required for acquiring and transferring knowledge) is a determinant of successful knowledge management. We also suggest that clinicians' age—and more specifically, the cognitive and motivational changes that accompany aging—moderates these relationships.

Conclusion:

This study contributes to existing research by offering a set of testable propositions for future research. These propositions will hopefully encourage empirical research into this important topic and lead to guidelines for reducing the risks of organizational knowledge loss due to aging.

Practice Implications:

We suggest several ways that health care organizations can tailor managerial practices in order to help capitalize on the knowledge-based resources held by their younger and older clinicians. Such initiatives may affect employees’ ability (e.g., by providing specific training programs), motivation (e.g., by expanding subjective perceptions of future time at work), and opportunities (e.g., by providing mentoring, reverse mentoring, and coaching programs) to acquire and transfer knowledge.
Analysis of Patient Follow-Up at a Level I Trauma Center in Ohio
Authors: Fletcher Brian , Meyers Tami , Guilliams Michelle , Poliseno Teresa , Burton Josh , Lieber Michael , Buggie Ed , O'Mara M. Shay
Published: November 2017

Trauma patients report being unprepared for hospital discharge. The purpose of this study was to identify follow-up compliance rates at our trauma clinic and identify factors associated with trauma patients' adherence to follow-up appointment. We recruited patients 15 years and older who were discharged from the trauma service between December 2014 and August 2015. Demographic information and injury-related variables were obtained from the trauma registry for patients who attended their follow-up and those who did not attend. Follow-up appointment weather data were collected. All patients were surveyed regarding barriers to compliance. There was no difference in demographics, number of intensive care unit days, length of stay, or distance to the clinic. On days with rain or snow, patients were less likely to follow-up. Patients were more likely to follow-up on warmer days, and maximum daily air temperature was an independent predictor of follow-up compliance. Mechanism of injury and trauma activations were associated with higher follow-up compliance. Trauma patients are overall compliant with postdischarge follow-up appointments. There are no consistent factors related to trauma follow-up when compared with similar follow-up studies.
Improving Patient Experience Through Nursing Satisfaction
Authors: McNicholas Amanda , McCall Abby , Werner Alanna , Wounderly Ronda , Marinchak Erin , Jones Pamela
Published: November 2017

Patient experience is a vital component of quality health care. In our institution we sought to improve both nursing satisfaction and collaboration, in conjunction with improving patient experience, predicting the two are directly proportional. We hypothesized that a more satisfied nursing team would result in an overall improvement in patient experience. To explore this hypothesis, we implemented multiple process changes to create an advanced practitioner-directed floor (APDF) on our 28-bed trauma, medical-surgical unit. These changes included advanced practitioner (AP) 24-hr coverage, implementation of trauma patient information packets, consistent daily rounds with the nurse facilitator and/or bedside registered nurse (RN), and increased floor presence of the AP, to facilitate improved communication between the multidisciplinary team. Nursing satisfaction surveys, postdischarge patient telephone debriefings, and patient Press Ganey scores were analyzed to assess nursing satisfaction, as well as patient satisfaction pre- and postimplemented changes. Our findings demonstrated that, following APDF implementation, RNs felt more respected, stated that the trauma team was more collaborative, and, in addition, overall patient and nursing satisfaction improved. On the basis of our data collection and perspective from nursing staff and nursing management, we support the institution of an APDF to target improvements in nursing satisfaction, by focusing on collaboration and professional practice.
eFAST Simulation Training for Trauma Providers
Authors: Pencil Kristie
Published: November 2017

Current trauma recommendations include completing chest and pelvis radiographs and Focused Abdominal Sonography in Trauma (FAST) examination in the trauma bay; however, expanding literature indicates that thoracic ultrasound scans are more sensitive than chest radiography in the detection of pneumothorax. In an urban, Level II trauma center in central Ohio, the author implemented an evidence-based practice project. This project focused on a lack of provider knowledge of the expanded Focused Abdominal Sonography in Trauma (eFAST) examination. The training consisted of a lecture and a simulation training session. To monitor the success of the implementation, pre- and postimplementation testing of the provider's competence with the eFAST technique using the Objective Structured Assessment of Ultrasound Skills (OSAUS) was completed. The pre- and posttest implementation showed an increase of the OSAUS score by 16.9%. The author also reviewed charts pre- and postimplementation to demonstrate the utilization rates of eFAST. After training, the utilization rates increased by 66% (p < .05). Overall, the project implementation was a success and demonstrated the importance of frequent literature review and implementation of this literature into practice.
The Application of Observational Practice and Educational Networking in Simulation-Based and Distributed Medical Education Contexts
Authors: Welsher Arthur , Rojas David , Khan Zain , VanderBeek Laura , Kapralos Bill , Grierson Lawrence E.M.
Published: November 2017

Introduction

Research has revealed that individuals can improve technical skill performance by viewing demonstrations modeled by either expert or novice performers. These findings support the development of video-based observational practice communities that augment simulation-based skill education and connect geographically distributed learners. This study explores the experimental replicability of the observational learning effect when demonstrations are sampled from a community of distributed learners and serves as a context for understanding learner experiences within this type of training protocol.

Methods

Participants from 3 distributed medical campuses engaged in a simulation-based learning study of the elliptical excision in which they completed a video-recorded performance before being assigned to 1 of 3 groups for a 2-week observational practice intervention. One group observed expert demonstrations, another observed novice demonstrations, and the third observed a combination of both. Participants returned for posttesting immediately and 1 month after the intervention. Participants also engaged in interviews regarding their perceptions of the usability and relevance of video-based observational practice to clinical education.

Results

Checklist (P < 0.0001) and global rating (P < 0.0001) measures indicate that participants, regardless of group assignment, improved after the intervention and after a 1-month retention period. Analyses revealed no significant differences between groups. Qualitative analyses indicate that participants perceived the observational practice platform to be usable, relevant, and potentially improved with enhanced feedback delivery.

Conclusions

Video-based observational practice involving expert and/or novice demonstrations enhances simulation-based skill learning in a group of geographically distributed trainees. These findings support the use of Internet-mediated observational learning communities in distributed and simulation-based medical education contexts.
Nystagmus
Authors: Tarnutzer Alexander A. , Straumann Dominik
Published: November 2017

Purpose of review

The clinical and laboratory assessment of nystagmus in patients with neurologic disorders can provide crucial elements for a state-of-the-art differential diagnosis. An increasing number of publications in the fields of neuro-otology and neuro-ophthalmology have nystagmus in the center of interest, which makes frequent updates on the diagnostic and therapeutic relevance of these contributions indispensable. This review covers important clinical studies and studies in basic research relevant for the neurologist published from January 2016 to August 2017.

Recent findings

Current themes include vestibular nystagmus, positional nystagmus, optokinetic nystagmus and after-nystagmus, vibration-induced nystagmus, head-shaking nystagmus, postrotatory nystagmus, caloric nystagmus, nystagmus in cerebellar disorders, differential diagnosis of nystagmus and treatment approaches (whereas infantile nystagmus syndrome is not addressed in this review). These studies address mechanisms/pathomechanisms, differential diagnoses and treatment of different forms of nystagmus.

In clinical practice, a structured description of nystagmus including its three-dimensional beating direction, trigger factors and duration is of major importance. The differential diagnosis of downbeat nystagmus is broad and includes acute intoxications, neurodegenerative disorders and cerebrovascular causes amongst others. In patients with positional nystagmus, the distinction between frequent benign peripheral and rare but dangerous central causes is imperative.
Physical trade-offs shape the evolution of buoyancy control in sharks
Authors: Gleiss Adrian C. , Potvin Jean , Goldbogen Jeremy A.
Published: November 2017

Buoyancy control is a fundamental aspect of aquatic life that has major implications for locomotor performance and ecological niche. Unlike terrestrial animals, the densities of aquatic animals are similar to the supporting fluid, thus even small changes in body density may have profound effects on locomotion. Here, we analysed the body composition (lipid versus lean tissue) of 32 shark species to study the evolution of buoyancy. Our comparative phylogenetic analyses indicate that although lean tissue displays minor positive allometry, liver volume exhibits pronounced positive allometry, suggesting that larger sharks evolved bulkier body compositions by adding lipid tissue to lean tissue rather than substituting lean for lipid tissue, particularly in the liver. We revealed a continuum of buoyancy control strategies that ranged from more buoyant sharks with larger livers in deeper ecosystems to relatively denser sharks with small livers in epipelagic habitats. Across this eco-morphological spectrum, our hydrodynamic modelling suggests that neutral buoyancy yields lower drag and more efficient steady swimming, whereas negative buoyancy may be more efficient during accelerated movements. The evolution of buoyancy control in sharks suggests that ecological and physiological factors mediate the selective pressures acting on these traits along two major gradients, body size and habitat depth.
Anticipatory flexibility: larval population density in moths determines male investment in antennae, wings and testes
Authors: Johnson Tamara L. , Symonds Matthew R. E. , Elgar Mark A.
Published: November 2017

Developmental plasticity provides individuals with a distinct advantage when the reproductive environment changes dramatically. Variation in population density, in particular, can have profound effects on male reproductive success. Females may be easier to locate in dense populations, but there may be a greater risk of sperm competition. Thus, males should invest in traits that enhance fertilization success over traits that enhance mate location. Conversely, males in less dense populations should invest more in structures that will facilitate mate location. In Lepidoptera, this may result in the development of larger antennae to increase the likelihood of detecting female sex pheromones, and larger wings to fly more efficiently. We explored the effects of larval density on adult morphology in the gum-leaf skeletonizer moth,Uraba lugens, by manipulating both the number of larvae and the size of the rearing container. This experimental arrangement allowed us to reveal the cues used by larvae to assess whether absolute number or density influences adult responses. Male investment in testes size depended on the number of individuals, while male investment in wings and antennae depended upon larval density. By contrast, the size of female antennae and wings were influenced by an interaction of larval number and container size. This study demonstrates that male larvae are sensitive to cues that may reveal adult population density, and adjust investment in traits associated with fertilization success and mate detection accordingly.
EpiModel: AnRPackage for Mathematical Modeling of Infectious Disease over Networks
Authors: Jenness Samuel M. , Goodreau Steven M. , Morris Martina
Published: November 2017

EpiModelprovides tools for building, simulating, and analyzing mathematical models for the population dynamics of infectious disease transmission in R. Several classes of models are included, but the unique contribution of this software package is a general stochastic framework for modeling the spread of epidemics on networks. This framework integrates recent advances in statistical methods for network analysis, temporal exponential random graph models, which allows the epidemic modeling to be firmly grounded in empirical data on the contacts and persistent partnerships that can spread infection. This article provides an overview of both the modeling tools built intoEpiModel, designed to facilitate learning for students new to modeling, and the application programming interface for extendingEpiModel, designed to facilitate the exploration of novel research questions for advanced modelers.
Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks
Authors: Leland Bryan A. , Chen Angela C. , Zhao Amy Y. , Wharton Robert C. , King Megan C.
Published: November 2017

Poly(ADP ribose) polymerase inhibitors (PARPi) target cancer cells deficient in homology-directed repair of DNA double-strand breaks (DSBs). In preclinical models, PARPi resistance is tied to altered nucleolytic processing (resection) at the 5’ ends of a DSB. For example, loss of 53BP1 or Rev7/MAD2L2/FANCV derepresses resection to drive PARPi resistance, although the mechanisms are poorly understood. Long-range resection can be catalyzed by two machineries: the exonuclease Exo1, or the combination of a RecQ helicase and Dna2. Here, we develop a single cell microscopy assay that allows the distinct phases and machineries of resection to be interrogated simultaneously in living S. pombe cells. Using this assay, we find that the 53BP1 orthologue and Rev7 specifically repress long-range resection through the RecQ helicase-dependent pathway, thereby preventing hyper-resection. These results suggest that “rewiring” of BRCA1-deficient cells to employ an Exo1-independent hyper-resection pathway is a driver of PARPi resistance.
Genome-wide analysis yields new loci associating with aortic valve stenosis
Authors: Helgadottir Anna , Thorleifsson Gudmar , Gretarsdottir Solveig , Stefansson Olafur A. , Tragante Vinicius , Thorolfsdottir Rosa B. , Jonsdottir Ingileif , Bjornsson Thorsteinn , Steinthorsdottir Valgerdur , Verweij Niek , Nielsen Jonas B. , Zhou Wei , Folkersen Lasse , Martinsson Andreas , Heydarpour Mahyar , Prakash Siddharth , Oskarsson Gylfi , Gudbjartsson Tomas , Geirsson Arnar , Olafsson Isleifur , Sigurdsson Emil L. , Almgren Peter , Melander Olle , Franco-Cereceda Anders , Hamsten Anders , Fritsche Lars , Lin Maoxuan , Yang Bo , Hornsby Whitney , Guo Dongchuan , Brummett Chad M. , Abecasis Gonçalo , Mathis Michael , Milewicz Dianna , Body Simon C. , Eriksson Per , Willer Cristen J. , Hveem Kristian , Newton-Cheh Christopher , Smith J. Gustav , Danielsen Ragnar , Thorgeirsson Gudmundur , Thorsteinsdottir Unnur , Gudbjartsson Daniel F. , Holm Hilma , Stefansson Kari
Published: November 2017

Aortic valve stenosis (AS) is the most common valvular heart disease, characterized by a thickened and calcified valve causing left ventricular outflow obstruction. Severe AS is a significant cause of morbidity and mortality, affecting approximately 5% of those over 70 years of age1,2,3. Little is known about the genetics of AS, although recently a variant at the LPA locus4 and a rare MYH6 missense variant were found to associate with AS5. We report a large genome-wide association study (GWAS) with a follow-up in up to 7,307 AS cases and 801,073 controls. We identified two new AS loci, on chromosome 1p21 near PALMD (rs7543130; OR=1.20, P=1.2×10−22) and on chromosome 2q22 in TEX41 (rs1830321; OR=1.15, P=1.8×10−13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR=1.28, P=6.6×10−10) and aortic root diameter (P=1.30×10−8) and rs1830321 associates with BAV (OR=1.12, P=5.3×10−3 and coronary artery disease (CAD) (OR=1.05, P=9.3×10−5). These results indicate that AS is partly rooted in the same processes as cardiac development and atherosclerosis.
Influence of APOA5 locus on the treatment efficacy of three statins: evidence from a randomized pilot study in Chinese subjects
Authors: Hua Sha , Ma Chuanxiang , Zhang Jun , Li Jing , Wu Weiwei , Xu Ning , Luo Guanghua , Zhao Jianrong
Published: November 2017

Pharmacogenetics or pharmacogenomics approaches are important for addressing the individual variabilities of drug efficacy especially in the era of precision medicine. One particular interesting gene to investigate is APOA5 which has been repeatedly linked with the inter-individual variations of serum triglycerides. Here, we explored APOA5-statin interactions in 195 Chinese subjects randomized to rosuvastatin (5-10 mg/day), atorvastatin (10-20 mg/day), or simvastatin (40 mg/day) for 12 weeks by performing a targeted genotyping analysis of the APOA5 promoter SNP rs662799 (-1131T>C). There were no significant differences between the treatment arms for any of the statin-induced changes in clinical biomarkers. Reductions in LDL cholesterol were influenced by the APOA5 genotype in all three treatment groups. By contrast, changes in HDL cholesterol and triglycerides were only affected by the APOA5 genotype in the atorvastatin and simvastatin groups and not in the rosuvastatin group. Our results support earlier findings indicating that rosuvastatin is a better treatment option and that future studies should consider stratifying subjects not only by genetic background but also by statin type.

Abbreviations

ApoA5

apolipoprotein A5

BMI

body mass index

FFA

free fatty acids

HDLc

high-density lipoprotein cholesterol

LDLc

low-density lipoprotein cholesterol

Lp(a)

lipoprotein(a)

SNP

single nucleotide polymorphism

T2D

type 2 diabetes

Tc

total cholesterol

Tg

triglycerides.
The spent culture supernatant ofPseudomonas syringaecontains azelaic acid
Authors: Javvadi Sree Gowrinadh , Cescutti Paola , Rizzo Roberto , Lonzarich Valentina , Navarini Luciano , Licastro Danilo , Guarnaccia Corrado , Venturi Vittorio
Published: November 2017

Pseudomonas syringaepv.actinidiae(PSA) is an emerging kiwifruit bacterial pathogen which since 2008 has caused considerable losses. No quorum sensing (QS) signaling molecule has yet been reported from PSA and the aim of this study was to identify possible intercellular signals produced by PSA. A metabolome analysis resulted in the identification of 83 putative compounds, one of them was the nine carbon saturated dicarboxylic acid azelaic acid which for several reasons was decided to further study. Firstly azelaic acid, which is a straight chained nine-carbon (C9) saturated dicarboxylic acid, has been reported in plants as mobile signal that primes systemic defenses. Secondly its structure, which is associated with fatty acid biosynthesis, is similar to other known bacterial QS signals like the Diffusible Signal Facor (DSF). Analytical and structural studies by NMR spectroscopy confirmed that in the PSA spent supernatant azelaic acid was present. Quantification studies further revealed that 20 µg/L of azelaic acid was present and was also found in spent supernatants of several otherP. syringaepathovars. An RNAseq transcriptome study however did not reveal whether azelaic acid behaved as a QS molecule. This is the first report of the possible natural biosynthesis of azelaic acid by bacteria.
RNA virus interference via CRISPR/Cas13a system in plants
Authors: Aman Rashid , Ali Zahir , Butt Haroon , Mahas Ahmed , Aljedaani Fatima , Khan Muhammad Zuhaib , Ding Shouwei , Mahfouz Magdy
Published: November 2017

CRISPR/Cas systems confer immunity against invading nucleic acids and phages in bacteria and archaea. CRISPR/Cas13a (known previously as C2c2) is a class 2 type VI-A ribonuclease capable of targeting and cleaving single stranded RNA (ssRNA) molecules of the phage genome. Here, we employ CRISPR/Cas13a to engineer interference with an RNA virus, Turnip Mosaic Virus (TuMV), in plants. CRISPR/Cas13a produced interference against green fluorescent protein (GFP) expressing TuMV in transient assays and stable overexpression lines of Nicotiana benthamiana. crRNAs targeting the HC-Pro and GFP sequences exhibited better interference than those targeting other regions such as coat protein (CP) sequence. Cas13a can also process pre-crRNAs into functional crRNAs. Our data indicate that CRISPR/Cas13a can be used for engineering interference against RNA viruses, providing a potential novel mechanism for RNA-guided immunity against RNA viruses, and for other RNA manipulations in plants.
Machine Learning of the Cardiac Phenome and Skin Transcriptome to Categorize Heart Disease in Systemic Sclerosis
Authors: Hinchcliff Monique E. , Frech Tracy M. , Wood Tammara A. , Huang Chiang-Ching , Lee Jungwha , Aren Kathleen , Ryan John J. , Wilson Brent , Beussink-Nelson Lauren , Whitfield Michael L. , Deo Rahul C. , Shah Sanjiv J.
Published: November 2017

Background

Cardiac involvement is a leading cause of death in systemic sclerosis (SSc/scleroderma). The complexity of SSc cardiac manifestations is not fully captured by the current clinical SSc classification, which is based on extent of skin involvement and specific autoantibodies. Therefore, we sought to develop a clinically relevant SSc cardiac disease classification to improve clinical care and increase understanding of SSc cardiac disease pathobiology. We hypothesized that machine learning could identify novel SSc cardiac disease subgroups, and that gene expression assessment of skin could provide insights into molecular pathogenesis of these SSc pheno-groups.

Methods

We used unsupervised model-based clustering (phenomapping) of SSc patient echocardiographic and clinical data to identify clinically relevant SSc pheno-groups in a discovery cohort (n=316), and validated these findings in an external SSc validation cohort (n=67). Cox regression was used to evaluate survival differences among groups. Gene expression profiles from skin biopsies from a subset of SSc patients (n=68) and controls (n=18) were analyzed with weighted gene co-expression network analyses to identify gene modules that were associated with cardiac pheno-groups and echocardiographic parameters.

Results

Four SSc cardiac pheno-groups were identified with distinct profiles. Pheno-group #1 displayed a predominant cutaneous phenotype without cardiac involvement; pheno-group #2 had long-standing SSc with limited skin and cardiac involvement; pheno-group #3 had diffuse skin involvement, a high frequency of interstitial lung disease (88%), and significant right heart remodeling/dysfunction; and pheno-group #4 had prolonged SSc disease duration, limited skin involvement, and marked biventricular cardiac involvement. After multivariable adjustment, pheno-group #3 (hazard ratio [HR] 7.8, 95% confidence interval [CI] 1.5–33.0) and pheno-group #4 (HR 10.5, 95% CI 2.1–52.7) remained associated with mortality (P<0.05). The addition of pheno-group classification was additive to conventional survival models (P<0.05 by likelihood ratio test for all models), a finding that was replicated in the validation cohort. Skin gene expression analysis identified 2 gene modules (representing fibrosis and skin integrity, respectively) that differed among the cardiac pheno-groups and were associated with specific echocardiographic parameters.

Conclusions

Machine learning of echocardiographic and skin gene expression data in SSc identifies clinically relevant subgroups with distinct cardiac phenotypes, survival, and associated molecular pathways in skin.
Distinct types of short open reading frames are translated in plant cells
Authors: Fesenko Igor , Kirov Ilya , Kniazev Andrey , Khazigaleeva Regina , Lazarev Vassili , Kharlampieva Daria , Grafskaia Ekaterina , Zgoda Viktor , Butenko Ivan , Arapidi Georgy , Mamaeva Anna , Ivanov Vadim , Govorun Vadim
Published: November 2017

Genomes contain millions of short (<100 codons) open reading frames (sORFs), which are usually dismissed during gene annotation. Nevertheless, peptides encoded by such sORFs can play important biological roles, and their impact on cellular processes has long been underestimated. Here, we analyzed approximately 70,000 transcribed sORFs in the model plantPhyscomitrella patens(moss). Several distinct classes of sORFs that differ in terms of their position on transcripts and the level of evolutionary conservation are present in the moss genome. Over 5000 sORFs were conserved in at least one of ten plant species examined. Mass spectrometry analysis of proteomic and peptidomic datasets suggested that 584 sORFs located on distinct parts of mRNAs and long non-coding RNAs (lncRNAs) are translated, including 73 conservative sORFs. Translational analysis of the sORFs and main ORFs at a single locus suggested the existence of genes that code for multiple proteins and peptides with tissue-specific expression. Alternative splicing is likely involved in the excision of translatable sORFs from such transcripts. We identified a group of sORFs homologous to known protein domains and suggested they function as small interfering peptides. Functional analysis of candidate lncRNA-encoded peptides showed it to be involved in regulating growth and differentiation in moss. The high evolutionary rate and wide translation of sORFs suggest that they may provide a reservoir of potentially active peptides and their importance as a raw material for gene evolution. Our results thus open new avenues for discovering novel, biologically active peptides in the plant kingdom.
Multivariate analysis of the cotton seed ionome reveals a shared genetic architecture
Authors: Pauli Duke , Ziegler Greg , Ren Min , Jenks Matthew A. , Hunsaker Douglas J. , Zhang Min , Baxter Ivan , Gore Michael A.
Published: November 2017

To mitigate the effects of heat and drought stress, a better understanding of the genetic control of physiological responses to these environmental conditions is needed. To this end, we evaluated an upland cotton (Gossypium hirsutumL.) mapping population under water-limited and well-watered conditions in a hot, arid environment. The elemental concentrations (ionome) of seed samples from the population were profiled in addition to those of soil samples taken from throughout the field site to better model environmental variation. The elements profiled in seeds exhibited moderate to high heritabilities, as well as strong phenotypic and genotypic correlations between elements that were not altered by the imposed irrigation regimes. Quantitative trait loci (QTL) mapping results from a Bayesian classification method identified multiple genomic regions where QTL for individual elements colocalized, suggesting that genetic control of the ionome is highly interrelated. To more fully explore this genetic architecture, multivariate QTL mapping was implemented among groups of biochemically related elements. This analysis revealed both additional and pleiotropic QTL responsible for coordinated control of phenotypic variation for elemental accumulation. Machine learning algorithms that utilized only ionomic data predicted the irrigation regime under which genotypes were evaluated with very high accuracy. Taken together, these results demonstrate the extent to which the seed ionome is genetically interrelated and predictive of plant physiological responses to adverse environmental conditions.

One sentence summary

The cotton seed ionome has a shared genetic basis that provides insight into the physiological status of the plant.
A phase separated organelle at the root of motile ciliopathy
Authors: Huizar Ryan L. , Lee Chanjae , Boulgakov Alex A. , Horani Amjad , Tu Fan , Drew Kevin , Marcotte Edward M. , Brody Steven L. , Wallingford John B.
Published: November 2017

Hundreds of different cell types emerge in the developing embryo, each of which must compartmentalize cell type specific biochemical processes in a crowded intracellular environment. To study cell type specific compartmentalization, we examined motile ciliated cells, which must assemble vast numbers of dynein motors to drive ciliary beating, as mutation of dyneins or their assembly factors causes motile ciliopathy. We show that dyneins, their assembly factors, and chaperones all concentrate together in Dynein Assembly Particles (DynAPs). These phase-separated organelles are specific to ciliated cells but share machinery with stress granules. Our data suggest that a common framework underlies ubiquitous and cell-type specific phase separated organelles and that one such organelle is defective in a human genetic disease.
The internal audit dilemma – the impact of executive directors versus audit committees on internal auditing work
Authors: Eulerich Marc , Henseler Jörg , Köhler Annette G.
Published: November 2017

Purpose

The purpose of this study is to analyze how internal audit function (IAF) activities differ, depending on the impact of executive boards (EBs) and audit committees (ACs).

Design/methodology/approach

This study is based on data collected from the Common Body of Knowledge (CBOK) study conducted by the Institute of Internal Auditors Research Foundation in 2010. Using 524 responses from US Chief audit executives the authors examine the direct and interaction effects of ACs and EBs on the probability to perform specific activities with a logistic regression model.

Findings

This manuscript shows that ACs and EBs have different direct and interaction effects on the portfolio of activities performed by the IAF. Furthermore, a varying prevalence among activities was identified, which pinpoints to the maturity of IAFs. All findings contribute to the prior and recent discussion about the position of IAFs between the stakeholders’ AC and EB.

Research limitations/implications

When the CBOK study was designed by the Institute of Internal Auditors, the investigators did not have the research questions in mind. The authors are therefore limited to those variables that have been collected as part of a larger questionnaire. Nevertheless, the new approach tries to open a new research direction, analyzing different activities performed by IAFs.

Practical implications

The identified portfolio of IAF activities can help practitioners to double-check their own work and to evaluate the impact of the EB and the AC on their activities.

Originality/value

This study provides the first empirical evidence of the influence of ACs and EBs on IAF activities.
Is the spatial pattern of a tree population in a seasonally dry tropical climate explained by density‐dependent mortality?
Authors: Silveira Andréa Pereira , Martins Fernando Roberto , Menezes Bruno Sousa , Araújo Francisca Soares
Published: November 2017

Spatial pattern of tropical plants is initially generated by limited seed dispersal, but the role of density‐dependent and independent mechanisms as modifiers of these patterns across ontogeny is poorly understood. We investigated whether density‐dependent mortality (DDM) and environmental heterogeneity can drive spatial pattern across the ontogeny of a tree in a seasonally dry tropical climate. We used Moran's I correlograms and spatial analysis by distance indices (SADIE) to assess the spatial patterns of the pre‐ and post‐germinative stages of Cordia oncocalyx (Boraginaceae), an abundant tree endemic in the deciduous thorny woodland in the northeastern Brazilian semiarid region. We also used RDA to analyse the effect of DDM and environmental heterogeneity (measured by microtopography and canopy openness) in the mortality and recruitment. Seeds, seedlings, juveniles and adults showed aggregated spatial patterns; infants and immatures were randomly distributed; adults, seeds and seedlings attracted each other while adult, juveniles and immatures repulsed each other. Infant and seedling mortality rates were related to DDM and the recruitment from infant to juvenile was more influenced by spatial heterogeneity. Attraction was determined by local dispersal; repulsion was related to DDM and environment heterogeneity, which allowed the return to aggregation in adult stage. Together, these results indicated that spatial pattern can change across ontogeny, in which the initial stages are responsive to DDM and the final stages are influenced by spatial heterogeneity.
Efficacy of predetermined therapeutic measures against bleb‐related infection in the Collaborative Bleb‐related Infection Incidence and Treatment Study
Authors: Shoji Nobuyuki , Arakaki Yoshikuni , Nakamoto Kenji , Yamamoto Tetsuya , Kuwayama Yasuaki ,   The Collaborative Bleb‐related Infection Incidence and Treatment Study Group
Published: November 2017

Purpose

To report the efficacy of the predetermined treatment protocol of the Collaborative Bleb‐related Infection Incidence and Treatment Study (CBIITS) for bleb‐related infection (BRI) patients.

Methods

A prospective, observational cohort study was conducted at 34 clinical centres in Japan. Nineteen eyes from 19 patients that developed BRI were treated using the CBIITS protocol at 34 clinical centres. The visual acuity (VA) and intraocular pressure (IOP) were monitored for 6 and 12 months after treatment with the predetermined protocol.

Results

The logMAR was 0.623 ± 0.748 (mean ± standard deviation) before the infection developed. It was 1.054 ± 1.156 and 0.950 ± 1.168 at 6 months and 12 months post‐infection, respectively. However, in subgroup analyses, there was no significant decrease in post‐infection logMAR in stages I and II. In contrast, decimal VA was decreased ≥2 lines in all four cases in stage III. The IOP did not change after infection. It was 10.2 ± 5.0 mmHg (range, 3–22 mmHg) before the infection developed, and 12.9 ± 5.2 mmHg (5–24 mmHg) and 10.7 ± 4.7 mmHg (3–18 mmHg) at 6 months and 12 months after infection, respectively.

Conclusion

Because of the small number of BRI patients, the superiority of the treatment was not definitively determined. However, VA was almost maintained in stages I and II, and the IOP did not change after infection. Although further study is necessary, the treatment protocol shown in the study might be a valuable treatment regime.
Dicloxacillin induces CYP2C19, CYP2C9 and CYP3A4 in vivo and in vitro
Authors: Stage Tore Bjerregaard , Graff Magnus , Wong Susan , Rasmussen Louise Ladebo , Nielsen Flemming , Pottegård Anton , Brøsen Kim , Kroetz Deanna L. , Khojasteh S. Cyrus , Damkier Per
Published: November 2017

Aim

The aim of this study was to study potential cytochrome P450 (CYP) induction by dicloxacillin.

Methods

We performed an open‐label, randomized, two‐phase, five‐drug clinical pharmacokinetic cocktail crossover study in 12 healthy men with and without pretreatment with 1 g dicloxacillin three times daily for 10 days. Plasma and urine were collected over 24 h and the concentration of all five drugs and their primary metabolites was determined using a liquid chromatography coupled to triple quadrupole mass spectrometry method. Cryopreserved primary human hepatocytes were exposed to dicloxacillin for 48 h and changes in gene expression and the activity of CYP3A4, CYP2C9, CYP2B6 and CYP1A2 were investigated. The activation of nuclear receptors by dicloxacillin was assessed using luciferase assays.

Results

A total of 10 days of treatment with dicloxacillin resulted in a clinically and statistically significant reduction in the area under the plasma concentration–time curve from 0 to 24 h for omeprazole (CYP2C19) {geometric mean ratio [GMR] [95% confidence interval (CI)]: 0.33 [0.24, 0.45]}, tolbutamide (CYP2C9) [GMR (95% CI): 0.73 (0.65, 0.81)] and midazolam (CYP3A4) [GMR (95% CI): 0.54 (0.41, 0.72)]. Additionally, other relevant pharmacokinetic parameters were affected, indicating the induction of CYP2C‐ and CYP3A4‐mediated metabolism by dicloxacillin. Investigations in primary hepatocytes showed a statistically significant dose‐dependent increase in CYP expression and activity by dicloxacillin, caused by activation of the pregnane X receptor.

Conclusions

Dicloxacillin is an inducer of CYP2C‐ and CYP3A‐mediated drug metabolism, and we recommend caution when prescribing dicloxacillin to users of drugs with a narrow therapeutic window.
Towards an eco‐phylogenetic framework for infectious disease ecology
Authors: Fountain‐Jones Nicholas M. , Pearse William D. , Escobar Luis E. , Alba‐Casals Ana , Carver Scott , Davies T. Jonathan , Kraberger Simona , Papeş Monica , Vandegrift Kurt , Worsley‐Tonks Katherine , Craft Meggan E.
Published: November 2017

Identifying patterns and drivers of infectious disease dynamics across multiple scales is a fundamental challenge for modern science. There is growing awareness that it is necessary to incorporate multi‐host and/or multi‐parasite interactions to understand and predict current and future disease threats better, and new tools are needed to help address this task. Eco‐phylogenetics (phylogenetic community ecology) provides one avenue for exploring multi‐host multi‐parasite systems, yet the incorporation of eco‐phylogenetic concepts and methods into studies of host pathogen dynamics has lagged behind. Eco‐phylogenetics is a transformative approach that uses evolutionary history to infer present‐day dynamics. Here, we present an eco‐phylogenetic framework to reveal insights into parasite communities and infectious disease dynamics across spatial and temporal scales. We illustrate how eco‐phylogenetic methods can help untangle the mechanisms of host–parasite dynamics from individual (e.g. co‐infection) to landscape scales (e.g. parasite/host community structure). An improved ecological understanding of multi‐host and multi‐pathogen dynamics across scales will increase our ability to predict disease threats.
Maternal folic acid use during pregnancy, methylenetetrahydrofolate reductase gene polymorphism, and child's lung function and asthma
Authors: den Dekker H. T. , Jaddoe V. W.V. , Reiss I. K. , de Jongste J. C. , Duijts L.
Published: November 2017

Background

Folic acid supplement use during pregnancy might affect childhood respiratory health, potentially mediated by methylenetetrahydrofolate reductase polymorphism C677T (MTHFR‐C677T) carriership.

Objectives

We examined the associations of maternal folic acid supplement use and folate, vitamin B12 and homocysteine concentrations during pregnancy with childhood lung function and asthma.

Methods

This study was embedded in a population‐based prospective cohort study among 5653 children. Folic acid supplement use was assessed by questionnaires. Folate, vitamin B12 and homocysteine plasma concentrations were measured in early pregnancy and at birth. At age 10 years, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow between 25% and 75% (FEF25‐75), at 75% of FVC (FEF75), and asthma were examined.

Results

Maternal folic acid supplement use during pregnancy was associated with higher childhood FEV1 and FVC and with a lower FEV1/FVC, compared with no folic acid supplement use. Among mothers carrying MTHFR‐C677T variants, preconceptional start of folic acid supplement use was associated with lower FEV1/FVC (−0.17 [−0.32, −0.02]) and FEF25‐75 (−0.24 [−0.40, −0.07]). Among children carrying MTHFR‐C677T wild‐type, a higher vitamin B12 level at birth was associated with a lower FEV1 (−0.07 [−0.12, −0.01]) and FVC (−0.09 [−0.15, −0.04]). Folate and homocysteine concentrations were not consistently associated with lower childhood lung function or asthma.

Conclusions

Preconceptional start of maternal folic acid supplement use and higher vitamin B12 concentrations at birth might adversely affect childhood lung function depending on MTHFR‐C677T carriership. The clinical implications need to be evaluated.
Allergic contact dermatitis caused by calcipotriol
Authors: Gilissen Liesbeth , Huygens Sara , Goossens An
Published: November 2017

Background

Calcipotriol, a synthetic vitamin D analogue, is widely used for the topical treatment of psoriasis. It often causes irritant reactions, whereas allergic contact dermatitis has less commonly been reported.

Objectives

To report on 6 patients (among them an 11‐year‐old child) who presented with eczematous lesions complicating pre‐existing dermatitis, observed in our tertiary referral patch test clinic between 2004 and 2016.

Methods

Patch tests were performed with the commercial preparation used by the patients and/or its ingredients, including calcipotriol (2 or 10 µg/ml in isopropyl alcohol), according to ESCD patch test guidelines.

Results

Allergic contact dermatitis was confirmed in all cases, and the lesions improved following treatment with topical corticosteroids and/or oral medication.

Conclusions

When topical treatment with calcipotriol fails to improve, or even worsens, existing skin lesions, contact allergy should be suspected. A patch test concentration of 2 µg/ml in isopropyl alcohol seems to be the most suitable. According to the literature, patients sensitized to calcipotriol may tolerate topical therapy with other vitamin D3 analogues, particularly tacalcitol.