bluuebunny/crossref_metadata_2025 huggingface dataset:
Early‐onset aging and mitochondrial defects associated with loss of histone acetyltransferase 1 (Hat1)
Authors: Nagarajan Prabakaran , Agudelo Garcia Paula A. , Iyer Chitra C. , Popova Liudmila V. , Arnold William D. , Parthun Mark R.
Published: July 2019

Histone acetyltransferase 1 (Hat1) is responsible for the acetylation of newly synthesized histone H4 on lysines 5 and 12 during the process of chromatin assembly. To understand the broader biological role of Hat1, we have generated a conditional mouse knockout model of this enzyme. We previously reported that Hat1 is required for viability and important for mammalian development and genome stability. In this study, we show that haploinsufficiency of Hat1 results in a significant decrease in lifespan. Defects observed in Hat1+/− mice are consistent with an early‐onset aging phenotype. These include lordokyphosis (hunchback), muscle atrophy, minor growth retardation, reduced subcutaneous fat, cancer, and paralysis. In addition, the expression of Hat1 is linked to the normal aging process as Hat1 mRNA and protein becomes undetectable in many tissues in old mice. At the cellular level, fibroblasts from Hat1 haploinsufficient embryos undergo early senescence and accumulate high levels of p21. Hat1+/− mouse embryonic fibroblasts (MEFs) display modest increases in endogenous DNA damage but have significantly higher levels of reactive oxygen species (ROS). Consistently, further studies show that Hat1−/− MEFs exhibit mitochondrial defects suggesting a critical role for Hat1 in mitochondrial function. Taken together, these data show that loss of Hat1 induces multiple hallmarks of early‐onset aging.
Exit as governance: do blockholders affect corporate innovation in large US firms?
Authors: Helling Axel R. , Maury Benjamin , Liljeblom Eva
Published: July 2019

Using a sample of large US firms, this study shows that blockholders in combination with liquidity can contribute positively to innovation (R&D investments). We contribute to the literature on managerial myopia that has focused mainly on large owners and their type (short‐term/long‐term). Our results are in line with recent theoretical studies arguing that blockholders in combination with market liquidity can mitigate managerial myopia, as suggested by the exit model of governance. The results indicate that blockholders can be efficient in resolving agency problems and that they can enhance long‐term prosperity, even when the individual blockholder investment horizon may not be long.
Report on the current status of the use of real‐world data (RWD) and real‐world evidence (RWE) in drug development and regulation
Authors: Breckenridge Alasdair M. , Breckenridge Ross A. , Peck Carl C.
Published: July 2019

Radically expanding use of real‐world data (RWD) and real‐world evidence (RWE) holds the potential to substantially impact drug development, pharmaceutical regulation, and payment within health care systems. Central to this is the reconfiguration of data gathering and transformation of data to information, which can be used as evidence for decision making. We discuss applications of this paradigm in the light of recent developments in both the United States and Europe on RWD and RWE.
A diagnostic solution for haemostasis laboratories for patients taking direct oral anticoagulants using DOAC‐Remove
Authors: Cox‐Morton Sally , MacDonald Stephen , Thomas Will
Published: July 2019

This study describes the use of a simple charcoal product (DOAC‐RemoveTM) to allow haemostasis assays on patients taking direct oral anticoagulants (DOAC). In the proposed algorithm, patients taking DOAC are screened using the dilute thrombin time (dTT) and anti‐Xa assay. If either are positive then DOAC‐Remove is utilised. In a validation, DOAC‐Remove did not interfere with coagulation testing in normal plasma or in patients on DOAC with a known lupus anticoagulant (LA). Of 1566 routine patient samples tested, 125 (8%) had evidence of anti‐Xa activity (>0·1 iu/ml) or prolonged dTT suggestive of either a direct/indirect Xa inhibitor or direct thrombin inhibitor. All of these 125 patients had a prolonged dilute Russell viper venom time (dRVVT) screening test and 106 had a LA detected by dRVVT after phospholipid correction. After DOAC‐Remove, 91 patients (73%) had a negative dRVVT screen. After further investigation only 9 (7%) had a positive LA. DOAC‐Remove prevented 5% of patients having a LA inappropriately detected. DOAC did not significantly affect the LA activated partial thromboplastin time (aPTT) ratio, protein S antigen or protein C activity. DOAC cause low intrinsic factor assays, high prothrombin time/aPTT and high activated protein C sensitivity ratio, which DOAC‐Remove reversed (P < 0·05). Despite recommendations, haemostasis testing for patients on DOAC continues; this algorithm aids diagnostic accuracy. Further validation and research are warranted.
A cross‐cultural comparison of the roles of emotional intelligence, metacognition, and negative coping for health‐related quality of life in German versus Pakistani patients with chronic heart failure
Authors: Ghafoor Hina , Ahmad Rana Altaf , Nordbeck Peter , Ritter Oliver , Pauli Paul , Schulz Stefan M.
Published: July 2019

Objectives

Low emotional intelligence (EI) may predispose individuals to applying maladaptive coping strategies. This may maintain anxious worrying, which is highly prevalent in patients with chronic heart failure (CHF) and may affect mental (MCS) and physical component summaries (PCS) of health‐related quality of life (HRQoL).

Design

The current study is a cross‐sectional and cross‐cultural survey.

Methods

N = 200 outpatients with CHF were recruited at cardiology institutes in Germany and Pakistan and assessed with self‐report questionnaires.

Results

Path analysis (χ2(4) = 7.59, p = .11, GFI = .99) revealed that the expected associations between low EI and lower SF‐36 MCS and PCS of HRQoL were fully mediated by negative metacognition and maladaptive coping in the Pakistani sample (p's ≤ .05). The German sample applied different maladaptive coping strategies, which also led to lower MCS and PCS scores, but did not mediate a direct positive effect of EI on HRQoL.

Conclusion

The current findings support culture‐independent validity of the metacognitive model but also reveal major cultural differences regarding the application and effect of specific maladaptive coping strategies. This has important implications for caregivers in a cross‐cultural context and highlights the need for culture‐specific tailoring of psychosocial interventions.

Statement of contribution

What is already known on this subject?

Worry, an integral component of generalized anxiety disorder (GAD) and highly comorbid in chronic heart failure (CHF) patients, contributes to anxiety and resulting stress as evident from metacognitive model of GAD. In addition, previous literature has also established the protective role of emotional intelligence (EI) against stress, thus maintaining quality of life.

What does this study add?

Cross‐cultural (Pakistan vs. Germany) validation of the metacognitive model of GAD.

Supportive evidence for the metacognitive model in patients with CHF.

Mediation of maladaptive metacognitions and negative coping in the relationship of low trait EI and low health‐related quality of life.
Optimizing Stepwise Animation in Dynamic Set Diagrams
Authors: Mizuno Kazuyo , Wu Hsiang‐Yun , Takahashi Shigeo , Igarashi Takeo
Published: July 2019

A set diagram represents the membership relation among data elements. It is often visualized as secondary information on top of primary information, such as the spatial positions of elements on maps and charts. Visualizing the temporal evolution of such set diagrams as well as their primary features is quite important; however, conventional approaches have only focused on the temporal behavior of the primary features and do not provide an effective means to highlight notable transitions within the set relationships. This paper presents an approach for generating a stepwise animation between set diagrams by decomposing the entire transition into atomic changes associated with individual data elements. The key idea behind our approach is to optimize the ordering of the atomic changes such that the synthesized animation minimizes unwanted set occlusions by considering their depth ordering and reduces the gaze shift between two consecutive stepwise changes. Experimental results and a user study demonstrate that the proposed approach effectively facilitates the visual identification of the detailed transitions inherent in dynamic set diagrams.
ClustMe: A Visual Quality Measure for Ranking Monochrome Scatterplots based on Cluster Patterns
Authors: Abbas Mostafa M. , Aupetit Michaël , Sedlmair Michael , Bensmail Halima
Published: July 2019

We propose ClustMe, a new visual quality measure to rank monochrome scatterplots based on cluster patterns. ClustMe is based on data collected from a human‐subjects study, in which34participants judged synthetically generated cluster patterns in1000scatterplots. We generated these patterns by carefully varying the free parameters of a simple Gaussian Mixture Model with two components, and asked the participants to count the number of clusters they could see (1 or more than 1). Based on the results, we form ClustMe by selecting the model that best predicts these human judgments among7different state‐of‐the‐art merging techniques (Demp). To quantitatively evaluate ClustMe, we conducted a second study, in which31human subjects ranked 435 pairs of scatterplots of real and synthetic data in terms of cluster patterns complexity. We use this data to compare ClustMe's performance to 4 other state‐of‐the‐art clustering measures, including the well‐known Clumpiness scagnostics. We found that of all measures, ClustMe is in strongest agreement with the human rankings.
Route‐Aware Edge Bundling for Visualizing Origin‐Destination Trails in Urban Traffic
Authors: Zeng W. , Shen Q. , Jiang Y. , Telea A.
Published: July 2019

Origin‐destination (OD) trails describe movements across space. Typical visualizations thereof use either straight lines or plot the actual trajectories. To reduce clutter inherent to visualizing large OD datasets, bundling methods can be used. Yet, bundling OD trails in urban traffic data remains challenging. Two specific reasons hereof are the constraints implied by the underlying road network and the difficulty of finding good bundling settings. To cope with these issues, we propose a new approach called Route Aware Edge Bundling (RAEB). To handle road constraints, we first generate a hierarchical model of the road‐and‐trajectory data. Next, we derive optimal bundling parameters, including kernel size and number of iterations, for a user‐selected level of detail of this model, thereby allowing users to explicitly trade off simplification vs accuracy. We demonstrate the added value of RAEB compared to state‐of‐the‐art trail bundling methods on both synthetic and real‐world traffic data for tasks that include the preservation of road network topology and the support of multiscale exploration.
Bird's‐Eye ‐ Large‐Scale Visual Analytics of City Dynamics using Social Location Data
Authors: Krueger Robert , Han Qi , Ivanov Nikolay , Mahtal Sanae , Thom Dennis , Pfister Hanspeter , Ertl Thomas
Published: July 2019

The analysis of behavioral city dynamics, such as temporal patterns of visited places and citizens' mobility routines, is an essential task for urban and transportation planning. Social media applications such as Foursquare and Twitter provide access to large‐scale and up‐to‐date dynamic movement data that not only help to understand the social life and pulse of a city but also to maintain and improve urban infrastructure. However, the fast growth rate of this data poses challenges for conventional methods to provide up‐to‐date, flexible analysis. Therefore, planning authorities barely consider it. We present a system and design study to leverage social media data that assist urban and transportation planners to achieve better monitoring and analysis of city dynamics such as visited places and mobility patterns in large metropolitan areas. We conducted a goal‐and‐task analysis with urban planning experts. To address these goals, we designed a system with a scalable data monitoring back‐end and an interactive visual analytics interface. The monitoring component uses intelligent pre‐aggregation to allow dynamic queries in near real‐time. The visual analytics interface leverages unsupervised learning to reveal clusters, routines, and unusual behavior in massive data, allowing to understand patterns in time and space. We evaluated our approach based on a qualitative user study with urban planning experts which demonstrates that intuitive integration of advanced analytical tools with visual interfaces is pivotal in making behavioral city dynamics accessible to practitioners. Our interviews also revealed areas for future research.
A stable graph layout algorithm for processes
Authors: Mennens Robin J.P. , Scheepens Roeland , Westenberg Michel A.
Published: July 2019

Process mining enables organizations to analyze data about their (business) processes. Visualization is key to gaining insight into these processes and the associated data. Process visualization requires a high‐quality graph layout that intuitively represents the semantics of the process. Process analysis additionally requires interactive filtering to explore the process data and process graph. The ideal process visualization therefore provides a high‐quality, intuitive layout and preserves the mental map of the user during the visual exploration. The current industry standard used for process visualization does not satisfy either of these requirements. In this paper, we propose a novel layout algorithm for processes based on the Sugiyama framework. Our approach consists of novel ranking and order constraint algorithms and a novel crossing minimization algorithm. These algorithms make use of the process data to compute stable, high‐quality layouts. In addition, we use phased animation to further improve mental map preservation. Quantitative and qualitative evaluations show that our approach computes layouts of higher quality and preserves the mental map better than the industry standard. Additionally, our approach is substantially faster, especially for graphs with more than 250 edges.
External Labeling Techniques: A Taxonomy and Survey
Authors: Bekos Michael A. , Niedermann Benjamin , Nöllenburg Martin
Published: July 2019

External labeling is frequently used for annotating features in graphical displays and visualizations, such as technical illustrations, anatomical drawings, or maps, with textual information. Such a labeling connects features within an illustration by thin leader lines with their labels, which are placed in the empty space surrounding the image. Over the last twenty years, a large body of literature in diverse areas of computer science has been published that investigates many different aspects, models, and algorithms for automatically placing external labels for a given set of features. This state‐of‐the‐art report introduces a first unified taxonomy for categorizing the different results in the literature and then presents a comprehensive survey of the state of the art, a sketch of the most relevant algorithmic techniques for external labeling algorithms, as well as a list of open research challenges in this multidisciplinary research field.
Endoscopic ultrasound‐guided fistulation between bile duct and afferent limb for treatment of complete choledochojejunal obstruction using forward‐viewing echoendoscope
Authors: Kin Toshifumi , Hayashi Tsuyoshi , Katanuma Akio
Published: July 2019

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Benextramine and derivatives as novel human monoamine oxidases inhibitors: an integrated approach
Authors: Di Paolo Maria Luisa , Cozza Giorgio , Milelli Andrea , Zonta Francesca , Sarno Stefania , Minniti Elirosa , Ursini Fulvio , Rosini Michela , Minarini Anna
Published: July 2019

The two human monoamine oxidase isoforms (namely MAO A and MAO B) are enzymes involved in the catabolism of monoamines, including neurotransmitters, and for this reason are well‐known and attractive pharmacological targets in neuropsychiatric and neurodegenerative diseases, for which novel pharmacological approaches are necessary. Benextramine is a tetraamine disulfide mainly known as irreversible α‐adrenergic antagonist, but able to hit additional targets involved in neurodegeneration. As the molecular structures of monoamine oxidases contain nine cysteine residues, the aim of this study was to evaluate benextramine and eleven structurally related polyamine disulfides as potential MAO inhibitors. Most of the compounds were found to induce irreversible inactivation of MAOs with inactivation potency depending on both the polyamine structure and the enzyme isoform. The more effective compounds generally showed preference for MAO B. Structure‐activity relationships studies revealed the key role played by the disulfide core of these molecules in the inactivation mechanism. Docking experiments pointed to Cys323, in MAO A, and Cys172, in MAO B, as target of this type of inhibitors thus suggesting that their covalent binding inside the MAO active site sterically impedes the entrance of substrate towards the FAD cofactor. The effectiveness of benextramine in inactivating MAOs was demonstrated in SH‐SY5Y neuroblastoma cell line. These results demonstrated for the first time that benextramine and its derivatives can inactivate human MAOs exploiting a mechanism different from that of the classical MAO inhibitors and could be a starting point for the development of pharmacological tools in neurodegenerative diseases.
Targeting CGRP and 5‐HT1FReceptors for the Acute Therapy of Migraine: A Literature Review
Authors: Moreno‐Ajona David , Chan Calvin , Villar‐Martínez María Dolores , Goadsby Peter J.
Published: July 2019

Objective

To review and highlight current literature on emerging acute migraine treatments, focusing on CGRP receptor antagonists, gepants, and 5‐HT1Freceptor agonists (ditans).

Background

Current acute migraine therapy consists of nonspecific analgesia and triptans. Limitations to these medicines, including lack of efficacy in many patients, side effects and the contraindication of triptans in patients with cardiovascular disease, suggest that there is an unmet need for new treatments. Studies of serotonin pharmacology led to the development of triptans, 5‐HT1B/1Dreceptor agonists, some of which have actions at the 5‐HT1Freceptor. Exploration of the role of calcitonin gene‐related peptide (CGRP) has resulted in the development of CGRP receptor antagonists.

Method

The authors performed a literature search of Pubmed and Cochrane databases as well as reviewed abstracts presented at meetings: American Headache Society, American Academy of Neurology, European Headache Federation and the Migraine Trust International Symposium, as well as on‐line sources. The authors briefly detail the relevant migraine pathophysiology pertaining to 5‐HT1Freceptor and the CGRP pathway relevant to acute therapies. Recent clinical trials of acute therapies in which 5‐HT1Freceptor agonists or CGRP receptor antagonists were studied are summarized.

Results

Two 5‐HT1Freceptor agonists have reached phase II clinical trials. One, lasmiditan, has completed 2 phase III clinical trials, demonstrating a significant effect for pain freedom and most bothersome symptom at 2 hours. Among the 6 gepants tested for the acute treatment of migraine to date, after issues for some of hepatic safety or efficacy, 2 CGRP receptor antagonists, rimegepant and ubrogepant, have completed phase III trials showing efficacy and safety.

Conclusion

Current available therapies have either been nonspecific or had important limitations, including in patients with cardiovascular risk factors. Phase III clinical trials of lasmiditan, rimegepant and ubrogepant all met their primary endpoints, so the options for migraine‐targeted acute therapy will likely soon increase.
Brown adipose tissue estimated with the magnetic resonance imaging fat fraction is associated with glucose metabolism in adolescents
Authors: Lundström Elin , Ljungberg Joy , Andersson Jonathan , Manell Hannes , Strand Robin , Forslund Anders , Bergsten Peter , Weghuber Daniel , Mörwald Katharina , Zsoldos Fanni , Widhalm Kurt , Meissnitzer Matthias , Ahlström Håkan , Kullberg Joel
Published: July 2019

Background

Despite therapeutic potential against obesity and diabetes, the associations of brown adipose tissue (BAT) with glucose metabolism in young humans are relatively unexplored.

Objectives

To investigate possible associations between magnetic resonance imaging (MRI) estimates of BAT and glucose metabolism, whilst considering sex, age, and adiposity, in adolescents with normal and overweight/obese phenotypes.

Methods

In 143 subjects (10‐20 years), MRI estimates of BAT were assessed as cervical‐supraclavicular adipose tissue (sBAT) fat fraction (FF) and
from water‐fat MRI. FF and
of neighbouring subcutaneous adipose tissue (SAT) were also assessed. Adiposity was estimated with a standardized body mass index, the waist‐to‐height ratio, and abdominal visceral and subcutaneous adipose tissue volumes. Glucose metabolism was represented by the 2h plasma glucose concentration, the Matsuda index, the homeostatic model assessment of insulin resistance, and the oral disposition index; obtained from oral glucose tolerance tests.

Results

sBAT FF and
correlated positively with adiposity before and after adjustment for sex and age. sBAT FF, but not
, correlated with 2h glucose and Matsuda index, also after adjustment for sex, age, and adiposity. The association with 2h glucose persisted after additional adjustment for SAT FF.

Conclusions

The association between sBAT FF and 2h glucose, observed independently of sex, age, adiposity, and SAT FF, indicates a role for BAT in glucose metabolism, which potentially could influence the risk of developing diabetes. The lacking association with sBAT
might be due to FF being a superior biomarker for BAT and/or to methodological limitations in the
quantification.
Orthostatic hypotension and the risk of atrial fibrillation and other cardiovascular diseases: An updated meta‐analysis of prospective cohort studies
Authors: Min Min , Shi Tingting , Sun Chenyu , Liang Mingming , Zhang Yun , Bo Guang , Sun Yehuan
Published: July 2019

The relationships between orthostatic hypotension (OH) and some kinds of cardiovascular disease are inconsistent among studies. This updated meta‐analysis was conducted in hopes of producing progress on this topic. A systematic database search was performed in electronic databases, including the Chinese Biomedical Database (CBM), PubMed, Web of Science, and the Cochrane Library. Summary hazard ratio (HR) estimates with 95% confidence intervals (CIs) were calculated by a random‐effects model. Statistical heterogeneity was assessed with Cochran's Q test and the I2 statistic. From 1462 potentially eligible records, 15 studies met the inclusion criteria. Subjects with OH had a high risk of heart failure (HF) and atrial fibrillation (AF) (pooled HR 1.34, 95% CI 1.17‐1.52, P < 0.001 and pooled HR 1.51, 95% CI 1.28‐1.79, P < 0.001, respectively). This meta‐analysis also showed significant associations between OH and the risks of developing coronary heart disease (CHD) (pooled HR 1.44, 95% CI 1.18‐1.75, P < 0.001) and myocardial infarction (MI) (pooled HR 1.52, 95% CI 1.12‐2.06, P = 0.008). Our study suggests that OH is positively associated with high risks of HF and AF. Moreover, it may be related to high risks of CHD and MI.
IDENTITY ECONOMICS: SOCIAL INFLUENCE AND SKILL DEVELOPMENT
Authors: Norris Jonathan
Published: July 2019

Within the economic literature, studies in identity economics, peer effects, and skill development have all suggested that social influences have an important role in determining choices. In this review, I draw on lessons learned from the identity economics literature to examine implications from the peer effects and skill development literature. I focus on the role of social identity in generating social group effects from peers and what role identity may have in shaping the development of skills from broader environments, parents and peers during childhood and adolescence.
Boomeranging around Australia: Historical biogeography and population genomics of the anti‐equatorial fish Microcanthus strigatus (Teleostei: Microcanthidae)
Authors: Tea Yi‐Kai , Van Der Wal Cara , Ludt William B. , Gill Anthony C. , Lo Nathan , Ho Simon Y. W.
Published: July 2019

The geographic distributions of marine fishes have been shaped by ancient vicariance and ongoing dispersal events. Some species exhibit anti‐equatorial distributions, inhabiting temperate regions on both sides of the tropics while being absent from equatorial latitudes. The perciform fish Microcanthus strigatus (the stripey) exhibits such a distribution with disjunct populations occurring in East Asia, Hawaii, Western Australia, and the southwest Pacific. Here, we examine the historical biogeography and evolutionary history of M. strigatus, based on more than 80 specimens sampled from the four major populations. We analysed 36 morphological characters, three mitochondrial markers, and two sets of 7,120 and 12,771 single‐nucleotide polymorphisms from the nuclear genome. Our results suggest that M. strigatus represents a cryptic species complex comprising at least two genetically distinct populations worthy of species‐level recognition, with one population exhibiting strong genetic structuring but with intermittent, historical gene flow. We provide evidence for a southwest Pacific origin for the ancestral Microcanthus and explain how past connectivity between these regions might have given rise to the relationships observed in present‐day marine fauna. Our ancestral range reconstructions and molecular‐clock analyses support a southwest Pacific centre of origin for Microcanthus, with subsequent colonization of Western Australia through the Bass Strait followed by transequatorial dispersals to the Northern Hemisphere during the Pleistocene. Our results detail an anti‐tropical dispersal pattern that is highly unusual and previously undocumented, thereby emphasizing the importance of integrative systematics in the evaluation of widespread species.
Early life social and ecological determinants of global DNA methylation in wild spotted hyenas
Authors: Laubach Zachary M. , Faulk Christopher D. , Dolinoy Dana C. , Montrose Luke , Jones Tamara R. , Ray Donna , Pioon Malit O. , Holekamp Kay E.
Published: July 2019

Environmental factors early in life can have lasting influence on the development and phenotypes of animals, but the underlying molecular modifications remain poorly understood. We examined cross‐sectional associations among early life socioecological factors and global DNA methylation in 293 wild spotted hyenas (Crocuta crocuta) in the Masai Mara National Reserve, Kenya, grouped according to three age classes (cub, subadult and adult). Explanatory variables of interest included annual maternal rank based on outcomes of dyadic agonistic interactions, litter size, wild ungulate prey density and anthropogenic disturbance in the year each hyena was born based on counts of illegal livestock in the Reserve. The dependent variable of interest was global DNA methylation, assessed via the LUminometric Methylation Assay, which provides a percentage methylation value calculated at CCGG sites across the genome. Among cubs, we observed approximately 2.75% higher CCGG methylation in offspring born to high‐ than low‐ranking mothers. Among cubs and subadults, higher anthropogenic disturbance corresponded with greater %CCGG methylation. In both cubs and adults, we found an inverse association between prey density measured before a hyena was 3 months old and %CCGG methylation. Our results suggest that maternal rank, anthropogenic disturbance and prey availability early in life are associated with later life global DNA methylation. Future studies are required to understand the extent to which these DNA methylation patterns relate to adult phenotypes and fitness outcomes.
A novel resistance against powdery mildew found in winter barley cultivars
Authors: Dreiseitl Antonín
Published: July 2019

Barley powdery mildew caused by Blumeria graminis f. sp. hordei can be effectively controlled using genetic resistance. Moreover, specific resistances are also important for characterizing cultivars and verifying their origin, purity and authenticity. Winter barley is distinguished by several specific resistances, which are usually absent in spring barley. Besides responses caused by known genes, many cultivars showed a response suggesting the presence of an unknown resistance. Therefore, the aim of this research was firstly, to test winter barley cultivars, suspected to carry an unknown resistance gene, using a large collection of pathogen isolates for their expression of this specific response and to characterise the corresponding resistance. A set of 16 winter barley accessions originating from four gene banks was studied where each accession was represented by five single plant progenies. For resistance tests, 56 isolates of the pathogen were used. A new resistance with a proposed designation of Lu was found in all 16 selected accessions. Apart from Lu, eight well‐known Ml genes (a6, a8, a12, g, h, Lo, ra and Ru2) were postulated. Two accessions of cv. 'Borwina' originating from different gene banks were found to differ in their set of resistance genes.
Barretts's carcinogenesis
Authors: Mukaisho Ken‐ichi , Kanai Shunpei , Kushima Ryoji , Nakayama Takahisa , Hattori Takanori , Sugihara Hiroyuki
Published: July 2019

Barrett's esophagus is considered a precancerous lesion of esophageal adenocarcinoma (EAC). Long‐segment Barrett's esophagus, which is generally associated with intestinal metaplasia, has a higher rate of carcinogenesis than short‐segment Barrett's esophagus, which is mainly composed of cardiac‐type mucosa. However, a large number of cases reportedly develop EAC from the cardiac‐type mucosa which has the potential to involve intestinal phenotypes. There is no consensus regarding whether the definition of Barrett's epithelium should include intestinal metaplasia. Basic researches using rodent models have provided information regarding the origins of Barrett's epithelium. Nevertheless, it remains unclear whether differentiated gastric columnar epithelium or stratified esophageal squamous epithelium undergo transdifferentiation into the intestinal‐type columnar epithelium, transcommittment into the columnar epithelium, or whether the other pathways exist. Reflux of duodenal fluid including bile acids into the stomach may occur when an individual lies down after eating, which could cause the digestive juices to collect in the fornix of the stomach. N‐nitroso‐bile acids are produced with nitrites that are secreted from the salivary glands, and bile acids can drive expression of pro‐inflammatory cytokines via EGFR or the NF‐κB pathway. These steps may contribute significantly to carcinogenesis.
A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP‐I trial (Editorial, p. 2759)
Authors: Reade Michael C. , Marks Denese C. , Bellomo Rinaldo , Deans Renae , Faulke Daniel J. , Fraser John F. , Gattas David J. , Holley Anthony D. , Irving David O. , Johnson Lacey , Pearse Bronwyn L. , Royse Alistair G. , Wong Janet ,   for the Cryopreserved vs Liquid Platelet (CLIP) Investigators, the Australian and New Zealand College of Anaesthetists Clinical Trials Network, and the Australian and New Zealand Intensive Care Society Clinical Trials Group
Published: July 2019

BACKGROUND

Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval.

STUDY DESIGN AND METHODS

The Cryopreserved vs. Liquid Platelet (CLIP) study was a double‐blind, pilot, multicenter RCT involving high‐risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid‐stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought.

RESULTS

A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid‐stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, –343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid‐stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid‐stored PLTs (difference between groups, 1 unit [95% CI, –3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh‐frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, –0.03 to 2.0 units]; p = 0.012). There were no between‐group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group.

CONCLUSION

In this pilot RCT, compared to liquid‐stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted.
Feline bacterial keratitis: Clinical features, bacterial isolates, and in vitro antimicrobial susceptibility patterns
Authors: Goldreich Jennifer E. , Franklin‐Guild Rebecca J. , Ledbetter Eric C.
Published: July 2019

Objective

To describe clinical characteristics, bacterial isolates, and in vitro antimicrobial susceptibility patterns for cats with bacterial keratitis.

Animals Studied

Eighty one cats with bacterial keratitis.

Procedures

Medical records of cats with a clinical diagnosis of bacterial keratitis, confirmed by corneal culture, were reviewed from June 2004 to July 2017. Animal signalment, bacterial isolates, aerobic bacteria in vitro antimicrobial susceptibility test results, and pertinent clinical features were recorded. Percentages of susceptible aerobic bacterial isolates were statistically compared among selected antimicrobials.

Results

There were 102 aerobic bacterial isolates recovered from corneal samples of the 81 cats presented with bacterial keratitis. The most frequent bacteria isolated wereStaphylococcusspecies, which constituted 55% (56/102) of total isolates. All aerobic bacterial isolates grouped together had the highest percentage of susceptibility to ofloxacin (100%), ciprofloxacin (94%), chloramphenicol (93%), doxycycline (92%), ticarcillin (90%), gentamicin (89%), moxifloxacin (89%), tobramycin (86%), neomycin (85%), amikacin (84%), and cefazolin (84%). The same isolates had the lowest percentage of susceptibility to polymyxin B (2%), bacitracin (15%), and clindamycin (31%). When analyzed separately, the isolatedStaphylococcusspecies had the highest percentage of susceptibility to ofloxacin (100%), tobramycin (93%), and neomycin (85%) and the lowest percentage of susceptibility to polymyxin B (3%) and bacitracin (13%).

Conclusions

Members of theStaphylococcusgenus were the most frequent bacteria isolated from cases of feline bacterial keratitis. On the basis of in vitro susceptibility testing and mechanism of action, ofloxacin, ciprofloxacin, ticarcillin, gentamicin, or moxifloxacin are recommended for initial antimicrobial therapy of suspected bacterial keratitis in cats.
All of Us Must Work to Put Him There
Authors: Dicht Burton
Published: July 2019

When President John F. Kennedy set the goal for landing astronauts on the Moon, NASA was an organization less than three years old and had achieved only 15 minutes of human spaceflight experience. Some experts doubted Kennedy’s aggressive timeline could be met—but not NASA’s young technical workforce. Those engineers would engineers would confront hundreds of technical challenges in the years leading to the Apollo 11 lunar landing. This article tells some of those stories.
The Return of Manned Missions
Authors: Sethi Chitra
Published: July 2019

The United States space program has been without a launch vehicle for human spaceflight since 2011. That was when the space shuttle Atlantis returned on its final flight. Since then, NASA has relied on the Russian Soyuz spacecraft to take its astronauts to the International Space Station. However, if all goes to plan this could soon change, as two private companies are working with NASA to launch the first astronauts into orbit. The companies, SpaceX and Boeing, are building crew capsules and rockets, designing space suits, and training astronauts to fly these new vehicles into space.
Uncertainty Quantification of NOx and CO Emissions in a Swirl-Stabilized Burner
Authors: Yousefian Sajjad , Bourque Gilles , Monaghan Rory F. D.
Published: July 2019

Uncertainty quantification (UQ) is becoming an essential attribute for development of computational tools in gas turbine combustion systems. Prediction of emissions with a variety of gaseous fuels and uncertain conditions requires probabilistic modeling tools, especially at part load conditions. The aim of this paper was to develop a computationally efficient tool to integrate uncertainty, sensitivity, and reliability analyses of CO and NOx emissions for a practical swirl-stabilized premixed burner. Sampling-based method (SBM), nonintrusive polynomial chaos expansion (NIPCE) based on point collocation method (PCM), Sobol sensitivity indices, and first-order reliability method (FORM) approaches are integrated with a chemical reactor network (CRN) model to develop a UQ-enabled emissions prediction tool. The CRN model consisting of a series of perfectly stirred reactors (PSRs) to model CO and NOx is constructed in Cantera. Surrogate models are developed using NIPCE-PCM approach and compared with the results of CRN model. The surrogate models are then used to perform global sensitivity and reliability analyses. The results show that the surrogate models substantially reduce the required computational costs by 2 to 3 orders of magnitude in comparison with the SBM to calculate sensitivity indices, importance factors and perform reliability analysis. Moreover, the results obtained by the NIPCE-PCM approach are more accurate in comparison with the SBM. Therefore, the developed UQ-enabled emissions prediction tool based on CRN and NIPCE-PCM approaches can be used for practical combustion systems as a reliable and computationally efficient framework to conduct probabilistic modeling of emissions.
Coach and Athlete Personality Interaction: A Critical Variable in Athletic Success
Authors: Lanning Wayne
Published: July 2019

An athletic program is always a reflection of the personality of the coach of the program. Within that program certain athletes will function better than others. This article presents a discussion of the importance of the personality interaction between coaches and the athletes with whom they work. It discusses the implications of that interaction for coaching, recruiting, and/or drafting athletes into a program, hiring of assistant coaches, and the selection of coaches and athletes for our national teams.
Pygmalion in Youth Sport: A Field Study
Authors: Rejeski Walter , Darracott Charles , Hutslar Sally
Published: July 2019

To determine whether the “pygmalion effect” operated in youth sport, a total sample of 14 coaches and 71 male youth league basketball players ranging in age from 8 to 12 were evaluated in naturalistic settings. Coach-player interactions were observed for both high and low expectancy children with the Coaching Behavior Assessment System (CBAS) as an observational tool. Results demonstrated that whereas high expectancy children received more reinforcement, low expectancy children experienced fewer incidences of nonreinforcement and received more general technical instruction. Findings were discussed from both a theoretical and practical perspective.
Expectations and Performance: An Empirical Test of Bandura's Self-efficacy Theory
Authors: Weinberg Robert , Gould Daniel , Jackson Allen
Published: July 2019

The present investigation was designed to test the predictions of Bandura's (1977) theory of self-efficacy in a competitive, motor-performance situation. Subjects (30 males and 30 females) were randomly assigned to either a high or low self-efficacy condition in a 2 × 2 × 2 (sex × self-efficacy × trials) factorial design. Self-efficacy was manipulated by having subjects compete against a confederate on a muscular leg-endurance task where the confederate was said to be either a varsity ;rack athlete who exhibited higher performance on a related task (low self-efficacy) or an individual who had a knee injury and exhibited poorer performance on a related task (high self-efficacy). Because self-efficacy theory predicts that expectation-performance differences are maximized in the face of obstacles and aversive consequences, the experiment was rigged so that subjects lost in competition to the confederate on both trials. The results supported self-efficacy predictions with the high self-efficacy subjects extending their legs significantly longer than low self-efficacy subjects. Moreover, after failing on the first trial, high self-efficacy subjects extended their legs for a longer time than low self-efficacy subjects on the second trial. A postexperimental questionnaire revealed significant differences in cognitive states (e.g., expectations, attributions, self-talk) between high and low self-efficacy subjects, as well as between males and females. Results are discussed in terms of learned helplessness and differing patterns of sex-role socialization.
An IgG-induced neutrophil activation pathway contributes to human drug-induced anaphylaxis
Authors: Jönsson Friederike , de Chaisemartin Luc , Granger Vanessa , Gouel-Chéron Aurélie , Gillis Caitlin M. , Zhu Qianqian , Dib Fadia , Nicaise-Roland Pascale , Ganneau Christelle , Hurtado-Nedelec Maria , Paugam-Burtz Catherine , Necib Skander , Keita-Meyer Hawa , Le Dorze Matthieu , Cholley Bernard , Langeron Olivier , Jacob Laurent , Plaud Benoit , Fischler Marc , Sauvan Caroline , Guinnepain Marie-Thérèse , Montravers Philippe , Aubier Michel , Bay Sylvie , Neukirch Catherine , Tubach Florence , Longrois Dan , Chollet-Martin Sylvie , Bruhns Pierre
Published: July 2019

Co-existence of drug-specific IgE and IgG antibodies aggravates neuromuscular-blocking agent-induced anaphylaxis in humans.
Gut microbes prevent marathoners from pooping out
Authors: Sowalsky Adam G.
Published: July 2019

Veillonella atypica
within the human gut converts lactate to propionate to improve marathoners’ endurance.
Global Analysis of Furfural-Induced Genomic Instability Using a Yeast Model
Authors: Qi Lei , Zhang Ke , Wang Yu-Ting , Wu Jian-Kun , Sui Yang , Liang Xiao-Zhuan , Yu Lin-Zi , Wu Xue-Chang , Wang Pin-Mei , Xu Jin-Zhong , Zheng Dao-Qiong
Published: July 2019

Whether and how furfural affects genome integrity have not been clarified. Using a
Saccharomyces cerevisiae
model, we found that furfural exposure leads to
in vivo
DSBs and elevation in mitotic recombination by orders of magnitude. Gross chromosomal rearrangements and aneuploidy events also occurred at a higher frequency in furfural-treated cells. In a genome-wide analysis, we show that the patterns of mitotic recombination and point mutations differed dramatically in furfural-treated cells and wild-type cells.
Single-Dose Vaccination with a Hepatotropic Adeno-associated Virus Efficiently Localizes T Cell Immunity in the Liver with the Potential To Confer Rapid Protection against Hepatitis C Virus
Authors: Mekonnen Zelalem A. , Grubor-Bauk Branka , English Kieran , Leung Preston , Masavuli Makutiro G. , Shrestha Ashish C. , Bertolino Patrick , Bowen David G. , Lloyd Andrew R. , Gowans Eric J. , Wijesundara Danushka K.
Published: July 2019

There are currently at least 71 million individuals with chronic HCV worldwide and almost two million new infections annually. Although the advent of direct-acting antivirals (DAAs) offers highly effective therapy, considerable remaining challenges argue against reliance on DAAs for HCV elimination, including high drug cost, poorly developed health infrastructure, low screening rates, and significant reinfection rates. Accordingly, development of an effective vaccine is crucial to HCV elimination. An HCV vaccine that elicits T cell immunity in the liver will be highly protective for the following reasons: (i) T cell responses against nonstructural proteins of the virus are associated with clearance of primary infection, and (ii) long-lived liver-resident T cells alone can protect against malaria infection of hepatocytes. Thus, in this study we exploit promising vaccination platforms to highlight strategies that can be used to evoke highly functional and long-lived T cell responses in the liver for protection against HCV.
Complete Genome Sequence of Leptospira kmetyi LS 001/16, Isolated from a Soil Sample Associated with a Leptospirosis Patient in Kelantan, Malaysia
Authors: Yusof Nik Yusnoraini , Muhammad Yusoff Farhana , Muhammad Harish Salwani , Ahmad Muhammad Nuramin , Khalid Muhammad Fazli , Mohd Nor Fauziah , Ismail Nabilah , Aziah Ismail
Published: July 2019

The Gram-negative pathogenic spirochetal bacteria
Leptospira
spp. cause leptospirosis in humans and livestock animals.
Leptospira kmetyi
strain LS 001/16 was isolated from a soil sample associated with a leptospirosis patient in Kelantan, which is among the states in Malaysia with a high reported number of disease cases. Here, we report the complete genome sequence of
Leptospira kmetyi
strain LS 001/16.
Genome Sequences of an H9N2 Avian Influenza Virus Strain Found in Pakistan in 2017
Authors: Lee Dong-Hun , Swayne David E. , Criado Miria F. , Killmaster Lindsay , Iqbal Shumaila , Rashid Hamad Bin , Chaudhry Mamoona
Published: July 2019

In 2017, we isolated an H9N2 avian influenza virus in Pakistan. Genetic analysis showed that the A/chicken/Kasoor/SI36/2017(H9N2) isolate belongs to the G1 lineage. In addition, this isolate possesses mammalian host-specific mutations which could possibly favor interspecies transmission, suggesting that Pakistani H9N2 viruses are still potentially infectious for mammals.
Draft Genomic Sequence of Multidrug-Resistant Klebsiella pneumoniae B8S35, Isolated from Retail Chicken Skin
Authors: Xu Aixia , Mackay William , Sommers Christopher H.
Published: July 2019

Here, we report the draft genome sequence of
Klebsiella pneumoniae
strain B8S35, isolated from retail chicken skin. It carries genes for resistance to multiple antibiotics, as well as quaternary ammonium compounds used by the food and health care industries.
Complete Genome Sequence of Thermoactinomyces vulgaris Strain CDF, a Thermophilic Bacterium Capable of Degrading Chicken Feathers
Authors: Li Binbin , Liu Feng , Ren Yuxia , Ding Yidi , Li Yu , Tang Xiao-Feng , Tang Bing
Published: July 2019

Thermoactinomyces vulgaris
strain CDF was isolated from soil and shown to have the ability to degrade chicken feathers at high temperatures. Here, we report the complete genome sequence of this bacterium, which is 2,595,509 bp long with 2,642 predicted genes and an average G+C content of 48.14%.