bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient awareness and beliefs about the risk factors and comorbidities associated with chronic kidney disease : A mixed‐methods study
Authors: Lopez‐Vargas Pamela A , Tong Allison , Howell Martin , Phoon Richard KS , Chadban Steven J , Shen Yvonne , Craig Jonathan C
Published: June 2016

Aim

Diabetes, hypertension and smoking may contribute to the development and progression of chronic kidney disease (CKD) and its complications. The aim of this study was to assess patients' awareness and beliefs about these and other risk factors associated with CKD.

Methods

Participants with CKD Stages 1–5 were purposively sampled for participation in a mixed methods study. Focus group participants completed a survey on CKD risk factors and discussed the reasons for their choices. Thematic analysis was used to analyse the qualitative data.

Results

Of the 38 participants, the proportion who identified hypertension, family history, diabetes and obesity as risk factors for CKD were 89%, 87%, 87% and 70% respectively. Only 54% and 38% recognized that smoking and Aboriginal or Torres Strait Islander status were risk factors. Participants considered the risks of heart attack, stroke and premature mortality to be 20–40% lower in people with CKD than those with diabetes or pre‐existing cardiovascular disease. Five themes were identified: invisibility (lack of signs and symptoms of CKD), invincibility (participants did not feel they were at risk), lacking awareness (identified not knowing much about their disease), cumulative comorbidities (concerned about the increased risks of associated diseases) and inevitability of death (there is no cure for CKD).

Conclusion

Participants had good understanding of some risk factors for CKD (hypertension and diabetes) but limited understanding of others. Awareness of comorbidities was also less than for other chronic conditions. Compared with diabetes and cardiovascular disease, CKD was perceived to pose less of a threat to life. Patient education that addresses CKD risk factors, comorbidities and outcomes may increase awareness and foster better self‐management for people with CKD.
Activity and MeCP2‐dependent regulation of nNOS levels in enteric neurons
Authors: Wahba G. , Schock S. C. , Cudd S. , Grynspan D. , Humphreys P. , Staines W. A.
Published: June 2016

Background

Rett syndrome (RTT) is a neurological disorder characterized by severe cognitive impairment, motor dyspraxia, and seizures. Rett syndrome arises predominantly from mutations in MECP2, the gene coding for methyl‐CpG‐binding protein 2 (MeCP2). MeCP2 is an important mediator of synaptic development and is essential in regulating homeostatic synaptic plasticity (HSP) in the brain. In addition to demonstrating central nervous system impairment, RTT patients also suffer from gastrointestinal (GI) dysmotility. We hypothesize that this is due to a similar impairment of plasticity‐dependent synaptic function in the enteric nervous system (ENS). We recently reported that MeCP2 is expressed in the ENS, providing evidence that neuronal dysfunction may mediate the GI pathology.

Methods

Baseline measures of MeCP2‐KO vs wild‐type (WT) GI neuronal nitric oxide synthase (nNOS) were assessed in tissue samples and in vitro. Experiments were carried out to measure nNOS in baseline vs activated plasticity states in vitro. Functional in vivo studies were carried out to determine whether MeCP2‐KO mice reproduced the RTT GI hypomotility.

Key Results

Methyl‐CpG‐binding protein 2‐KO mice reproduced the GI hypomotility seen in RTT. MeCP2‐KO GI tissue demonstrated elevated nNOS levels. Cultured WT enteric neurons showed upregulation of nNOS following moderate, prolonged stimulation by hyperkalemia; neurons from MeCP2‐KO mice failed to show this nNOS upregulation.

Conclusions & Inferences

MeCP2 is required for proper GI motility and normal nNOS levels. Neuronal nitric oxide synthase imbalances could mediate the GI dysmotility seen in RTT. Disruption of MeCP2‐dependent HSP may be the basis for aberrant nNOS levels and hence GI dysmotility in MeCP2‐KO and RTT.
Forms of Appropriation: A Typology
Authors: McCann Anthony
Published: June 2016

Since the enactment of the Congressional Budget and Impoundment Control Act, spending has been categorized as either “discretionary” or “mandatory.” However, over the last 40 years Congress has created and utilized many forms within each category and many agencies are funded via several forms, some of which are better understood than others. Consequently, budget and financial management officials must deal with differing levels of congressional control in obligating funds, variations in the length of time to expend obligated funds and varying levels of transparency. This article identifies 13 different forms of appropriations and develops a categorization of forms—“Discretionary,” “Transitional,” “Mandatory/Entitlement,” and “other.” For each form the article provides a description and examples. In each case the article also identifies issues of congressional control and budget execution raised by the form. The article concludes by advancing research questions raised by the analysis and categorizations.
Angiotensin II type 1 receptor antibodies in childhood kidney transplantation
Authors: Bjerre Anna , Tangeraas Trine , Heidecke Harald , Dragun Duska , Dechend Ralf , Staff Anne Cathrine
Published: June 2016

Angiotensin II type 1 receptor antibodies (AT1RAb) have emerged as non‐HLA Ab present in patients with acute AMR and risk of graft loss. Furthermore, AT1RAb have been shown to increase angiotensin II sensitivity which may play a role in the development of CVD and hypertension. Data on AT1RAb in stable transplant recipients are lacking. The aim of this study was to analyze the levels of AT1RAb in a cohort of stable patients after kidney transplantation (tx) in childhood. A cross‐sectional study of 30 children (median age 14, range 3–19 yr, median time since tx five yr) and 28 adults who were transplanted in childhood (median age 26, range 20–40 yr, median time since tx 18 yr) transplanted between 1993–2006 and 1983–2002, respectively, was performed. Healthy controls were 51 healthy children (5–8 yr) and 199 healthy donors (median age 56.5 yr, range 42–83 yr). Plasma AT1RAb were analyzed by immunoassay. Median total AT1RAb IgG concentration was significantly higher in the pediatric‐tx group as compared to the adult‐tx group (40.0 and 10.95 U/mL, p < 0.0001). For both groups, the tx group showed higher levels: the pediatric‐tx group vs. control group (40.0 vs. 13.3 U/mL, p = 0.0006) and the adult‐tx group vs. adult control group (10.95 vs. 6.5 U/mL, p < 0.0001). Age was the strongest indicator of high levels of AT1RAb IgG (p = 0.0003). AT1RAb total IgG levels are significantly higher in a stable pediatric‐tx cohort as compared to adult‐tx patients and healthy controls of comparable age groups. The relevance of our findings in relation to age, time since tx, previous or future rejection, and CVD risk merits future studies.
Building Global Public Administration Knowledge
Authors: Perry James L.
Published: June 2016

Perry Podcast Episode
Predictors of clinical outcome in emphysema patients with atelectasis following endoscopic valve therapy: A retrospective study
Authors: Gompelmann Daniela , Hofbauer Tobias , Gerovasili Vasiliki , Eberhardt Ralf , Lim Hyun‐ju , Herth Felix , Heussel Claus‐Peter
Published: June 2016

Background and objective

The aim of endoscopic valve therapy in patients with emphysema is complete lobar atelectasis of the most emphysematous lobe. However, even after the radiological advent of atelectasis, great variability in clinical outcomes can be observed.

Methods

The baseline clinical measures (vital capacity (VC), forced expiratory flow in 1 s (FEV1), residual volume (RV) and 6‐min walk test (6‐MWT)) and computed tomography variables (low attenuation volume (LAV) of the target lobe, LAV% of the target and the ipsilateral untreated lobe and LAV of the target lobe to LAV of the target lung and to LAV of the total lung) of 77 patients with complete atelectasis following valve therapy were retrospectively examined to determine their impact on patient´s outcome (changes in VC, FEV1, RV and 6‐MWT from baseline to the time of atelectasis).

Results

Low attenuation volume of the target lobe to LAV of the target lung predicts a significant FEV1 improvement in patients with complete lobar atelectasis following valve therapy. A 10% difference in that computed tomography predictor was associated with a 82‐mL improvement in FEV1 (P = 0.006). Lower 6‐MWT scores, low VC and high RV at baseline were significantly associated with greater improvement in the respective parameter (all P < 0.001).

Conclusion

Low attenuation volume of the target lobe to LAV of the target lung and baseline clinical measures seem to significantly predict clinical outcomes in patients with complete lobar atelectasis following valve treatment.
Improved resiliency and well‐being among military personnel in a Swedish Naval Force after a counter‐piracy operation off the coast of Somalia
Authors: Bäccman Charlotte , Hjärthag Fredrik , Almqvist Kjerstin
Published: June 2016

The aim of this study was to explore: (1) how the psychological health of the members of the first European Union Naval Force (ME01) was affected by international deployment off the coast of Somalia; and (2) if and how organizational and personal factors (e.g., type of personnel category, previous experiences, and resilience) affected their psychological health and well‐being post‐deployment. The study had an exploratory longitudinal design, where the participants were assessed both before and after deployment (i.e., T1 and T2). The participants (n = 129, 120 men, 9 women) were equally distributed between officers (n = 68; 64 men, 4 women) and sailors (n = 61; 56 men, 5 women). The members' average age was 31 years, ranging from 20 to 61. For the majority (78%) ME01 was their first international deployment and officers were, in general, more experienced than sailors. The overall results showed that the members' reported a positive experience with improved resilience and well‐being (e.g., sense of coherence). However, the result also showed that type of personnel category (i.e., officer or sailor) affected their psychological health. Why and how these differences among military personnel arise is discussed, but deserves further attention.
Animal Mindreading and the Principle of Conservatism
Authors: Fagan Tyler K.
Published: June 2016

Skeptics about nonlinguistic mindreading often use an inferential rule of thumb—the principle of conservatism—to cast doubt on purported empirical evidence of mindreading abilities in nonlinguistic creatures. This principle, if warranted, would seem to count generally against explanatory hypotheses that posit nonlinguistic mindreading, instead favoring mere behavior‐reading hypotheses. Using a test case from research with chimpanzees, I show that this principle is best understood as an appeal to parsimony; that, regardless of how one conceives of parsimony, the principle is unwarranted; and that, once we put the principle aside, the prospects for nonlinguistic mindreading are brighter than traditionally thought.
Horror, Fear, and the Sartrean Account of Emotions
Authors: Elpidorou Andreas
Published: June 2016

Phenomenological approaches to affectivity have long recognized the vital role that emotions occupy in our lives. In this paper, I engage with Jean‐Paul Sartre's well‐known and highly influential theory of the emotions as it is advanced in his Sketch for a Theory of the Emotions. I examine whether Sartre's account offers two inconsistent explications of the nature of emotions. I argue that despite appearances there is a reading of Sartre's theory that is free of inconsistencies. Ultimately, I highlight a novel reading of Sartre's account of the emotions: one that is both phenomenologically accurate and supported by textual evidence.
Kant and Husserl on the Contents of Perception
Authors: van Mazijk Corijn
Published: June 2016

This paper focuses on the contents of perception in Kant's first Critique and Husserl's later writings. Both Kant and Husserl are known for their appeal to synthesis in their transcendental accounts of perceptual experience and objective judgment. Especially regarding Kant, the precise nature of perceptual synthesis has recently been the cause of much debate. Whereas some argue that for Kant perception must have nonconceptual content, others believe he is a conceptualist. After offering an alternative solution to this interpretative problem in Kant's philosophy, I turn to Husserl's later theory of perception. My main claims here are that Husserl departs from Kant specifically regarding (i) the sort of synthetic contents that govern affective perception and (ii) the role of conceptual capacities in the contents of attentive perception.
Descartes and the Dissolution of Life
Authors: Hutchins Barnaby R.
Published: June 2016

I argue that Descartes is not a reductionist about life, but dissolves or eliminates the category entirely. This is surprising both because he repeatedly refers to the life of humans, animals, and plants and because he appears to rely on the category of life to construct his physiology and medicine. Various attempts have been made in the scholarship to attribute a principled concept of life to Descartes. Most recently, Detlefsen (2016) has argued that Descartes “is a reductionist with respect to explanation of life phenomena but not an eliminativist with respect to life itself” (143). I show that all these attempts either result in arbitrariness or force Descartes's wider philosophical project into incoherence. I argue that Descartes's ontological commitments make a principled concept of life impossible, that he does not need such a concept, and that his project ends up more coherent without one.
Conceptualizing Journalistic Careers: Between Interpretive Community and Tribes of Professionalism
Authors: Meyers Oren , Davidson Roei
Published: June 2016

Professionalism is a concept that centers on specialization of labor and control of occupational practice. It has traditionally been used to describe and define individuals who are affiliated with an occupational community that has managed to secure a certain measure of autonomy and jurisdiction over an area of expertise and has a claim to a public service ethos. In this review essay, we consider the changing professional status of journalism. Whether or not journalism is “truly” a profession, it is clear that a discourse of journalistic professionalism plays a crucial role in legitimizing the journalistic occupation. Consequently, this essay explores different approaches towards the professionalization of journalism and positions this discussion within two interrelated contexts: first, it investigates the ramifications of the current crisis in western news media on journalistic professionalism. Next, the essay probes the professional standing of journalism in view of the development of new digital technologies that are re‐shaping essential aspects of journalistic work. We conclude that journalism has lost some of its cohesion and fragmented into tribes of professionalism practiced by a diverse set of actors.
Varieties of Field Theory and the Sociology of the Non‐profit Sector
Authors: Barman Emily
Published: June 2016

This paper reviews the use of field theory in the sociological study of the non‐profit sector. The review first shows how field theory, as a conceptual framework to explain social action, provides a valuable sociological counterweight to prevailing economic and psychological orientations in the interdisciplinary scholarship on the non‐profit sector. However, despite its certain shared assumptions, field theory in sociology encompasses three distinct, albeit interrelated, approaches: the Bourdieusian, New Institutionalist, and Strategic Action Fields perspectives. I comparatively outline the key analytical assumptions and causal claims of each version of field theory, whether and how it recognizes the specificity of the non‐profit sector and then delineate its application by sociologists to the non‐profit sector. I show how scholars' employment of each articulation of field theory to study non‐profit activity has been influenced by pre‐existing scholarly assumptions and normative claims about this third space. The article concludes by summarizing the use of these varieties of field theory in the sociology of the non‐profit sector and by identifying future directions in this line of research.
Association of vitamin D status with incidence of enterotoxigenic, enteropathogenic and enteroaggregative Escherichia coli diarrhoea in children of urban Bangladesh
Authors: Ahmed A. M. S. , Soares Magalhaes R. J. , Long K. Z. , Ahmed T. , Alam Md. A. , Hossain Md. I. , Islam Md. M. , Mahfuz M. , Mondal D. , Haque R. , Mamun A. A.
Published: June 2016

Objective

To evaluate the association between vitamin D status and diarrhoeal episodes by enterotoxigenic (ETEC), enteropathogenic (EPEC) and enteroaggregative (EAEC) E. coli in underweight and normal‐weight children aged 6–24 months in urban Bangladesh.

Methods

Cohorts of 446 normal‐weight and 466 underweight children were tested separately for ETEC, EPEC and EAEC from diarrhoeal stool samples collected during 5 months of follow‐up while considering vitamin D status at enrolment as the exposure. Cox proportional hazards models with unordered failure events of the same type were used to determine diarrhoeal risk factors after adjusting for sociodemographic and concurrent micronutrient status.

Results

Vitamin D status was not independently associated with the risk of incidence of ETEC, EPEC and EAEC diarrhoea in underweight children, but moderate‐to‐severe retinol deficiency was associated with reduced risk for EPEC diarrhoea upon adjustment. Among normal‐weight children, insufficient vitamin D status and moderate‐to‐severe retinol deficiency were independently associated with 44% and 38% reduced risk of incidence of EAEC diarrhoea, respectively. These children were at higher risk of ETEC diarrhoea with vitamin D deficiency status when adjusted for micronutrient status only.

Conclusion

This study demonstrates for the first time that normal‐weight children with insufficient vitamin D status have a reduced risk of EAEC diarrhoea than children with sufficient status. Moderate‐to‐severe deficiency of serum retinol is associated with reduced risk of EPEC and EAEC diarrhoea in underweight and normal‐weight children.
Contribution of polymeric materials to progress in xenotransplantation of microencapsulated cells: a review
Authors: Mahou Redouan , Passemard Solène , Carvello Michele , Petrelli Alessandra , Noverraz François , Gerber‐Lemaire Sandrine , Wandrey Christine
Published: June 2016

Cell microencapsulation and subsequent transplantation of the microencapsulated cells require multidisciplinary approaches. Physical, chemical, biological, engineering, and medical expertise has to be combined. Several natural and synthetic polymeric materials and different technologies have been reported for the preparation of hydrogels, which are suitable to protect cells by microencapsulation. However, owing to the frequent lack of adequate characterization of the hydrogels and their components as well as incomplete description of the technology, many results of in vitro and in vivo studies appear contradictory or cannot reliably be reproduced. This review addresses the state of the art in cell microencapsulation with special focus on microencapsulated cells intended for xenotransplantation cell therapies. The choice of materials, the design and fabrication of the microspheres, as well as the conditions to be met during the cell microencapsulation process, are summarized and discussed prior to presenting research results of in vitro and in vivo studies. Overall, this review will serve to sensitize medically educated specialists for materials and technological aspects of cell microencapsulation.
Improved Friction Joint With Self-Locking Grips
Authors: Costache Andrei , Glejbøl Kristian , Sivebæk Ion Marius , Berggreen Christian
Published: June 2016

Flexible risers are used in the oil industry to transport liquids and gas from the seafloor to extraction and production equipment at the sea surface. Ongoing research aims at using composite materials instead of steel, in order to reduce weight and increase stiffness. Ensuring an optimal load transfer between the composite and metal components is very important. This paper presents an improved method for anchoring a flat fiber-reinforced tendon using a double grip system with self-locking grips. The novelty is the combination of new experimental results and finite element (FE) analysis to develop a superior dry friction grip. Experimental results are carried using a dedicated test setup, through which the test parameters can be accurately controlled. The efficiency of the grip system during pullout is superior to results obtained with flat grips. Numerical results offer an in-depth understanding of the influence between friction, geometrical parameters, and performance, making it possible to optimize the design. Results show that this grip system offers immediate technical applications, in a variety of conditions.
Bipolar resistive switching characteristics of cobalt-doped HfO2-based memory films
Authors: Guo Tingting , Tan Tingting , Liu Zhengtang
Published: June 2016

In this work, the resistive switching behavior of HfO2 and cobalt-doped (Co:HfO2) films were demonstrated. X-ray photoelectron spectroscopy was used to explore the effect of Co dopants upon the chemical composition of HfO2 film. Both films showed bipolar resistive switching behaviors, while the Co:HfO2 film exhibited decreased switching voltages and narrower variations in the switching parameters, including voltages and resistances, than those of the HfO2 film owing to the modulation of defects. The Pt/Co:HfO2/Cu device also exhibited an increased ON/OFF ratio because of the increased resistance in the high resistance state, as well as good endurance and retention. The switching mechanisms for the fabricated devices were discussed based on the conductive filament model.
Outcome measures based on classification performance fail to predict the intelligibility of binary-masked speech
Authors: Kressner Abigail Anne , May Tobias , Rozell Christopher J.
Published: June 2016

To date, the most commonly used outcome measure for assessing ideal binary mask estimation algorithms is based on the difference between the hit rate and the false alarm rate (H-FA). Recently, the error distribution has been shown to substantially affect intelligibility. However, H-FA treats each mask unit independently and does not take into account how errors are distributed. Alternatively, algorithms can be evaluated with the short-time objective intelligibility (STOI) metric using the reconstructed speech. This study investigates the ability of H-FA and STOI to predict intelligibility for binary-masked speech using masks with different error distributions. The results demonstrate the inability of H-FA to predict the behavioral intelligibility and also illustrate the limitations of STOI. Since every estimation algorithm will make errors that are distributed in different ways, performance evaluations should not be made solely on the basis of these metrics.
Physical Activity and Anthropometric Characteristics Among Urban Youth in Mexico: A Cross-Sectional Study
Authors: Parker Nathan , Atrooshi Darran , Lévesque Lucie , Jauregui Edtna , Barquera Simón , Taylor Juan Lopez y , Lee Rebecca E.
Published: June 2016

Background:

Obesity is a critical problem among Mexican youth, but few studies have investigated associations among physical activity (PA) modes and anthropometrics in this population. This study examined associations among active commuting to school (ACS), sports or other organized PA, outdoor play, and body mass index (BMI) percentile and waist circumference (WC) among Mexican youth.

Methods:

Parents of school children (N = 1996, ages 6 to 14 years, 53.1% female) in 3 Mexican cities reported PA participation using the (modified) fourth grade School Physical Activity and Nutrition Survey. Trained assessors measured BMI percentile and WC in person.

Results:

Parents reported that 52.3% of children engaged in ACS, 57.3% participated in sports or organized PA, and a median of 2 days in the previous week with at least 30 minutes of outdoor play. In complete case analyses (n = 857), ACS was negatively associated with BMI percentile, and outdoor play was negatively associated with WC after adjusting for school, age, sex, and income. In analyses incorporating data from multiple imputation (N = 1996), outdoor play was negatively associated with WC (all Ps < . 05).

Conclusions:

ACS and outdoor play are favorably associated with anthropometrics and may help prevent childhood obesity in Mexico. ACS and outdoor play should be priorities for increasing youth PA in Mexico.
Changes in Policy Maker Attitudes Toward Active Living Communities Issues in Hawaii, 2007–2013
Authors: McGurk Meghan , Maddock Jay
Published: June 2016

Background:

Obesity and lack of physical activity are major public health problems in the United States. Well-designed, active living communities (ALCs) can help support physically active lifestyles. This study assessed attitudes of Hawaii decision makers in 2007 and 2013 to determine if priorities toward ALCs changed.

Methods:

Elected and appointed state and county officials were mailed surveys both years. Respondents rated the importance of 23 specified problems, which included 1 obesity variable and 5 ALC variables.

Results:

The survey was completed by 126 (70.4%) respondents in 2007 and 117 (60.9%) in 2013. Among the specific problems, only obesity increased in rank from 14th to ninth place. Three variables fell more than 2 places: increasing traffic (fifth to seventh place), poorly planned development and sprawl (seventh to 11th place) and pedestrian safety (12th to 17th place). The other 2 stayed relatively the same: lack of pedestrian walkways, sidewalks, and crosswalks (16th to 15th place) and lack of recreational activities (22nd to 23rd place).

Conclusions:

Across years, obesity concerns have increased but do not appear to be tied to increases in concern for ALC variables. More education for policymakers on the link between obesity, physical activity, and the built environment is necessary.
Mosquito hunters search for Zika vectors
Authors: Vogel Gretchen
Published: June 2016

Yellow fever mosquito is confirmed, but others may contribute.
‘Culinary frontier’ tracks Madagascar's Asian settlers
Authors: Lawler Andrew
Published: June 2016

Crop remains record wave of arrivals from the East.
CRISPR views of embryos and cells
Authors: Kupferschmidt Kai
Published: June 2016

Genome editor helps record development, cell influences.
ADP-ribose–derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling
Authors: Wright Roni H. G. , Lioutas Antonios , Le Dily Francois , Soronellas Daniel , Pohl Andy , Bonet Jaume , Nacht A. S. , Samino Sara , Font-Mateu Jofre , Vicent Guillermo P. , Wierer Michael , Trabado Miriam A. , Schelhorn Constanze , Carolis Carlo , Macias Maria J. , Yanes Oscar , Oliva Baldo , Beato Miguel
Published: June 2016

A nuclear power source in the cell

DNA is packaged onto nucleosomes, the principal component of chromatin. This chromatin must be remodeled to allow gene transcription, DNA replication, and DNA repair machineries access to the enclosed DNA. Chromatin-remodeling complexes require high levels of cellular energy to do their job. Wright
et al.
show that the energy needed to remodel chromatin can be derived from a source, poly-ADP-ribose, in the cell nucleus, rather than by diffusion of ATP from mitochondria in the cytoplasm, the usual powerhouse of the cell. Poly-ADP-ribose is converted to ADP-ribose and then to ATP, which can be used to fuel chromatin remodeling within the nucleus.

Science
, this issue p.
1221
Photonic multitasking enabled with geometric phase
Authors: Litchinitser Natalia M.
Published: June 2016

Metasurface-based phased-array antennas help implement flat optical devices that perform multiple functions
A lipid arsenal to control inflammation
Authors: Napier Brooke A. , Monack Denise M.
Published: June 2016

Lipids released from dying cells control immune responses to microbial products
Taking up TOP
Authors: McNutt Marcia
Published: June 2016

Nearly 1 year ago, a group of researchers boldly suggested that the standards for research quality, transparency, and trustworthiness could be improved if journals banded together to adopt eight standards called TOP (Transparency and Openness Promotion).
*
Since that time, more than 500 journals have been working toward their implementation of TOP. The editors at
Science
have held additional retreats and workshops to determine how best to adapt TOP to a general science journal and are now ready to announce our new standards, effective 1 January 2017.
†
Single-Molecule Sequencing Reveals Complex Genome Variation of Hepatitis B Virus during 15 Years of Chronic Infection following Liver Transplantation
Authors: Betz-Stablein B. D. , Töpfer A. , Littlejohn M. , Yuen L. , Colledge D. , Sozzi V. , Angus P. , Thompson A. , Revill P. , Beerenwinkel N. , Warner N. , Luciani F.
Published: June 2016

Chronic hepatitis B (CHB) is prevalent worldwide. The infectious agent, hepatitis B virus (HBV), replicates via an RNA intermediate and is error prone, leading to the rapid generation of closely related but not identical viral variants, including those that can escape host immune responses and antiviral treatments. The complexity of CHB can be further enhanced by the presence of HBV variants with large deletions in the genome generated via splicing (spHBV variants). Although spHBV variants are incapable of autonomous replication, their replication is rescued by wild-type HBV. spHBV variants have been shown to enhance wild-type virus replication, and their prevalence increases with liver disease progression. Single-molecule deep sequencing was performed on whole HBV genomes extracted from samples, including the liver explant, longitudinally collected from a subject with CHB over a 15-year period after liver transplantation. By employing novel bioinformatics methods, this analysis showed that the dynamics of the viral population across a period of changing treatment regimens was complex. The spHBV variants detected in the liver explant remained present posttransplantation, and a highly diverse novel spHBV population as well as variants with multiple deletions in the pre-S genes emerged. The identification of novel mutations outside the HBV reverse transcriptase gene that co-occurred with known drug resistance-associated mutations highlights the relevance of using full-genome deep sequencing and supports the hypothesis that drug resistance involves interactions across the full length of the HBV genome.

IMPORTANCE
Single-molecule sequencing allowed the characterization, in unprecedented detail, of the evolution of HBV populations and offered unique insights into the dynamics of defective and spHBV variants following liver transplantation and complex treatment regimens. This analysis also showed the rapid adaptation of HBV populations to treatment regimens with evolving drug resistance phenotypes and evidence of purifying selection across the whole genome. Finally, the new open-source bioinformatics tools with the capacity to easily identify potential spliced variants from deep sequencing data are freely available.
Using the E4orf6-Based E3 Ubiquitin Ligase as a Tool To Analyze the Evolution of Adenoviruses
Authors: Gilson Timra , Blanchette Paola , Ballmann Mónika Z. , Papp Tibor , Pénzes Judit J. , Benkő Mária , Harrach Balázs , Branton Philip E.
Published: June 2016

E4orf6 proteins from all human adenoviruses form Cullin-based ubiquitin ligase complexes that, in association with E1B55K, target cellular proteins for degradation. While most are assembled with Cul5, a few utilize Cul2. BC-box motifs enable all these E4orf6 proteins to assemble ligase complexes with Elongins B and C. We also identified a Cul2-box motif used for Cul2 selection in all Cul2-based complexes. With this information, we set out to determine if other adenoviruses also possess the ability to form the ligase complex and, if so, to predict their Cullin usage. Here we report that all adenoviruses known to encode an E4orf6-like protein (mastadenoviruses and atadenoviruses) maintain the potential to form the ligase complex. We could accurately predict Cullin usage for E4orf6 products of mastadenoviruses and all but one atadenovirus. Interestingly, in nonhuman primate adenoviruses, we found a clear segregation of Cullin binding, with Cul5 utilized by viruses infecting great apes and Cul2 by Old/New World monkey viruses, suggesting that a switch from Cul2 to Cul5 binding occurred during the period when great apes diverged from monkeys. Based on the analysis of Cullin selection, we also suggest that the majority of human adenoviruses, which exhibit a broader tropism for the eye and the respiratory tract, exhibit Cul5 specificity and resemble viruses infecting great apes, whereas those that infect the gastrointestinal tract may have originated from monkey viruses that share Cul2 specificity. Finally, aviadenoviruses also appear to contain E4orf6 genes that encode proteins with a conserved XCXC motif followed by, in most cases, a BC-box motif.

IMPORTANCETwo early adenoviral proteins, E4orf6 and E1B55K, form a ubiquitin ligase complex with cellular proteins to ubiquitinate specific substrates, leading to their degradation by the proteasome. In studies with representatives of each human adenovirus species, we (and others) previously discovered that some viruses use Cul2 to form the complex, while others use Cul5. In the present study, we expanded our analyses to all sequenced adenoviruses and found that E4orf6 genes from all mast- and atadenoviruses encode proteins containing the motifs necessary to form the ligase complex. We found a clear separation in Cullin specificity between adenoviruses of great apes and Old/New World monkeys, lending support for a monkey origin for human viruses of theHuman mastadenovirus A,F, andGspecies. We also identified previously unrecognized E4orf6 genes in the aviadenoviruses that encode proteins containing motifs permitting formation of the ubiquitin ligase.
Suppression of IRG-1 Reduces Inflammatory Cell Infiltration and Lung Injury in Respiratory Syncytial Virus Infection by Reducing Production of Reactive Oxygen Species
Authors: Ren Ke , Lv Yuanzi , Zhuo Yujie , Chen Changmai , Shi Hengfei , Guo Lin , Yang Guang , Hou Yayi , Tan Ren Xiang , Li Erguang
Published: June 2016

Respiratory syncytial virus (RSV) infection is a common cause of lower respiratory tract illness in infants and children. RSV is a negative-sense, single-strand RNA (ssRNA) virus that mainly infects airway epithelial cells. Accumulating evidence indicates that reactive oxygen species (ROS) production is a major factor for pulmonary inflammation and tissue damage of RSV disease. We investigated immune-responsive gene-1 (IRG1) expression during RSV infection, since IRG1 has been shown to mediate innate immune response to intracellular bacterial pathogens by modulating ROS and itaconic acid production. We found that RSV infection induced IRG1 expression in human A549 cells and in the lung tissues of RSV-infected mice. RSV infection or IRG1 overexpression promoted ROS production. Accordingly, knockdown of IRG1 induction blocked RSV-induced ROS production and proinflammatory cytokine gene expression. Finally, we showed that suppression of IRG1 induction reduced immune cell infiltration and prevented lung injury in RSV-infected mice. These results therefore link IRG1 induction to ROS production and immune lung injury after RSV infection.

IMPORTANCE
RSV infection is among the most common causes of childhood diseases. Recent studies identify ROS production as a factor contributing to RSV disease. We investigated the cause of ROS production and identified IRG1 as a critical factor linking ROS production to immune lung injury after RSV infection. We found that IRG1 was induced in A549 alveolar epithelial cells and in mouse lungs after RSV infection. Importantly, suppression of IRG1 induction reduced inflammatory cell infiltration and lung injury in mice. This study links IRG1 induction to oxidative damage and RSV disease. It also uncovers a potential therapeutic target in reducing RSV-caused lung injury.
CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis
Authors: Price Valerie J. , Huo Wenwen , Sharifi Ardalan , Palmer Kelli L.
Published: June 2016

Enterococcus faecalis
is a bacterium that normally inhabits the gastrointestinal tracts of humans and other animals. Although these bacteria are members of our native gut flora, they can cause life-threatening infections in hospitalized patients. Antibiotic resistance genes appear to be readily shared among high-risk
E. faecalis
strains, and multidrug resistance in these bacteria limits treatment options for infections. Here, we find that CRISPR-Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, significantly impact the spread of antibiotic resistance genes in
E. faecalis
populations. The loss of these systems in high-risk
E. faecalis
suggests that they are immunocompromised, a tradeoff that allows them to readily acquire new genes and adapt to new antibiotics.
To Defend or Not To Defend: That’s the Question
Authors: Varahan Sriram , Hancock Lynn E.
Published: June 2016

Enterococcus faecalis
is an opportunistic pathogen and is one of the leading causes of nosocomial infections.
E. faecalis
harbors a number of antibiotic resistance genes, and most of these are present on mobile genetic elements (MGEs) that can be disseminated within the species, as well as to other members of the human microflora. In an article by Price and colleagues [V. J. Price et al., mSphere 1(3):e00064-16, 2016,
http://dx.doi.org/10.1128/mSphere.00064-16
], the authors demonstrated how
E. faecalis
uses a restriction-modification system along with a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas to function as a bacterial innate and adaptive immune system to regulate the influx of MGEs. The absence of these systems in high-risk hospital-adapted lineages of
E. faecalis
, including the prototypical V583 strain, appears to allow the ready acquisition of new traits that aid in the adaptation to new environmental stresses, including the evolution of resistance to many of our best antibiotics.
Prevalence of metabolic syndrome and its related factors among North Korean refugees in South Korea: a cross-sectional study
Authors: Kim Yoon Jung , Lee Yo Han , Lee Yun Jeong , Kim Kyeong Jin , An Jee Hyun , Kim Nam Hoon , Kim Hee Young , Choi Dong Seop , Kim Sin Gon
Published: June 2016

Objectives

To determine the prevalence of metabolic syndrome (MetS) and its related factors among North Korean refugees (NKR) in South Korea.

Design

Cross-sectional study conducted using a questionnaire and anthropometric and biochemical data on NKR in South Korea.

Setting

Seoul, South Korea.

Participants

A sample of NKR who voluntarily underwent medical examinations in Anam Hospital of Korea University, Seoul, South Korea (N=708, consisting of 161 males and 547 females). To compare the prevalence of MetS, 1416 age- and gender-matched individuals from the South Korean population (SKP, at a ratio of 1:2 to NKR) were randomly selected from the fifth Korean National Health and Nutrition Examination Survey.

Main outcome measures

The prevalence of MetS and its related factors among NKR in South Korea and comparison with its prevalence among the general SKP.

Results

The prevalence of MetS among male and female NKR in South Korea was 19.7% and 17.2%, respectively. Although obesity is more prevalent in South than in North Korea, we found no difference in the prevalence of MetS between the female NKR and SKP groups (17.2% vs 16.6%, respectively; p=0.830). As regards the males, the small sample size of the NKR group yielded insufficient evidence of any difference in MetS prevalence between the NKR and SKP groups (19.7% vs 26.2%, respectively; p=0.134). We found that excess weight gain (≥5%) in South Korea was significantly associated with MetS among NKR.

Conclusions

The prevalence of MetS among NKR did not differ from that in the SKP group despite the lower prevalence of obesity in NKR than in the general SKP. The fact that excess weight gain in South Korea was associated with the risk of MetS suggests that public health policy makers should focus on preventing excess weight gain in NKR during resettlement in South Korea.
Feasibility of EEG to monitor cognitive performance during venous cannulation: EEG Distracted Intravenous Access (E-DIVA)
Authors: Lowe David J , James Scott A , Lloyd Adam , Clegg Gareth R
Published: June 2016

Background

The feasibility study aims to evaluate the use of EEG in measuring workload during a simulated intravenous cannulation task. Cognitive workload is strongly linked to performance, but current methods to assess workload are unreliable. The paper presents the use of EEG to compare the cognitive workload between an expert and novice group completing a simple clinical task.

Methods

2 groups of volunteers (10 final year medical students and 10 emergency medicine consultants) were invited to take part in the study. Each participant was asked to perform 3 components of the simulation protocol: intravenous cannulation, a simple arithmetic test and finally these tasks combined. Error rate, speed of task completion and an EEG-based measure of cognitive workload were recorded for each element.

Results

EEG cognitive workload during the combined cannulation and arithmetic task is significantly greater in novice participants when compared with expert operators performing the same task combination. EEG workload mean measured for novice and experts was 0.62 and 0.54, respectively (p=0.001, 95% CI 0.09 to 0.30). There was no significant difference between novice and expert EEG workload when the tasks were performed individually.

Conclusions

EEG provides the opportunity to monitor and analyse the impact of cognitive load on clinical performance. Despite the significant challenges in set up and protocol design, there is a potential to develop educational interventions to optimise clinician's awareness of cognitive load. In addition, it may enable the use of metrics to monitor the impact of different interventions and select those that optimise clinical performance.
New Antiepileptic Drugs: Focus on Ezogabine, Clobazam, and Perampanel
Authors: Rudzinski Leslie A , Vélez-Ruiz Naymeé J , Gedzelman Evan R , Mauricio Elizabeth A , Shih Jerry J , Karakis Ioannis
Published: June 2016

Ezogabine, clobazam, and perampanel are among the newest antiseizure drugs approved by the Food and Drug Administration between 2011 and 2012. Ezogabine and perampanel are approved for adjunctive treatment of partial epilepsy. Perampanel is also approved for adjunctive treatment of primary generalized tonic–clonic seizures. Ezogabine and perampanel have novel mechanisms of action. Ezogabine binds to voltage-gated potassium channels and increases the M-current thereby causing membrane hyperpolarization. Perampanel is a selective, non-competitive 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid receptor antagonist, which reduces neuronal excitation. Clobazam has been used worldwide since the 1970s and is approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. Clobazam is the only 1,5-benzodiazepine currently in clinical use, which is less sedating than the commonly used 1,4-benzodiazepines. Phase III multicenter, randomized, double-blind, placebo-controlled trials demonstrated efficacy and good tolerability of these 3 new antiepileptic drugs. These drugs represent a welcome addition to the armamentarium of practitioners, but it remains to be seen how they will affect the landscape of pharmacoresistant epilepsy.
Academia or practice?
Authors: Barstow Amy
Published: June 2016

Amy Barstow's friends and family always knew she was destined for veterinary medicine. Her aim initially was clinical practice; however, an interest in equine lameness has led her into a PhD in equine biomechanics
Unifying framework for modeling swelling soil behaviour
Authors: Lim B.F. , Siemens G.A.
Published: June 2016

The destructive effect of expansive soils on infrastructure is one of the classical issues associated with unsaturated soils. Given the continuing challenges associated with swelling soils there is still a need for a practical analysis method. The swelling equilibrium limit (SEL) provides a concept for modeling expansive soil behaviour. The SEL is an upper bound swelling limit, which depends on the soil’s initial state and the boundary conditions upon wetting. The SEL is obtained experimentally from swelling tests performed by applying a range of swelling scenarios from rigid boundary condition to free swelling without confinement. In this paper, improvements to the triaxial swelling apparatus are reported, SELs for two new swelling soils are characterized, and a framework for SEL prediction is developed. The SEL framework is developed to relate SEL parameters to index properties as well as the soil’s initial volume. SEL parameters are correlated to liquid limit, plasticity index, free swell potential, and specific volume. The relationships are used to estimate the SEL for Regina clay, which is shown to agree with experimental data.
Interaction between 2-(p-toluidino)-6-naphthalenesulfonic acid sodium salt (TNS) and β-lactoglobulin
Authors: Li Huiqing , Wei Jing , Dong Youming , Yu Zhiyue
Published: June 2016

The major bovine milk protein β-lactoglobulin (β-LG), a member of the lipocalin superfamily, can bind a wide range of ligands and act as a transporter. In the present study, the combination of the hydrophobic molecule 2-(p-toluidino)-6-naphthalenesulfonic acid sodium salt (TNS) with β-LG was analyzed using fluorescence spectroscopy and AutoDock modeling to discern the major binding sites of the protein and to determine the capacity of other small ligands to bind with β-LG by utilizing TNS as a reference. The experimental data indicate that in a neutral pH environment, TNS is located in the hydrophobic domain of the protein, 2.5 nm away from the Trp19 residues of β-LG. The binding constant of the small molecule to β-LG is (3.30 ± 0.32) × 106 (mol L–1)−1. An interaction model between the ligand and β-LG was developed, and AutoDock modeling also demonstrates that the ligand is located in the central hydrophobic calyx of β-LG within the regions covered by the Förster radius of the Trp19–ligand pair. Although the interaction between the ligand and β-LG is affected by increasing ion strength, pH change, and heat treatment, the complex is maintained until the secondary structure of β-LG is destroyed. Additionally, the ligand binding stabilizes the folding of β-LG. The binding constants of sodium dodecyl sulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) to β-LG were obtained using competitive ligand binding measurements. With a sensitive fluorescence signal and stable complex, the ligand could be utilized as a reference to detect the binding of other small ligands to β-LG.