bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase I study to determine the pharmacokinetic profile, safety and tolerability of sildenafil (Revatio®) in cardiac surgery: the REVAKI‐1 study
Authors: Ring Arne , Morris Tom , Wozniak Marcin , Sullo Nikol , Dott William , Verheyden Veerle , Kumar Tracy , Brunskill Nigel , Vaja Rakesh , Murphy Gavin J.
Published: October 2016

Aims

Acute kidney injury (AKI) is a common and severe complication of cardiac surgery. There is no effective prevention or treatment. Sildenafil citrate (Revatio®, Pfizer Inc.), a phosphodiesterase type 5 inhibitor, prevents post cardiac surgery AKI in pre‐clinical studies, however its use is contraindicated in patients with symptomatic cardiovascular disease. The aim of this study is to assess the safety and pharmacokinetics of intravenous sildenafil in cardiac surgery patients.

Methods

We conducted an open label, dose escalation study with six patients per dose level. The six doses were 2.5 mg, 5 mg or 10 mg as a bolus, either alone or followed by an additional 2 h infusion of 2.5 mg sildenafil.

Results

Thirty‐six patients entered the trial, of which 33 completed it. The mean age was 69.9 years. One patient died during surgery, two others were removed from the trial before dosing (all at dose level 5 mg + 2.5 mg). The pharmacokinetic profile of sildenafil was similar to previously published studies. For a dose of 10 mg administered as a bolus followed by 2.5 mg administered over 2 h the results were AUC∞ 537 ng h ml−1, Cmax 189.4 ng ml−1 and t1/2 10.5 h. The drug was well tolerated with no serious adverse events related to drug administration. Higher sildenafil doses stabilized post‐surgery nitric oxide bioavailability.

Conclusions

Pharmacokinetics of sildenafil during cardiopulmonary bypass were comparable to those of other patient groups. The drug was well tolerated at therapeutic plasma levels. These results support the further evaluation of sildenafil for the prevention of AKI in cardiac surgery.
Maturation of oxycodone pharmacokinetics in neonates and infants: Oxycodone and its metabolites in plasma and urine
Authors: Kokki Merja , Heikkinen Marja , Välitalo Pyry , Hautajärvi Heidi , Hokkanen Juho , Pitkänen Hanna , Sankilampi Ulla , Ranta Veli‐Pekka , Kokki Hannu
Published: October 2016

Aims

This study aimed to characterize the pharmacokinetics of oxycodone and its major metabolites in infants and covered the age range between extremely preterm neonates and 2‐year‐old infants.

Methods

Seventy‐nine infants (gestational age 23–42 weeks; postnatal age 0–650 days) received intravenous oxycodone hydrochloride trihydrate at a dose of 0.1 mg kg−1 during or after surgery. Three to seven blood samples were taken from each infant, and plasma concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were quantified. The unconjugated forms of these compounds were determined in urine collected after up to 24 or 48 h from 25 infants. Pharmacokinetics was determined using noncompartmental analysis and reported for six clinically relevant age groups based on postmenstrual age.

Results

Oxycodone pharmacokinetics changed markedly with patient age. Preterm neonates were found to have the highest pharmacokinetic variability out of the study population. In extremely preterm neonates (n = 6) median of elimination half‐life was 8.8 h (range 6.8–12.5), in preterm (n = 11) 7.4 h (4.2–11.6), and in older neonates (n = 22) 4.1 h (2.4–5.8), all of which were significantly longer than that in infants aged 6–24 months (n = 12) 2.0 h (1.7–2.6). Median renal clearance was fairly constant in all age groups, whereas non‐renal clearance markedly increased with age. Noroxycodone was the major metabolite in plasma and urine.

Conclusions

Oxycodone elimination is slower and pharmacokinetic variability more pronounced in neonates when compared to older infants. These findings highlight the importance of careful dose titration for neonates.
Lessons learned on the design and the conduct of Post‐Authorization Safety Studies: review of 3 years of PRAC oversight
Authors: Engel Pierre , Almas Mariana Ferreira , De Bruin Marieke Louise , Starzyk Kathryn , Blackburn Stella , Dreyer Nancy Ann
Published: October 2016

Aims

To describe and characterize the first cohort of Post‐Authorization Safety Study (PASS) protocols reviewed under the recent European pharmacovigilance legislation.

Methods

A systematic approach was used to compile all publicly available information on PASS protocols and assessments submitted from July 2012 to July 2015 from Pharmacovigilance Risk Assessment Committee (PRAC) minutes, European Medicines Agency (EMA) and European Network of Pharmacovigilance and Pharmacoepidemiology (ENCePP) webpages.

Results

During the study period, 189 different PASS protocols were submitted to the PRAC, half of which were entered in the ENCePP electronic register of post‐authorization studies (EU‐PAS) by July 2015. Those protocols were assessed during 353 PRAC reviews. The EMA published only 31% of the PRAC feedback, of which the main concerns were study design (37%) and feasibility (30%). Among the 189 PASS, slightly more involved primary data capture (58%). PASS assessing drug utilization mainly leveraged secondary data sources (58%). The majority of the PASS did not include a comparator (65%) and 35% of PASS also evaluated clinical effectiveness endpoints.

Conclusions

To the best of our knowledge this is the first comprehensive review of three years of PASS protocols submitted under the new pharmacovigilance legislation. Our results show that both EMA and PASS sponsors could respectively increase the availability of protocol assessments and documents in the EU‐PAS. Protocol content review and the high number of PRAC comments related to methodological issues and feasibility concerns should raise awareness among PASS stakeholders to design more thoughtful studies according to pharmacoepidemiological principles and existing guidelines.
The use of incretins and fractures – a meta‐analysis on population‐based real life data
Authors: Driessen Johanna H. M. , de Vries Frank , van Onzenoort Hein , Harvey Nicholas C. , Neef Cees , van den Bergh Joop P. W. , Vestergaard Peter , Henry Ronald M. A.
Published: October 2016

The aim of the present study was to estimate the effect of incretins on fracture risk in the real‐world situation by meta‐analysis of the available population‐based cohort data. Pubmed and Embase were searched for original articles investigating use of incretin agents, and fracture risk up to December 2015. Adjusted results were extracted and pooled by use of generic inverse variance methods, assuming a random‐effects model. Neither current dipeptidyl peptidase 4‐inhibitor use nor current glucagon‐like peptide 1 receptor agonist use was associated with a decreased risk of fracture: pooled relative risk (pooled RR [95% confidence interval]: 1.02 [0.91–1.13] and 1.03 [0.87–1.22]), respectively. This meta‐analysis demonstrated that current use of incretin agents, was not associated with decreased fracture risk. Our findings show the value of representative real‐world populations, and the risks associated with suggesting benefits for medications on the basis of safety reporting in randomized controlled trials.
Collaborative youth mental health service users, immigration, poverty, and family environment
Authors: Nadeau Lucie , Lecompte Vanessa , Johnson‐Lafleur Janique , Pontbriand Annie , Rousseau Cécile
Published: October 2016

Background

This article examines the association between immigration, poverty and family environment, and the emotional and behavioral problems reported by youth and their family receiving mental health (MH) services within a collaborative care model in a multiethnic neighborhood.

Method

Participants in this study were 140 parent–child dyads that are part of an ongoing longitudinal project looking at the association between individual, familial, social and organizational factors, and outcomes of youth receiving MH services in local health and social service organizations in the Montreal area. Measures included in this study were collected at the initial phase of the longitudinal project (Time 0). Parents completed a sociodemographic questionnaire and the Family Environment Scale (FES), and both parents and children completed the Strength and Difficulties questionnaire (SDQ).

Results

Results suggest that the family environment, especially family conflicts, has a significant role in the MH problems of children seeking help in collaborative MH services. In this specific population, results also show a trend, but not a statistically significant association, between poverty or immigration and emotional and behavioral problems. They suggest as well that boys show more MH problems, although this could be a contamination effect (parents’ perspective).

Conclusions

The results support the importance of interventions that not only target the child symptomatology but also address family dynamics, especially conflicts. Collaborative care models may be particularly well suited to allow for a coherent consideration of family environmental factors in youth mental health and to support primary care settings in addressing these issues.
Synthesis and biological evaluation of 1, 2, 4‐oxadiazole derivatives as novel GPR119 agonists
Authors: Fu Suhong , Xiang Wei , Chen Jinying , Ma Liang , Chen Lijuan
Published: October 2016

A series of 1, 2, 4‐oxadiazole derivatives have been designed and synthesized, and 25 compounds were evaluated their abilities by the assay of cAMP concentration in GPR119‐transfected HEK293T cells. All compounds showed acceptable agonistic effects on GPR119. Among these compounds, 4p exhibited the best agonistic effects with the EC50 of 20.6 nm, which was comparable to that of positive control GPR119 agonist GSK1292263. The agonistic activity of these 1,2,4‐oxadiazole derivatives led to the establishment of a structure–activity relationship.
Positive cooperative regulation of double binding sites for human acetylcholinesterase
Authors: Liu Hao , Ye Wei , Chen Hai‐Feng
Published: October 2016

Acetylcholinesterase is a potent enzyme that regulates neurotransmission by rapidly hydrolyzing the neurotransmitter acetylcholine in synapses of the nervous system. As drug target of anti‐AD, it has catalytic and peripheral anionic sites. However, the regulation relation between these two sites is unclear. Therefore, we constructed dynamics fluctuation network based on all‐atom molecular dynamics simulations to reveal the regulation mechanism. The results suggest that the correlation network in double‐site system (hAChE/TZ5) is distinctly different from that in the free state and single‐site systems (hAChE/huprine and hAChE/1YL). The community network analysis indicates that the information freely transfers from the peripheral anionic site to the catalytic active site in hAChE/TZ5. Furthermore, the binding free energy between the inhibitor and hAChE for hAChE/TZ5 is significantly lower than of either hAChE/huprine or hAChE/1YL. Thus, a hypothesis of ‘positive cooperative regulation’ is proposed for the regulation of double binding sites and further confirmed by the weakening and mutation community analyses. Finally, one possible cooperative regulation pathway of W86‐TZ5‐W286 was identified based on the shortest path algorithm and was confirmed by the network perturbation analysis. Interestingly, the regulation pathway for single‐site systems is significantly different from that of dual‐site system. The process targeting on the shortest pathway can better regulate the hydrolyzing the neurotransmitter acetylcholine and significantly inhibit the aggregation of Aβ amyloid.
Genetic abnormalities leading to qualitative defects of sperm morphology or function
Authors: Ray P.F. , Toure A. , Metzler‐Guillemain C. , Mitchell M.J. , Arnoult C. , Coutton C.
Published: October 2016

Infertility, defined by the inability of conceiving a child after 1 year is estimated to concern approximately 50 million couples worldwide. As the male gamete is readily accessible and can be studied by a simple spermogram it is easier to subcategorize male than female infertility. Subjects with a specific sperm phenotype are more likely to have a common origin thus facilitating the search for causal factors. Male infertility is believed to be often multifactorial and caused by both genetic and extrinsic factors, but severe cases of male infertility are likely to have a predominant genetic etiology. Patients presenting with a monomorphic teratozoospermia such as globozoospermia or macrospermia with more than 85% of the spermatozoa presenting this specific abnormality have been analyzed permitting to identify several key genes for spermatogenesis such as AURKC and DPY19L2. The study of patients with other specific sperm anomalies such as severe alteration of sperm motility, in particular multiple morphological anomalies of the sperm flagella (MMAF) or sperm unability to fertilize the oocyte (oocyte activation failure syndrome) has also enable the identification of new infertility genes. Here we review the recent works describing the identification and characterization of gene defects having a direct qualitative effect on sperm morphology or function.
Walking on two legs: culture and calculus in European Union development cooperation
Authors: Gavas Mikaela , Maxwell Simon
Published: October 2016

In this essay, we examine member state approaches to European development cooperation through the lens of collective action. We observe that successful collective action requires a combination of both culture and calculus. We suggest that the European debate sometimes suffers from an excess of one and a shortfall in the other – and vice‐versa. We note that different perspectives can be explained by different geopolitical realities. We conclude that it is better to walk on two legs than hop along on one – and that judicious application of collective action theory can help this happen.
Left ventricular stiffness predicts outcome in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation
Authors: Conte Lorenzo , Fabiani Iacopo , Pugliese Nicola R. , Giannini Cristina , La Carruba Salvatore , Angelillis Marco , Spontoni Paolo , De Carlo Marco , Petronio Anna Sonia , Di Bello Vitantonio
Published: October 2016

Objectives

Assessment of the prognostic role of left ventricular stiffness (LVS) in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI).

Methods

We performed a complete two‐dimensional transthoracic echocardiographic study before and after TAVI in patients with severe AS at high surgical risk. In order to assess LVS, we measured LV end‐diastolic pressure (EDP) invasively during TAVI and LV end‐diastolic volume (EDV) by means of echocardiography. We defined LVS as the EDV indexed by body surface area at an EDP of 20 mm Hg (EDVI20). Our aim was to assess the impact of LVS on one‐year all‐cause mortality after TAVI.

Results

One hundred sixty‐six patients undergoing TAVI (64% female; mean age 82.7 ± 5.1 years) were enrolled. Seven patients died within the first 30 days after TAVI and 21 within 1 year. Overall follow‐up duration was 580 ± 478 days. At multivariate analysis, independent predictors of 1‐year all‐cause mortality were moderate‐to‐severe paravalvular leak (PVL; HR 4.7, 95% confidence interval [CI] 1.9‐11, P=.0003), female gender (HR 3.5, 95% CI 1.0‐12, P=.045), and EDVI20 (HR 0.94, 95% CI 0.90‐0.98, P=.015). In particular, patients with higher LVS (EDVI20≤48 mL/m2) had a 1‐year mortality of 26.9% vs 7.4% in patients with lower LVS (EDVI20>48 mL/m2; HR 4.2, 95% CI 1.6‐10.6, P=.0007). Patients with higher LVS who developed moderate‐to‐severe PVL had the worst outcome (incremental chi‐square test, P=.014).

Conclusion

In patients with AS, an increased LVS has a negative prognostic impact. Development of significant PVL in patients with higher LVS had an incremental adverse effect.
Medication adherence in women with epilepsy who are planning pregnancy
Authors: Ernst Lia de Leon , Harden Cynthia L. , Pennell Page B. , Llewellyn Nichelle , Lau Connie , Barnard Sarah , Bartfeld Eyal , French Jacqueline A.
Published: October 2016

Objective

This study examines medication adherence among women with epilepsy via use of an electronic diary, as part of a prospective multicenter observational study designed to evaluate fertility in women with epilepsy (WWE) versus age‐matched controls.

Methods

WWE and healthy age‐matched controls, seeking pregnancy, were given an iPod Touch using a customized mobile application (the WEPOD App) for daily data tracking. Eighty‐six WWE tracked seizures and antiepileptic drugs (AEDs). Tracking of nonepilepsy medications was optional. Diary data were counted from enrollment date until date of delivery, or up to 12 months if pregnancy was not achieved. Each day that subjects reported missing one or more AED was counted as nonadherence. Because adherence can only be determined in women who track consistently, we elected to include adherence data only for women who tracked >80% of days in the study.

Results

Approximately 75% of WWE tracked >80% of days and were included in medication adherence data analysis. In this group, medication adherence rate was 97.71%; 44% of women admitted to missing an AED on at least 1 day. Among the subgroup of WWE who recorded nonepilepsy medications, AED adherence rate was 98.56%, versus 93.91% for non‐AEDs.

Significance

The 75% compliance rate with an electronic diary suggests that it may be useful to track medication adherence in future studies and in the clinical setting. In those who tracked, the observed medication adherence rate was considerably higher than the 75% adherence rate seen in previous epilepsy studies. This might be explained in part by selection bias, but may also result from properties of the diary itself (daily reminders, real time feedback given to the provider). Women reported a higher rate of adherence to AEDs than to other prescribed medications and supplements, suggesting that perceived importance of medications likely influences medication adherence, and warrants future study.
The industrialization of farming may be driving virulence evolution
Authors: Rozins Carly , Day Troy
Published: October 2016

Farming practices have changed dramatically over the years. The industrialization of farming has provided parasites with an abundance of hosts and is thought to have influenced parasite evolution. For example, the parasite that causes the highly contagious poultry disease, Marek's disease, has evolved over the past 60 years into a highly virulent pathogen. It is assumed that the industrialization of the industry and vaccination have selected for more virulent strains of the virus. Here, with the use of an impulsive differential equation model, we investigate how modern broiler farm practices could independently lead to virulence evolution. Our model suggests that longer cohort durations and more densely stocked barns both select for less virulent strains of the virus. Our model also suggests that if intensive cleaning between cohorts does not rid the barn of disease, it may drive evolution and cause the disease to become more virulent.
The Safe Yield and Climatic Variability: Implications for Groundwater Management
Authors: Loáiciga Hugo A.
Published: October 2016

Methods for calculating the safe yield are evaluated in this paper using a high‐quality and long historical data set of groundwater recharge, discharge, extraction, and precipitation in a karst aquifer. Consideration is given to the role that climatic variability has on the determination of a climatically representative period with which to evaluate the safe yield. The methods employed to estimate the safe yield are consistent with its definition as a long‐term average extraction rate that avoids adverse impacts on groundwater. The safe yield is a useful baseline for groundwater planning; yet, it is herein shown that it is not an operational rule that works well under all climatic conditions. This paper shows that due to the nature of dynamic groundwater processes it may be most appropriate to use an adaptive groundwater management strategy that links groundwater extraction rates to groundwater discharge rates, thus achieving a safe yield that represents an estimated long‐term sustainable yield. An example of the calculation of the safe yield of the Edwards Aquifer (Texas) demonstrates that it is about one‐half of the average annual recharge.
Optimization of home treatment in haemophilia: effects of transmural support by a haemophilia nurse on adherence and quality of life
Authors: Lock J. , Raat H. , Peters M. , Scholten M. , Beijlevelt M. , Oostenbrink R. , Leebeek F.W.G. , Moll H.A. , Cnossen M.H.
Published: October 2016

Background

Transmural support by a haemophilia nurse may improve treatment and may empower parents and patients.

Aim

To measure the effect of structured home visits by a haemophilia nurse in (parents of) patient on aspects of prophylactic home treatment.

Methods

A multicentre intervention study in two paediatric haemophilia treatment centres was performed. Primary outcome measures were: adherence to prescribed treatment, health‐related quality of life and behavioural scores. Secondary outcome measures were: total clotting factor consumption, self‐efficacy and number of joint bleeds.

Results

Over a period of 22 months (median, IQR 21–23), four to seven home visits in 46 patients (mean age 9.4 ± 4.2 years) were made. No difference in adherence to prescribed treatment was seen after the home visits when compared to baseline measurements. Both the Child Health Questionnaire (CHQ) scales on ‘Role functioning – Emotional/Behavioural’ (P = 0.02, d = 0.53) and ‘Parental Time Impact’ (P = 0.04, d = 0.33) were reduced after intervention. The disease‐specific Haemo‐QoL questionnaire showed improvement in domains: ‘Family’ (P = 0.04, d = −0.14), ‘Friends’ (P = 0.03, d = −0.29) and ‘Perceived support’ (P = 0.03, d = −0.37). Significant improvement was observed with regard to domain ‘Communication’ of the VERITAS‐Pro scale (P = 0.03, d = −0.28).

Conclusions

After a period of transmural care by a haemophilia nurse, significant but small positive effects were demonstrated with regard to communication and increase of perceived support between parents and haemophilia treatment centre. No improvement was observed in other outcome measures.
Hydrophobicity‐modulating self‐assembled morphologies of α‐zein in aqueous ethanol
Authors: An Baozhen , Wu Xiaochen , Li Mingjie , Chen Yijun , Li Fei , Yan Xiaofei , Wang Jialin , Li Chaoxu , Brennan Charles
Published: October 2016

Protein fibrillation serves a broad range of biological functions from surface colonising to mechanically reinforcing structures; it is also associated with the development of neurodegenerative disorders. Although fibrillation is considered to be an inherent ability of polypeptides to form backbones, relevant studies have long concentrated on aqueous‐soluble proteins rather than on insoluble structures. In this study, the self‐assembly of hydrophobic proteins into amyloid nanofibrils was studied using α‐zein as a model protein. The self‐assembled morphologies of α‐zein were determined by hydrophobic–hydrophilic characters of both the protein and the solvent. Upon thermally incubating in aqueous ethanol, α‐zein formed amyloid nanofibrils with lower ethanol compositions and near‐neutral pHs, while acidic conditions and high ethanol compositions result in the formation of spherical aggregations. The fibrillation of α‐zein shows a great potential in serving as bio‐based gels or reinforced fillers in food, cosmetic and pharmaceutical applications.
Oxygen‐ion conduction in scandia‐stabilized zirconia‐ceria solid electrolyte (xSc2O3–1CeO2–(99−x)ZrO2, 5 ≤ x ≤ 11)
Authors: Kumar Ashutosh , Jaiswal Abhishek , Sanbui Mohit , Omar Shobit
Published: October 2016

Solid oxide fuel cells (SOFCs) operating at intermediate temperature (500°C‐700°C) provide advantages of better durability, lower cost, and wider target application market. In this work, we have studied Sc2O3 (5‐11 mol%) stabilized ZrO2–CeO2 as a potential solid electrolyte for application in IT‐SOFCs. Lower Sc2O3 doping range than the traditional 11 mol% Sc2O3‐stabilized ZrO2 is an interesting research topic as it could potentially lead to an electrolyte with reduced oxygen vacancy ordering, lower cost, and higher mechanical strength. XRD and Raman spectroscopy was used to study the phase equilibrium in ZrO2–CeO2–Sc2O3 system and impedance spectroscopy was done to estimate the grain, grain boundary, and total ionic conductivities. Maximum for the grain and grain‐boundary conductivities as well as the tetragonal‐cubic phase boundary was found at 8‐9 Sc2O3 mol% in ZrO2‐1 mol% CeO2 system. It is suggested that the addition of 1 mol% CeO2 in the ZrO2 host lattice has improved the phase stability of high‐conductivity cubic and tetragonal phases at the expense of low‐conductivity t′‐ and β‐phases.
Elastic constants of polycrystalline Ti3AlC2 and Ti3SiC2 measured using coherent inelastic neutron scattering
Authors: Gray Veronica , Kisi Erich H. , Kirstein Oliver , Stampfl Anton P. J.
Published: October 2016

The magnitude of the single‐crystal elastic constant c44 in the MAX phase Ti3SiC2 is under debate. In this paper, estimates for the magnitude of c44 for MAX phases Ti3AlC2 and Ti3SiC2 are determined from a partially oriented polycrystalline sample via coherent inelastic neutron scattering. The largely quasi‐isotropic nature of these Mn+1AXn phase elastic constants as previously predicted by density functional theory calculations is confirmed experimentally for Ti3AlC2 to be c44=115.3 ± 30.7 GPa. In contrast, Ti3SiC2 is confirmed to be shear stiff with c44=402.7 ± 78.3 GPa supporting results obtained by earlier elastic neutron diffraction experiments.
Left Atrial Size and Left Ventricular End‐Systolic Dimension Predict the Progression of Paroxysmal Atrial Fibrillation After Catheter Ablation
Authors: LIAO YING‐CHIEH , LIAO JO‐NAN , LO LI‐WEI , LIN YENN‐JIANG , CHANG SHIH‐LIN , HU YU‐FENG , CHAO TZE‐FAN , CHUNG FA‐PO , TUAN TA‐CHUAN , TE ABIGAIL LOUISE D. , WALIA ROHIT , YAMADA SHINYA , LIN CHUNG‐HSING , LIN CHIN‐YU , CHANG YAO‐TING , ALLAMSETTY SURESH , YU WEN‐CHUNG , HUANG JING‐LONG , WU TSU‐JUEY , CHEN SHIH‐ANN
Published: October 2016

Predictors of AF Progression After Ablation

Introduction

Although rare, some paroxysmal atrial fibrillations (AF) still progress despite radiofrequency (RF) ablation. In the study, we evaluated the long‐term efficacy of RF ablation and the predictors of AF progression.

Methods

A total of 589 paroxysmal AF patients (404 men and 185 women; aged 54 ± 12 years) who received 3‐dimensional mapping and ablation were enrolled. Their clinical parameters and electrophysiological characteristics were collected. They were divided into Group 1 (N = 13, with AF progression) and Group 2 (N = 576, no AF progression). AF progression was defined as recurrence of persistent AF.

Results

Group 1 patients had larger left atrial (LA) diameter, larger left ventricle (LV) end‐systolic and end‐diastolic diameters, poorer LV systolic function, and more amiodarone use at baseline. After 1.2 ± 0.5 procedures, 123 (21%) patients experienced recurrence during 56 ± 29 months’ follow‐up. In the multivariate analysis, LA diameter (P = 0.018, HR = 1.12, 95% CI = 1.02–1.24) and LV end‐systolic diameter (P = 0.005, HR = 1.10, 95% CI = 1.03–1.17) independently predicted AF progression. LA diameter >43 mm and LV end‐systolic diameter >31 mm were the best cut‐off values for predicting AF progression by ROC analysis. AF progression rate achieved 19% if they had both larger LA diameter (>43 mm) and LV end‐systolic diameter (>31 mm).

Conclusion

RF ablation prevents the progression of paroxysmal AF effectively, except in patients with increased LA diameter and LV end‐systolic diameter on echocardiogram, suggesting more aggressive rhythm control therapies should be considered in these patients.
A new forest pest in Europe: a review of Emerald ash borer (Agrilus planipennis) invasion
Authors: Valenta V. , Moser D. , Kapeller S. , Essl F.
Published: October 2016

In this publication, we review the biology, ecology, invasion history, impacts and management options of Emerald ash borer (EAB) Agrilus plannipennis, with a particular focus on its invasion in Europe. Agrilus planipennis (EAB) is a wood‐boring beetle native to East Asia. Having caused massive damages on ash species in North America in the last decades, it was first recorded in Europe in 2003 in Russia (Moscow). All ash (Fraxinus) species native to Europe and North America are known to be susceptible to EAB attacks, which cause high tree mortality even among formerly healthy trees. Recorded expansion rates are between 2.5 and 80 km/year in North America and between 13 and 41 km/year in European Russia. Given current expansion rates, EAB is expected to reach Central Europe within 15–20 years. A combination of mechanical, biological and chemical control and phytosanitary measures may reduce its impact, which nevertheless most likely will be substantial. There is an urgent need to identify native enemies in Europe, to test suitable biocontrol agents and to develop early detection and management measures. Although it is obvious that EAB will become a major pest in Europe, early and dedicated response will likely be able to reduce the level of ash mortality, and thus improve the opportunity for long‐term survival of ash as an important component in European forests.
Societal perceptions of male nurses inSouthKorea:A Q‐methodological study
Authors: Kim Ick‐Jee , Kim Sang‐Hee , Sohn Sue‐Kyung
Published: October 2016

Aim

One of the remarkable changes in today's nursing profession is the emergence of male nurses. In order to promote the development of nursing, it would be beneficial for a positive perception of male nurses to be established in society. This study identified the public perceptions of male nurses inSouthKorea by usingQmethodology and offered basic strategies for enhancing the perception of male nurses.

Methods

AQ‐methodological approach, suitable for subjective research, was used for a survey. Q statements were based on 600Qconcourses that were collected through a literature review and individual interviews. Thirty‐seven finalQstatements were selected from those. ThePsample was collected from 45 persons who were likely to represent a diverse range of views about male nurses. The collected data were analyzed withPQMethod software; a principal component factor analysis with varimax rotation was used to identify the patterns of the public's perception of male nurses.

Results

Four distinct perspectives were identified: progressive occupational; conservative occupational; negative occupational; and supportive occupational.

Conclusion

This study provided strategies for improving the public's views of male nurses in a conservative country with gender stereotypes. These findings also could attract more male nurses into the profession and increase their retention.
Maternal protein restriction during gestation and lactation in the rat results in increased brain levels of kynurenine and kynurenic acid in their adult offspring
Authors: Honório de Melo Martimiano Paula , de Sa Braga Oliveira André , Ferchaud‐Roucher Véronique , Croyal Mikaël , Aguesse Audrey , Grit Isabelle , Ouguerram Khadija , Lopes de Souza Sandra , Kaeffer Bertrand , Bolaños‐Jiménez Francisco
Published: October 2016

Early malnutrition is a risk factor for depression and schizophrenia. Since the offspring of malnourished dams exhibit increased brain levels of serotonin (5‐HT), a tryptophan‐derived neurotransmitter involved in the pathophysiology of these mental disorders, it is believed that the deleterious effects of early malnutrition on brain function are due in large part to altered serotoninergic neurotransmission resulting from impaired tryptophan (Trp) metabolism. However, tryptophan is also metabolized through the kynurenine (KYN) pathway yielding several neuroactive compounds including kynurenic (KA), quinolinic (QA) and xanthurenic (XA) acids. Nevertheless, the impact of perinatal malnutrition on brain kynurenine pathway metabolism has not been examined to date. Here, we used ultra‐performance liquid chromatography‐tandem mass spectrometry for the simultaneous quantification of tryptophan and a set of seven compounds spanning its metabolism through the serotonin and kynurenine pathways, in the brain of embryos and adult offspring of rat dams fed a protein‐restricted (PR) diet. Protein‐restricted embryos showed reduced brain levels of Trp, serotonin and KA, but not of KYN, XA, or QA. In contrast, PR adult rats exhibited enhanced levels of Trp in the brainstem and cortex along with increased concentrations of 5‐HT, kynurenine and XA. The levels of XA and KA were also increased in the hippocampus of adult PR rats. These results show that early protein deficiency induces selective and long‐lasting changes in brain kynurenine metabolism. Given the regulatory role of KYN pathway metabolites on brain development and function, these changes might contribute to the risk of developing psychiatric disorders induced by early malnutrition.

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‘Clinical Chatter’: every nurse informed
Authors: Talbott Carolyn , Watson Lynn , Tariman Joseph , Sorenson Matthew
Published: October 2016

Aims and objectives

To assess the acceptability and usability of a standardised communication tool for nurses.

Background and significance

Communication is key in health care. On a daily, if not hourly, basis, nursing staff is inundated with new information regarding tools and resources, practice changes and the work environment. However, there is currently no standardised messaging or delivery method to effectively communicate new information. Even with a plethora of communication tools such as flyers, posters, emails, unit huddles and unit meetings, there is no means to guarantee attendance to crucial information.

Design

Descriptive, cross‐sectional online survey, implemented at a nonacademic, suburban hospital with 280 nurses.

Methods

The Clinical Chatter, an online tool developed by nursing leadership to standardise messages regarding the organisation, new tools and resources, professional development, recognition and unit updates, was delivered to each nurse on a weekly basis followed by administration of Acceptability and Usability scales.

Results

The Clinical Chatter tool has adequate acceptability and usability as a method of communication among nurses in a hospital organisation. Sociodemographic variables of age and years of experience had no statistically significant association with perceived acceptance and usefulness of the tool.

Conclusion

The findings indicate that the Clinical Chatter tool can be used as a standardised communication tool to deliver key information among nurses working in a hospital organisation. Nursing leadership must establish and support a clear communication system to enhance patient care and outcomes and improve nursing job satisfaction.

Relevance to clinical practice

Communication is vital to advancing health care. Lack of communication among nursing has been linked to unsafe patient care: medication errors, unhealthy work environments and decreased nurse retention rates. Clinical Chatter is an effective communication tool for presentation of institutional information to nursing personnel.
Yihiella yeosuensis gen. et sp. nov. (suessiaceae, dinophyceae), a novel dinoflagellate isolated from the coastal waters of Korea
Authors: Jang Se Hyeon , Jeong Hae Jin , Moestrup Øjvind , Kang Nam Seon , Lee Sung Yeon , Lee Kyung Ha , Seong Kyeong Ah
Published: October 2016

A small (7–11 μm long) dinoflagellate with thin amphiesmal plates was isolated into culture from a water sample collected in coastal waters of Yeosu, southern Korea, and examined by LM, SEM, and TEM, and molecular analyses. The hemispheric episome was smaller than the hyposome. The nucleus was oval and situated from the central to the episomal region of the cell. A large yellowish‐brown chloroplast was located at the end of the hyposome, and some small chloroplasts extended into the periphery of the episome. The dinoflagellate had a single elongated apical vesicle (EAV) and a type E eyespot, which are key characteristics of the family Suessiaceae. Unlike other genera in this family, it had two long furrow lines, one on the episome and the other on the hyposome, and encircling the dorsal, and lateral sides of the cell body. The pyrenoid lacked starch sheaths, but tubular invaginations into the pyrenoid matrix from the cytoplasm were observed. In the TEM, the dinoflagellate was observed to have cable‐like structures (CLSs) near the eyespot but so far not observed in other dinoflagellates. The SSU rDNA sequences examined were 1.2%–5.1% different from those of other genera in the family Suessiaceae, whereas the LSU (D1‐D3) rDNA sequences of this dinoflagellate were 15.1%–31.5% different. The dinoflagellate lacked a 51‐bp fragment in domain D2 of the LSU rDNA, but it had an ~100‐bp fragment in domain D2. This feature has been found previously only in the genera Leiocephalium and Polarella, two other genera of the Suessiaceae. The molecular phylogeny and sequence divergence based on SSU, and LSU rDNA indicate that the Korean dinoflagellate holds a taxonomically distinctive position and we consider it to be a new species in a new genus in the family Suessiaceae, named Yihiella yeosuensis gen. et sp. nov.
The promise and pitfalls of β‐diversity in ecology and conservation
Authors: Myers Jonathan A. , LaManna Joseph A.
Published: October 2016

A key challenge in ecology and conservation is to determine how processes at different scales create variation in community composition (β‐diversity). In this issue, Oldén & Halme show that grazers increase β‐diversity through multiple processes at different scales. We discuss how β‐diversity can elucidate fundamental processes of community assembly, challenges in linking processes to patterns, and unresolved questions across scales.
It's Politics, Stupid! Political Constraints Determined Governments' Reactions to the Great Recession
Authors: Gunzinger Fabian , Sturm Jan‐Egbert
Published: October 2016

This paper quantifies the effect of political constraints, as measured by legislative control by the incumbent government, on the size of fiscal stimulus packages that have been put in place as a reaction to the Great Recession. On average, political constraints reduced the size of a country's fiscal stimulus package by between 1 and 2.7 percentage points of GDP. This finding is robust to a number of alternative dependent variables, control variables, and sample specifications and is in line with the widely held, but never tested, perception that political reality limits the de facto application of discretionary fiscal policy as reaction to economic shocks.
The Effects of 9/11 on Attitudes toward Immigration and the Moderating Role of Education
Authors: Schüller Simone
Published: October 2016

The 9/11 terror attacks are likely to have induced an increase in anti‐immigrant and anti‐foreigner sentiments, not only among US residents but also beyond US borders. Using unique longitudinal data from the German Socio‐Economic Panel and exploiting exogenous variation in interview timing throughout 2001, I find that the 9/11 events caused an immediate shift of around 40 percent of one within‐standard deviation to more negative attitudes toward immigration and resulted in a considerable decrease in concerns over xenophobic hostility among the German population. The quasi‐experiment 9/11 provides evidence on the relevance of non‐economic factors in attitude formation and the role of education in moderating the negative terrorism shock. Additional descriptive analysis suggests that the effects have also been persistent in the years after the attacks.
Plasmapheresis exerts a long‐lasting antipruritic effect in severe cholestatic itch
Authors: Krawczyk Marcin , Liebe Roman , Wasilewicz Michał , Wunsch Ewa , Raszeja‐Wyszomirska Joanna , Milkiewicz Piotr
Published: October 2016

Background & Aims

The amelioration of refractory cholestatic pruritus after plasmapheresis has been reported in single patients. Here, we analyse the efficacy of plasmapheresis in a cohort of patients with primary biliary cholangitis (PBC).

Methods

Seventeen consecutive patients withPBC(age range 39‐85 years, 16 females, 9 with cirrhosis) and refractory pruritus underwent 129 plasmapheresis procedures during 40 admissions. Pruritus was quantified by the 10‐point numeric rating scale (NRS) before and after plasmapheresis, as well as ~30 and ~90 days later.

Results

The mean pruritus before plasmapheresis did not differ between patients with and without cirrhosis (P>.05). Cirrhotics presented, however, with significantly higher serum alanine aminotransferase (ALT), aspartate transaminase (AST), gamma‐glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and bilirubin before plasmapheresis. Plasmapheresis decreased itching to NRS≤5 in all but five admissions: Mean pruritus decreased from 8.3±1.4 to 3.1±2.2 (P<.0001) in the entire cohort. It also led to a significant decrease in serumALT,ALP,AST,GGT(allP<.001) and bilirubin (P=.002). Antipruritic effect persisted throughout the 90‐days follow‐up (P<.0001). The amelioration of pruritus was not affected by the presence of cirrhosis.

Conclusions

Plasmapheresis is a promising method for reducing intractable itch in a significant proportion ofPBCpatients regardless of liver fibrosis. Long‐lasting improvement of symptoms requires repeated procedures.
Multiparametric magnetic resonance imaging for the assessment of non‐alcoholic fatty liver disease severity
Authors: Pavlides Michael , Banerjee Rajarshi , Tunnicliffe Elizabeth M. , Kelly Catherine , Collier Jane , Wang Lai Mun , Fleming Kenneth A. , Cobbold Jeremy F. , Robson Matthew D. , Neubauer Stefan , Barnes Eleanor
Published: October 2016

Background & Aims

The diagnosis of non‐alcoholic steatohepatitis and fibrosis staging are central to non‐alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non‐alcoholic steatohepatitis and fibrosis using histology as standard in non‐alcoholic fatty liver disease.

Methods

Seventy‐one patients with suspected non‐alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0‐4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non‐alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non‐alcoholic fatty liver disease. Transient elastography was also performed.

Results

Magnetic resonance success rate was 95% vs 59% for transient elastography (P<.0001). Fibrosis stage on biopsy correlated with liver inflammation and fibrosis (rs=.51, P<.0001). The area under the receiver operating curve using liver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively (P<.05) with an area under the receiver operating characteristic curve of 0.83 for the diagnosis of ballooning. Patients with steatosis had lower liver inflammation and fibrosis (1.3) compared to patients with non‐alcoholic steatohepatitis (3.0) (P<.0001); area under the receiver operating characteristic curve for the diagnosis of non‐alcoholic steatohepatitis was 0.80. Liver inflammation and fibrosis scores for patients with mild and significant non‐alcoholic fatty liver disease were 1.2 and 2.9 respectively (P<.0001). The area under the receiver operating characteristic curve of liver inflammation and fibrosis for the diagnosis of significant non‐alcoholic fatty liver disease was 0.89.

Conclusions

Multiparametric magnetic resonance is a promising technique with good diagnostic accuracy for non‐alcoholic fatty liver disease histological parameters, and can potentially identify patients with non‐alcoholic steatohepatitis and cirrhosis.
Lonergan and Wittgenstein on the Dialectic of Methods
Authors: Friel Chris
Published: October 2016

Lindbeck's difficulties with Lonergan's account of religion stem from his radical methodological option in which he draws on Wittgenstein. I revisit ‘the dialectic of methods,’ by examining children's mistakes. I use Lonergan's distinction between ordinary and originary meaningfulness to argue that in Wittgenstein's account of rule‐following such mistakes highlight the publicity of norms in ordinary meaningfulness, but I show how alternatives can be cited in which originary meaningfulness is not obscured. I explain the core of Lonergan's foundational methodology and show how for Lonergan the desire to understand is an exigence which, as retorsion indicates, is difficult to deny. I conclude that in his account of religion Lonergan has an answer to a question posed by Wittgenstein on the purpose of thinking.
Does a Hermeneutical Clarification of “Presence” Advance O'Collins’ Christology?
Authors: Orji Cyril
Published: October 2016

The theme of “presence” holds an ambivalent place in Gerald O'Collins’ Christology. On the one hand the theme is O'Collins’ “most creative contribution to contemporary Christology” and on the other hand the notion itself is a difficult and stubborn concept that can be best understood in an evolutionary way. This deeper analysis of “presence,” which is not offered by O'Collins, occupies a center stage in Bernard Lonergan's Christology. This essay mediates O'Collins’ account of “presence” with Lonergan's evolutionary understanding of the term—a scientific theological account Lonergan worked out in dialogue with phenomenology and the sciences. The paper argues that such a mediation is necessitated by the fact that the meaning of “presence” is key to understanding the Chalcedonian definition of the union of the two natures of Christ, an important Christian dogmatic teaching that both O'Collins and Lonergan consider sacrosanct, and that a clarification of this meaning advances not only Christian understanding of Christ's presence in history, but also Christ's presence in non‐Christian religions.
Biochar‐stimulated plant performance is strongly linked to microbial diversity and metabolic potential in the rhizosphere
Authors: Kolton Max , Graber Ellen R. , Tsehansky Ludmila , Elad Yigal , Cytryn Eddie
Published: October 2016

The ‘biochar effect’ depicts a phenomenon in which biochar soil amendment enhances plant performance by promoting growth and suppressing disease. Although this phenomenon has been observed in numerous studies, the mode of action that explains it is currently unknown.

In order to elucidate mechanisms responsible for the ‘biochar effect’, we comprehensively monitored tomato plant development and resistance to the foliar fungal pathogen Botrytis cinerea, in biochar‐amended and nonamended soils using native biochar and washed biochar, striped of labile chemical constituents. We concomitantly assessed bacterial community succession in the rhizosphere by high‐throughput 16S rRNA gene amplicon sequencing and carbon‐source utilization profiling.

Biochar had little impact on plant physiological parameters. However, both native and washed biochar treatments were characterized by higher rhizosphere bacterial diversity and enhanced carbohydrate and phenolic compound utilization rates coupled to stimulation of bacteria known to degrade phenolic compounds.

This study indicates that the ‘biochar effect’ is at least partially dictated by increased diversity and changes in metabolic potential in the rhizosphere microbiome, which is primarily triggered by the recalcitrant carbon backbone of the biochar and tightly bound compounds. It corresponds to the growing consensus that soil amendments which enhance microbial diversity have important benefits to ecosystem functioning.