bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecological factors influencing the beneficial endosymbionts of the hemlock woolly adelgid (Hemiptera: Adelgidae)
Authors: Mech Angela M. , Harper Sherilyn J. , Havill Nathan P. , von Dohlen Carol D. , Burke Gaelen R.
Published: August 2017

Bacterial endosymbionts of sap‐sucking insects provide their host with a number of beneficial qualities, including the supply of nutrition, defense against parasitoids, and protection from heat stress. Damage to these bacterial associates can therefore have a negative impact on the fitness of their insect host. We evaluated observational and experimental factors regarding the nonnative hemlock woolly adelgid (Adelges tsugaeAnnand) (Hemiptera: Adelgidae) to help understand the roles of its three recently identified symbionts, including under heat stress conditions. The prevalence ofA. tsugae’s facultative symbiont (Serratia symbiotica) was examined at different spatial scales to determine how variable infection rates are for this symbiont. There was no significant difference found in infection rates between adelgids on a tree, within a plot, or within a state. However, significantly more adelgids in Georgia (95%) hadS. symbioticacompared to those in New York (68%). Microsatellite genotyping of the adelgids found that this difference was most likely not the result of a second introduction ofA. tsugaeinto eastern North America. Comparison ofS. symbioticaproportions between first and fourth instars showed that symbiont absence did not affect the ability ofA. tsugaeto survive aestivation. Evaluations of symbiont densities within each adelgid found that whenS. symbioticawas absent, the density of obligate symbionts was significantly higher. Exposure to heat stress (32.5 °C) was not consistently correlated with changes in symbiont densities over a 4‐d period. Overall, we have shown that symbiont prevalence and densities vary within the broad population ofA. tsugaein eastern North America, with potentially significant effects upon the ecology of this important pest.
Building the Ties that Bind, Breaking the Ties that Don't
Authors: Boman John H. , Mowen Thomas J.
Published: August 2017

Research Summary

Although family support is an important protective factor against recidivism, less is known about how the domain of family works with other elements of the risk–need–responsivity model. By using the Serious and Violent Offenders Reentry Initiative (SVORI) data, we explore whether family and criminal peers have (a) independent and (b) interdependent effects on substance abuse and crime after release from prison. The outcomes of multilevel models demonstrate that the risk factor of criminal peers is as strong, or stronger, of a predictor of substance abuse and crime as is the protective factor of family support for offenders during reentry.

Policy Implications

Institution‐based policies aimed primarily at improving family ties for reentering offenders must begin focusing as much on peers as they do on family. These programs should instead focus on improving family ties (thereby increasing a protective factor) while focusing on severing the offender's relationships with criminally inclined friends (thereby decreasing a risk factor).
Is two days of intermittent energy restriction per week a feasible weight loss approach in obese males? A randomised pilot study
Authors: Conley Marguerite , Le Fevre Lauren , Haywood Cilla , Proietto Joseph
Published: August 2017

Aim

The 5:2 diet (two non‐consecutive days of 2460 KJ (600 calories) and 5 days of ad libitum eating per week) is becoming increasingly popular. This pilot study aimed to determine whether the 5:2 diet can achieve ≥5% weight loss and greater improvements in weight and biochemical markers than a standard energy‐restricted diet (SERD) in obese male war veterans.

Methods

A total of 24 participants were randomised to consume either the 5:2 diet or a SERD (2050 KJ (500 calorie) reduction per day) for 6 months. Weight, waist circumference (WC), fasting blood glucose, blood lipids, blood pressure and dietary intake were measured at baseline, 3 and 6 months by a blinded investigator.

Results

After 6 months, participants in both groups significantly reduced body weight (P = <0.001), WC (P = <0.001) and systolic blood pressure (P = 0.001). Mean weight loss was 5.3 ± 3.0 kg (5.5 ± 3.2%) for the 5:2 group and 5.5 ± 4.3 kg (5.4 ± 4.2%) for the SERD group. Mean WC reduction for the 5:2 group was 8.0 ± 4.5 and 6.4 ± 5.8 cm for the SERD group. There was no significant difference in the amount of weight loss or WC reduction between diet groups. There was no significant change in diastolic blood pressure, fasting blood glucose or blood lipids in either dietary group.

Conclusions

Results suggest that the 5:2 diet is a successful but not superior weight loss approach in male war veterans when compared to a SERD. Future research is needed to determine the long‐term effectiveness of the 5:2 diet and its effectiveness in other population groups.
Infants with prenatally diagnosed kidney anomalies have an increased risk of urinary tract infections
Authors: Rasmussen Maria , Sunde Lone , Andersen René F. , Petersen Olav B. ,   Danish Fetal Medicine Research Group, Olsen Morten S.
Published: August 2017

Aim

This study estimated the urinary tract infection (UTI) risk in a nationwide cohort of infants prenatally diagnosed with parenchymal kidney anomalies compared with a comparison cohort.

Methods

A Danish population‐based nationwide cohort of foetuses diagnosed with parenchymal kidney anomalies between 2007 and 2012 had previously been identified. These were compared with foetuses without kidney anomalies who were prenatally scanned the same year. Live born infants were followed from birth until the diagnosis of UTI, emigration, death or two years of age. Cumulative incidences of UTIs were computed. Mortality was estimated using the Kaplan–Meier method.

Results

We identified 412 foetuses with parenchymal kidney anomalies out of 362 069 who underwent ultrasound scans and 277 were born alive. The overall risk of a UTI before the age of two years was 19%, and it was 14% among infants without prenatally diagnosed co‐occurring urinary tract malformations. The corresponding risk in the 4074 controls was 1%. After two years, mortality was 2.2% in infants with prenatally diagnosed parenchymal kidney anomalies and 0.2% in the controls.

Conclusion

Infants prenatally diagnosed with parenchymal kidney anomalies had a substantially increased risk of UTI. Awareness of this increased risk may facilitate earlier diagnosis of UTIs in this population.
Utilising Accounting and Accountants in the Management of Water Efficiency
Authors: Egan Matthew
Published: August 2017

This paper explores how five Australian organisations utilised accounting techniques and accountants as they developed an increasing focus on water efficiency during a period of drought. In those cases where top management were responsive to developing community logics that argued for the importance of efforts to maximise water efficiency, non‐accountants found space to experiment with a diversity of decision‐useful accounting initiatives. While initially bypassed, accountants ultimately became important for their ability to link evolving initiatives to core organisational concerns. Alternatively, in those organisations where senior responsiveness to evolving community concerns about water efficiency was limited, accountants dominated from the outset, presiding over a limited range of responses that offered an appearance, but little substance, of change.
The Business Model in Integrated Reporting: Evaluating Concept and Application
Authors: Tweedie Dale , Nielsen Christian , Martinov‐Bennie Nonna
Published: August 2017

A key feature of the International Integrated Reporting Council's (IIRC) agenda to improve corporate reporting is to encourage companies to use Integrated Reports to disclose their underlying business models. However, extant research suggests that the IIRC's distinctive business model concept is not well understood. This paper aims to unpack and critically evaluate the core features of the IIRC's business model concept. To unpack the IIRC's business model, the paper conducts a structured comparative analysis of the IIRC's model against eight influential alternatives in prior business model research. The paper then evaluates the extent to which Integrated Reporting's distinctive business model is: (1) internally coherent and consistent; and, (2) consistent with the IIRC's broader reporting objectives. The paper identifies tensions in both these areas. Since the IIRC's business model is central to its agenda to improve corporate reporting, these tensions are relevant to both Integrated Reporting research and broader discussions about whether, or how, disclosing business models advances mainstream reporting frameworks.
Infants preferentially approach and explore the unexpected
Authors: Sim Zi L. , Xu Fei
Published: August 2017

Looking time experiments based on the violation‐of‐expectation (VOE) method have consistently demonstrated that infants look longer when their expectations are violated. However, it remains an open question whether similar effects will be observed in infants’ approach behaviours. Specifically, do infants selectively approach and explore sources that violate their expectations? In this study, we address this question by examining how infants’ looking times are related to their approach and exploration behaviours. Using a traditional VOE method and a crawling paradigm, we demonstrate a strong correspondence between looking time and approach behaviours, which indicates that 13‐month‐old infants preferentially explore sources of unexpected events. Such spontaneous exploration may provide learning opportunities and allow infants to play an active role in driving their own development.

Statement of contribution

What is already known on this subject?

Infants look longer when their expectations are violated.

There is some evidence that infants also preferentially explore objects that violate their ‘core’ physical expectations.

What the present study adds?

There is a clear correspondence between infants’ looking behaviour and their approach behaviour.

Expectancy violations involving non‐core knowledge can similarly influence infants’ exploration.
Two‐year‐olds can socially learn to think divergently
Authors: Hoicka Elena , Powell Stephanie , Knight Jenny , Norwood Megan
Published: August 2017

This study aimed to discover whether 2‐year‐olds can socially learn to think divergently. Two‐year‐olds (N = 22) who saw an experimenter model a high level of divergent thinking on the Unusual Box Test (modelling 25 different actions, once each) went on to demonstrate a higher level of divergent thinking themselves than (N = 22) children who saw a low level of modelling (five different actions, once each), where divergent thinking was measured by the number of different actions children produced that had not been modelled by the experimenter. Additionally, all children in both High and Low Divergence conditions had higher divergent thinking than imitation scores, where imitation involved copying the experimenter's previous actions. This is the first experiment to show that 2‐year‐olds' divergent thinking can be increased, and that 2‐year‐olds do so by socially learning to think more divergently.

Statement of contribution

What is already known on this subject

Recent research found that children as young as 1 year can think divergently, and that this is influenced by parents' own divergent thinking.

What does this study add?

This paper is important as it provides the first method to increase divergent thinking in toddlers. It also shows that social learning can directly affect individual learning processes, which suggests current theories of social and individual learning should be revised to be more iterative.
Logistic regression in large rare events and imbalanced data: A performance comparison of prior correction and weighting methods
Authors: Maalouf Maher , Homouz Dirar , Trafalis Theodore B.
Published: August 2017

The purpose of this study is to use the truncated Newton method in prior correction logistic regression (LR). A regularization term is added to prior correction LR to improve its performance, which results in the truncated‐regularized prior correction algorithm. The performance of this algorithm is compared with that of weighted LR and the regular LR methods for large imbalanced binary class data sets. The results, based on the KDD99 intrusion detection data set, and 6 other data sets at both the prior correction and the weighted LRs have the same computational efficiency when the truncated Newton method is used in both of them. A higher discriminative performance, however, resulted from weighting, which exceeded both the prior correction and the regular LR on nearly all the data sets. From this study, we conclude that weighting outperforms both the regular and prior correction LR models in most data sets and it is the method of choice when LR is used to evaluate imbalanced and rare event data.
Learning over subconcepts: Strategies for 1‐class classification
Authors: Sharma Shiven , Somayaji Anil , Japkowicz Nathalie
Published: August 2017

In machine learning research and application, multiclass classification algorithms reign supreme. Their fundamental property is the reliance on the availability of data from all known categories to induce effective classifiers. Unfortunately, data from so‐called real‐world domains sometimes do not satisfy this property, and researchers use methods such as sampling to make the data more conducive for classification. However, there are scenarios in which even such explicit methods to rectify distributions fail. In such cases, 1‐class classification algorithms become the practical alternative. Unfortunately, domain complexity severely impacts their ability to produce effective classifiers. The work in this article addresses this issue and develops a strategy that allows for 1‐class classification over complex domains. In particular, we introduce the notion of learning along the lines of underlying domain concepts; an important source of complexity in domains is the presence of subconcepts, and by learning over them explicitly rather than on the entire domain as a whole, we can produce powerful 1‐class classification systems. The level of knowledge regarding these subconcepts will naturally vary by domain, and thus, we develop 3 distinct methodologies that take the amount of domain knowledge available into account. We demonstrate these over 3 real‐world domains.
Global Review of Social Indicators used in Protected Area Management Evaluation
Authors: Corrigan Colleen , J. Robinson Catherine , Burgess Neil D. , Kingston Naomi , Hockings Marc
Published: August 2017

Social considerations in conservation are increasingly recognized as important for successful environmental outcomes. However, social measures lack consistency and may underreport key issues. This article analyzes social indicators and well‐being dimensions used in protected area effectiveness tools, with specific attention to local communities and Indigenous peoples’ contexts. Using the Global Protected Area Management Effectiveness database, we reviewed 2,736 indicators from 38 methodologies applied in over 180 countries. We analyzed: (1) representation of human well‐being dimensions, (2) direction of impacts, and (3) level of neutrality in indicators. We found limited diversity and representation of important well‐being dimensions such as health and governance. While impacts on communities and nature are similarly measured, positive wording is used three times more often than negative, which may unintentionally bias evaluations. We recommend using and developing indicators with greater diversity, increased clarity, and reduced bias to enhance management and policy responses for biodiversity and human well‐being.
Advanced three‐dimensional culture of equine intestinal epithelial stem cells
Authors: Stewart A. Stieler , Freund J. M. , Gonzalez L. M.
Published: August 2017

Background

Intestinal epithelial stem cells are critical to epithelial repair following gastrointestinal injury. The culture of intestinal stem cells has quickly become a cornerstone of a vast number of new research endeavours that range from determining tissue viability to testing drug efficacy for humans. This study aims to describe the methods of equine stem cell culture and highlights the future benefits of these techniques for the advancement of equine medicine.

Objectives

To describe the isolation and culture of small intestinal stem cells into three‐dimensional (3D) enteroids in horses without clinical gastrointestinal abnormalities.

Study design

Descriptive study.

Methods

Intestinal samples were collected by sharp dissection immediately after euthanasia. Intestinal crypts containing intestinal stem cells were dissociated from the underlying tissue layers, plated in a 3D matrix and supplemented with growth factors. After several days, resultant 3D enteroids were prepared for immunofluorescent imaging and polymerase chain reaction (PCR) analysis to detect and characterise specific cell types present. Intestinal crypts were cryopreserved immediately following collection and viability assessed.

Results

Intestinal crypts were successfully cultured and matured into 3D enteroids containing a lumen and budding structures. Immunofluorescence and PCR were used to confirm the existence of stem cells and all post mitotic, mature cell types, described to exist in the horse intestinal epithelium. Previously frozen crypts were successfully cultured following a freeze‐thaw cycle.

Main limitations

Tissues were all derived from normal horses. Application of this technique for the study of specific disease was not performed at this time.

Conclusions

The successful culture of equine intestinal crypts into 3D “mini‐guts” allows for in vitro studies of the equine intestine. Additionally, these results have relevance to future development of novel therapies that harness the regenerative potential of equine intestine in horses with gastrointestinal disease (colic).
The role of DNA polymerase chain reaction, culture and histopathology in the diagnosis of cutaneous tuberculosis
Authors: Agarwal Puneet , Singh Elangbam Nelson , Agarwal Uma Shankar , Meena Ramsingh , Purohit Saroj , Kumar Surendra
Published: August 2017

Background

Cutaneous tuberculosis (TB) is re‐emerging as a significant problem in India due to increased incidence of human immunodeficiency virus (HIV), acquired immune deficiency syndrome (AIDS), other immunosuppressive states/factors like drugs, and emergence of multidrug resistance (MDR‐TB). Proper diagnosis is warranted as there is varied clinical presentation and similarity with many other diseases.

Objective

To assess the sensitivities of DNA polymerase chain reaction (PCR), culture, and histopathology for the diagnosis of cutaneous TB in clinically suspected skin lesions.

Methods

Clinically suspected cases of cutaneous TB were enrolled in the study. Two skin punch biopsies were taken from each patient and sent for histopathology examination and DNA PCR with culture, respectively.

Results

Of the total 70 cases enrolled, 49 were detected as cutaneous TB by the above tests. The sensitivities of DNA PCR, culture, and histopathology were 24.5, 16.3, and 91.8%, respectively.

Conclusion

DNA PCR and culture should be advised in cases of cutaneous TB with inconclusive histopathology. DNA PCR should be considered in preference over culture if facilities are available as it gives rapid results and has a higher sensitivity.
Participation in Workplace Pension Schemes and the Effect of Provision: Evidence from the United Kingdom*
Authors: Nunes Bernardo Fonseca
Published: August 2017

This study investigates the effect of public policies enforcing workplace pension plan provision on participation rates. Using British data covering almost two decades (1992–2009), I identify the potential opt‐in rate among private sector workers who have not been offered a workplace pension plan, had they been offered the opportunity to join such a saving scheme. I find that universal provision of workplace pension schemes alone could generate a major impact on pension coverage.
ECG morphology of premature ventricular contractions predicts the presence of myocardial fibrotic substrate on cardiac magnetic resonance imaging in patients undergoing ablation
Authors: Oebel Sabrina , Dinov Borislav , Arya Arash , Hilbert Sebastian , Sommer Philipp , Bollmann Andreas , Hindricks Gerhard , Paetsch Ingo , Jahnke Cosima
Published: August 2017

Background

The most likely origin of premature ventricular contractions (PVCs) may be deduced from surface electrocardiogram (ECG) analysis while planning an electrophysiological study (EPS). Apart from purely benign forms of increased ventricular ectopy, myocardial substrate (e.g., regional fibrosis) may be present in certain cases, which will significantly impact the ablation approach. Cardiac magnetic resonance (CMR) imaging can reliably identify fibrotic target lesions and, hence, may assist in adequate patient selection and procedural planning.

Methods and results

We analyzed 101 patients (59% males, mean age 57.15 ± 15.5 years, mean PVC count 19,801 ± 14,021 per 24 hours) referred for ablation of PVCs. The CMR (1.5T, Philips Ingenia, Best, The Netherlands) protocol included cine and three‐dimensional‐delayed enhancement imaging using standard cardiac geometries.

On surface, ECG right bundle branch block (RBBB) morphology was present in 43% of patients. Twenty‐one patients showed the fibrotic substrate on CMR. On univariate analysis, both RBBB morphology (P < 0.001) and presence of multiple PVC morphologies (≥2) significantly predicted the presence of fibrotic substrate (P = 0.01), which various baseline characteristics including left ventricular ejection fraction (45.7 ± 12.6% vs. 50.6 ± 11.0%, P = 0.08) failed to do. CMR‐identified fibrosis was associated with the site of origin of the clinical PVCs during EPS and was successfully treated by radiofrequency ablation in 93% (PVC reduction >95%).

Conclusion

In patients with RBBB morphology and/or multiple PVC patterns, CMR imaging before ablation may be helpful due to the increased prevalence of fibrotic lesions with regard to patient stratification and periprocedural management.
Granulocytes as models for human protein marker identification following nicotine exposure
Authors: Mulcahy Matthew J. , Lester Henry A.
Published: August 2017

Nicotinic acetylcholine receptors (nAChRs) are pentameric cation channels expressed in the mammalian CNS, in the peripheral nervous system, and in skeletal muscle. Neuronal‐type nAChRs are also found in several non‐neuronal cell types, including leukocytes. Granulocytes are a subtype of leukocytes that include basophils, eosinophils, and neutrophils. Granulocytes, also known as polymorphonuclear leukocytes, are characterized by their ability to produce, store, and release compounds from intracellular granules. Granulocytes are the most abundant type of leukocyte circulating in the peripheral blood. Granulocyte abundance, nAChR expression, and nAChR upregulation following chronic nicotine administration makes granulocytes interesting models for identifying protein markers of nicotine exposure. Nicotinic receptor subunits and several non‐nAChR proteins have been identified as protein markers of granulocyte nicotine exposure. We review methods to isolate granulocytes from human tissue, summarize present data about the expression of nAChRs in the three granulocyte cell types (basophils, eosinophils, and neutrophils), describe current knowledge of the effects of nicotine exposure on human granulocyte protein expression, and highlight areas of interest for future investigation.

This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.

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Redox properties of transitional milk from mothers of preterm infants
Authors: Minić Simeon , Ješić Miloš , Đurović Dijana , Miletić Srdjan , Lugonja Nikoleta , Marinković Vesna , Nikolić‐Kokić Aleksandra , Spasić Snežana , Vrvić Miroslav M
Published: August 2017

Aim

There is a discrepancy between the amount of transitional milk produced by mothers of preterm infants and the low capacity of premature infants to consume it. This milk can be used in milk banks, but previous studies found that there are large variations in the level of host‐defence proteins in individual samples of milk from mothers of premature infants, which implies that large individual variations in antioxidative defence composition are also possible.

Methods

Milk samples were collected from 20 healthy mothers of preterm infants. We determined the values for non‐enzymatic antioxidative capacity parameters (oxygen radical absorbance capacity (ORAC)), static oxidation–reduction potential (ORP), activities of antioxidant defence enzymes and the amount of vitamin C in whole milk, skim and whey fractions of transitional milk.

Results

The main low‐molecular‐weight antioxidant in transitional milk is vitamin C and most of it is contained in whey. ORAC is higher in whole transitional milk than in skim milk and whey, and ORP is lower in whole transitional milk than that in skim milk and whey. Antioxidative enzyme activities are similar in all individual samples of transitional milk from mothers of preterm infants.

Conclusions

Our results indicate that transitional milk of mothers of preterm infants shows slow individual variations in antioxidative defence composition; therefore, it can be used in human milk banks.
Exocuticular hyaline layer of sea scorpions and horseshoe crabs suggests cuticular fluorescence is plesiomorphic in chelicerates
Authors: Rubin M. , Lamsdell J. C. , Prendini L. , Hopkins M. J.
Published: August 2017

The cuticle of scorpions (Chelicerata: Arachnida) fluoresces under long‐wave ultraviolet (UV) light due to the presence of beta‐carboline and 7‐hydroxy‐4‐methylcoumarin in the hyaline layer of the exocuticle. The adaptive significance of cuticularUVfluorescence in scorpions is debated. Although several other chelicerate orders (e.g. Opiliones and Solifugae) have been reported to fluoresce on exposure toUVlight, the prevalence of cuticularUVfluorescence has not been confirmed beyond scorpions. A systematic study of living chelicerates revealed thatUVfluorescence of the unsclerotized integument is ubiquitous across Chelicerata, whereas only scorpions and horseshoe crabs (Xiphosura) exhibit cuticularUVfluorescence. Scanning electron microscopy and histological sectioning confirmed the presence of a hyaline layer in taxa exhibiting cuticular fluorescence. The hyaline layer is absent in all other chelicerates except sea scorpions (Eurypterida) in which a taphonomically altered hyaline layer, that may have fluoresced underUVlight, was observed in exceptionally preserved cuticle. CuticularUVfluorescence appears to be associated with the presence of a hyaline layer, as has long been recognized in scorpions, and may be plesiomorphic among chelicerates. The presence of a hyaline layer in horseshoe crabs and sea scorpions suggests that several putative functions for cuticularUVfluorescence in scorpions can be discounted.
Mucosal‐associated invariant T‐cell frequency and function in blood and liver of HCV mono‐ and HCV/HIV co‐infected patients with advanced fibrosis
Authors: Beudeker Boris J. B. , van Oord Gertine W. , Arends Joop E. , Schulze zur Wiesch Julian , van der Heide Marieke S. , de Knegt Robert J. , Verbon Annelies , Boonstra Andre , Claassen Mark A. A.
Published: August 2017

Background & Aims

Mucosal‐associated invariant T (MAIT) cells are important innate T cells with antimicrobial and immunoregulatory activity, recently found to be depleted in blood of patients with HIV and HCV mono‐infections. In this study, we assessed the impact of HIV, HCV and HCV/HIV co‐infection on circulating and intrahepatic MAIT‐cells and correlations with liver fibrosis.

Methods

In this cross‐sectional study, nine healthy subjects, nine HIV, 20 HCV and 22 HCV/HIV co‐infected patients were included. Blood and liver fine needle aspirate biopsies were studied using flowcytometry for CD3+CD161+Vα7.2+ MAIT‐cell frequency, phenotype and function in HCV mono‐infected and HCV/HIV co‐infected patients without or with mild fibrosis (Metavir‐score F0‐F1) or severe fibrosis to cirrhosis (Metavir‐score F3‐F4).

Results

Circulating MAIT‐cells were decreased in blood of HCV, HIV and HCV/HIV patients with F0‐F1. In HCV/HIV co‐infected individuals with severe fibrosis to cirrhosis, the frequency of circulating MAIT‐cells was even further depleted, whereas their function was comparable to HCV/HIV co‐infected patients with low or absent fibrosis. In contrast, in HCV mono‐infected patients, MAIT‐cell frequencies were not related to fibrosis severity; however, MAIT‐cell function was impaired in mono‐infected patients with more fibrosis. More advanced liver fibrosis in HCV or HCV/HIV‐infected patients was not reflected by increased accumulation of MAIT‐cells in the affected liver.

Conclusions

Severe liver fibrosis is associated with dysfunctional MAIT‐cells in blood of HCV mono‐infected patients, and lower MAIT frequencies in blood of HCV/HIV co‐infected patients, without evidence for accumulation in the liver.
Oral oxycodone/naloxone for pain control in cirrhosis: Observational study in patients with symptomatic metastatic hepatocellular carcinoma
Authors: Tovoli Francesco , De Lorenzo Stefania , Samolsky Dekel Boaz G. , Piscaglia Fabio , Benevento Francesca , Brandi Giovanni , Bolondi Luigi
Published: August 2017

Background & Aims

Pain management in cirrhosis is a clinical challenge. Most analgesics are metabolized in the liver and cirrhosis may deeply alter their concentration, favouring the appearance of side effects. We aimed to assess the efficacy and safety of oral prolonged‐release association of oxycodone/naloxone tablets (OXN) in the treatment of moderate/severe cancer pain in cirrhotic patients with metastatic hepatocellular carcinoma (HCC).

Methods

We enrolled n = 32 HCC patients with moderate/severe cancer pain unresponsive to paracetamol alone or associated with codeine or tramadol. All patients received an initial OXN dose of 5 mg bid to be gradually increased in case of insufficient analgesia. At baseline and follow‐up visits, we evaluated: pain intensity (using the Numerical Rating Scale, NRS), patients’ autonomy in daily activities (Barthel Functioning Index); bowel dysfunction (Bowel Function Index, BFI), signs of hepatic encephalopathy (HE) and other opioid‐induced side effects.

Results

No clinically significant adverse effects were reported (median follow‐up 122 days). No significant worsening of the BFI score was noted and no cases of HE were detected. Two patients (6.3%) discontinued treatment before T14 because of mild nausea and dizziness. The remaining n = 30 patients were assessed for efficacy. Treatment led to a significant reduction in the mean of pain scores both at T14 (−37.1 ± 16.3%, P < .001) and at T28 (−55.6 ± 21.5%, P < .001); Barthel scores showed gradual and significant increase from T0 (81.6 ± 13.0) to T14 (86.5 ± 11.4, P = .001) and to T28 (88.3 ± 13.6, P = .009).

Conclusions

OXN may be considered a safe and effective option in the fragile population of cirrhotic patients.
Mutations in the novel gene FOPV are associated with familial autosomal dominant and non‐familial obliterative portal venopathy
Authors: Besmond Claude , Valla Dominique , Hubert Laurence , Poirier Karine , Grosse Brigitte , Guettier Catherine , Bernard Olivier , Gonzales Emmanuel , Jacquemin Emmanuel
Published: August 2017

Background & Aims

Obliterative portal venopathy (OPV) is characterized by lesions of portal vein intrahepatic branches and is thought to be responsible for many cases of portal hypertension in the absence of cirrhosis or obstruction of large portal or hepatic veins. In most cases the cause of OPV remains unknown. The aim was to identify a candidate gene of OPV.

Methods

Whole exome sequencing was performed in two families, including 6 patients with OPV. Identified mutations were confirmed by Sanger sequencing and expression of candidate gene transcript was studied by real time qPCR in human tissues.

Results

In both families, no mutations were identified in genes previously reported to be associated with OPV. In each family, we identified a heterozygous mutation (c.1783G>A, p.Gly595Arg and c.4895C>T, p.Thr1632Ile) in a novel gene located on chromosome 4, that we called FOPV (Familial Obliterative Portal Venopathy), and having a cDNA coding for 1793 amino acids. The FOPV mutations segregated with the disease in families and the pattern of inheritance was suggestive of autosomal dominant inherited OPV, with incomplete penetrance and variable expressivity. In silico analysis predicted a deleterious effect of each mutant and mutations concerned highly conserved amino acids in mammals. A deleterious heterozygous FOPV missense mutation (c.4244T>C, p.Phe1415Ser) was also identified in a patient with non‐familial OPV. Expression study in liver veins showed that FOPV transcript was mainly expressed in intrahepatic portal vein.

Conclusions

This report suggests that FOPV mutations may have a pathogenic role in some cases of familial and non‐familial OPV.
Emotion processing in female youth: Testing the stability of the late positive potential
Authors: Bondy Erin , Stewart Jeremy G. , Hajcak Greg , Weinberg Anna , Tarlow Naomi , Mittal Vijay A. , Auerbach Randy P.
Published: August 2017

The Emotional Interrupt Task (EIT) has been used to probe emotion processing in healthy and clinical samples; however, research exploring the stability and reliability of behavioral measures and ERPs elicited from this task is limited. Establishing the psychometric properties of the EIT is critical, particularly as phenotypes and biological indicators may represent traitlike characteristics that underlie psychiatric illness. To address this gap, test‐retest stability and internal consistency of behavioral indices and ERPs resulting from the EIT in healthy, female youth (n = 28) were examined. At baseline, participants were administered the EIT while high‐density 128‐channel EEG data were recorded to probe the late positive potential (LPP). One month later, participants were readministered the EIT. Four principal findings emerged. First, there is evidence of an interference effect at baseline, as participants showed a slower reaction time for unpleasant and pleasant images relative to neutral images, and test‐retest of behavioral measures was relatively stable over time. Second, participants showed a potentiated LPP to unpleasant and pleasant images compared to neutral images, and these effects were stable over time. Moreover, in a test of the difference waves (unpleasant‐neutral vs. pleasant‐neutral), there was sustained positivity for unpleasant images. Third, behavioral measures and LPP demonstrated excellent internal consistency (odd/even correlations) across conditions. Fourth, highlighting important age‐related differences in LPP activity, younger age was associated with larger LPP amplitudes across conditions. Overall, these findings suggest that the LPP following emotional images is a stable and reliable marker of emotion processing in healthy youth.
Robustness of the KOF index of economic globalisation
Authors: Gozgor Giray
Published: August 2017

The KOF indices of globalisation are the most used globalisation measures in international economics literature, but it uses the nominal trade openness measure to construct the globalisation index. In this paper, we use real trade openness instead of nominal trade openness and recalculate the KOF economic globalisation index over the period 1970–2013. Using the panel data regressions for 146 countries, we revisit the economic globalisation–economic growth nexus to investigate the robustness of the KOF economic globalisation index. We consider several possibilities in model specifications, and the results show that using nominal trade openness measure in calculating the KOF globalisation index is statistically robust. In addition, the KOF economic globalisation index in logarithmic form introduces a more robust outlook in the panel data regressions—a lower bias is emerged by considering different trade openness measures to calculate the globalisation level.
Introduction
Authors: HICKEY RAYMOND , VAUGHAN ELAINE
Published: August 2017

Since the 1970s there has been a burgeoning interest in Irish English, which in its development and present‐day forms yields considerable insights into language variation and change. Scholarship in the field has proceeded from an initial concern with contact and shift, and the structures they engendered, to a more usage‐based orientation, both in sociolinguistic research into contemporary varieties of Irish English and in the investigation of its specific pragmatics. The basis for this expansion has been an increase in the database for Irish English currently available in a range of corpora which provide statistics and attestations for many features and phenomena.
Genetic analysis of human and swine influenza A viruses isolated in Northern Italy during 2010–2015
Authors: Chiapponi C. , Ebranati E. , Pariani E. , Faccini S. , Luppi A. , Baioni L. , Manfredi R. , Carta V. , Merenda M. , Affanni P. , Colucci M. E. , Veronesi L. , Zehender G. , Foni E.
Published: August 2017

Influenza A virus (IAV) infection in swine plays an important role in the ecology of influenza viruses. The emergence of new IAVs comes through different mechanisms, with the genetic reassortment of genes between influenza viruses, also originating from different species, being common. We performed a genetic analysis on 179 IAV isolates from humans (n. 75) and pigs (n. 104) collected in Northern Italy between 2010 and 2015, to monitor the genetic exchange between human and swine IAVs. No cases of human infection with swine strains were noticed, but direct infections of swine with H1N1pdm09 strains were detected. Moreover, we pointed out a continuous circulation of H1N1pdm09 strains in swine populations evidenced by the introduction of internal genes of this subtype. These events contribute to generating new viral variants—possibly endowed with pandemic potential—and emphasize the importance of continuous surveillance at both animal and human level.
The Effect of Fuel Staging on the Structure and Instability Characteristics of Swirl-Stabilized Flames in a Lean Premixed Multinozzle Can Combustor
Authors: Samarasinghe Janith , Culler Wyatt , Quay Bryan D. , Santavicca Domenic A. , O'Connor Jacqueline
Published: August 2017

Fuel staging is a commonly used strategy in the operation of gas turbine engines. In multinozzle combustor configurations, this is achieved by varying fuel flow rate to different nozzles. The effect of fuel staging on flame structure and self-excited instabilities is investigated in a research can combustor employing five swirl-stabilized, lean-premixed nozzles. At an operating condition where all nozzles are fueled equally and the combustor undergoes a self-excited instability, fuel staging successfully suppresses the instability: both when overall equivalence ratio is increased by staging as well as when overall equivalence ratio is kept constant while staging. Increased fuel staging changes the distribution of time-averaged heat release rate in the regions where adjacent flames interact and reduces the amplitudes of heat release rate fluctuations in those regions. Increased fuel staging also causes a breakup in the monotonic phase behavior that is characteristic of convective disturbances that travel along a flame. In particular, heat release rate fluctuations in the middle flame and flame–flame interaction region are out-of-phase with those in the outer flames, resulting in a cancelation of the global heat release rate oscillations. The Rayleigh integral distribution within the combustor shows that during a self-excited instability, the regions of highest heat release rate fluctuation are in phase-with the combustor pressure fluctuation. When staging fuel is introduced, these regions fluctuate out-of-phase with the pressure fluctuation, further illustrating that fuel staging suppresses instabilities through a phase cancelation mechanism.
Input matters: Multi-accent language exposure affects word form recognition in infancy
Authors: van Heugten Marieke , Johnson Elizabeth K.
Published: August 2017

Early language input is far from uniform, even among children learning the same language. For instance, while some children are exposed to a single accent in their linguistic environment, others have routine exposure to multiple accents. Nonetheless, few studies have taken this into account when examining word recognition, and none has examined this issue in infants prior to the emergence of phonological constancy (∼18 months). This study demonstrates that daily exposure to multiple accents strongly impacts infants' performance in a laboratory word form recognition task. Accent variability in the input thus needs to be carefully considered when studying speech development.
Bacterial-Chromatin Structural Proteins Regulate the Bimodal Expression of the Locus of Enterocyte Effacement (LEE) Pathogenicity Island in Enteropathogenic
Escherichia coli
Authors: Leh Hervé , Khodr Ahmad , Bouger Marie-Christine , Sclavi Bianca , Rimsky Sylvie , Bury-Moné Stéphanie
Published: August 2017

In enteropathogenic
Escherichia coli
(EPEC), the locus of enterocyte effacement (LEE) encodes a type 3 secretion system (T3SS) essential for pathogenesis. This pathogenicity island comprises five major operons (
LEE1
to
LEE5
), with the
LEE5
operon encoding T3SS effectors involved in the intimate adherence of bacteria to enterocytes. The first operon,
LEE1
, encodes Ler (LEE-encoded regulator), an H-NS (nucleoid structuring protein) paralog that alleviates the LEE H-NS silencing. We observed that the
LEE5
and
LEE1
promoters present a bimodal expression pattern, depending on environmental stimuli. One key regulator of bimodal
LEE1
and
LEE5
expression is
ler
expression, which fluctuates in response to different growth conditions. Under conditions
in vitro
considered to be equivalent to nonoptimal conditions for virulence, the opposing regulatory effects of H-NS and Ler can lead to the emergence of two bacterial subpopulations. H-NS and Ler share nucleation binding sites in the
LEE5
promoter region, but H-NS binding results in local DNA structural modifications distinct from those generated through Ler binding, at least
in vitro
. Thus, we show how two nucleoid-binding proteins can contribute to the epigenetic regulation of bacterial virulence and lead to opposing bacterial fates. This finding implicates for the first time bacterial-chromatin structural proteins in the bimodal regulation of gene expression.

IMPORTANCE
Gene expression stochasticity is an emerging phenomenon in microbiology. In certain contexts, gene expression stochasticity can shape bacterial epigenetic regulation. In enteropathogenic
Escherichia coli
(EPEC), the interplay between H-NS (a nucleoid structuring protein) and Ler (an H-NS paralog) is required for bimodal
LEE5
and
LEE1
expression, leading to the emergence of two bacterial subpopulations (with low and high states of expression). The two proteins share mutual nucleation binding sites in the
LEE5
promoter region.
In vitro
, the binding of H-NS to the
LEE5
promoter results in local structural modifications of DNA distinct from those generated through Ler binding. Furthermore,
ler
expression is a key parameter modulating the variability of the proportions of bacterial subpopulations. Accordingly, modulating the production of Ler into a nonpathogenic
E. coli
strain reproduces the bimodal expression of
LEE5
. Finally, this study illustrates how two nucleoid-binding proteins can reshape the epigenetic regulation of bacterial virulence.
Membrane Distribution of the
Pseudomonas
Quinolone Signal Modulates Outer Membrane Vesicle Production in
Pseudomonas aeruginosa
Authors: Florez Catalina , Raab Julie E. , Cooke Adam C. , Schertzer Jeffrey W.
Published: August 2017

The
Pseudomonas
quinolone signal (PQS) is an important quorum-sensing molecule in
Pseudomonas aeruginosa
that also mediates its own packaging and transport by stimulating outer membrane vesicle (OMV) formation. Because OMVs have been implicated in many virulence-associated behaviors, it is critical that we understand how they are formed. Our group proposed the bilayer-couple model for OMV biogenesis, where PQS intercalates into the outer membrane, causing expansion of the outer leaflet and consequently inducing curvature. In accordance with the model, we hypothesized that PQS must be transported from the cytoplasm to the outer membrane before it can initiate OMV formation. We initially examined two laboratory strains of
P. aeruginosa
and found significant strain-dependent differences. PQS export correlated strongly with OMV production, even though equivalent amounts of total PQS were produced by both strains. Interestingly, we discovered that poor OMV producers sequestered the majority of PQS in the inner membrane, which appeared to be the result of early saturation of the export pathway. Further analysis showed that strain-specific PQS export and OMV biogenesis patterns were stable once established but could be significantly altered by changing the growth medium. Finally, we demonstrated that the associations described for laboratory strains also held for three clinical strains. These results suggest that factors controlling the export of PQS dictate OMV biogenesis. This work provides new insight into PQS-controlled virulence in
P. aeruginosa
and provides important tools to further study signal export and OMV biogenesis.

IMPORTANCE
Bacterial secretion has been recognized as an essential facet of microbial pathogenesis and human disease. Numerous virulence factors have been found to be transported within outer membrane vesicles (OMVs), and delivery using these biological nanoparticles often results in increased potency. OMV biogenesis is an important but poorly understood process that is ubiquitous among Gram-negative organisms. Our group seeks to understand the biochemical mechanisms behind the formation of OMVs and has developed a model of small-molecule-induced membrane curvature as an important driver of this process. With this work, we demonstrate that PQS, a known small-molecule OMV inducer, must be exported to promote OMV biogenesis in both lab-adapted and clinical strains of
Pseudomonas aeruginosa
. In supporting and expanding the bilayer-couple model of OMV biogenesis, the current work lays the groundwork for studying environmental and genetic factors that modulate OMV production and, consequently, the packaging and delivery of many bacterial factors.