bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical management of umbilical basal cell carcinoma: Published work review and the optimal depth of surgical excision
Authors: Nakamura Yasuhiro , Teramoto Yukiko , Tanaka Ryota , Nakamura Yoshiyuki , Maruyama Hiroshi , Fujisawa Yasuhiro , Sato Sayuri , Fujimoto Manabu , Yamamoto Akifumi
Published: October 2014

Basal cell carcinoma (BCC) is a common malignant skin tumor. However, BCC that arise at the umbilicus is rare. We present three cases of umbilical BCC. Each BCC was excised at a different depth level, and all deep surgical margins were negative. All patients had no evidence of local recurrence or metastasis during the follow‐up periods (12, 24, and 52 months). Reviewing the reported cases of umbilical BCC, the BCC cells did not seem to invade into the umbilical scar in most cases, and the deepest invasion levels of tumor cells were up to the middle layer of the subcutaneous tissue. However, the dermatological surgeons have to consider the possibility of surgical excision down to and including the umbilical attachment to the peritoneum, and intraoperative margin assessment should be necessary to avoid the risk of excessive or incomplete excision.
Source–receiver two‐way wave extrapolation for prestack exploding‐reflector modelling and migration
Authors: Alkhalifah Tariq , Fomel Sergey , Wu Zedong
Published: October 2014

Most modern seismic imaging methods separate input data into parts (shot gathers). We develop a formulation that is able to incorporate all available data at once while numerically propagating the recorded multidimensional wavefield forward or backward in time. This approach has the potential for generating accurate images free of artiefacts associated with conventional approaches. We derive novel high‐order partial differential equations in the source–receiver time domain. The fourth‐order nature of the extrapolation in time leads to four solutions, two of which correspond to the incoming and outgoing P‐waves and reduce to the zero‐offset exploding‐reflector solutions when the source coincides with the receiver. A challenge for implementing two‐way time extrapolation is an essential singularity for horizontally travelling waves. This singularity can be avoided by limiting the range of wavenumbers treated in a spectral‐based extrapolation. Using spectral methods based on the low‐rank approximation of the propagation symbol, we extrapolate only the desired solutions in an accurate and efficient manner with reduced dispersion artiefacts. Applications to synthetic data demonstrate the accuracy of the new prestack modelling and migration approach.
‘A Cockroach Preserved in Amber’: The Significance of Class in Critics' Representations of Heavy Metal Music and its Fans
Authors: Brown Andy R. , Griffin Christine
Published: October 2014

In this paper we engage with new cultural theories of class that have identified media representations of ‘excessive’ white heterosexual working-class femininity as a ‘constitutive limit’ of incorporation into dominant (middle-class) modes of neoliberal subjectivity and Bourdieu's thesis that classification is a form of symbolic violence that constitutes both the classifier and the classified. However, what we explore are the implications of such arguments for those modes of white heterosexual working-class masculinity that continue to reproduce themselves in forms of overtly masculinist popular culture. We do so through a critical examination of the symbolic representation of the genre of heavy metal music within contemporary music journalism. Employing a version of critical discourse analysis, we offer an analysis of representative reviews, derived from a qualitative sample of the UK music magazine, New Musical Express (1999–2008). This weekly title, historically associated with the ideals of the ‘counter culture’, now offers leadership of musical tastes in an increasingly segmented, niche-oriented marketplace. Deploying a refined model of the inscription process outlined by Skeggs, our analysis demonstrates how contemporary music criticism symbolically attaches negative attributes and forms of personhood to the working-class male bodies identified with heavy metal culture and its audience, allowing dominant middle-class modes of cultural authority to be inscribed within matters of musical taste and distinction.
The contribution of job strain, social support and working hours in explaining work–family conflict
Authors: Samad Ataus , Reaburn Peter , Di Milia Lee
Published: October 2014

There is some debate whether job strain or working hours is more prominent in explaining work–family conflict. We tested a multi‐group structural equation model and the results suggested the model was equally applicable to academic and administrative staff employed at an Australian regional university. After controlling for demographic and work‐related factors the main predictors of work–family conflict were: job strain, total work hours, job satisfaction, employment as an academic and having dependent children. Social support was negatively related with work–family conflict but the association was not significant. Despite greater job control, academics reported greater job strain and work hours. The results suggest that strategies aimed at decreasing job strain and work hours may reduce the extent of work–family conflict.
Management of entomopathogenic fungi in cultures of Tenebrio molitor (Coleoptera: Tenebrionidae)
Authors: Lee Se Jin , Kim Si Hyeon , Nai Yu‐Shin , Je Yeon Ho , Parker Bruce L. , Kim Jae Su
Published: October 2014

Larvae of mealworms Tenebrio molitor L. (Coleoptera: Tenebrionidae) have been used as animal feed, but fungal pathogens rapidly downsize the populations, resulting in economic losses. In this work, we established an effective management strategy for fungal pathogens. An entomopathogenic fungus, Beauveria bassiana, was isolated from mealworm cadavers. The bioassay of some isolates of this species at >90% relative humidity revealed that the ERL1575 isolate had the highest virulence. At 20–30% RH, ERL1575 conidia when ingested produced 80% mortality but when sprayed topically produced only <10% mortality. Mealworms that had ingested conidia were exposed to 20, 25, 30 and 35°C and high humidity (>95%) for 5 days. This experiment produced about 90% mortality except at 35°C where mortality was <20%. When 40 fungicides were assayed against ERL1575, fluazinam (1000‐fold) and mancozeb (667‐fold) significantly inhibited conidial germination and/or hyphal growth. When fluazinam and mancozeb were added to the mealworm diet of conidia‐inoculated wheat bran, most were alive 3 days post application. However, 100% mortality resulted 3 days post application in the conidia‐inoculated wheat bran without any fungicides. In conclusion, B. bassiana isolates are pathogenic at <30°C when they are ingested by mealworms but fluazinam and mancozeb can be used for management to control the pathogen in their cultures.
Molecular annotation of ketol‐acid reductoisomerases from Streptomyces reveals a novel amino acid biosynthesis interlock mediated by enzyme promiscuity
Authors: Verdel‐Aranda Karina , López‐Cortina Susana T. , Hodgson David A. , Barona‐Gómez Francisco
Published: October 2014

The 6‐phosphogluconate dehydrogenase superfamily oxidize and reduce a wide range of substrates, making their functional annotation challenging. Ketol‐acid reductoisomerase (KARI), encoded by the ilvC gene in branched‐chain amino acids biosynthesis, is a promiscuous reductase enzyme within this superfamily. Here, we obtain steady‐state enzyme kinetic parameters for 10 IlvC homologues from the genera Streptomyces and Corynebacterium, upon eight selected chemically diverse substrates, including some not normally recognized by enzymes of this superfamily. This biochemical data suggested a Streptomyces biosynthetic interlock between proline and the branched‐chain amino acids, mediated by enzyme substrate promiscuity, which was confirmed via mutagenesis and complementation analyses of the proC, ilvC1 and ilvC2 genes in Streptomyces coelicolor. Moreover, both ilvC orthologues and paralogues were analysed, such that the relationship between gene duplication and functional diversification could be explored. The KARI paralogues present in S. coelicolor and Streptomyces lividans, despite their conserved high sequence identity (97%), were shown to be more promiscuous, suggesting a recent functional diversification. In contrast, the KARI paralogue from Streptomyces viridifaciens showed selectivity towards the synthesis of valine precursors, explaining its recruitment within the biosynthetic gene cluster of valanimycin. These results allowed us to assess substrate promiscuity indices as a tool to annotate new molecular functions with metabolic implications.
The accuracy of Fastloc‐GPS locations and implications for animal tracking
Authors: Dujon Antoine M. , Lindstrom R. Todd , Hays Graeme C.
Published: October 2014

Over recent years, a major breakthrough in marine animal tracking has occurred with the advent of Fastloc‐GPS that provides highly accurate location data even for animals that only surface briefly such as sea turtles, marine mammals and penguins.

We assessed the accuracy of Fastloc‐GPS locations using fixed trials of tags in which >45 000 locations were obtained. Procedures for determining the speed of travel and heading were developed by simulating tracks and then adding Fastloc‐GPS location errors. The levels of detail achievable for speed and heading estimates were illustrated by using empirical Fastloc‐GPS data for a green turtle (Chelonia mydas, Linnaeus, 1758) travelling over 3000 km across the Indian Ocean.

The accuracy of Fastloc‐GPS locations varied as a function of the number of GPS satellites used in the location calculation. For example, when Fastloc‐GPS locations were calculated using 4 GPS satellites, 50% of locations were within 36 m and 95% within 724 m of the true position. These values improved to 18 and 70 m, respectively, when 6 satellites were used. Simulations indicated that for animals travelling around 2·5 km h−1 (e.g. turtles, penguins and seals) and depending on the number of satellites used in the location calculation, robust speed and heading estimates would usually be obtained for locations only 1–6 h apart.

Fastloc‐GPS accuracy is several orders of magnitude better that conventional Argos tracking or light‐based geolocation and consequently will allow new insights into small‐scale movement patterns of marine animals.
A pharmacokinetic and pharmacodynamic comparison of a novel pegylated recombinant consensus interferon‐α variant with peginterferon‐α‐2a in healthy subjects
Authors: Zheng Li , Li Mao Ping , Gou Zhong Ping , Wang Ying , Xu Nan , Cai Yong Ming , Luo Hua
Published: October 2014

Aims

The aims of the study were to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of a novel, pegylated recombinant human consensus interferon‐α variant (PEG‐IFN‐SA) in healthy volunteers. A pharmacokinetic and pharmacodynamic comparison of PEG‐IFN‐SA and peginterferon‐α‐2a in healthy subjects was evaluated.

Methods

A randomized, dose‐escalating, single administration dose phase I clinical study was conducted. Thirty healthy subjects received PEG‐IFN‐SA as a single dose of 0.5–2.0 μg kg−1 by subcutaneous (s.c.) injection in four parallel groups. Eight subjects received peginterferon‐α‐2a as a single dose of 180 μg s.c.

Results

The incidence rates of adverse events for PEG‐IFN‐SA and peginterferon‐α‐2a were 29 of 30 and 7 of 8, respectively. The adverse events for PEG‐IFN‐SA were mild to moderate and similar to those of peginterferon‐α‐2a. Within 168 h after injection, the mean values of maximal concentration and area under the plasma concentration–time curve from time of dosing to 168 h [AUC(0–168h)] for 2′,5′‐oligoadenylate, neopterin and β2‐microglobulin for PEG‐IFN‐SA at 1.5 μg kg−1 s.c. were similar to or higher than those for peginterferon‐α‐2a at a dose of 180 μg s.c. After s.c. injection of PEG‐IFN‐SA at 1.5 μg kg−1, the mean geometric mean values of plasma half‐life, time to maximal concentration, maximal concentration and AUC(0–168h) were 55.3 h, 26.9 h, 0.53 μg l−1 and 44.0 μg l−1 h, respectively.

Conclusions

The tolerance, pharmacokinetic and pharmacodynamic characteristics of PEG‐IFN‐SA support its administration by s.c. injection as a single dose of 1.5 μg kg−1 or at 2.0 μg kg−1 per week.
Model Choice Problems Using Approximate Bayesian Computation with Applications to Pathogen Transmission Data Sets
Authors: Lee Xing Ju , Drovandi Christopher C. , Pettitt Anthony N.
Published: October 2014

Analytically or computationally intractable likelihood functions can arise in complex statistical inferential problems making them inaccessible to standard Bayesian inferential methods. Approximate Bayesian computation (ABC) methods address such inferential problems by replacing direct likelihood evaluations with repeated sampling from the model. ABC methods have been predominantly applied to parameter estimation problems and less to model choice problems due to the added difficulty of handling multiple model spaces. The ABC algorithm proposed here addresses model choice problems by extending Fearnhead and Prangle (2012, Journal of the Royal Statistical Society, Series B  74, 1–28) where the posterior mean of the model parameters estimated through regression formed the summary statistics used in the discrepancy measure. An additional stepwise multinomial logistic regression is performed on the model indicator variable in the regression step and the estimated model probabilities are incorporated into the set of summary statistics for model choice purposes. A reversible jump Markov chain Monte Carlo step is also included in the algorithm to increase model diversity for thorough exploration of the model space. This algorithm was applied to a validating example to demonstrate the robustness of the algorithm across a wide range of true model probabilities. Its subsequent use in three pathogen transmission examples of varying complexity illustrates the utility of the algorithm in inferring preference of particular transmission models for the pathogens.
Estimation of Treatment Effects in All-Comers Randomized Clinical Trials with a Predictive Marker
Authors: Choai Yuki , Matsui Shigeyuki
Published: October 2014

Recent advances in genomics and biotechnologies have accelerated the development of molecularly targeted treatments and accompanying markers to predict treatment responsiveness. However, it is common at the initiation of a definitive phase III clinical trial that there is no compelling biological basis or early trial data for a candidate marker regarding its capability in predicting treatment effects. In this case, it is reasonable to include all patients as eligible for randomization, but to plan for prospective subgroup analysis based on the marker. One analysis plan in such all-comers designs is the so-called fallback approach that first tests for overall treatment efficacy and then proceeds to testing in a biomarker-positive subgroup if the first test is not significant. In this approach, owing to the adaptive nature of the analysis and a correlation between the two tests, a bias will arise in estimating the treatment effect in the biomarker-positive subgroup after a non-significant first overall test. In this article, we formulate the bias function and show a difficulty in obtaining unbiased estimators for a whole range of an associated parameter. To address this issue, we propose bias-corrected estimation methods, including those based on an approximation of the bias function under a bounded range of the parameter using polynomials. We also provide an interval estimation method based on a bivariate doubly truncated normal distribution. Simulation experiments demonstrated a success in bias reduction. Application to a phase III trial for lung cancer is provided.
Spatial Variable Selection Methods for Investigating Acute Health Effects of Fine Particulate Matter Components
Authors: Boehm Vock Laura F. , Reich Brian J. , Fuentes Montserrat , Dominici Francesca
Published: October 2014

Multi-site time series studies have reported evidence of an association between short term exposure to particulate matter (PM) and adverse health effects, but the effect size varies across the United States. Variability in the effect may partially be due to differing community level exposure and health characteristics, but also due to the chemical composition of PM which is known to vary greatly by location and time. The objective of this article is to identify particularly harmful components of this chemical mixture. Because of the large number of highly-correlated components, we must incorporate some regularization into a statistical model. We assume that, at each spatial location, the regression coefficients come from a mixture model with the flavor of stochastic search variable selection, but utilize a copula to share information about variable inclusion and effect magnitude across locations. The model differs from current spatial variable selection techniques by accommodating both local and global variable selection. The model is used to study the association between fine PM (PM 2.5m) components, measured at 115 counties nationally over the period 2000–2008, and cardiovascular emergency room admissions among Medicare patients.
Protective effects of n‐6 fatty acids‐enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor
Authors: Gobbetti T , Ducheix S , le Faouder P , Perez T , Riols F , Boue J , Bertrand‐Michel J , Dubourdeau M , Guillou H , Perretti M , Vergnolle N , Cenac N
Published: October 2014

Background and Purpose

Long‐term intake of dietary fatty acids is known to predispose to chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury is unknown. The aim of this study was to determine the consequences of a diet rich in n‐3 or n‐6 polyunsaturated fatty acids (PUFA) on intestinal I/R‐induced damage.

Experimental Approach

Mice were fed three different isocaloric diets: a balanced diet used as a control and two different PUFA‐enriched diets, providing either high levels of n‐3 or of n‐6 PUFA. Intestinal injury was evaluated after intestinal I/R. PUFA metabolites were quantitated in intestinal tissues by LC‐MS/MS.

Key Results

In control diet‐fed mice, intestinal I/R caused inflammation and increased COX and lipoxygenase‐derived metabolites compared with sham‐operated animals. Lipoxin A4 (LxA4) was significantly and selectively increased after ischaemia. Animals fed a high n‐3 diet did not display a different inflammatory profile following intestinal I/R compared with control diet‐fed animals. In contrast, intestinal inflammation was decreased in the I/R group fed with high n‐6 diet and level of LxA4 was increased post‐ischaemia compared with control diet‐fed mice. Blockade of the LxA4 receptor (Fpr2), prevented the anti‐inflammatory effects associated with the n‐6 rich diet.

Conclusions and Implications

This study indicates that high levels of dietary n‐6, but not n‐3, PUFAs provides significant protection against intestinal I/R‐induced damage and demonstrates that the endogenous production of LxA4 can be influenced by diet.
Serelaxin‐mediated signal transduction in human vascular cells: bell‐shaped concentration–response curves reflect differential coupling to G proteins
Authors: Sarwar M , Samuel C S , Bathgate R A , Stewart D R , Summers R J
Published: October 2014

Background and Purpose

In a recently conducted phase III clinical trial, RELAX‐AHF, serelaxin infusion over 48 h improved short‐ and long‐term clinical outcomes in patients with acute heart failure. In this study we used human primary cells from the umbilical vasculature to better understand the signalling mechanisms activated by serelaxin.

Experimental Approach

We examined the acute effects of serelaxin on signal transduction mechanisms in primary human umbilical vascular cells and its chronic actions on markers of cardiovascular function and disease.

Key Results

The RXFP1 receptor, the cognate serelaxin receptor, was expressed at the cell surface in HUVECs and human umbilical vein smooth muscle cells (HUVSMCs), human umbilical artery smooth muscle cells (HUASMCs) and human cardiac fibroblasts (HCFs), but not human umbilical artery endothelial cells. In HUVECs and HUVSMCs, serelaxin increased cAMP, cGMP accumulation and pERK1/2, and the concentration–response curves (CRCs) were bell‐shaped. Similar bell‐shaped CRCs for cGMP and pERK1/2 were observed in HCFs, whereas in HUASMCs, serelaxin increased cAMP, cGMP and pERK1/2 with sigmoidal CRCs. Gαi/o and lipid raft disruption, but not Gαs inhibition, altered the serelaxin CRC for cAMP and cGMP accumulation in HUVSMC but not HUASMC. Longer term serelaxin exposure increased the expression of neuronal NOS, VEGF, ETβ receptors and MMPs (gelatinases) in RXFP1 receptor‐expressing cells.

Conclusions and Implications

Serelaxin caused acute and chronic changes in human umbilical vascular cells that were cell background dependent. Bell‐shaped CRCs that were observed only in venous cells and fibroblasts involved Gαi/o located within membrane lipid rafts.
Biased β2‐adrenoceptor signalling in heart failure: pathophysiology and drug discovery
Authors: Woo Anthony Yiu‐Ho , Song Ying , Xiao Rui‐Ping , Zhu Weizhong
Published: October 2014

The body is constantly faced with a dynamic requirement for blood flow. The heart is able to respond to these changing needs by adjusting cardiac output based on cues emitted by circulating catecholamine levels. Cardiac β‐adrenoceptors transduce the signal produced by catecholamine stimulation via Gs proteins to their downstream effectors to increase heart contractility. During heart failure, cardiac output is insufficient to meet the needs of the body; catecholamine levels are high and β‐adrenoceptors become hyperstimulated. The hyperstimulated β1‐adrenoceptors induce a cardiotoxic effect, which could be counteracted by the cardioprotective effect of β2‐adrenoceptor‐mediated Gi signalling. However, β2‐adrenoceptor‐Gi signalling negates the stimulatory effect of the Gs signalling on cardiomyocyte contraction and further exacerbates cardiodepression. Here, further to the localization of β1‐ and β2‐adrenoceptors and β2‐adrenoceptor‐mediated β‐arrestin signalling in cardiomyocytes, we discuss features of the dysregulation of β‐adrenoceptor subtype signalling in the failing heart, and conclude that Gi‐biased β2‐adrenoceptor signalling is a pathogenic pathway in heart failure that plays a crucial role in cardiac remodelling. In contrast, β2‐adrenoceptor‐Gs signalling increases cardiomyocyte contractility without causing cardiotoxicity. Finally, we discuss a novel therapeutic approach for heart failure using a Gs‐biased β2‐adrenoceptor agonist and a β1‐adrenoceptor antagonist in combination. This combination treatment normalizes the β‐adrenoceptor subtype signalling in the failing heart and produces therapeutic effects that outperform traditional heart failure therapies in animal models. The present review illustrates how the concept of biased signalling can be applied to increase our understanding of the pathophysiology of diseases and in the development of novel therapies.

Linked Articles

This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
Diadenosine tetraphosphate induces tight junction disassembly thus increasing corneal epithelial permeability
Authors: Loma P , Guzman‐Aranguez A , Pérez de Lara M J , Pintor J
Published: October 2014

Background and Purpose

Here, we have studied the effects of the dinucleotide P1, P4‐Di (adenosine‐5′) tetraphosphate (Ap4A) on corneal barrier function conferred by the tight junction (TJ) proteins and its possible involvement in ocular drug delivery and therapeutic efficiency.

Experimental Approach

Experiments in vitro were performed using human corneal epithelial cells (HCLEs) treated with Ap4A (100 μM) for 5 min. Western blot analysis and transepithelial electrical resistance (TEER) were performed to study the TJ protein levels and barrier function respectively. Intracellular pathways involved were determined using an ERK inhibitor and P2Y2 receptor siRNAs. In in vivo assays with New Zealand rabbits, TJ integrity was examined by zonula occludens‐1 (ZO‐1) staining. The hypotensive compound 5‐methoxycarbonylamino‐N‐acetyltryptamine (5‐MCA‐NAT) was used to assess improved delivery, measuring its levels by HPLC and measuring intraocular pressure using 5‐MCA‐NAT, P2Y receptor antagonists and P2Y2 siRNAs.

Key Results

Two hours after Ap4A pretreatment, TJ protein levels in HCLE cells were reduced around 40% compared with control. TEER values were significantly reduced at 2 and 4 h (68 and 52% respectively). TJ reduction and ERK activation were blocked by the ERK inhibitor U012 and P2Y2 siRNAs. In vivo, topical application of Ap4A disrupted ZO‐1 membrane distribution. 5‐MCA‐NAT levels in the aqueous humour were higher when Ap4A was previously instilled and its hypotensive effect was also increased. This action was reversed by P2Y receptor antagonists and P2Y2 siRNA.

Conclusions and Implications

Ap4A increased corneal epithelial barrier permeability. Its application could improve ocular drug delivery and consequently therapeutic efficiency.
miR‐185‐3p regulates nasopharyngeal carcinoma radioresistance by targeting WNT2B in vitro
Authors: Li Guo , Wang Yunyun , Liu Yong , Su Zhongwu , Liu Chao , Ren Shuling , Deng Tengbo , Huang Donghai , Tian Yongquan , Qiu Yuanzheng
Published: October 2014

Aberrant microRNA (miRNA) expression contributes to a series of malignant cancer behaviors, including radioresistance. Our previous study showed differential expression of miR‐185‐3p in post‐radiation nasopharyngeal carcinoma (NPC) cells. To investigate the role of miR‐185‐3p in NPC radioresistance, CNE‐2 and 5‐8F cells were transfected with miR‐185‐3p mimic and miR‐185‐3p inhibitor, respectively. CCK‐8 assay and colony formation experiment confirmed that the expression of miR‐185‐3p affected the radioresistance of NPC cells. A negative correlation between miR‐185‐3p and WNT2B expression was observed in NPC cells and tissues. Luciferase reporter assays confirmed that miR‐185‐3p directly targeted the coding region of WNT2B. Furthermore, we found radioresistance decreased in WNT2B‐silenced NPC cells. Activation of the WNT2B/β‐catenin pathway was accompanied by epithelial–mesenchymal transition biomarker changes in NPC. We concluded that miR‐185‐3p contributed to the radioresistance of NPC via modulation of WNT2B expression in vitro.
The relationship between parental fatigue, parenting self‐efficacy and behaviour: implications for supporting parents in the early parenting period
Authors: Chau V. , Giallo R.
Published: October 2014

Background

Emerging evidence indicates that parental fatigue is associated with low warmth and increased hostility in parent–child interactions. One possible pathway by which fatigue may impact on parenting behaviour is via parental self‐efficacy (PSE), whereby high fatigue may undermine PSE, which is often associated with suboptimal parenting behaviour. The current study sought to explore a model of the relationships between parental fatigue, parenting warmth and hostility, where PSE mediates these relationships and whether the nature of these relationships differ by social or family context.

Methods

The current sample was drawn from a larger Australian community sample survey on parent well‐being and parenting. It consisted of 1143 parents (mothers, n = 1003; fathers, n = 140) of children aged 0–4 years.

Results

Path analysis revealed that the relationship between fatigue and parenting warmth and hostility was fully mediated by PSE.

Conclusions

These results indicate that fatigue has the potential to negatively influence parenting behaviours that are important for their children's well‐being and development, and that fatigue plays a mediating role in this relationship. Implications of the study for psycho‐education and interventions targeting the management of parental fatigue are discussed.
The well‐being of children of parents with a mental illness: the responsiveness of crisis mental health services in Wellington, New Zealand
Authors: Pfeiffenberger Ari S. , D'Souza Amanda J. , Huthwaite Mark A. , Romans Sarah E.
Published: October 2014

Little is known about how mental health services consider the parenting role and the well‐being of children when assessing parents with acute mental illness. This paper investigated how crisis mental health services addressed child well‐being in the Wellington region, New Zealand. This mixed‐method case study included: (i) an audit of the electronic clinical records of all adults presenting to the crisis assessment team; (ii) interviews with 22 key informants; and (iii) a documentary review. We found that data about children were not systematically collected. Less than half of (49 of the 104) the records of patients who were parents included information on their child's well‐being; only six (6%) contained a specified plan for action. The focus for services was the adult patient. Key informants were unclear about their role. They identified inadequate training and institutional support, inflexible funding models and limited availability or inappropriateness of referral services as problems. They saw a need for children to become more visible, for collaborative working to improve the use of existing services and for new funding models, resources and roles. Existing national policy documents contained little guidance and no practice guidelines were in use. These were lost opportunities to improve support for the parenting role and promote child well‐being.
A single‐center experience with 200 dual kidney transplantations
Authors: Rigotti Paolo , Capovilla Giovanni , Di Bella Caterina , Silvestre Cristina , Donato Paola , Baldan Nicola , Furian Lucrezia
Published: October 2014

This study reports on a large series of 200 dual kidney transplantations (DKTs) from expanded criteria donors (ECDs) and proposes specific ways to optimize outcomes. Data concerning 200 DKTs performed in the last 14 yr were retrospectively analyzed. Kidneys from high‐risk ECD were allocated for use in DKTs on an old‐for‐old basis after histological assessment. Different surgical techniques and immunosuppressant regimens were used over time, and the outcomes are discussed. Donors and recipients were a median 73 (70–77) and a 62 (58–67) yr old, respectively. Delayed graft function occurred in 31.5% of cases, and acute rejection in 13.5%. Patient and graft survival at five yr were 90.4% and 85.8%, respectively. Unilateral kidney placement was preferred for 75% of patients, and was associated with a low rate of surgical complications. Our current standard therapy comprising low‐dose calcineurin inhibitors (CNIs) associated with mammalian target of rapamycin inhibitors (mTOR) and steroids appears to offer the best risk/benefit profile for elderly patients undergoing DKT. In our experience, outcomes after DKT can be improved by: (i) kidney clinical–histological assessment; (ii) unilateral kidney placement; (iii) minimal use of CNI associated with mTOR.
Underwater evaluation of habitat partitioning in a European river between a non‐native invader, the racer goby and a threatened native fish, the European bullhead
Authors: Kakareko Tomasz , Kobak Jarosław , Poznańska Małgorzata , Jermacz Łukasz , Copp Gordon H.
Published: October 2014

We conducted underwater surveys using SCUBA gear to examine habitat and microhabitat competition between the Ponto‐Caspian racer goby Babka gymnotrachelus and native European bullhead Cottus gobio to assess the potential for competitive displacement of the native species by the invading species. In summer, 88 surveys were made in a tributary of the River Vistula within defined benthic areas across the entire width of the river bed. The occurrence of fish by total length class (small: <6 cm; large: >6 cm) and environmental conditions (depth, water velocity, substratum type, plant cover, shelter type) was recorded. We found a substantial separation between the species and size classes in relation to substratum, shelter type and water velocity. European bullheads were limited to lotic areas with stony bottoms, whereas racer gobies also occupied lentic areas over sand or mud. European bullheads usually took refuge under stones in contrast to a wider range of shelters used by racer goby, including tree roots and rubbish. In general, the breadth of habitat used by the racer goby was wider than that of the European bullhead, although habitat overlap between the species was not statistically significant except for the type of shelter occupied by small fish, selecting smaller stones. An inverse relationship was observed between small European bullheads and all racer gobies in areas where they co‐occurred, suggesting that invader may be having an adverse effect on the distribution and habitat use of small native bullheads, particularly in areas of moderate water velocities over small stones and gravel.
The making of a fiscal state inSongChina, 960–1279
Authors: Liu William Guanglin
Published: October 2014

In light of theSchumpeterian paradigm, this article explores the rise of the tax state in eleventh‐centuryChina and its further transition towards a fiscal state until theMongol conquest in 1279. By the late eleventh century in the Song dynasty, two‐thirds of state revenues came from taxing non‐agricultural sectors, especially from the collection of excise. TheSong state became the first sustainable tax state in global history, as manifested in three major aspects: monetization; indirect taxation; and centralization and professionalization in the tax administration. The boundary of theSong tax state was largely confined to urban settlements. In rural areas, the state gave up the collection of commercial taxes by farming out this right to local elites. In the twelfth century, as traditional tax revenues fell far short of supporting military defence, theSong administration utilized credit instruments. Around 1200, the amount of redeemable promissory notes first exceeded that of annual tax revenues. This shift from tax‐based public finance to credit‐based public finance completed the transition towards a fiscal state. Nonetheless, this development in the fiscal state was still at an early stage and proved to be unstable. Toward the end of theSouthernSong, hyperinflation caused by the over‐issuance of promissory notes seriously threatened the economy.
WONOEP appraisal: Optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis
Authors: Mantoan Ritter Laura , Golshani Peyman , Takahashi Koji , Dufour Suzie , Valiante Taufik , Kokaia Merab
Published: October 2014

Optogenetics is a novel technology that combines optics and genetics by optical control of microbial opsins, targeted to living cell membranes. The versatility and the electrophysiologic characteristics of the light‐sensitive ion‐channels channelrhodopsin‐2 (ChR2), halorhodopsin (NpHR), and the light‐sensitive proton pump archaerhodopsin‐3 (Arch) make these optogenetic tools potent candidates in controlling neuronal firing in models of epilepsy and in providing insights into the physiology and pathology of neuronal network organization and synchronization. Opsins allow selective activation of excitatory neurons and inhibitory interneurons, or subclasses of interneurons, to study their activity patterns in distinct brain‐states in vivo and to dissect their role in generation of synchrony and seizures. The influence of gliotransmission on epileptic network function is another topic of great interest that can be further explored by using light‐activated Gq protein–coupled opsins for selective activation of astrocytes. The ever‐growing optogenetic toolbox can also be combined with emerging techniques that have greatly expanded our ability to record specific subtypes of cortical and hippocampal neurons in awake behaving animals such as juxtacellular recording and two‐photon guided whole‐cell recording, to identify the specific subtypes of neurons that are altered in epileptic networks. Finally, optogenetic tools allow rapid and reversible suppression of epileptic electroencephalography (EEG) activity upon photoactivation. This review outlines the most recent advances achieved with optogenetic techniques in the field of epilepsy by summarizing the presentations contributed to the 13th ILAE WONOEP meeting held in the Laurentian Mountains, Quebec, in June 2013.
Cementless total hip arthroplasty for haemophilic arthropathy: follow‐up result of more than 10 years
Authors: Lee S. H. , Rhyu K. H. , Cho Y. J. , Yoo M. C. , Chun Y. S.
Published: October 2014

The improvement of prophylaxis and adequate replacement of clotting factors, the quality of life and natural history of haemophilia have been significantly improved. However, significant functional impairment is inevitable. This study was performed to evaluate over 10 years clinical and radiographic outcomes of cementless total hip arthroplasty (THA) for treatment of haemophilic hip arthropathy. Between 1995 and 2003, 27cases of cementless total hip arthroplasties were performed in 23 haemophilic patients. A total of 21 cases from 17 patients were available for follow‐up analysis over 10 years. Modified Harris hip score, the range of motion of the hip joint, perioperative coagulation factor requirements and complications associated with bleeding were evaluated as part of the clinical assessment. For the radiographic assessment, fixation of component, osteolysis, loosening and other complications were evaluated. Clinically, the mean Harris hip score improved from 57 points before the operation to 94 points at the last follow‐up. The mean flexion contracture was 10° preoperatively and 0.9° at the final follow‐up. The further flexion improved from 68.4° to 90.5° after surgery. The mean monthly requirement of factor VIII reduced from 3150 units before surgery to 1800 units at the time of the last follow‐up. There were three cases of rebleeding. In one case, a progressive haemophilic pseudotumour was found. Reoperation for any reason including revision was performed in three cases. We believe that cementless THA in patient with haemophilic hip arthropathy can bring reliable pain relief and functional improvement for longer than 10 years.
Real‐World Economic Impact of OnabotulinumtoxinA in Patients With Chronic Migraine
Authors: Rothrock John F. , Bloudek Lisa M. , Houle Timothy T. , Andress‐Rothrock Diane , Varon Sepideh F.
Published: October 2014

Objective

To determine whether the utilization of healthcare resources is reduced after chronic migraine patients are treated for 6 months with onabotulinumtoxinA.

Background

OnabotulinumtoxinA is indicated for headache prophylaxis in patients with chronic migraine, but its effect on healthcare resource use is unknown.

Methods

We analyzed data from an open‐label study of 230 chronic migraine patients refractory to ≥2 oral prophylactics who presented to a headache specialty clinic and who were treated with two cycles of onabotulinumtoxinA. Frequency and cost of migraine‐related healthcare resource use, including visits to emergency departments, urgent care, or hospitalization, were compared for the 6 months before and after initial treatment. Costs were based on publicly available sources.

Results

Compared with the 6 months predating initial treatment, patients had 55% fewer emergency department visits (174 vs 385), 59% fewer urgent care visits (61 vs 150), and 57% fewer hospitalizations (19 vs 45) during the 6‐month treatment period (P < .01 for all). Analysis of treatment‐related costs yielded an average reduction of $1219.33/patient, off‐setting 49.7% of the total estimated cost for 6 months of treatment with onabotulinumtoxinA.

Conclusions

Although we are unable to distinguish onabotulinumtoxinA's treatment effect from other potential confounding variables, our analysis showed that severely afflicted, treatment‐refractory patients with chronic migraine experienced a significant cost‐offset through reduced migraine‐related emergency department visits, urgent care visits, and hospitalizations in the 6 months following treatment initiation of onabotulinumtoxinA. Future analyses will assess the longer‐term effect of onabotulinumtoxinA treatment and the potential contribution of regression to the mean.
Statin use and risk of gallstone disease: A meta‐analysis
Authors: Kan He‐Ping , Guo Wen‐bin , Tan Yong‐Fa , Zhou Jie , Liu Cun‐dong , Huang Yu‐Qi
Published: October 2014

Aim

There is emerging evidence from animal and human studies that current statins can decrease the formation of gallbladder cholesterol gallstones and subsequently decrease the risk of gallstone disease, but consistent results have not been reported. We performed a meta‐analysis to provide an overview of the relevant studies.

Methods

Relevant studies published between January 1980 and February 2014 were identified by searching Medline, Embase and the Cochrane Library. Studies were selected using a priori defined criteria. The strength of the relationship between statin use and risk of gallstone disease was assessed by adjusted odds ratio (OR).

Results

A total of 622 868 participants from six studies (four case–control studies, one cohort study and one cross‐sectional study) were identified in this meta‐analysis. The studies provided adjusted overall OR estimates for current statin use versus non‐use, leading to a pooled OR of 0.86 (95% confidence interval [CI], 0.77–0.97; P < 0.001). The overall OR of population‐based case–control studies and cholecystectomy due to gallstone disease were 0.83 (95% CI, 0.73–0.95; P = 0.0131) and 0.78 (95% CI, 0.74–0.82; P = 0.615), respectively.

Conclusion

There is evidence that current statin use lowers the risk of gallstone disease compared with non‐use, especially for cholecystectomy due to gallstone disease. Low statin use (1–4 prescriptions) did not decrease the risk of gallstone disease, but moderate and high statin use significantly decreased the risk. Further multicenter and better controlled studies are needed to confirm these findings.
Synthetic lethal interaction of combined CD26 and Bcl‐xL inhibition is a powerful anticancer therapy against hepatocellular carcinoma
Authors: Kawaguchi Tsukasa , Kodama Takahiro , Hikita Hayato , Makino Yuki , Saito Yoshinobu , Tanaka Satoshi , Shimizu Satoshi , Sakamori Ryotaro , Miyagi Takuya , Wada Hiroshi , Nagano Hiroaki , Hiramatsu Naoki , Tatsumi Tomohide , Takehara Tetsuo
Published: October 2014

Aim

CD26 is a membrane glycoprotein that has multiple functions, including dipeptidyl peptidase IV activity. CD26 expression varies in different tumor types, and its role in tumor growth in hepatocellular carcinoma (HCC) remains unclear.

Methods

CD26 expression levels were examined in resected HCC and surrounding non‐cancerous lesions. The effect of CD26 knockdown on the cellular proliferation of HepG2 or Huh7 cells, both of which highly express CD26, was studied in vitro.

Results

CD26 mRNA expression levels were significantly increased in HCC compared with their surrounding non‐cancerous lesions. We confirmed that various HCC cell lines, especially HepG2 and Huh7 cells, showed high expression levels of CD26. siRNA‐mediated knockdown of CD26 suppressed hepatoma cell growth in vitro. CD26 knockdown induced cell cycle arrest through the upregulation of Cip/Kip family proteins, p21 in HepG2 cells and p27 in Huh7 cells. CD26 knockdown did not affect apoptosis, but it increased expressions of the pro‐apoptotic proteins Bim and Bak and the anti‐apoptotic protein Bcl‐xL, suggesting an addiction of CD26 knockdown cells to Bcl‐xL for survival. We thus treated CD26 knockdown cells with ABT‐737, a Bcl‐xL/‐2/‐w inhibitor, and observed that the synthetic lethal interaction of combined Bcl‐xL and CD26 inhibition induced significant apoptosis and impaired cellular viability.

Conclusion

CD26 mRNA was overexpressed in HCC, and its inhibition suppressed cellular proliferation through cell cycle arrest. The combined use of CD26 knockdown with a Bcl‐xL inhibitor further elicited substantial apoptosis and therefore may serve as a powerful anticancer combination therapy against HCC.
Aurora kinase A is superior to Ki67 as a prognostic indicator of survival in neuroblastoma
Authors: Ramani Pramila , Nash Rachel , Rogers Chris A
Published: October 2014

Aims

To compare the expression and prognostic value of the cell cycle markers Aurora kinase A (AURKA) and Ki67 in neuroblastoma, because AURKA expression levels have greater prognostic significance than those of Ki67 in some cancers.

Methods and results

Eighty‐eight neuroblastomas were immunostained with anti‐AURKA and Ki67 antibodies. Digitally scanned slides were scored using imaging analysis software. Median AURKA and Ki67 proliferation indices (PIs) were 1.5% and 26%, respectively. Higher than median AURKA and Ki67 levels were detected in the neuroblastomas from patients belonging to the high‐risk group, those with MYCN amplification, and those with unfavourable pathology, including a high mitosis–karyorrhexis index (MKI). High AURKA and Ki67 levels were significantly associated with shorter overall survival (OS) and event‐free survival (EFS) in univariate analyses. In multivariate analyses, high AURKA level was associated with significantly shorter OS and EFS, independently of risk group, and of MYCN amplification and MKI. High Ki67 level was not associated with shorter OS or EFS after adjustment for risk group or MYCN amplification and MKI.

Conclusions

High AURKA and Ki67 levels were associated with adverse prognostic factors and shorter survival, but AURKA provides more valuable prognostic information than Ki67 in neuroblastoma.
Human equilibrative nucleoside transporter 1 testing in pancreatic ductal adenocarcinoma: a comparison between murine and rabbit antibodies
Authors: Svrcek Magali , Cros Jérôme , Maréchal Raphael , Bachet Jean‐Baptiste , Fléjou Jean‐François , Demetter Pieter
Published: October 2014

Aims

The human equilibrative nucleoside transporter 1 (hENT1) expression level in pancreatic ductal adenocarcinoma (PDAC) may predict survival in gemcitabine‐treated patients after resection. These results have been obtained with a murine anti‐hENT1 antibody (10D7G2) that is not commercially available. Another antibody, which is rabbit‐derived (SP120), appears to have no predictive value in local, advanced or metastatic PDAC. We aimed to study whether the two antibodies are equivalent.

Methods and results

We compared hENT1 expression with both antibodies in resected PDAC. The results were correlated with overall survival (OS) following gemcitabine treatment. Tissues from two sets of patients (n = 147 each) were stained with SP120 by the use of different equipment, with an amplification technique being used for set 2. The rate of ‘hENT1 high' cases was lower with SP120 (set 1, 7% versus 48%; set 2, 11% versus 38%). With the amplification technique, the rate of hENT1 high cases was globally similar between both antibodies. However, concordance between the antibodies was found in only 50% of cases. High hENT1 expression was predictive of OS only with 10D7G2 (hazard ratio 0.49; 95% confidence interval 0.24–0.98; P = 0.045).

Conclusions

The two antibodies are not equivalent. Further prospective studies seem to be warranted before hENT1 testing for PDAC is used in daily practise.