bluuebunny/crossref_metadata_2025 huggingface dataset:
Loci, genes, and gene networks associated with life history variation in a model ecological organism,Daphnia pulex(complex)
Authors: Malcom Jacob W. , Juenger Thomas E. , Leibold Mathew A.
Published: October 2018

Background

Identifying the molecular basis of heritable variation provides insight into the underlying mechanisms generating phenotypic variation and the evolutionary history of organismal traits. Life history trait variation is of central importance to ecological and evolutionary dynamics, and contemporary genomic tools permit studies of the basis of this variation in non-genetic model organisms. We used high density genotyping, RNA-Seq gene expression assays, and detailed phenotyping of fourteen ecologically important life history traits in a wild-caught panel of 32Daphnia pulexclones to explore the molecular basis of trait variation in a model ecological species.

Results

We found extensive phenotypic and a range of heritable genetic variation (~0 < H2< 0.44) in the panel, and accordingly identify 75-261 genes—organized in 3-6 coexpression modules—associated with genetic variation in each trait. The trait-related coexpression modules possess well-supported promoter motifs, and in conjunction with marker variation at trans- loci, suggest a relatively small number of important expression regulators. We further identify a candidate genetic network with SNPs in eight known transcriptional regulators, and dozens of differentially expressed genes, associated with life history variation. The gene-trait associations include numerous un-annotated genes, but also support several a priori hypotheses, including an ecdysone-induced protein and several Gene Ontology pathways.

Conclusion

The genetic and gene expression architecture ofDaphnialife history traits is complex, and our results provide numerous candidate loci, genes, and coexpression modules to be tested as the molecular mechanisms that underlieDaphniaeco-evolutionary dynamics.
Variation in the plasma membrane monoamine transporter (PMAT, encoded in SLC29A4) and organic cation transporter 1 (OCT1, encoded in SLC22A1) and gastrointestinal intolerance to metformin in type 2 diabetes: an IMI DIRECT study
Authors: Dawed Adem Y , Zhou Kaixin , van Leeuwen Nienke , Mahajan Anubha , Robertson Neil , Koivula Robert , Elders Petra JM , Rauh Simone P , Jones Angus G , Holl Reinhard W , Stingl Julia C , Franks Paul W , McCarthy Mark I , Hart Leen ‘t , Pearson Ewan R ,   for the IMI DIRECT Consortium.
Published: October 2018

Objectives

20-30% of patients with metformin treated type 2 diabetes experience gastrointestinal side effects leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localised high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin into the circulation via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe GI side effects.

Research Design and Methods

The study included 286 severe metformin intolerant and 1128 tolerant individuals from the IMI DIRECT consortium. We assessed the association of patient characteristics, concomitant medication and the burden of mutations in the SLC29A4 and SLC22A1, genes that encode PMAT and OCT1, respectively, on odds of metformin intolerance using a logistic regression model.

Results

Women (p < 0.001) and older people (p < 0.001) were more likely to develop metformin intolerance. Concomitant use of metformin transporter inhibiting drugs increased the odds of intolerance by more than 70% (OR = 1.72 [1.26-2.32], p < 0.001). In a logistic regression model adjusted for age, sex, weight and population substructure, the G allele at rs3889348 (SLC29A4) was associated with GI intolerance (OR = 1.34[1.09-1.65], p = 0.005). rs3889348 is the top cis-eQTL for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with metformin transporter inhibiting drugs had over three times higher odds of intolerance compared to carriers of no G allele and not treated with inhibiting drugs (OR = 3.23 [1.71-6.39], p < 0.001). Using a genetic risk score (GRS) derived from SLC29A4 (rs3889348) and previously reported SLC22A1 variants (M420del, R61C, G401S), the odds of intolerance was more than twice in individuals who carry three or more risk alleles compared with those carrying none (OR = 2.15 [1.20-4.12], p = 0.01).

Conclusions

These results suggest that intestinal metformin transporters and concomitant medications play an important role in gastrointestinal side effects of metformin.
DNA damage in telophase leads to coalescence between segregated sister chromatid loci
Authors: Ayra-Plasencia Jessel , Machín Félix
Published: October 2018

The generation of DNA double strand breaks (DSBs) pose a high risk for the maintenance of the genome. Cells repair DSBs through two major mechanisms: non-homologous end joining (NHEJ) and homologous recombination (HR). HR is usually preferred when a sister chromatid is available, thus cells have coupled the activity of the cycling dependent kinase (CDK) to the selection of HR (Symington et al. 2014). Paradoxically, there is a window in the cell cycle where CDK is high despite a sister chromatid is not physically available for HR: late anaphase/telophase. We have here studied in budding yeast the response to DSBs generated in telophase by means of the radiomimetic drug phleomycin. We first show that phleomycin treatment activates the DNA damage response and leads to a delay in the telophase-to-G1 transition. Outstandingly, we also found a partial reversion of sister chromatid segregation, which includes approximation of spindle pole bodies (SPBs) and sister centromeres, de novo formation of anaphase bridges, trafficking of DNA back and forth through the cytokinetic plane and events of coalescence between segregated sister telomeres. We importantly show that phleomycin promotes a massive change in the structure and dynamic of mitotic microtubules (MTs), which coincides with dephosphorylation and re-localization of kinesin-5 Cin8. We propose that anaphase is not entirely irreversible and that there could still be a window to repair DSBs using the sister chromatid after segregation.
Retinal stem cells modulate proliferative parameters to coordinate post-embryonic morphogenesis in the eye of fish
Authors: Tsingos Erika , Höckendorf Burkhard , Sütterlin Thomas , Kirchmaier Stephan , Grabe Niels , Centanin Lázaro , Wittbrodt Joachim
Published: October 2018

A fundamental question in biology is how anatomically and functionally distinct tissues coordinate to direct growth and shape in complex organs. We address this question using as a model the eye of teleost fish, which grow while maintaining the precise shape needed for vision throughout the animal’s life.

Combining clonal analysis in the eye of the teleost medaka (Oryzias latipes) with a computational agent based model, we find that the neural retina (NR) and retinal pigmented epithelium (RPE) differentially modulate cell divisions to coordinate their growth rates. Cell divisions in the NR are less stochastic, consistent with an upstream role as an inducer of growth in nearby tissues. Cells in the RPE display much higher stochasticity, consistent with a downstream role responding to inductive signals.

Our simulation predicts that the segregation of stem- and progenitor cell domains in the retinal ciliary marginal zone niche is an emergent property, as the topology of the niche preconditions the system to undergo a spatially biased stochastic neutral drift. Clone properties in the NR support this prediction, and further suggest that NR cells control the direction of division axes to regulate organ shape and retinal cell topology.

This work highlights an as yet unappreciated mechanism for growth coordination in a complex organ, where one tissue integrates external and internal cues as a hub to synchronize growth rates in nearby tissues. In the eye of fish, proliferation parameters of neuroretinal stem cells are a minimal target node for evolution to exploit to adapt whole-organ morphogenesis in a complex vertebrate organ.
Hide-and-seek in corporate disclosure: evidence from negative corporate incidents
Authors: Rudkin Bradley , Kimani Danson , Ullah Subhan , Ahmed Rizwan , Farooq Syed Umar
Published: October 2018

Purpose

This paper investigates the legitimacy tactics used in the annual reports of UK listed companies in the aftermath of major corporate scandals.

Design/methodology/approach

We carried out a content analysis of annual reports of 19 companies that have been involved in corporate scandals with a view to understand how firms communicate negative scandals affecting them.

Findings

The findings reveal that firms use a wide range of legitimisation strategies in the manner that contribute to shape disclosure communications concerning negative incidents. For instance, some firms may offset the negativity linked to an incident by rendering such explanations amidst positive information.

Originality/value

Contrary to earlier studies conducted on accounting scandals, the authors incorporated extensive corporate scandals such as human rights violations, controversies concerning child labour, environmental scandals, corruption, financial embezzlement and tax evasion.
Facilitating apps recommendation in Google Play
Authors: Wu Fan , Chuang Yung-Ting , Lai Hung-Wei
Published: October 2018

Purpose

The purpose of this paper is to present a system that analyzes trustworthiness and ranks applications to improve the search experience.

Design/methodology/approach

The system adopts pointwise mutual information to calculate comment semantics. It examines subjective (signed opinions, anonymous opinions and star ratings) and objective factors (download numbers, reputation ratings) before filtering, ranking and displaying). The authors invited three experts to check three categories and compared the results using Spearman and two statistics.

Findings

A high correlation between the proposed system and the expert ranking system suggests that the system can act as decision support.

Research limitations/implications

First, the authors have only tested the correlation between the proposed system and an expert ranking system; user satisfaction was not evaluated. The authors plan to conduct a later survey to gather user feedback. Second, the ranking system evaluates applications using fixed weights and disregards time. Therefore, in the future, the authors plan to enable their system to weight recent records over older ones.

Practical implications

User discussion forums, although helpful, have drawbacks. Not all reviews are trustworthy, and forums provide no filtering mechanisms to combat information overload. The solution to this is the authors’ system that crawls a forum, filters information, analyzes the trustworthiness of each comment and ranks the application for the user.

Originality/value

This paper develops a formula to analyze the trustworthiness of opinions, enabling the system to act as decision support when no professional advice is available.
Unlocking the underlying information of golden ratio in the Hogarth curves
Authors: Zhu Xuyun , Luo Yun , Huang Yanlin , Wen Xuming
Published: October 2018

Purpose

Curves with various profiles have been demonstrated to be more attractive and decorative than the straight lines by William Hogarth. Among all kinds of curves, Hogarth proposed seven serpentine lines as the most beautiful curves, i.e., Hogarth curves. Those seven Hogarth curves are subsequently applied in a wide range of fields, e.g., sculpture, painting, architecture and fashion design, indicating their significance to the development of the formal beauty. Recently, the beauty of Hogarth curves has been suspected to be induced by their special-designed curvature, which could have the potential relationship with the Golden Ratio. The purpose of this paper is to explore the relationship between the Hogarth curves and golden ratio by comparing the curvature of curves with the Fibonacci sequence.

Design/methodology/approach

Each of the Hogarth curves was fully restored and divided into two parts according to the turning point of the curvature; the ratios of span, curvature and angles between these two parts were compared with the Fibonacci sequence.

Findings

The experimental results disclosed that the ratio of the fourth Hogarth curve, which was considered as the most beautiful line by Hogarth, was infinitely approaching the golden ratio. Based on the relationship between the fourth Hogarth curve and the golden ratio, the ratios of each curve were employed to define and normalize these curves, providing a quantitative way to redraw the Hogarth curves.

Originality/value

This research work unlocked the information of the relationship between the Hogarth curves and golden ratio, and proposed an effective and convenient mathematic way to quantify the Hogarth curves. The experimental findings disclosed the underlying mechanisms of the beauty of the forth Hogarth curves. Such a fundamental study will promote the establishment of the normalized methods for evaluating the beauty of arts and provide novel ideas for researchers and industrial technologists to use the Hogarth curves.
The impact of interlocking directorates on innovation: the effects of business and social ties
Authors: Hernández-Lara Ana B. , Gonzales-Bustos Juan P.
Published: October 2018

Purpose

Boards of directors of large companies all over the world frequently have a certain number of shared directors, which can be motivated by social structures that foster different types of links, including investments and vertical relationships. The purpose of this paper is to identify the effects that board interlocking exerts on innovation, considering the different nature of shared directors that finally determines the type of links dominating the boards.

Design/methodology/approach

Panel regression analyses were conducted using data collected from 69 Spanish listed innovative sector companies during the period 2010–2014, which provided an unbalanced panel of 325 data observations.

Findings

The results suggested that the typology of interlocks determined their effects on innovation, which had a positive influence when independent and extra-industry directors held multiple directorships, whereas it was negative in the case of intra-industry and women interlocking directors.

Practical implications

This study provided evidence for the diverse effects of interlocking directorates and contributed to the open debate on the best board composition for improving business innovation, considering the common feature of shared directorships.

Originality/value

The value of this research was twofold. On the one hand, the study considered a wide typology of interlocking directorates, such as women, affiliated and independent directors, intra- and extra-industry directorships, as well as shared directors from the same country. On the other hand, the effects of these different interlocking directorate typologies were analysed on innovation by considering different innovation indicators.
Larger plants promote a greater diversity of symbiotic nitrogen‐fixing soil bacteria associated with an Australian endemic legume
Authors: Dinnage Russell , Simonsen Anna K. , Barrett Luke G. , Cardillo Marcel , Raisbeck‐Brown Nat , Thrall Peter H. , Prober Suzanne M.
Published: October 2018

A major goal in microbial ecology is to understand the factors that structure bacterial communities across space and time. For microbes that are plant symbionts, community assembly processes can lead to either a positive or negative relationship between plant size or age and soil microbe diversity. Here, we evaluated the extent to which such relationships exist within a single legume species (Acacia acuminata) and their naturally occurring symbiotic nitrogen‐fixing bacteria (rhizobia).

We quantified the diversity of rhizobia that associate with A. acuminata trees of variable size spanning a large environmental gradient in southwest Australia (72 trees in 24 sites spread across ~300,000 km2), using metabarcoding. We modelled rhizobia diversity using 16S exact genetic variants, in a binomial multivariate statistical framework that controlled for climate and local soil characteristics.

We identified two major phylogenetic clades of rhizobia that associate with A. acuminata. Soil sampled at the base of larger Acacia trees contained a higher richness of rhizobia genetic variants. Each major clade responds differently to environmental factors (climate and soil characteristics), but the positive association between tree size and rhizobia genetic diversity was mainly driven by responses from one of the two clades. Overall tree size explained more variation than any other factor, resulting in a ~3‐fold increase in total richness and clade diversity from the smallest to the largest trees.

Synthesis. Previous studies have shown that plant host species is important in structuring microbial soil communities in the rhizosphere. Our results show that host size or age within a single plant species can also structure diversity of at least one group of soil microbes. A positive relationship between plant host size and rhizobia diversity suggests that hosts may modify the niche space of their surrounding soil (niche construction hypothesis) enabling a higher richness of microbial taxa. That different rhizobial groups responded differently to host size and other ecological factors suggests that rhizobia is not an ecologically uniform group, and that entirely neutral explanations for our results are unlikely. Host plants may be analogous to “islands,” where larger plant hosts may accumulate diversity over time, through migration opportunities.
Maternal L‐carnitine supplementation ameliorates renal underdevelopment and epigenetic changes in male mice offspring due to maternal smoking
Authors: Stangenberg Stefanie , Nguyen Long The , Chan Yik Lung , Zaky Amgad , Pollock Carol A. , Chen Hui , Saad Sonia
Published: October 2018

Objectives

Epidemiological and animal studies showed that L‐carnitine (LC) supplementation can ameliorate oxidative stress‐induced tissues damage. We have previously shown that maternal cigarette smoke exposure (SE) can increase renal oxidative stress in newborn offspring with postnatal kidney underdevelopment and renal dysfunction in adulthood, which were normalised by LC administration in the SE dams during pregnancy. Exposure to an adverse intrauterine environment may lead to alteration in the epigenome, a mechanism by which adverse prenatal conditions increase the susceptibility to chronic disease later in life. The current study aimed to determine whether maternal SE induces epigenetic changes in the offspring's kidney are associated with renal underdevelopment, and the protective effect of maternal LC supplementation.

Method

Female Balb/c mice (7 weeks) were exposed to cigarette smoke (SE) or air (Sham) for 6 weeks prior to mating, during gestation and lactation. A subgroup of the SE dams received LC via drinking water (SE + LC, 1.5 mmol/L) throughout gestation and lactation. Male offspring were studied at postnatal day (P)1, P20, and 13 weeks.

Results

Maternal SE altered the expression of renal development markers glial cell line‐derived neurotrophic factor and fibroblast growth factor 2, which were associated with increased renal global DNA methylation and DNA methyltransferase 1 mRNA expression at birth. These disorders were reversed by maternal LC administration.

Conclusion

The effect of maternal SE on renal underdevelopment involves global epigenetic alterations from birth, which can be prevented by maternal LC supplementation.
Optimal pollution control in a mixed oligopoly with research spillovers
Authors: Haruna Shoji , Goel Rajeev K.
Published: October 2018

We study optimal pollution abatement under a mixed oligopoly when firms engage in emissions‐reducing research and development (R&D) with imperfect appropriation. The regulator uses a tax to curb emissions. Results show that in a mixed oligopoly, the public firm has positive emissions reduction in equilibrium; however, emissions reductions of the private firm could be positive or zero. Under certain conditions, the optimal pollution tax is positive; otherwise, the tax reverts to a subsidy. Comparing mixed and private duopolies, privatisation leads to reductions in R&D and output, but to an increase in overall emissions, so privatisation tends to make the environment worse.
‘All the arts of a radical agitation’: transnational perspectives on British and Irish landowners and estates, 1800–1921*
Authors: Tindley Annie
Published: October 2018

This article examines the perceptions and responses of landed elites towards their evolving territorial, political and social position and interrogates the ways in which these differed across Britain, Ireland and the empire. It considers the utility of a transnational framework in understandings of the landed classes, defining this as a development in which historians seek to take subjects out of national frameworks and into wider settings, to challenge notions of national exceptionalism. It explores its potential to open new directions in the study of landed families and estates during a period of challenge and argues that as a fundamentally transnational class, landed and aristocratic elites must be contextualized beyond the nation.
The Mechanisms of Alpha‐Amylase Inhibition by Flavan‐3‐Ols and the Possible Impacts of Drinking Green Tea on Starch Digestion
Authors: Desseaux Véronique , Stocker Pierre , Brouant Pierre , Ajandouz El Hassan
Published: October 2018

Many studies have shown that flavan‐3‐ols inhibit mammalian alpha‐amylases but the published IC50 and Ki values vary up to a thousand times. We therefore tested the effects of 6 pure flavan‐3‐ols—abundant in green tea—on the activity of pure porcine pancreatic alpha‐amylase (PPA) under steady‐state kinetic conditions. We used both amylose and maltopentaose as substrates, along with spectrophotometry and chromatography as analytical tools, respectively. A Docking approach was also used to probe the interaction between PPA and each flavan‐3‐ol. The results showed that the 6 flavan‐3‐ols inhibit amylose hydrolysis with Ki comprised between 7 and 34 μM, according to a mixed inhibition profile for gallocatechin gallate, and a competitive inhibition profile for the 5 other flavanols. Only the galloyl‐containing flavan‐3‐ols inhibited the maltopentaose hydrolysis with a Ki of about 30 μM according to a noncompetitive profile. We conclude that dietary flavan‐3‐ols could inhibit starch digestion nonnegligibly. The results of the docking trials were concordant with the kinetic data and have noticeably revealed that the cis‐flavan‐3‐ols epigallocatechin gallate and epicatechin gallate bind similarly to PPA, involving π‐stacking with Trp59.
Measurement of Biodiversity (MoB): A method to separate the scale‐dependent effects of species abundance distribution, density, and aggregation on diversity change
Authors: McGlinn Daniel J. , Xiao Xiao , May Felix , Gotelli Nicholas J. , Engel Thore , Blowes Shane A. , Knight Tiffany M. , Purschke Oliver , Chase Jonathan M. , McGill Brian J.
Published: October 2018

Little consensus has emerged regarding how proximate and ultimate drivers such as productivity, disturbance and temperature may affect species richness and other aspects of biodiversity. Part of the confusion is that most studies examine species richness at a single spatial scale and ignore how the underlying components of species richness can vary with spatial scale.

We provide an approach for the measurement of biodiversity that decomposes changes in species rarefaction curves into proximate components attributed to: (a) the species abundance distribution, (b) density of individuals and (c) the spatial arrangement of individuals. We decompose species richness by comparing spatial and nonspatial sample‐ and individual‐based species rarefaction curves that differentially capture the influence of these components to estimate the relative importance of each in driving patterns of species richness change.

We tested the validity of our method on simulated data, and we demonstrate it on empirical data on plant species richness in invaded and uninvaded woodlands. We integrated these methods into a new r package (mobr).

The metrics that mobr provides will allow ecologists to move beyond comparisons of species richness in response to ecological drivers at a single spatial scale toward a dissection of the proximate components that determine species richness across scales.
Bond market integration of emerging economies and bilateral linkages
Authors: Balli Faruk , Hu Xuan , Rana Faisal
Published: October 2018

Although there are numerous studies that have looked at the spillover effects in equity markets, little attention has been paid to explore the integration of bond markets of developed and emerging economies. Our paper is an attempt to fill this void by quantifying the spillovers from developed countries on the bond markets of 25 emerging economies. We apply volatility and return spillover models to quantify the extent of the spillovers from developed markets (i.e. the United States, UK and Japan) into emerging bond markets. We find that the extent of the return spillovers and volatility spillovers has not been symmetric across emerging markets. We explain these differences using bilateral factors such as trade volume, portfolio investment, cultural and geographical factors. The bilateral trade volume turns out to be the leading explanation for the extent of spillovers between our set of countries.
The impacts of multiperil crop insurance on Indonesian rice farmers and production
Authors: Fadhliani Zaura , Luckstead Jeff , Wailes Eric J.
Published: October 2018

This article analyzes the effect of multiperil crop insurance policy for risk‐averse Indonesian rice farmers located in Tuban and Gresik Regencies of the East Java Province. Based on the model, comparative static analysis of a change in policy variables (coverage levels and premium subsidies) on input use through the coupling, wealth, and insurance effects are presented. The comparative static results are largely ambiguous and left as empirical questions. Consequently, the model is numerically simulated to quantify the effects of different coverage levels and subsidy rates on input use, expected net insurance payments, and certainty equivalents. The empirical analysis shows that MPCI crop insurance results in a decline in expected yield for coverage levels above about 82.5% for both regencies. Furthermore, higher subsidy rates amplify the reduction in input use and yield. Therefore, incomplete coverage with relatively low premium subsidies is the best policy to minimize the impact on input use and yield. However, from the farmers’ perspective, the optimal policy combination results from the highest coverage level and subsidy, which offer the largest expected net insurance payments and certainty equivalent.
Land fragmentation, climate change adaptation, and food security in the Gamo Highlands of Ethiopia
Authors: Cholo Tesfaye C. , Fleskens Luuk , Sietz Diana , Peerlings Jack
Published: October 2018

Household food security among smallholder farmers is sensitive to a variable and changing climate, requiring farmers in the Gamo Highlands of Ethiopia to adopt new land management practices to improve food security. Agricultural land in the Gamo Highlands is highly fragmented. The extent to which land fragmentation (LF) moderates the food security effects of sustainable land management (SLM) practices is unknown. This study used probit and Poisson models to explain this relationship. The study found that food insecurity was severe during the food shortfall season. LF provides more potential opportunities for improving food security than challenges. Furthermore, SLM practices had both positive and negative effects on food security and their effects were conditioned by the magnitude of LF. Reducing severe LF through the assembly of small parcels into larger heterogeneous plot clusters could enhance food security by exploiting synergies between adaptation practices and LF.
Geography of plant breeding systems, agroclimatic similarity, and agricultural productivity: evidence from Nigeria
Authors: Takeshima Hiroyuki
Published: October 2018

Agroclimatic conditions and agricultural research and development (R&D) including plant breeding activities by the public sector are some of the most significant exogenous factors in the agricultural sector. However, the effects of the interactions between these two sets of factors on agricultural productivity have not been studied widely in developing countries, despite potentially important implications on their plant breeding strategies. Using three‐wave panel data of agricultural households in Nigeria and spatial data on various agroclimatic parameters, we show that agricultural productivity and technical efficiency at the agricultural household level is significantly positively affected by the similarity of agroclimatic conditions between locations where agricultural households are located, and locations where major plant breeding institutes are located. These results hold after controlling for various socioeconomic characteristics of these households, including their physical distances to the breeding institutes. Findings are robust across parametric and nonparametric specifications such as Data Envelopment Method, and after addressing potential endogeneity of agroclimatic similarity and agricultural inputs variables in the production function. Productivity effects due to the locations of plant breeding institutes and resulting agroclimatic similarity can be potentially sizable given Nigeria's past productivity growth speed.
The role of retail market power and state regulations in the heterogeneity of farm‐retail price transmission of private label and branded products
Authors: Liu Yizao , Chen Xuan , Rabinowitz Adam N.
Published: October 2018

Given the leading role of private label brands in the fluid milk market, it is of special interest to focus on possible differences in farm‐retail price transmission between private label and branded milk as well as the causes of heterogeneity. This article examines the heterogeneous effects of private label and branded products on price transmission in the fluid milk market using a panel threshold asymmetric error correction model. Results indicate that upward retail‐price adjustment is faster than the downward price adjustment for both private label and branded milk. The speed of adjustment of private label products is significantly faster than branded products in three different price regimes. We further investigate the reasons of heterogeneity in farm‐retail price transmission of private label milk. We find that both retailer market power and state pricing regulations contribute to the heterogeneity in asymmetric price transmission. Higher retailer market power causes retail prices of private label milk to rise faster and to fall slower. The existence of a state pricing regulation slows down the adjustment speed of retail prices of private labels back to the long‐run equilibrium, regardless of whether the retail price is low or high.
Hormone receptor positive, HER2 negative metastatic breast cancer: Impact of CDK4/6 inhibitors on the current treatment paradigm
Authors: Boyle Frances , Beith Jane , Burslem Katie , de Boer Richard , Hui Rina , Lim Elgene , McCarthy Nicole , Redfern Andrew , Woodward Natasha
Published: October 2018

Resistance to endocrine therapy is a significant therapeutic challenge in the treatment of women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2–) advanced breast cancer. Cyclin‐dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy have been shown to improve progression free survival, overall response rate and clinical benefit rate in women with HR+ HER2– metastatic breast cancer compared with endocrine therapy alone. This review examines the clinical evidence to support the use of CDK4/6 inhibitors in first and second line settings. Practical guidance is provided for the use of CDK4/6 inhibitors, including tolerability data, monitoring requirements and management of key toxicities for each of the available agents.
“Poor little Queensland”: Resisting Six O’clock Closing in the “Hot‐bed of Disloyalty”, 1915‐1918
Authors: Cryle Mark
Published: October 2018

The First World War precipitated an upsurge in temperance campaigning. Inspired by a dominant discourse of sacrifice and self‐denial, most state legislatures introduced reduced trading hours for hotels. Queensland was the exception. Six o’clock closing was resisted in the northern state despite a vigorous and rancorous campaign for its introduction. This paper maps the contours of the debates around early closing and temperance in Queensland. Like so many other tensions induced by the war, the campaign both generated and was evidence for deep divisions in Queensland society around class, politics and religion.
Settling Scores in New Caledonia and Australia: French Convictism and Settler Legitimacy
Authors: Neilson Briony
Published: October 2018

This article explores the entanglements of Australia and New Caledonia as settler colonies with convict histories. Existing historiography focuses on the importance of the Australian model in inspiring the French to transport convicts to settler colonies, and has explored the moral panic that erupted over the menace of escaped French convicts invading the Australian colonies after the abolition of British convict transportation. My analysis shifts the focus onto the construction of settler colonial authority, analysing the ways in which comparisons drawn by contemporary observers of New Caledonia and Australia served primarily to solidify the legitimacy of settler rule in Australia and increase its regional hegemony into the first few decades of the twentieth century. Drawing on original French and English‐language sources, including the writing of the obscure French convict poet Julien de Sanary, this article makes the case for understanding New Caledonia and its bagne not as unwanted reminders of Australia’s penal origins, but rather as useful sites of projection for settlers in Australia. Constant arguments about the archaic and authoritarian nature of French penal policy and colonialism helped erase the memory of convictism and strengthen settler authority and legitimacy in Australia and internationally. By considering the trans‐imperial entanglements of Australia and New Caledonia, we can further reveal the dynamics of settler colonialism and the processes of disavowal and disassociation that sustain it.
FoxO1 is a critical regulator of M2‐like macrophage activation in allergic asthma
Authors: Chung Sangwoon , Kim Ji Y. , Song Min‐Ae , Park Gye Y. , Lee Yong G. , Karpurapu Manjula , Englert Joshua A. , Ballinger Megan N. , Pabla Navjot , Chung Hae Y. , Christman John W.
Published: October 2018

Background

The pathogenesis of asthma and airway obstruction is the result of an abnormal response to different environmental exposures. The scientific premise of our study was based on the finding that FoxO1 expression is increased in lung macrophages of mice after allergen exposure and human asthmatic patients. Macrophages are capable of switching from one functional phenotype to another, and it is important to understand the mechanisms involved in the transformation of macrophages and how their cellular function affects the peribronchial stromal microenvironment.

Methods

We employed a murine asthma model, in which mice were treated by intranasal insufflation with allergens for 2‐8 weeks. We used both a pharmacologic approach using a highly specific FoxO1 inhibitor and genetic approaches using FoxO1 knockout mice (FoxO1fl/flLysMcre). Cytokine level in biological fluids was measured by ELISA and the expression of encoding molecules by NanoString assay and qRT‐PCR.

Results

We show that the levels of FoxO1 gene are significantly elevated in the airway macrophages of patients with mild asthma in response to subsegmental bronchial allergen challenge. Transcription factor FoxO1 regulates a pro‐asthmatic phenotype of lung macrophages that is involved in the development and progression of chronic allergic airway disease. We have shown that inhibition of FoxO1 induced phenotypic conversion of lung macrophages and downregulates pro‐asthmatic and pro‐fibrotic gene expression by macrophages, which contribute to airway inflammation and airway remodeling in allergic asthma.

Conclusion

Targeting FoxO1 with its downstream regulator IRF4 is a novel therapeutic target for controlling allergic inflammation and potentially reversing fibrotic airway remodeling.
The effect of force applied to the left paratracheal oesophagus on air entry into the gastric antrum during positive‐pressure ventilation using a facemask
Authors: Gautier N. , Danklou J. , Brichant J. F. , Lopez A. M. , Vandepitte C. , Kuroda M. M. , Hadzic A. , Gautier P. E.
Published: October 2018

Cricoid force is widely applied to decrease the risk of pulmonary aspiration and gastric antral insufflation of air during positive‐pressure ventilation, yet its efficacy remains controversial. We compared manual oesophageal compression at the low left paratracheal and cricoid levels for the prevention of gastric antral air insufflation during positive‐pressure ventilation by facemask in patients scheduled for elective surgery under general anaesthesia. After gaining written consent, participants were randomly allocated by sealed envelope to one of three groups: oesophageal compression by 30 N paratracheal force (paratracheal group); oesophageal compression by 30 N cricoid force (cricoid group); or no oesophageal compression (control group). Gastric insufflation of air was assessed before and after positive‐pressure ventilation by ultrasound measurement of the antral cross‐sectional area and/or presence of air artefacts in the antrum. The primary outcome measure was the proportion of participants with ultrasound evidence of gastric insufflation. We recruited 30 patients into each group. Before facemask ventilation, no air artefacts were visible in the antrum in any of the participants. After facemask ventilation of the participant's lungs, no air artefacts were seen in the paratracheal group, compared with six subjects in the cricoid group and eight subjects in the control group (p = 0.012). Our results suggest that oesophageal compression can be achieved by the application of manual force at the low left paratracheal level and that this is more effective than cricoid force in preventing air entry into the gastric antrum during positive‐pressure ventilation by facemask.
Paradox of meritocracy in surgical selection, and of variation in the attractiveness of individual specialties: to what extent are women still disadvantaged?
Authors: Beasley Spencer W. , Khor Sue‐Lynne , Boakes Cassandra , Jenkins Deborah
Published: October 2018

Background

Evidence from outside surgery suggests that meritocracy‐based processes around selection tend to reduce, rather than increase, diversity. In recent years, the surgical training boards have gone to considerable effort to achieve greater transparency and fairness in their selection processes, and to identify those attributes that are believed to best predict future success as a surgeon. This is consistent with the Royal Australasian College of Surgeons Diversity and Inclusion Plan, which places emphasis on gender equity and has goals that include increasing the attractiveness of surgery as a vocation for women, removing impediments to them applying to the surgical training programmes and removing any biases that might disadvantage them during the selection process.

Methods

This study uses the Female Opportunity Index and rate ratio metrics to measure the level of female disadvantage in surgical selection, whether it be by the perception of its attractiveness to women which influences their application rates, or by the likelihood of successful selection for those who have applied, compared with their male counterparts.

Results

There are marked differences between the nine surgical specialties and 13 specialty training boards in both the proportion of women who apply, and the proportion who are successful in gaining entry onto the Surgical Education and Training programmes. The Female Opportunity Index ranged from 0.21 to 0.87, which represents a wide variation between surgical specialties.

Conclusion

These data raise the question as to whether unconscious bias is occurring in an apparently meritocracy‐based selection process in some specialties. The data also suggest that some specialties are relatively unattractive to women, for which the reasons are likely to be complex.
Blood draws up to 3% of blood volume in clinical trials are safe in children
Authors: Peplow Claudia , Assfalg Robin , Beyerlein Andreas , Hasford Joerg , Bonifacio Ezio , Ziegler Anette‐G
Published: October 2018

Aim

Recommendations for maximum blood draw in children range from 1 to 5% despite limited evidence. The aim of the study was to assess the safety of blood draws in children aged six months to 12 years targeting volumes of 3% of total blood volume.

Methods

Children who experienced three‐monthly blood draws during participation in one of three investigators initiated clinical trials conducted in our institution were examined. In total, 629 venous blood draws were performed in 141 children. Adverse events and blood counts were assessed.

Results

Overall, 608 adverse events were reported. None of these included symptoms that reflected concerns on blood draw volumes or frequency. Anaemia and red cell or haemoglobin measurements outside the normal age range were not observed. A reduction in haemoglobin, haematocrit, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and mean corpuscular volume was noted in children participating in one of the three trials analysed.

Conclusion

Regular blood draws of up to 3% of total blood volume were not associated with signs of anaemia or hypovolaemia in young children. We suggest that the European recommendations be revised for clinical studies in which children are not exposed to treatments that are associated with anaemia risk.
Facing Multiple Barriers to Exercise: Does Stronger Efficacy Help Individuals with Arthritis?
Authors: Sessford James D. , Brawley Lawrence R. , Cary Miranda A. , Flora Parminder K. , Blouin Jocelyn E. , Strachan Shaelyn M. , Gyurcsik Nancy C.
Published: October 2018

Background

Research about exercise adherence amongst adults with arthritis has been largely correlational, and theoretically based causal studies are needed. We used an experimental design to test the social cognitive theory premise that high self‐efficacy helps to overcome challenging barriers to action.

Methods

Exercising individuals (N = 86; female = 78%; M age = 53; BMI = 27) with differential self‐regulatory efficacy for managing salient, non‐disease barriers were randomly assigned to many or few barrier conditions. Individuals responded about the strength of their anticipated persistence to continue exercise, and their self‐regulatory efficacy to use exercise‐enabling coping strategies.

Results

In the many barriers condition, higher barriers‐efficacy individuals expressed (a) greater persistence (Cohen's d = 0.75 [−0.029, 1.79]) and (b) more confidence in their coping solutions (Cohen's d = 0.65 [−0.30, 1.60]) than lower barriers‐efficacy counterparts.

Conclusion

Experimental support was obtained for the theoretical premise that when facing the greatest barrier challenge, individuals highest in self‐regulatory efficacy still view exercise as possible. Findings suggest that identifying lower efficacy exercisers with arthritis to tailor their exercise to increase self‐regulatory efficacy might also improve their adherence.
Editorial: less acid, less cancer? Is this the question?
Authors: Triadafilopoulos George , Singh Gurkirpal
Published: October 2018

Linked Content

This article is linked to Tan et al Tan and Thrift papers. To view these articles visit https://doi.org/10.1111/apt.14895 and https://doi.org/10.1111/apt.14971.
Predictors of advanced fibrosis in non‐cirrhotic non‐alcoholic fatty liver disease in Germany
Authors: Labenz Christian , Huber Yvonne , Kalliga Eva , Nagel Michael , Ruckes Christian , Straub Beate K. , Galle Peter R. , Wörns Marcus‐Alexander , Anstee Quentin M. , Schuppan Detlef , Schattenberg Jörn M.
Published: October 2018

Background

Advanced fibrosis has been established as the most important predictor of overall mortality in patients with non‐alcoholic fatty liver disease (NAFLD). In contrast to cirrhosis, advanced, non‐cirrhotic NAFLD is difficult to identify and data from Germany are lacking.

Aim

To identify clinical factors associated with advanced, non‐cirrhotic fibrosis.

Methods

Patients were recruited in the prospectively enrolling European NAFLD Registry. Clinical characteristics and the performance of non‐invasive surrogate scores compared with vibration‐controlled transient elastography are reported.

Results

Two hundred and sixty‐one patients with non‐cirrhotic NAFLD on liver biopsy (mean age 51 years, equal sex distribution) were included. The prevalence of stage 3 fibrosis on liver biopsy was 15.7%. These patients were significantly older (57 vs 50 years, P < 0.01), had a higher body mass index (32.3 vs 30.5, P < 0.05), and more frequent arterial hypertension (78% vs 50%, P = 0.001) and type 2 diabetes (61% vs 24.1%, P < 0.001). On multivariate logistic regression, diabetes (OR = 4.68, 95% CI 2.17‐10.10) and hypertension (OR = 2.91, 95% CI 1.12‐7.18) were independent predictors of advanced fibrosis. Comedication included metformin in 50% and insulin in 33% of patients with diabetes. Despite the presence of cardiovascular risk factors, the use of statins was low. Liver stiffness measurement identified advanced fibrosis with an AUROC of 0.81 (95% CI 0.72‐0.91). The performance of NAFLD fibrosis score, Fibrosis‐4, and AST to platelet ratio index were lower with AUCs of 0.74, 0.71, and 0.67, respectively.

Conclusions

The prevalence of metabolic comorbidities in a German population with non‐cirrhotic biopsy‐proven NAFLD is high. While the examined scores exhibit an acceptable specificity, liver stiffness measurement appeared to be superior to blood‐based non‐invasive surrogate scores in ruling out advanced fibrosis.
Review article: novel antivirals for hepatitis C—sofosbuvir/velpatasvir/voxilaprevir, glecaprevir/pibrentasvir
Authors: Pearlman Brian L. , Hinds Andrew E.
Published: October 2018

Background

In 2017, the hepatitis C treatment regimens sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) and glecaprevir/pibrentasvir (G/P) received approval from the U.S. Food and Drug Administration. Although both SOF/VEL/VOX (NS5B polymerase inhibitor/NS5A inhibitor/NS3/4A protease inhibitor) and G/P (NS3/4A protease inhibitor/NS5A inhibitor) are pangenotypic regimens, they are indicated for distinct subsets of patients with hepatitis C.

Aim

To compare and contrast available safety and efficacy data for SOF/VEL/VOX and G/P and outline their clinical utility.

Methods

For each of the regimens, this review outlines the indications, safety information, and the major clinical studies in which SOF/VEL/VOX and G/P were evaluated.

Results

SOF/VEL/VOX is positioned as a salvage regimen for patients previously treated with NS5A inhibitors and for genotype 1a‐ and 3‐infected patients who had failed other sofosbuvir‐containing regimens. G/P is the first pangenotypic regimen with an 8‐week duration for treatment‐naïve, non‐cirrhotic patients, and it is indicated for patients with any genotype who have advanced kidney disease, including those on dialysis.

Conclusion

The addition of SOF/VEL/VOX and G/P to existing hepatitis C treatment options will expand the number of patients who are eligible for and responsive to treatment, thus increasing the possibility of eliminating hepatitis C as a public health issue.