bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Root-Knot Nematode Resistance QTL on Chromosome Vu01 in Cowpea
Authors: Ndeve Arsenio D. , Santos Jansen R. P. , Matthews William. C. , Huynh Bao L. , Guo Yi-Ning , Lo Sassoum , Muñoz-Amatriaín Maria , Roberts Philip A.
Published: November 2018

The root-knot nematode (RKN) speciesMeloidogyne incognitaandM. javanicacause substantial root system damage and suppress yield of susceptible cowpea cultivars. The narrow-based genetic resistance conferred by theRkgene, present in some commercial cultivars, is not effective againstRk-virulent populations found in several cowpea production areas. The dynamics of virulence within RKN populations require a broadening of the genetic base of resistance in elite cowpea cultivars. As part of this goal, F1and F2populations from the cross CB46-Null (susceptible) x FN-2-9-04 (resistant) were phenotyped forM. javanicainduced root-galling (RG) and egg-mass production (EM) in controlled growth chamber and greenhouse infection assays. In addition, F2:3families of the same cross were phenotyped for RG on field sites infested withRk-avirulentM. incognitaandM. javanica. The response of F1to RG and EM indicated that resistance to RKN in FN-2-9-04 is partially dominant, as supported by the degree of dominance in the F2and F2:3populations. Two QTLs associated with both RG and EM resistance were detected on chromosomes Vu01 and Vu04. The QTL on Vu01 was most effective against aggressiveM. javanica, whereas both QTLs were effective against avirulentM. incognita. Allelism tests with CB46 x FN-2-9-04 progeny indicated that these parents share the same RKN resistance locus on Vu04, but the strong, broad-based resistance in FN-2-9-04 is conferred by the additive effect of the novel resistance QTL on Vu01. This novel resistance in FN-2-9-04 is an important resource for broadening RKN resistance in elite cowpea cultivars.
Biobank-wide association scan identifies risk factors for late-onset Alzheimer’s disease and endophenotypes
Authors: Yan Donghui , Hu Bowen , Darst Burcu F. , Mukherjee Shubhabrata , Kunkle Brian W. , Deming Yuetiva , Dumitrescu Logan , Wang Yunling , Naj Adam , Kuzma Amanda , Zhao Yi , Kang Hyunseung , Johnson Sterling C. , Cruchaga Carlos , Hohman Timothy J. , Crane Paul K. , Engelman Corinne D. ,   Alzheimer’s Disease Genetics Consortium (ADGC), Lu Qiongshi
Published: November 2018

Rich data from large biobanks, coupled with increasingly accessible association statistics from genome-wide association studies (GWAS), provide great opportunities to dissect the complex relationships among human traits and diseases. We introduce BADGERS, a powerful method to perform polygenic score-based biobank-wide association scans. Compared to traditional approaches, BADGERS uses GWAS summary statistics as input and does not require multiple traits to be measured in the same cohort. We applied BADGERS to two independent datasets for late-onset Alzheimer’s disease (AD; N=61,212). Among 1,738 traits in the UK biobank, we identified 48 significant associations for AD. Family history, high cholesterol, and numerous traits related to intelligence and education showed strong and independent associations with AD. Further, we identified 41 significant associations for a variety of AD endophenotypes. While family history and high cholesterol were strongly associated with AD subgroups and pathologies, only intelligence and education-related traits predicted pre-clinical cognitive phenotypes. These results provide novel insights into the distinct biological processes underlying various risk factors for AD.
Measuring hospital spatial wingspan by using a discrete choice model with utility-threshold
Authors: Issa Saley , Mathieu Ribatet , Nicolas Molinari
Published: November 2018

Policy makers increasingly rely on hospital competition to incentivize patients to choose high-value care. Travel distance is one of the most important drivers of patients’ decision. The paper presents a method to numerically measure, for a given hospital, the distance beyond which no patient is expected to choose the hospital for treatment by using a new approach in discrete choice models. To illustrate, we compared 3 hospitals attractiveness related to this distance for asthma patients admissions in 2009 in Hérault (France), showing, as expected, CHU Montpellier is the one with the most important spatial wingspan. For estimation, Monte Carlo Markov Chain (MCMC) methods are used.
TAK-071, a muscarinic M1 receptor positive allosteric modulator, attenuates scopolamine-induced quantitative electroencephalogram power spectral changes in cynomolgus monkeys
Authors: Kurimoto Emi , Nakashima Masato , Kimura Haruhide , Suzuki Motohisa
Published: November 2018

Activation of the muscarinic M1 receptor is a promising approach to improve cognitive deficits associated with cholinergic dysfunction in Alzheimer’s disease, dementia with Lewy bodies, and schizophrenia. TAK-071 is an M1-selective positive allosteric modulator that improves cognitive deficits induced by scopolamine, a non-selective muscarinic receptor antagonist, with reduced side effects on gastrointestinal function in rats. In this study, we explored changes in quantitative electroencephalography (qEEG) power bands, with or without scopolamine challenge, as a non-invasive translational biomarker for the effect of TAK-071 in cynomolgus monkeys. Scopolamine has been reported to increase theta and delta power bands and decrease alpha power band in healthy volunteers. In line with the clinical observations, scopolamine (25–100 µg/kg, subcutaneous administration [s.c.]) increased theta and delta power bands in cynomolgus monkeys in a dose-dependent manner, whereas it had the opposite effect on alpha power band. The effects of TAK-071 on scopolamine (25 µg/kg, s.c.)-induced qEEG spectral changes were examined using an acetylcholinesterase inhibitor donepezil and a muscarinic M1/M4 receptor agonist xanomeline as comparative cholinomimetics. TAK-071 (0.3–3 mg/kg, oral administration [p.o.]), donepezil (3 mg/kg, p.o.), and xanomeline (1 mg/kg, s.c.) suppressed the scopolamine-induced increases in alpha, theta, and delta power bands. These results suggest that changes in specific qEEG power bands, in particular theta and delta power bands in the context of scopolamine challenge, could be used as translational biomarkers for the evaluation of TAK-071 in clinical studies.
Triple layered QSAR Studies on Substituted 1,2,4-Trioxanes as potential antimalarial agents: Superiority of the Quantitative Pharmacophore-Based Alignment, Over Common Substructure based Alignment
Authors: Gupta Amit K. , Saxena Anil K.
Published: November 2018

The present study reports the utilization of three approaches viz Pharmacophore, CoMFA, CoMSIA and HQSAR studies to identify the essential structural requirements in 3D chemical space for the modulation of the antimalarial activity of substituted 1,2,4 trioxanes. The superiority of Quantitative pharmacophore based alignment (QuantitativePBA) over global minima energy conformer-based alignment (GMCBA) has been reported in CoMFA and CoMSIA studies. The developed models showed good statistical significance in internal validation (q2, group cross-validation and bootstrapping) and performed very well in predicting antimalarial activity of test set compounds. Structural features in terms of their steric, electrostatic, and hydrophobic interactions in 3D space have been found important for the antimalarial activity of substituted 1,2,4-trioxanes. Further, the HQSAR studies based on the same training and test set acted as an additional tool to find the sub-structural fingerprints of substituted 1,2,4 trioxanes for their antimalarial activity. Together, these studies may facilitate the design and discovery of new substituted 1,2,4-trioxane with potent antimalarial activity.
A bump in the road: speed bumps’ impact on property values
Authors: Graham John Edward , Jones Adam Talbot
Published: November 2018

Purpose

Speed bumps invite varied responses from homeowners, drivers and policymakers. Parents of small children like speed bumps, if they slow the passing traffic, but prospective home buyers may reject a home with a speed bump nearby, contemplating the traversal of it thousand times during an ownership period. The purpose of this study is to empirically identify the effect of speed bumps on home values.

Design/methodology/approach

Analysis presented here is based on an examination of home sales prices and exploits variation in the number of speed bumps traversed and the installation of speed bumps to identify the effect of speed bumps on home values. An anonymous online survey is also used to shed light on drivers of the empirical results.

Findings

Initial results exploiting variation in the number of bumps traversed suggest speed bumps are associated with reduced residential property values. An estimated treatment effect of speed bump installation underscores the original findings. Finally, survey results imply that older homeowners and homeowners with children may favor speed bumps but less than the disfavor of those who do not.

Research limitations/implications

The research presented here applies to speed bumps in residential areas and on streets not considered through streets.

Practical implications

The findings suggest that planners should investigate options such as medians and roundabouts instead of speed bumps.

Social implications

These results suggest that communities can be visually improved and home values lifted through the removal of speed bumps and installation of other traffic control devices.

Originality/value

This research is valuable to residential developers, planners and neighborhood associations across the country.
Seeing through touch: a conceptual framework of visual-tactile interplay
Authors: Eklund Andreas Aldogan , Helmefalk Miralem
Published: November 2018

Purpose

The purpose of this paper is to develop a comprehensive conceptual framework of visual-tactile interplay and consumer responses in brand, product and servicescape contexts.

Design/methodology/approach

This paper performs a literature review of visual-tactile interplay by reviewing prior research in marketing and psychology.

Findings

The review reveals that visual-tactile interplay provokes various consumer responses depending on whether brands, products or servicescapes are used. The paper develops a comprehensive conceptual framework mapping out visual-tactile interplay and the relationship with consumers’ cognition, emotions and behaviors.

Research limitations/implications

A conceptual model was developed with a novel view on how visual and tactile cues can together influence consumer responses.

Practical implications

This paper shows how visual-tactile interplay is successful in brand, product and servicescape contexts and provides practical insight for firms into how to provoke consumers’ cognitive, emotional and behavioral responses.

Originality/value

This paper contributes to existing literature by developing a conceptual framework and model of visual-tactile interplay and consumer responses by drawing on research in marketing and psychology.
Risk aversion decomposition and the impact of monetary policy surprises on aggregate tail risk aversion
Authors: Chen Denghui
Published: November 2018

Purpose

The purpose of this paper is to present theoretical and empirical support that the fear component associated with rare events has an impact on risk premium and market returns.

Design/methodology/approach

Extension of jump-diffusion model to extract the fear component from representative agent risk aversion, Standard VAR and impulse response function analysis, Event study analysis.

Findings

The model implicates that investor fear of tail jumps in the financial market impacts equity risk premium. The empirical findings show both positive stock and monetary policy shocks decrease investor’s fear. It can be attributed to that a bullish stock market and an increase in interest rate reflects expanding economy, and it leads to a decrease in fear. Moreover, a surprise decline in the expected short-term rate has a mixed impact on tail risk aversion. A plausible explanation is that investors believe a surprise drop in an expected short-term rate reflects a fast deteriorating economic outlook during unconventional monetary policy period.

Originality/value

This paper provides theoretical framework to decompose risk aversion into two separate components: one component associated with daily volatility, and the fear component associated with rare events. The study uses risk premiums decomposed from Chicago Board Options Exchange volatility index as proxies for the two components of risk aversion, and then utilizes standard value at risk and event study analysis to show the fear component plays a role in risk premium and market return.
Context-aware restricted Boltzmann machine meets collaborative filtering
Authors: Zhang Jingshuai , Ouyang Yuanxin , Xie Weizhu , Rong Wenge , Xiong Zhang
Published: November 2018

Purpose

The purpose of this paper is to propose an approach to incorporate contextual information into collaborative filtering (CF) based on the restricted Boltzmann machine (RBM) and deep belief networks (DBNs). Traditionally, neither the RBM nor its derivative model has been applied to modeling contextual information. In this work, the authors analyze the RBM and explore how to utilize a user’s occupation information to enhance recommendation accuracy.

Design/methodology/approach

The proposed approach is based on the RBM. The authors employ user occupation information as a context to design a context-aware RBM and stack the context-aware RBM to construct DBNs for recommendations.

Findings

The experiments on the MovieLens data sets show that the user occupation-aware RBM outperforms other CF models, and combinations of different context-aware models by mutual information can obtain better accuracy. Moreover, the context-aware DBNs model is superior to baseline methods, indicating that deep networks have more qualifications for extracting preference features.

Originality/value

To improve recommendation accuracy through modeling contextual information, the authors propose context-aware CF approaches based on the RBM. Additionally, the authors attempt to introduce hybrid weights based on information entropy to combine context-aware models. Furthermore, the authors stack the RBM to construct a context-aware multilayer network model. The results of the experiments not only convey that the context-aware RBM has potential in terms of contextual information but also demonstrate that the combination method, the hybrid recommendation and the multilayer neural network extension have significant benefits for the recommendation quality.
The USA as a victim of international/transnational terrorism targeting what it is or what it does?
Authors: Zahra Heba
Published: November 2018

Purpose

The USA has been suffering from international/transnational terrorism for decades. There is no consensus on whether this situation is a result of the international status of the USA and the principles it upholds or the policies it embraces in its interaction with the outside world.

Design/methodology/approach

This study adopts both the “American Primacy” theory and the “anti-Americanism” theory in its effort to reach a conclusion concerning this issue. This study aims to examine previous research that linked international terrorism to the US hegemony and the principles it abides by and showed the relevance of this perception to the “American Primacy” theory. It also examines the research that considered international/transnational terrorism as a result of the American foreign policy in its various aspects (economic, military, assistance or a whole combination of policies).

Findings

This literature on the American foreign policy and international/transnational terrorism was extensive and manifested the explanatory power of the “anti-Americanism” theory, especially in its three variants: issue-oriented, ideological and instrumental. While examining the foreign policy terrorism studies, the relevance of the “American Primacy” theory appeared at very few instances.

Originality/value

The study was able to prove that explaining the international/transnational terrorism is related to the foreign policy decisions taken by the American policymakers and cause harm to the outside world. The envy of “American Primacy” is of secondary importance.
Financial Stress and Indigenous Australians
Authors: Breunig Robert , Hasan Syed , Hunter Boyd
Published: November 2018

We examine the high levels of financial stress among Indigenous populations in Australia. We estimate separate models for the determinants of financial stress for Indigenous and non‐Indigenous households and show the importance of separately considering Indigenous disadvantage. We use these models to build equivalence scales for both groups. We find evidence consistent with financial stress being exacerbated by demand sharing (‘humbugging’). The evidence also suggests that financial stress is reduced by engagement in traditional hunting and gathering activities.
El Niño‐Southern Oscillation, rainfall variability and sustainable agricultural development in the Ho Municipality, Ghana
Authors: Owusu Kwadwo , Darkey Selorm K. , Boadi Sylvester A.
Published: November 2018

El Niño‐Southern Oscillation (ENSO), which occurs in the Equatorial Pacific Ocean, has been identified to have significant influence on rainfall variability throughout the world, especially in the tropics. Such variability in rainfall has implications for agrarian economies, such as that in Ghana. This study therefore sought to demonstrate the effect of ENSO‐induced variability in annual and seasonal rainfall on the development of sustainable agriculture in the Ho Municipality of Ghana. Using 61 years of monthly rainfall data (1955–2015) for the Ho Municipality and ENSO indices, this study showed that 15% of the variability in total annual rainfall is explained by the ENSO phenomena. Mean annual rainfall and rainfall in the major rainy season decreased for El Niño years, in addition to a more variable rainfall compared to that received in La Niña years. The major growing season was observed to be longer in La Niña years and shorter in El Niño years. This means that the potential for crop cultivation will be severely hampered in an El Niño year. Farmers within the municipality are therefore encouraged to harness other complementary water sources for farming activities and also employ water management strategies during El Niño years.
Spillovers from entry: the impact of bank branch network expansion
Authors: Kuehn Joseph
Published: November 2018

I study why local banking markets became dominated by multimarket firms following deregulation in the 1990s. I estimate a model of branch entry that allows for spillovers across markets. The spillovers complicate estimation, and so I develop a revealed preference approach that also deals with unobserved firm and market heterogeneity. I then analyze the impact of multimarket banks and find that they increase local competition, but that they also open more branches than single‐market firms, and subsequently offer lower deposit rates. Ultimately, their welfare impact differs across markets based on the availability of outside alternatives and consumer sensitivity to rates.
Massive release of the histamine‐degrading enzyme diamine oxidase during severe anaphylaxis in mastocytosis patients
Authors: Boehm Thomas , Reiter Birgit , Ristl Robin , Petroczi Karin , Sperr Wolfgang , Stimpfl Thomas , Valent Peter , Jilma Bernd
Published: November 2018

Background

Histaminolytic activity mediated by diamine oxidase (DAO) is present in plasma after induction of severe anaphylaxis in rats, guinea pigs, and rabbits. Heparin released during mast cell degranulation in the gastrointestinal tract might liberate DAO from heparin‐sensitive storage sites. DAO release during anaphylaxis has not been demonstrated in humans.

Methods

Plasma DAO, tryptase, and histamine concentrations of four severe anaphylaxis events were determined at multiple serial time points in two patients with systemic mastocytosis. The histamine degradation rates were measured in anaphylaxis samples and in pregnancy sera and plasma with comparable DAO concentrations.

Results

Mean DAO (132 ng/mL) and tryptase (304 ng/mL) concentrations increased 187‐ and 4.0‐fold, respectively, over baseline values (DAO 0.7 ng/mL, tryptase 76 ng/mL) during severe anaphylaxis. Under non‐anaphylaxis conditions, DAO concentrations were not elevated in 29 mastocytosis patients compared to healthy volunteers and there was no correlation between DAO and tryptase levels in mastocytosis patients. The histamine degradation rate of DAO in plasma from mastocytosis patients during anaphylaxis is severely compromised compared to DAO from pregnancy samples.

Conclusion

During severe anaphylaxis in mastocytosis patients, DAO is likely released from heparin‐sensitive gastrointestinal storage sites. The measured concentrations can degrade histamine, but DAO activity is compromised compared to pregnancy samples. For accurate histamine measurements during anaphylaxis, DAO inhibition is essential to inhibit further histamine degradation after blood withdrawal. Determination of DAO antigen levels might be of clinical value to improve the diagnosis of mast cell activation.
Impact of knowledge, attitude and preceptor behaviour in pharmacovigilance education
Authors: Yu Yun Mi , Kim Seungyeon , Choi Kyung Hee , Jeong Kyeong Hye , Lee Euni
Published: November 2018

This study aimed to determine the level of pharmacovigilance (PV) education in pharmacy programmes and to evaluate the predictive factors for the intent to report adverse drug reactions (ADRs) by pharmacy students in South Korea. Self‐administered questionnaires were collected from a regionally stratified nationwide convenience sample of pharmacy students in September 2017. The association between students' intent to report ADRs and their knowledge and attitude was evaluated by using multivariate logistic regression analysis. In total, 303 pharmacy students participated in the survey; the average age of students was 26.7 (standard deviation 2.9) years and 40.6% were males. Eighty‐eight students (29%) marked the degree of their intent as “strongly high.” Increased knowledge of ADR reporting methods and positive attitude towards the need for ADR reporting were significant predictors of the intent to report ADRs. Further, witnessing reporting by the preceptor (adjusted odds ratio, 2.37; 95% confidence interval, 1.26‐4.46; P < 0.01) was significantly correlated with the knowledge on and attitude towards ADR reporting of pharmacy students. The findings of our study indicated the need for improvements in PV curriculum, such as educational content focused on ADR reporting methods and demonstration of a preceptor's reporting in pharmacy practice experiential rotation, within Korean college of pharmacy curriculum.
Impact of abusive supervision on deviant work behavior: The role of Islamic work ethic
Authors: Javed Basharat , Fatima Tasneem , Yasin Raja Mehtab , Jahanzeb Sadia , Rawwas Muhammad Y. A.
Published: November 2018

In this article, we examined the relationship between abusive supervision and deviant workplace behavior and the moderating role of an Islamic Work Ethic. Three hundred and thirty‐six employees in different organizations (specializing in software development, medicine, law enforcement, telecommunication, pharmaceutics, and banking) across Pakistan completed our questionnaire. The results revealed that abusive supervision was positively related to deviant workplace behavior. Moreover, the moderation of an Islamic Work Ethic on the relationship between abusive supervision and deviant work behavior was confirmed. The study contributed in many ways. It expanded literature by revealing a weaker relationship between abusive supervision and deviant behavior when Islamic Work Ethic (IWE) was high. It also tested the conservation of resources theory by providing a plausible reasoning of the role of IWE in employee motivation. By integrating IWE as a resource in the workplace, practitioners would learn that the proper use of resources would produce satisfied workers who would not indulge in deviant workplace behaviors.
Alternative RNA splicing of the GIT1 gene is associated with neuroendocrine prostate cancer
Authors: Lee Ahn R. , Gan Yu , Xie Ning , Ramnarine Varune R. , Lovnicki Jessica M. , Dong Xuesen
Published: November 2018

Potent androgen receptor pathway inhibition (ARPI) therapies have given rise to a lethal, aggressive subtype of castration‐resistant prostate cancer (CRPC) called treatment‐induced neuroendocrine prostate cancer (t‐NEPC). Now, t‐NEPC poses a major clinical problem as approximately 20% of CRPC cases bear this subtype—a rate of occurrence that is predicted to rise with the widespread use of ARPI therapies. Unfortunately, there are no targeted therapies currently available to treat t‐NEPC as the origin and molecular underpinnings of t‐NEPC development remain unclear. In the present study, we identify that RNA splicing of the G protein‐coupled receptor kinase‐interacting protein 1 (GIT1) gene is a unique event in t‐NEPC patients. Specifically, upregulation of the GIT1‐A splice variant and downregulation of the GIT1‐C variant expressions are associated with t‐NEPC patient tumors, patient‐derived xenografts, and cell models. RNA‐binding assays show that RNA splicing of GIT1 is directly driven by SRRM4 and is associated with the neuroendocrine phenotype in CRPC cohorts. We show that GIT1‐A and GIT1‐C regulate differential transcriptomes in prostate cancer cells, where GIT1‐A regulates genes associated with morphogenesis, neural function, environmental sensing via cell‐adhesion processes, and epigenetic regulation. Consistent with our transcriptomic analyses, we report opposing functions of GIT1‐A and GIT1‐C in the stability of focal adhesions, whereby GIT1‐A promotes focal adhesion stability. In summary, our study is the first to report that alternative RNA splicing of the GIT1 gene is associated with t‐NEPC and reprograms its function involving FA‐mediated signaling and cell processes, which may contribute to t‐NEPC development.
Establishment and characterization of CRISPR/Cas9‐mediated NF2−/− human mesothelial cell line: Molecular insight into fibroblast growth factor receptor 2 in malignant pleural mesothelioma
Authors: Wahiduzzaman Md , Karnan Sivasundaram , Ota Akinobu , Hanamura Ichiro , Murakami Hideki , Inoko Akihito , Rahman Md Lutfur , Hyodo Toshinori , Konishi Hiroyuki , Tsuzuki Shinobu , Hosokawa Yoshitaka
Published: November 2018

Malignant pleural mesothelioma (MPM), a highly refractory tumor, is currently incurable due to the lack of an early diagnosis method and medication, both of which are urgently needed to improve the survival and/or quality of life of patients. NF2 is a tumor suppressor gene and is frequently mutated in MPM. Using a CRISPR/Cas9 system, we generated an NF2‐knockout human mesothelial cell line, MeT‐5A (NF2‐KO). In NF2‐KO cell clones, cell growth, clonogenic activity, migration activity, and invasion activity significantly increased compared with those in NF2‐WT cell clones. Complementary DNA microarray analysis clearly revealed the differences in global gene expression profile between NF2‐WT and NF2‐KO cell clones. Quantitative PCR analysis and western blot analysis showed that the upregulation of fibroblast growth factor receptor 2 (FGFR2) was concomitant with the increases in phosphorylation levels of JNK, c‐Jun, and retinoblastoma (Rb) in NF2‐KO cell clones. These increases were all abrogated by the exogenous expression of NF2 in the NF2‐KO clone. In addition, the disruption of FGFR2 in the NF2‐KO cell clone suppressed cell proliferation as well as the phosphorylation levels of JNK, c‐Jun, and Rb. Notably, FGFR2 was found to be highly expressed in NF2‐negative human mesothelioma tissues (11/12 cases, 91.7%) but less expressed in NF2‐positive tissues. Collectively, these findings suggest that NF2 deficiency might play a role in the tumorigenesis of human mesothelium through mediating FGFR2 expression; FGFR2 would be a candidate molecule to develop therapeutic and diagnostic strategies for targeting MPM with NF2 loss.
Single fraction carbon ion radiotherapy for colorectal cancer liver metastasis: A dose escalation study
Authors: Makishima Hirokazu , Yasuda Shigeo , Isozaki Yuka , Kasuya Goro , Okada Naomi , Miyazaki Masaru , Mohamad Osama , Matsufuji Naruhiro , Yamada Shigeru , Tsuji Hiroshi , Kamada Tadashi ,   the Liver Cancer Working Group
Published: November 2018

Prognosis is usually grim for those with liver metastasis from colorectal cancer (CRC) who cannot receive resection. Radiation therapy can be an option for those unsuitable for resection, with carbon ion radiotherapy (CIRT) being more effective and less toxic than X‐ray due to its physio‐biological characteristics. The objective of this study is to identify the optimal dose of single fraction CIRT for colorectal cancer liver metastasis. Thirty‐one patients with liver metastasis from CRC were enrolled in the present study. Twenty‐nine patients received a single‐fraction CIRT, escalating the dose from 36 Gy (RBE) in 5% to 10% increments until unacceptable incidence of dose‐limiting toxicity was observed. Dose‐limiting toxicity was defined as grade ≥3 acute toxicity attributed to radiotherapy. The prescribed doses were as follows: 36 Gy (RBE) (3 cases), 40 Gy (2 cases), 44 Gy (4 cases), 46 Gy (6 cases), 48 Gy (3 cases), 53 Gy (8 cases) and 58 Gy (3 cases). Dose‐limiting toxicity was not observed, but late grade 3 liver toxicity due to biliary obstruction was observed in 2 patients at 53 Gy (RBE). Both cases had lesions close to the hepatic portal region, and, therefore, the dose was escalated to 58 Gy (RBE), limited to peripheral lesions. The 3‐year actuarial overall survival rate of all 29 patients was 78%, and the median survival time was 65 months. Local control improved significantly at ≥53 Gy (RBE), with a 3‐year actuarial local control rate of 82%, compared to 28% in lower doses. Treatment for CRC liver metastasis with single‐fraction CIRT appeared to be safe up to 58 Gy (RBE) as long as the central hepatic portal region was avoided.
Social Networks of Children With Developmental Language Disorder in Inclusive Preschool Programs
Authors: Chen Jing , Justice Laura M. , Rhoad‐Drogalis Anna , Lin Tzu‐Jung , Sawyer Brook
Published: November 2018

This study takes an ecological approach to examine how children with developmental language disorder (DLD) interact with their classmates within early childhood special education (ECSE) inclusive classrooms. Participants were 124 children with DLD, 56 children with other disabilities, and 247 typically developing children (Mage = 52.42 months, SD = 6.27) from 56 ECSE inclusive classrooms. Results of social network analysis showed that children with DLD had significantly smaller peer social networks and were more likely to be isolated. Children tended to interact with peers with the same DLD status. These effects of children's DLD status were above and beyond the effects of children's social pragmatics skills.
Mosaic MECP2 variants in males with classical Rett syndrome features, including stereotypical hand movements
Authors: Schönewolf‐Greulich Bitten , Bisgaard Anne‐Marie , Dunø Morten , Jespersgaard Cathrine , Rokkjær Mette , Hansen Lars K. , Tsoutsou Eirini , Sofokleous Christalena , Topcu Meral , Kaur Simran , Van Bergen Nicole J. , Brøndum‐Nielsen Karen , Larsen Martin J. , Sørensen Kristina P. , Christodoulou John , Fagerberg Christina R. , Tümer Zeynep
Published: November 2018

Rett syndrome is rarely suspected in males because of the X‐linked dominant inheritance. In the literature, only six male patients have been reported with methyl‐CpG‐binding protein 2 (MECP2) mosaicism. Next‐generation sequencing (NGS) methods have enabled better detection of somatic mosaicism compared to conventional Sanger sequencing; however, mosaics can still be difficult to detect. We present clinical and molecular findings in two males mosaic for a pathogenic MECP2 variant. Both have been reexamined using deep sequencing of DNA isolated from four different cell tissues (blood, muscle, fibroblasts and oral mucosa). Deep sequencing of the different tissues revealed that the variants were present in all tissues. In one patient, the molecular diagnosis could only be established by reexamination after a normal whole exome sequencing, and the other case is an example of reverse genetic diagnostics. Rett syndrome should be considered in males with neurodevelopmental delay and stereotypical hand movements. Subsequent to clinical diagnosis males should be investigated with NGS‐based technologies of MECP2 with high read depth and a low threshold for variant calls. If the initial analysis on full blood derived DNA fails to confirm the suspicion, we recommend repeating the analysis on another tissue, preferentially fibroblasts to increase the diagnostic yield.
Preferences for in‐person disclosure: Patients declining telephone disclosure characteristics and outcomes in the multicenter Communication Of GENetic Test Results by Telephone study
Authors: Beri Nina , Patrick‐Miller Linda J. , Egleston Brian L. , Hall Michael J. , Domchek Susan M. , Daly Mary B. , Ganschow Pamela , Grana Generosa , Olopade Olufunmilayo I. , Fetzer Dominique , Brandt Amanda , Chambers Rachelle , Clark Dana F. , Forman Andrea , Gaber Rikki , Gulden Cassandra , Horte Janice , Long Jessica , Lucas Terra , Madaan Shreshtha , Mattie Kristin , McKenna Danielle , Montgomery Susan , Nielsen Sarah , Powers Jacquelyn , Rainey Kim , Rybak Christina , Savage Michelle , Seelaus Christina , Stoll Jessica , Stopfer Jill E. , Yao Xinxin (Shirley) , Bradbury Angela R.
Published: November 2018

Telephone disclosure of cancer genetic test results is noninferior to in‐person disclosure. However, how patients who prefer in‐person communication of results differ from those who agree to telephone disclosure is unclear but important when considering delivery models for genetic medicine. Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone to in‐person disclosure of genetic test results. We evaluated preferences for in‐person disclosure, factors associated with this preference and outcomes compared to those who agreed to randomization. Among 1178 enrolled patients, 208 (18%) declined randomization, largely given a preference for in‐person disclosure. These patients were more likely to be older (P = 0.007) and to have had multigene panel testing (P < 0.001). General anxiety (P = 0.007), state anxiety (P = 0.008), depression (P = 0.011), cancer‐specific distress (P = 0.021) and uncertainty (P = 0.03) were higher after pretest counseling. After disclosure of results, they also had higher general anxiety (P = 0.003), depression (P = 0.002) and cancer‐specific distress (P = 0.043). While telephone disclosure is a reasonable alternative to in‐person disclosure in most patients, some patients have a strong preference for in‐person communication. Patient age, distress and complexity of testing are important factors to consider and requests for in‐person disclosure should be honored when possible.
“Still We Need Friends!”: “Partnership in Mission” in the History of the World Council of Churches, 1948–2018
Authors: Han Kang‐Hee
Published: November 2018

This article aims to investigate the missiological development and conceptual understanding of “partnership in mission,” a major subject of inquiry through the history of the World Council of Churches (WCC), and to consider how ecumenical partners can enter into authentic friendship by embracing one another in the era of World Christianity. In ecumenical movements, the issue of the partner relationship has been illuminated through diverse missiological notions and themes based on profound reflections on missionary imperialism of the past. Since the 20th century, partnership in mission has provided a crucial practical and strategic framework for repositioning the unequal relationships between global South countries, as well as between the global North and South. Tracing a genealogy of partnership of the WCC, this paper discusses its deeper significance as “sharing life” articulated in the terminology of the Ecumenical Sharing of Resources (ESR). Furthermore, it proposes a model of “partnership in mission as incarnation” by relating debates about the ESR to God’s incarnation and crucifixion.
Belief in a Liminal State of Health: A Christological Review of In the Name of Jesus! Healing in the Age of HIV
Authors: Soko‐de Jong Thandi
Published: November 2018

This article examines the Ecumenical HIV and AIDS Initiative in Africa publication In the Name of Jesus! Healing in the Age of HIV by discussing some of the issues of faith that are at the core of healing in relation to HIV. This publication challenges Christian beliefs and faith‐healing practices that deter people from adhering to anti‐retroviral therapy (ART). However, it does not adequately address the contextual “Jesus as Healer Christologies” that are among the reasons such beliefs and practices remain attractive and popular, even among those who have been adhering to ART for many years. This article argues that treatable but incurable health conditions such as HIV raise questions about what it means to be in the liminal space where one’s health is dependent on treatment. The article calls for more engagement with Jesus as Healer Christologies alongside activism in this liminal space and suggests that the doctrine of incarnation may provide some helpful ways of addressing some of the theological questions posed by liminality.
Usefulness of digital and optical refractometers for the diagnosis of failure of transfer of passive immunity in neonatal foals
Authors: Elsohaby I. , Riley C. B. , McClure J. T.
Published: November 2018

Background

Neonatal foals with failure of transfer of passive immunity (FTPI) are at higher risk of morbidity and mortality. Successful treatment ofFTPIis time‐dependent, thus rapid and accurate measurement of serum IgG concentration is important for the management and care of neonatal foals.

Objectives

To validate the use of digital and optical refractometers for assessingFTPIin neonatal foals and compare the diagnostic performance and level of agreement of the two refractometers to the reference standard radial immunodiffusion (RID) assay.

Study design

A retrospective validation study.

Methods

Serum samples (n = 253) were collected from 230 foals admitted to the Veterinary Teaching Hospital and Ambulatory Equine Service between 2012 and 2017. The serum IgG concentrations were measured by the referenceRIDassay, digital Brix and optical refractometers. The correlation between results of two refractometers andRIDassay was assessed. A receiver operating characteristic curve was created and used to identify the optimal cut‐offs for evaluating sensitivity and specificity of the two refractometers to detect foals with complete and partialFTPI.

Results

TheRID‐IgG concentrations were positively correlated with the Brix scores obtained from a digital refractometer (r = 0.73, P = 0.001) and serum total protein obtained from an optical refractometer (r = 0.72, P = 0.001). The sensitivity and specificity of the digital Brix refractometer at optimal cut‐off (≤7.8% Brix) were 88.1 (95%CI: 74.4–96.0) and 67.7% (95%CI: 60.6–74.3) to detectRID‐IgG<4 g/L and 79.0 (95%CI: 68.5–87.3) and 77.3% (95%CI: 69.8–83.8) to detectRID‐IgG≤8 g/L, respectively. The sensitivity and specificity of the optical refractometer at optimal cut‐off (≤42 g/L) were 86.1 (95%CI: 72.1–94.7) and 70.9% (95%CI: 63.9–77.3) to detectRID‐IgG<4 g/L and at cut‐off (≤44 g/L) were 82.9 (95%CI: 73.0–90.3) and 72.7% (95%CI: 64.8–79.6) to detectRID‐IgG≤8 g/L, respectively.

Main limitations

The number of diseased foals was small to investigate the validity of the selected cut‐off values for assessingFTPIin sick foals.

Conclusions

The two refractometers exhibit utility as rapid, inexpensive screening tests and have a good sensitivity for assessingFTPIin neonatal foals.
IL‐36 receptor antagonistic antibodies inhibit inflammatory responses in preclinical models of psoriasiform dermatitis
Authors: Su Zhi , Paulsboe Stephanie , Wetter Joseph , Salte Katherine , Kannan Arun , Mathew Sheeba , Horowitz Amanda , Gerstein Clare , Namovic Marian , Todorović Viktor , Seagal Jane , Edelmayer Rebecca M. , Viner Michelle , Rinaldi Lisa , Zhou Li , Leys Laura , Huang Susan , Wang Leyu , Sadhukhan Ramkrishna , Honore Prisca , McGaraughty Steve , Scott Victoria E.
Published: November 2018

Psoriasis vulgaris (PV) results from activation of IL‐23/Th17 immune pathway and is further amplified by cytokines/chemokines from skin cells. Among skin‐derived pro‐inflammatory cytokines, IL‐36 family members are highly upregulated in PV patients and play a critical role in general pustular psoriasis. However, there is limited data showing crosstalk between the IL‐23 and IL‐36 pathways in PV. Herein, potential attenuation of skin inflammation in the IL‐23‐induced mouse model of psoriasiform dermatitis by functional inhibition of IL‐36 receptor (IL‐36R) was interrogated. Anti‐mouse IL‐36R monoclonal antibodies (mAbs) were generated and validated in vitro by inhibiting IL‐36α‐induced secretion of CXCL1 from NIH 3T3 cells. Antibody target engagement was demonstrated by inhibition of CXCL1 production in a novel acute model of IL‐36α systemic injection in mice. In addition, anti‐IL‐36R mAbs inhibited tissue inflammation and inflammatory gene expression in an IL‐36α ear injection model of psoriasiform dermatitis demonstrating engagement of the target in the ear skin. To elucidate the possible role of IL‐36 signalling in IL‐23/Th17 pathway, the ability of anti‐IL‐36R mAbs to inhibit skin inflammation in an IL‐23 ear injection model was assessed. Inhibiting the IL‐36 pathway resulted in significant attenuation of skin thickening and psoriasis‐relevant gene expression. Taken together, these data suggest a role for IL‐36 signalling in the IL‐23/Th17 signalling axis in PV.
Nonlinear fatigue damage accumulation and life prediction of metals: A comparative study
Authors: Zhu Shun‐Peng , Hao Yong‐Zhen , de Oliveira Correia José A.F. , Lesiuk Grzegorz , de Jesus Abílio M.P.
Published: November 2018

Fatigue damage modelling and life prediction of engineering components under variable amplitude loadings are critical for ensuring their operational reliability and structural integrity. In this paper, five typical nonlinear fatigue damage accumulation models are evaluated and compared by considering the influence of load sequence and interaction on fatigue life of P355NL1 steels. Moreover, a new nonlinear fatigue damage accumulation model is proposed to account for these two effects. Experimental datasets of pressure vessel steel P355NL1 and four other materials under two‐block loadings are used for model comparative study. Results indicate that the proposed model yields more accurate fatigue life predictions for the five materials than the other models.
The influence of low‐plasticity burnishing process on the fatigue life of friction‐stir‐processed Al 7075‐T6 samples
Authors: Hassanifard Soran , Mousavi Hojjat , Varvani‐Farahani Ahmad
Published: November 2018

The effects of low‐plasticity burnishing (LPB) on the fatigue life of friction‐stir‐processed (FSP) Al 7075‐T6 plates were examined experimentally and numerically. Aluminum samples were taken from plates to test fatigue response in the presence of heat‐affected zone (HAZ) at different loading magnitudes. Finite element method was employed to numerically evaluate fatigue life of FSPed samples by means of the Smith–Watson–Topper (SWT) model. Through numerical analysis, the FSP and its cooling procedure were modelled on the basis of the arbitrary Lagrangian–Eulerian technique, and then, the effect of the LPB to assess fatigue response of samples was examined. Aluminum samples undergoing friction‐stir process presented lower‐fatigue life as stresses were highly concentrated within FSP regions. Involvement of LPB regained fatigue durability through compressive residual stress induced on the aluminum samples. The higher applied force over the LPB promoted compressive residual stress on the sample surface and improved fatigue life of samples. The predicted life results were found twice more in magnitude than those of experimentally obtained.
Post‐release predation mortality of age‐0 hatchery‐reared Chinook salmon from non‐native smallmouth bass in the Snake River
Authors: Erhardt John M. , Tiffan Kenneth F.
Published: November 2018

Release of age‐0 hatchery‐reared fall Chinook salmon, Oncorhynchus tshawytscha (Walbaum), in the Snake River resulted in up to 30‐fold increases in salmon consumption by non‐native smallmouth bass, Micropterus dolomieu Lacepѐde. In an upper river reach, smallmouth bass fed intensively during a release in May, but Chinook salmon consumption returned to pre‐release levels within 1–2 days as hatchery‐reared fish quickly emigrated downstream. The predation response during a June release located farther downstream was dissimilar. Chinook salmon consumption increased to a lesser extent (11‐fold), lasted several days (~4) and no changes in feeding intensity were evident. Estimated numbers of age‐0 hatchery‐reared Chinook salmon lost to short‐term predation varied by year and study reach and ranged from 12,007 (6.03% of those released) to 210,580 (14.6% of those released) fish. Short‐term, intense feeding by smallmouth bass can contribute significantly to mortality of hatchery‐reared fish and should be considered when supplementing populations with hatchery juveniles.
Whole‐river manipulation of olfactory cues affects upstream migration of sockeye salmon
Authors: Drenner S. Matthew , Harrower William L. , Casselman Matt T. , Bett Nolan N. , Bass Aurthor L. , Middleton Collin T. , Hinch Scott G.
Published: November 2018

This study experimentally manipulated olfactory cues in a river by adjusting hydropower operation and monitored behavioural responses of 193 adult sockeye salmon, Oncorhynchus nerka (Walbaum), using radio telemetry. Experimental dilution of olfactory cues in a tributary to 72% natal water relative to non‐natal water was associated with 80% reduced odds of fish entering the tributary from a river mainstem and increased migration times by an average of 12.2 hr, with females taking 4.6 hr longer than males to enter the tributary. Additionally, males delayed 2.7 hr longer than females at a diversion outlet in the river mainstem that discharged a natal water source during experimentally diluted olfactory conditions. Increased migration time associated with dilute olfactory cues would decrease energy available for reproduction and potentially reduce fitness. Hydropower managers should continue to regulate natal water conditions in the Seton River during sockeye salmon migrations to avoid negative impacts on migration timing and success.