bluuebunny/crossref_metadata_2025 huggingface dataset:
The long-run performance of US firms pursuing IPOs in foreign markets
Authors: Killins Robert , Egly Peter V.
Published: December 2017

Purpose

The purpose of this paper is to investigate the long-run performance of a unique set of US domiciled firms that have bypassed the US capital markets in pursuit of their initial public offering (IPO) overseas. Additionally, this paper then tests the popular underwriter prestige impact and the window of opportunity hypothesis on this unique subset of IPOs.

Design/methodology/approach

Using a sample of foreign and purely domestic IPOs made by US firms from 2000 to 2011, this study investigates the long-term performance, one-, two- and three-year by using two measures (buy-and-hold return and cumulative abnormal returns) to test the long-run returns of newly listed companies. Finally, the research incorporates both the traditional matching methodology (issue year and size) along with propensity score matching methodology.

Findings

FIPOs of US companies underperform DIPOs and their matched DIPOs; furthermore, FIPOs underperform the index of the two listing countries they use the most (UK and Canada). Although the choice of a reputable underwriter mitigates underperformance, the choice of listing in a foreign country only may be a result of possible high valuations accorded by foreign investors who buy US-listed companies on the domestic exchange possibly for reducing exchange rate risk and gaining US diversification without incurring additional costs. It is, thus, possible that US companies that undertake Foreign IPOs not only escape potentially higher Security and Exchange Commission regulations and disclosure but also benefit from higher valuations in the foreign markets.

Originality/value

To the best of the authors’ knowledge, this is the first study to investigate the long-term performance of US firms bypassing the US capital markets in pursuit of their initial equity offering elsewhere. Caglio et al. (2016) investigated why firms decide to pursue such equity raising activity but fail to investigate the firms’ actual performance after issuing equity. This research fills such a gap in the literature and is important for both academics and practitioners. Practitioners can use this information in assessing the quality of such investments in the long-run, and firms can use such information when determining the different options of issuing equity. Further, regulators should be aware of the implications that increased regulations have on capital raising activities in their domestic market.
Measuring accelerometer dynamic range from seismic data using Allan deviation
Authors: McDonald Matt , Stigborg Patrik
Published: December 2017

We propose a new approach for calculating the dynamic range of an accelerometer based on an Allan deviation analysis of production seismic data. This test is intended as a field audit technique and does not require an unconditioned dataset from a low‐noise environment. We first show that Allan deviation can measure white noise levels using two commercial accelerometers. The analysis accurately captures the manufacturing noise density specifications and known relationships between white noise, preamplifier gain, and group forming. We then show that a production seismic dataset is suitable for an Allan deviation analysis because the results are not critically affected by a recording filter. Finally, we illustrate the proposed technique by calculating the dynamic range of an accelerometer channel in a seismic streamer using a production dataset.
Syntax and semantics of modal predicates in Indo‐European
Authors: Viti Carlotta
Published: December 2017

This paper discusses the syntactic variation of modal predicates between structures with a nominative primary argument and those with an oblique primary argument. In the literature, this variation is related to a change from deontic to epistemic meanings, whereby epistemicity seems to be more commonly expressed by highly grammaticalized impersonal constructions. After having shown the weakness of this relationship, I suggest a new explanation for the variation of modal predicates on the basis of diverse ancient Indo‐European languages, such as Vedic, Ancient Greek and Latin, as well as of some of their modern descendants, especially Hindi, Modern Greek, and standard and colloquial Italian. I argue that modal predicates with an oblique primary argument are favoured for functions of necessity, while modal predicates with a nominative primary argument preferably express functions of possibility. This reflects the different meanings of the lexical sources of these predicates, that is, capacity or power for predicates of possibility, and lack or obligation for predicates of necessity, which also imply different degrees of agentivity and control.
The Effects of Direct Payments on Technical Efficiency of Irish Beef Farms: A Stochastic Frontier Analysis
Authors: Martinez Cillero Maria , Thorne Fiona , Wallace Michael , Breen James , Hennessy Thia
Published: December 2017

The 2003 Mid‐Term Review of the CAP sought to refocus the EU's farm support policy to foster a more competitive and market‐orientated agricultural sector. The foundation of this reform comprised the introduction of decoupled payments to farmers, replacing the EU's previous system of supports that were directly linked to production of designated crops and livestock. This paper explores the effect of coupled payments and their subsequent replacement by decoupled support, on the technical efficiency of specialist beef farms in Ireland. Given the high reliance of beef farmers in Ireland on CAP payments, the decoupling of payments has been especially important for the sector. A stochastic production frontier is estimated using a panel dataset comprising detailed accountancy data for Irish beef farms between the years 2000 and 2013. Our results indicate that technical efficiency in the beef farming sector has been consistently poor, with an average efficiency score of only 0.53 during the period analysed. However, we found that direct income received in the form of coupled payments had a positive impact on farm efficiency, and that this positive effect was maintained after their replacement with decoupled income support.
Systemic RNAi of V‐ATPase subunit B causes molting defect and developmental abnormalities in Periplaneta fuliginosa
Authors: Sato Kazuki , Miyata Keita , Ozawa Sota , Hasegawa Koichi
Published: December 2017

The vacuolar (H+)‐ATPases (V‐ATPases) are ATP‐driven proton pumps with multiple functions in many organisms. In this study, we performed structural and functional analysis of vha55 gene that encodes V‐ATPase subunit B in the smokybrown cockroach Periplaneta fuliginosa (Blattodea). We observed a high homology score of the deduced amino acid sequences between 10 species in seven orders. RNAi of the vha55 gene in P. fuliginosa caused nymphal/nymphal molting defects with incomplete shedding of old cuticles, growth inhibition, as well as bent and wrinkled cuticles of thoraxes and abdominal segments. Since growth inhibition caused by vha55 RNAi did not interfere in the commencement of cockroach molting, molting timing and body growth might be controlled by independent mechanism. Our study suggested V‐ATPases might be a good candidate molecule for evolutionary and developmental studies of insect molting.
REVISITING JUVENILE WAIVER: INTEGRATING THE INCAPACITATION EXPERIENCE*
Authors: AUGUSTYN MEGAN BEARS , MCGLOIN JEAN MARIE
Published: December 2017

More than 20 years after an expansion of juvenile transfer policies, questions remain regarding the specific deterrent effect of juvenile waiver given the singular focus on the court of jurisdiction and neglect of other critical aspects of the provision, such as the incapacitation experience. Prior research has also not been focused on identifying the mediating mechanisms that produce criminogenic, null, or deterrent effects. We use data from the Pathways to Desistance Study, propensity score methodology, and mediational analyses to examine how and why the waiver‐incapacitation experience is related to recidivism rates during emerging adulthood. We find that the prior focus on a binary “waiver effect” is potentially misleading as it masks meaningful variation. Furthermore, we find that the path to increased recidivism in emerging adulthood is indirect and we identify stymied educational attainment as a mediator. Our discussion is focused on the criminogenic effects of incapacitation for juveniles and its implications for juvenile transfer research. The discussion also calls for future research to explore treatment heterogeneity further.
Effect of Gabapentin on Sleep and Event‐Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal
Authors: Sanchez‐Alavez Manuel , Wills Derek N. , Amodeo Leslie , Ehlers Cindy L.
Published: December 2017

Background

Disturbances in sleep architecture, especially reductions in slow‐wave sleep (SWS), are symptoms commonly observed in individuals with alcohol use disorders. Recent clinical trials have demonstrated that the anticonvulsant and analgesic drug gabapentin may have therapeutic value in normalizing sleep quality in recovering alcoholics. However, the brain mechanisms underlying this improvement in sleep following gabapentin treatment remain unknown.

Methods

In this study, adult Wistar rats were exposed to 8 weeks of chronic intermittent ethanol [EtOH] vapor (blood EtOH concentrations averaged 128.2 ± 17.4 mg/dl) or control conditions and then withdrawn. Sleep electroencephalograms [EEGs] and event‐related oscillations (EROs) were evaluated at baseline prior to EtOH exposure and 24 hours following EtOH withdrawal. Four weeks following EtOH withdrawal the effects of saline and 2 doses of gabapentin (30, 120 mg/kg), on EROs and sleep EEGs, were evaluated.

Results

As compared to baseline, 24 hours following alcohol withdrawal SWS became fragmented as indexed by a significant increase in the number and a decrease in the duration of SWS episodes. Compared to controls, the EtOH‐exposed group had more ERO energy in the beta frequency band in the parietal cortex. Gabapentin induced a dose‐dependent decrease in the latency to the first SWS episode, and a reduction in sleep fragmentation. Gabapentin also produced a dose‐dependent increase in ERO energy in the control group that was significantly attenuated in the EtOH‐exposed group in the theta, and beta frequency bands.

Conclusions

Taken together, these studies suggest that gabapentin can reverse some of the alcohol‐induced sleep and EEG deficits but does not eliminate all of the enduring brain effects of EtOH exposure.
Effects of Initiating Abstinence from Alcohol on Daily Craving and Negative Affect: Results from a Pharmacotherapy Clinical Trial
Authors: Hallgren Kevin A. , Delker Brianna C. , Simpson Tracy L.
Published: December 2017

Background

Craving and negative affect are distressing and commonly experienced during alcohol use disorder (AUD) treatment. Patients may assume that initiating abstinence will intensify their cravings and negative affect despite limited empirical data to support this assumption. This study extends and replicates, under improved methodological conditions, previous work that found reductions in daily craving associated with initiating abstinence.

Methods

Seventy‐eight adults (80.8% male, 57.1% Caucasian) in a clinical trial testing prazosin for AUD provided daily reports of drinking, craving, and negative affect for up to 12 weeks (mean = 64.77 daily reports). Participants were classified into 3 subgroups based on whether and when they initiated 14 days of continuous abstinence, including (i) “abstinence initiators” who quit drinking during treatment (n = 17), (ii) “already abstainers” who were abstinent at the start of treatment (n = 20), and (iii) “continued drinkers” who never initiated abstinence (n = 41). The timing and degree of change in craving and negative affect were compared across these groups using multivariate growth curve modeling.

Results

All participant subgroups reported gradual reductions in craving over the course of treatment, with “abstinence initiators” reporting additional sudden reductions in craving upon initiating abstinence from alcohol. “Continued drinkers” reported higher levels of craving than “already abstainers” throughout the full course of treatment. Negative affect followed a different pattern of change, with “abstinence initiators” experiencing gradual reductions in negative affect after initiating abstinence but no changes prior to or immediately upon initiating abstinence, and with “already abstainers” and “continued drinkers” experiencing no changes in negative affect over time.

Conclusions

Initiating abstinence is associated with immediate reductions in craving, followed by gradual reductions in both craving and negative affect. Results provide insight into the timing and magnitude of changes in theoretically and clinically important variables and may help patients anticipate when to expect improvement in craving and negative effect.
Increase in the number of admissions to psychiatric hospitals immediately after the Great East Japan Earthquake
Authors: Sakuma Atsushi , Ueda Ikki , Rengi Shigehito , Shingai Toshiyasu , Matsuoka Hiroo , Matsumoto Kazunori
Published: December 2017

Introduction

Major natural disasters have a significant impact on the mental health of survivors in affected communities. Although it has been speculated that the number of survivors requiring admission to psychiatric hospital increases immediately after a major disaster, few studies have examined the issue.

Methods

On March 11, 2011, the Great East Japan Earthquake and subsequent tsunami devastated the relatively isolated city of Kesennuma. We therefore compared the weekly number of patients admitted to 2 psychiatric hospitals in Kesennuma in the 4 weeks immediately after the earthquake with those in the 4 weeks immediately preceding the earthquake. We also made comparisons between this 8‐week period and the corresponding 8‐week periods in 2009, 2010, and 2012.

Results

The number of patients admitted to the 2 psychiatric hospitals increased in 4 weeks after the disaster in 2011, with a weekly median (range) of 13 (9‐16), compared with 6 (5‐9) in the preceding 4 weeks in 2011. The corresponding figures were 5.5 (2‐10) in 2009, 6.5 (5‐9) in 2010, and 4 (3‐7) in 2012 (P = .01, H = 13.05). By diagnostic category, admissions for schizophrenia spectrum disorder and neurotic stress‐related disorder increased significantly following the disaster.

Discussion

Demands for inpatient psychiatric treatment increased immediately after the Great East Japan Earthquake. Government officials and mental health professionals must strengthen support for survivors with mental illness, especially those with schizophrenia spectrum disorder. This should include support for mental health authorities and medical staff in the affected community.
A Comparison of the Effectiveness of Silibinin and Resveratrol in Preventing Alpha‐Amanitin‐Induced Hepatotoxicity
Authors: Sahin Aynur , Arici Mualla Aylin , Yilmaz Yeliz , Kalkan Sule , Durmus Nergiz , Ergur Bekir Ugur , Yakut Aksu Ilkay , Atabey Neşe , Tuncok Yesim
Published: December 2017

Amanita phalloides species mushrooms containing alpha‐amanitin (α‐AMA) are responsible for the majority of fatal mushroom intoxications and can lead to severe poisonings resulting in hepatotoxicity and acute hepatic failure. Existing antidotes, such as silibinin, are not sufficiently effective in the prevention and/or resolution of α‐AMA‐induced hepatotoxicity. We investigated the effects of resveratrol on α‐AMA‐induced hepatotoxicity and compared with silibinin, a known antidote using in vivo and in vitro toxicity models. In the in vivo protocol, resveratrol (30 mg/kg) was given simultaneously with α‐AMA (α‐AMA + SR) or 12 (α‐AMA + 12R) or 24 (α‐AMA + 24R) hr after α‐AMA administration. Silibinin (5 mg/kg) (α‐AMA + Sil) and normal saline (α‐AMA + NS) were given simultaneously with α‐AMA. We found that liver transaminase levels in α‐AMA + SR and α‐AMA + 12R groups and histomorphologic injury score in the α‐AMA + SR, α‐AMA + 12R, α‐AMA + 24R and α‐AMA + Sil groups were significantly lower than that of the α‐AMA + NS group. Resveratrol decreased mononuclear cell infiltration, necrosis and active caspase‐3 immunopositivity in the liver. In the in vitro protocol, the effects of resveratrol and silibinin were evaluated in a reduction in cell viability induced by α‐AMA in THLE‐2 and THLE‐3 hepatocytes. Neither resveratrol nor silibinin was found to be effective in increasing cell viability decreased by α‐AMA + NS. As a conclusion, resveratrol was found to be effective in α‐AMA‐induced hepatotoxicity with its anti‐inflammatory properties in in vivo conditions. It is a promising compound with the potential for use in the treatment of hepatotoxicity associated with Amanita phalloides type mushroom poisonings.
Linking owner–managers' personal sustainability behaviors and corporate practices in SMEs: The moderating roles of perceived advantages and environmental hostility
Authors: Chassé Sonia , Courrent Jean‐Marie
Published: December 2017

Drawing on managerial discretion and conflicting institutional logics literature, this study investigates the relation between the personal sustainability behaviors (PSB) of owner–managers and the corporate sustainability practices (CS practices) of SMEs. The research proposes a contingency model that assesses the moderating effects of perceived economic advantages and environmental hostility on this relationship. Based on linear hierarchical multiple regression analyses of a cross‐sectoral sample of French SMEs, the results suggest a positive influence of the manager's PSB on the SME's CS practices that appears to be differently moderated depending on the type of practice considered. The influence on environmental practices is fostered through the perception of economic advantages. The influence on workplace practices is only effective when the business environment is deemed benign and the influence on community practices is dampened by the perception of environmental hostility. Highlighting the trade‐off between the manager's personal values and the SME's economic constraints, these findings contribute to a better understanding of the critical antecedents of sustainability in small businesses.
Nimotuzumab combined with concurrent chemoradiotherapy in Japanese patients with esophageal cancer: A phase I study
Authors: Kato Ken , Ura Takashi , Koizumi Wasaburo , Iwasa Satoru , Katada Chikatoshi , Azuma Mizutomo , Ishikura Satoshi , Nakao Yoshinori , Onuma Hiroshi , Muro Kei
Published: December 2017

Nimotuzumab is a humanized anti‐epidermal growth factor receptor IgG1 monoclonal antibody. This phase I study assessed the tolerability, safety, efficacy, and pharmacokinetics of nimotuzumab in combination with chemoradiotherapy in Japanese patients with esophageal cancer. Patients with stage II, III, and IV esophageal cancer were enrolled. Patients were planned to receive nimotuzumab (level 1: 200 mg/wk for 25 weeks; or level 2: 400 mg/wk in the chemoradiation period, 400 mg biweekly in an additional chemotherapy period [8 weeks after the chemoradiation period] and a maintenance therapy period [after chemotherapy to 25 weeks]) combined with cisplatin (75 mg/m2 on day 1) and fluorouracil (1000 mg/m2 on days 1‐4) in the chemoradiation and additional chemotherapy periods. Radiotherapy was given concurrently at 50.4 Gy. A total of 10 patients were enrolled in level 1. Dose‐limiting toxicities were observed in 2 patients (grade 3 infection and renal disorder). Maximum‐tolerated dose was estimated to be at least 200 mg/wk and the dose was not escalated to level 2. The most common grade ≥3 toxicities were lymphopenia (90%), leukopenia (60%), neutropenia (50%), and febrile neutropenia, decreased appetite, hyponatremia, and radiation esophagitis (30% each). Neither treatment‐related death nor grade ≥3 skin toxicity was observed in any patient. Complete response rate was 50%. Progression‐free survival was 13.9 months. One‐ and 3‐year survival rates were 75% and 37.5%, respectively. Immunogenicity was not reported in any patient. Nimotuzumab in combination with concurrent chemoradiotherapy was tolerable and effective for Japanese patients with esophageal cancer.
New metformin derivative HL156A prevents oral cancer progression by inhibiting the insulin‐like growth factor/AKT/mammalian target of rapamycin pathways
Authors: Lam Thuy Giang , Jeong Yun Soo , Kim Soo‐A , Ahn Sang‐Gun
Published: December 2017

Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of the present study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD‐10B cell viability and colony formation in a dose‐dependent way. HL156A also markedly reduced wound closure and migration of FaDu and YD‐10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced reactive oxygen species (ROS) levels and apoptotic cells with caspase‐3 and ‐9 activation. HL156A inhibited the expression and activation of insulin‐like growth factor (IGF)‐1 and its downstream proteins, AKT, mammalian target of rapamycin (mTOR), and ERK1/2. In addition, HL156A activated AMP‐activated protein kinase/nuclear factor kappa B (AMPK‐NF‐κB) signaling of FaDu and YD‐10B cells. A xenograft mouse model further showed that HL156A suppressed AT84 mouse oral tumor growth, accompanied by down‐regulated p‐IGF‐1, p‐mTOR, proliferating cell nuclear antigen (PCNA) and promoted p‐AMPK and TUNEL expression. These results suggest the potential value of the new metformin derivative HL156A as a candidate for a therapeutic modality for the treatment of oral cancer.
Regulatory mechanisms of hypoxia‐inducible factor 1 activity: Two decades of knowledge
Authors: Koyasu Sho , Kobayashi Minoru , Goto Yoko , Hiraoka Masahiro , Harada Hiroshi
Published: December 2017

Hypoxia‐inducible factor 1 (HIF‐1) is a transcriptional activator of various genes related to cellular adaptive responses to hypoxia. Dysfunctions in the regulatory systems of HIF‐1 activity have been implicated in the pathogenesis of various diseases including malignant tumors and, thus, elucidating the molecular mechanisms underlying the activation of HIF‐1 is eagerly desired for the development of novel anti‐cancer strategies. The importance of oxygen‐dependent and ubiquitin‐mediated proteolysis of the regulatory subunit of HIF‐1 (HIF‐1α) was first reported in 1997. Since then, accumulating evidence has shown that HIF‐1α may become stable and active even under normoxic conditions; for example, when disease‐associated genetic and functional alterations in some genes trigger the aberrant activation of HIF‐1 regardless of oxygen conditions. We herein review the last two decades of knowledge, since 1997, on the regulatory mechanisms of HIF‐1 activity from conventional oxygen‐ and proteolysis‐dependent mechanisms to up‐to‐the‐minute information on cancer‐associated genetic and functional alteration‐mediated mechanisms.
Proposal for reclassification of N staging system in penile cancer patients, based on number of positive lymph nodes
Authors: Li Zhiyong , Guo Shengjie , Wu Zhiming , Han Hui , Li Zaishang , Wang Yanjun , Chen Jieping , Deng Chuangzhong , Qin Zike , Liu Zhuowei , Li Yonghong , Chen Dong , Zhou Fangjian , Yao Kai
Published: December 2017

In the present study, we aim to compare the rationality of proposed N classification based on the number of metastatic lymph nodes (LNs) with the current one. A total of 509 penile cancer patients at our institute were analyzed. Univariable and multivariable statistical analyses were used to assess cancer‐specific survival (CSS) in 2 staging systems. Harrell's concordance index was applied to evaluate predictive accuracy of the current and proposed N classification in predicting CSS. We propose a new classification: pN1 (metastasis in 1‐2 regional LNs), pN2 (metastasis in 3 regional LNs, or 3 or fewer regional lymph nodes with extranodal extension), and pN3 (metastasis in 4 or more regional LNs). According to the current and proposed N classification, the 5‐year CSS of penile cancer patients with pN1, pN2 and pN3 was 85.8%, 39.0%, and 19.7%; and with pN1, pN2 and pN3 was 79.8%, 39.3% and 15.3%, which almost all showed significant difference (P < .001, P = .259) (P < .001, P < .001). Multivariable predictive accuracy of the proposed and current N staging was 76.48% and 70.92% (5.56% gain; P < .001). With a multivariable model of clinical features, both current (hazard ratio [HR], 7.761, 10.612; P < .001, P < .001) and proposed N stages (HR, 3.792, 3.971; P < .001, P < .001) exhibited independent effects on survival. The proposed N classification is superior to the current one, which is simpler and provides more accurate prognosis.
Cancer immunotherapy‐targeted glypican‐3 or neoantigens
Authors: Shimizu Yasuhiro , Suzuki Toshihiro , Yoshikawa Toshiaki , Tsuchiya Nobuhiro , Sawada Yu , Endo Itaru , Nakatsura Tetsuya
Published: December 2017

Immune checkpoint inhibitors have ushered in a new era in cancer therapy, although other therapies or combinations thereof are still needed for many patients for whom these drugs are ineffective. In this light, we have identified glypican‐3 an HLA‐24, HLA‐A2 restriction peptide with extreme cancer specificity. In this paper, we summarize results from a number of related clinical trials showing that glypican‐3 peptide vaccines induce specific CTLs in most patients (UMIN Clinical Trials Registry: UMIN000001395, UMIN000005093, UMIN000002614, UMN000003696, and UMIN000006357). We also describe the current state of personalized cancer immunotherapy based on neoantigens, and assess, based on our own research and experience, the potential of such therapy to elicit cancer regression. Finally, we discuss the future direction of cancer immunotherapy.
C‐C chemokine receptor type 1 mediates osteopontin‐promoted metastasis in hepatocellular carcinoma
Authors: Zhu Ying , Gao Xiao‐Mei , Yang Jing , Xu Da , Zhang Yu , Lu Ming , Zhang Ze , Sheng Yuan‐Yuan , Li Jian‐Hua , Yu Xin‐Xin , Zheng Yan , Dong Qiong‐Zhu , Qin Lun‐Xiu
Published: December 2017

In the hepatocellular carcinoma (HCC) microenvironment, chemokine receptors play a critical role in tumorigenesis and metastasis. Our previous studies have found that osteopontin (OPN) is a promoter for HCC metastasis. However, the role of chemokine receptors in OPN‐induced HCC metastasis remains unclear. In this study, we demonstrate that OPN is dramatically elevated in HCC tissues with metastasis and that high expression of OPN correlates with poorer overall survival and higher recurrence rate. OPN upregulates chemokine receptor expression, migration, invasion and pulmonary metastasis in HCC. We find that C‐C chemokine receptor type 1 (CCR1) and C‐X‐C chemokine receptor type 6 (CXCR6) are the most upregulated chemokine receptors induced by OPN. CCR1 knockdown results in reduction of migration, invasion and pulmonary metastasis induced by OPN in vitro and in vivo, whereas CXCR6 knockdown does not reverse OPN‐promoted migration and invasion. Moreover, OPN upregulates the expression of CCR1 through activating phosphoinositide 3‐kinase (PI3K)/AKT and hypoxia‐inducible factor 1α (HIF‐1α) in HCC cells. Furthermore, blockade of OPN‐CCR1 axis with CCR1 antagonist significantly restrains the promoting effects of OPN on HCC progression and metastasis. In human HCC tissues, OPN expression shows significantly positive correlation with CCR1 expression, and the patients with high levels of both OPN and CCR1 have the most dismal prognosis. Collectively, our results indicate that the OPN‐CCR1 axis in HCC is important for accelerating tumor metastasis and that CCR1 is a potential therapeutic target for controlling metastasis in HCC patients with high OPN.
Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor siRNA
Authors: Zhang Haiyang , Wang Yi , Bai Ming , Wang Junyi , Zhu Kegan , Liu Rui , Ge Shaohua , Li JiaLu , Ning Tao , Deng Ting , Fan Qian , Li Hongli , Sun Wu , Ying Guoguang , Ba Yi
Published: December 2017

Exosomes derived from cells have been found to mediate signal transduction between cells and to act as efficient carriers to deliver drugs and small RNA. Hepatocyte growth factor (HGF) is known to promote the growth of both cancer cells and vascular cells, and the HGF‐cMET pathway is a potential clinical target. Here, we characterized the inhibitory effect of HGF siRNA on tumor growth and angiogenesis in gastric cancer. In addition, we showed that HGF siRNA packed in exosomes can be transported into cancer cells, where it dramatically downregulates HGF expression. A cell co‐culture model was used to show that exosomes loaded with HGF siRNA suppress proliferation and migration of both cancer cells and vascular cells. Moreover, exosomes were able to transfer HGF siRNA in vivo, decreasing the growth rates of tumors and blood vessels. The results of our study demonstrate that exosomes have potential for use in targeted cancer therapy by delivering siRNA.
Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice
Authors: Tumienė B. , Maver A. , Writzl K. , Hodžić A. , Čuturilo G. , Kuzmanić‐Šamija R. , Čulić V. , Peterlin B.
Published: December 2017

Although genetic revolution of recent years has vastly expanded a list of genes implicated in epilepsies, complex architecture of epilepsy genetics is still largely unknown, consequently, universally accepted workflows for epilepsy genetic testing in a clinical practice are missing. We present a comprehensive NGS‐based diagnostic approach addressing both the clinical and genetic heterogeneity of disorders involving epilepsy or seizures. A bioinformatic panel of 862 epilepsy‐ or seizure‐associated genes was applied to Mendeliome (4813 genes) or whole‐exome sequencing data as a first stage, while the second stage included untargeted variant interpretation. Eighty‐six consecutive patients with epilepsy or seizures associated with neurodevelopmental disorders and/or congenital malformations were investigated. Of the 86 probands, 42 harbored pathogenic and likely pathogenic variants, giving a diagnostic yield of 49%. Two patients were diagnosed with pathogenic copy number variations and 2 had causative mitochondrial DNA variants. Eleven patients (13%) were diagnosed with diseases with specific treatments. Besides, genomic approach in diagnostics had multiple additional benefits due to mostly non‐specific, overlapping, not full‐blown phenotypes and abilities to diagnose novel and ultra rare epilepsy‐associated diseases. Likely pathogenic variants were identified in SOX5 gene, not previously associated with epilepsy, and UBA5, a recently associated with epilepsy gene.
Independent introductions and sequential founder events shape genetic differentiation and diversity of the invasive green anole (Anolis carolinensis) on Pacific Islands
Authors: Michaelides Sozos N. , Goodman Rachel M. , Crombie Ronald I. , Kolbe Jason J.
Published: December 2017

Aim

Natural range expansions and human‐mediated colonizations usually involve a small number of individuals that establish new populations in novel habitats. In both cases, founders carry only a fraction of the total genetic variation of the source populations. Here, we used native and non‐native populations of the green anole,Anolis carolinensis, to compare the current distribution of genetic variation in populations shaped by natural range expansion and human‐mediated colonization.

Location

North America, Hawaiian Islands, Western Pacific Islands.

Methods

We analysed 401 mtDNAhaplotypes to infer the colonization history ofA. carolinensison nine islands in the Pacific Ocean. We then genotyped 576 individuals at seven microsatellite loci to assess the levels of genetic diversity and population genetic differentiation for both the native and non‐native ranges.

Results

Our findings support two separate introductions to the Hawaiian Islands and several western Pacific islands, with subsequent colonizations within each region following a stepping‐stone model. Genetic diversity at neutral markers was significantly lower in the non‐native range because of founder effects, which also contributed to the increased population genetic differentiation among the non‐native regions. In contrast, a steady reduction in genetic diversity with increasing distance from the ancestral population was observed in the native range following range expansion.

Main conclusions

Range expansions cause serial founder events that are the spatial analogue of genetic drift, producing a pattern of isolation‐by‐distance in the native range of the species. In human‐mediated colonizations, after an initial loss of genetic diversity, founder effects appear to persist, resulting in overall high genetic differentiation among non‐native regions but an absence of isolation‐by‐distance. Contrasting the processes influencing the amount and structuring of genetic variability during natural range expansion and human‐mediated biological invasions can shed new light on the fate of natural populations exposed to novel and changing environments.
Fetal echocardiography for planning perinatal and delivery room care of neonates with congenital heart disease
Authors: Sanapo Laura , Pruetz Jay D. , Słodki Maciej , Goens M. Beth , Moon‐Grady Anita J. , Donofrio Mary T.
Published: December 2017

Fetal echocardiography facilitates the prenatal diagnosis of infants with congenital heart disease (CHD) and through sequential examinations, allows assessment of fetal hemodynamics and cardiovascular status from the time of diagnosis to delivery. Fetal cardiologists have created diagnostic protocols aimed at risk stratifying severity and potential postnatal compromise in fetuses with CHD, and identifying those who may require special intervention at birth or within the first days of life. In this article, we review fetal cardiovascular physiology, the progression of CHD in utero and fetal echocardiographic findings used for risk stratification of newborns with CHD, as well as some of the basic principles of planning for the neonatal resuscitation and initial transitional care of these complex newborns.
Prenatal diagnosis of total anomalous pulmonary venous connection by 2D and 3D fetal echocardiography
Authors: Zhang Ye , Shao Qin , Sun Lin , Ge Shuping , He Yihua
Published: December 2017

Objective

Prenatal diagnosis of total anomalous pulmonary venous connection (TAPVC) by fetal echocardiography (FE) remains a challenge. We sought to ascertain the diagnostic accuracy of 2D and 3D spatiotemporal image correlation (STIC) FE and the potential incremental value of 3D STIC FE for prenatal diagnosis and assessment of TAPVC.

Methods

This study was conducted retrospectively in a single tertiary referral center. The study population consisted of 74 TAPVC from 17 063 fetuses by FE from August 2010 to April 2016. The 3D volume acquisition was also performed by STIC.

Results

A total of 17 063 fetal echocardiograms in our institution were queried and 74 (0.4%) were identified with TAPVC. In the TAPVC group, 11 had postnatal echocardiographic study, 25 had autopsies, 36 declined autopsy and 2 lost for follow‐up. The sensitivity of FE for diagnosis of TAPVC was 97.14%, specificity 99.98%, respectively. In our cohort, 31 fetuses were evaluated by both 2D and 3D STIC and were confirmed by postnatal echocardiography or autopsies. TAPVC was diagnosed in all 31 patients (100%) by both 2D FE and 3D STIC. Furthermore, the classification of subtypes of TAPVC and accurate diagnosis of the drainage pathway was correct in 26 (83.9%) and 24 (77.4%) cases by 2D FE, respectively; but in 31 (100%) and 31 (100%) cases by 3D STIC.

Conclusion

2D and 3D STIC FE provide accurate diagnosis of TAPVC with excellent sensitivity and specificity. 3D STIC FE has incremental value in further evaluation of classification of TAPVC types and drainage pathways.
Unserious but Serious Pilgrimages: What Educational Philosophy Can Learn about Fiction and Reality from Children's Artful Play
Authors: Johansson Viktor
Published: December 2017

What happens if we think of children's play as a form of great art that we turn to and return to for inspiration, for education? If we can see play as art, then what and how can we learn from children's play or from playing with them? What can philosophy, or philosophers, learn from children's play? In this essay Viktor Johansson gives examples of what and when children can teach philosophers through play or, more specifically, how children's play can teach philosophers about the relation between fiction and reality. It begins by exploring the educational relation between fiction and reality in recent revivals of literary humanism. Johansson gives examples from a preschool project of how children use fiction picture books and create new fiction in their play, and how they do so in ways that relate to previous philosophical considerations of literary fiction. To explore this, the essay enters into conversation with the work of Iris Murdoch on the playfulness of art. Through, and in contrast to, Murdoch's work, Johansson establishes that play can be great art through its nonpurposefulness and its use of skill and imagination. Moreover, turning to children's play becomes a method for attending to what Ludwig Wittgenstein calls philosophy's “natural history,” that is, a historicization of philosophical thinking that enables philosophers to learn from children. Johansson concludes by showing that encounters between fiction and play, and with children playing, can be an educational embroilment, not only between teacher and child, but between teacher, child, the visual, the material, and the philosophical in which all learn from one another.
Seascape genetics and biophysical connectivity modelling support conservation of the seagrass Zostera marina in the Skagerrak–Kattegat region of the eastern North Sea
Authors: Jahnke Marlene , Jonsson Per R. , Moksnes Per‐Olav , Loo Lars‐Ove , Nilsson Jacobi Martin , Olsen Jeanine L.
Published: December 2017

Maintaining and enabling evolutionary processes within meta‐populations are critical to resistance, resilience and adaptive potential. Knowledge about which populations act as sources or sinks, and the direction of gene flow, can help to focus conservation efforts more effectively and forecast how populations might respond to future anthropogenic and environmental pressures. As a foundation species and habitat provider, Zostera marina (eelgrass) is of critical importance to ecosystem functions including fisheries. Here, we estimate connectivity of Z. marina in the Skagerrak–Kattegat region of the North Sea based on genetic and biophysical modelling. Genetic diversity, population structure and migration were analysed at 23 locations using 20 microsatellite loci and a suite of analytical approaches. Oceanographic connectivity was analysed using Lagrangian dispersal simulations based on contemporary and historical distribution data dating back to the late 19th century. Population clusters, barriers and networks of connectivity were found to be very similar based on either genetic or oceanographic analyses. A single‐generation model of dispersal was not realistic, whereas multigeneration models that integrate stepping‐stone dispersal and extant and historic distribution data were able to capture and model genetic connectivity patterns well. Passive rafting of flowering shoots along oceanographic currents is the main driver of gene flow at this spatial–temporal scale, and extant genetic connectivity strongly reflects the “ghost of dispersal past“ sensu Benzie, . The identification of distinct clusters, connectivity hotspots and areas where connectivity has become limited over the last century is critical information for spatial management, conservation and restoration of eelgrass.
Repeatability of gait analysis measurements in Thoroughbreds in training
Authors: Sepulveda Caviedes M. F. , Forbes B. S. , Pfau T.
Published: December 2017

Background

With the view of implementing gait symmetry measurements in Thoroughbreds in training for early detection of injuries, repeatability of inertial measurement unit (IMU) gait parameters needs to be established.

Objectives

To assess the variation of head and pelvis movement symmetry in Thoroughbreds in training.

Study design

Repeated observations in horses in race training.

Methods

Daily and weekly repeat gait assessments were conducted in 14 Thoroughbreds equipped withIMUs on poll, sacrum and right (RTC) and left (LTC) tuber coxae. Gait was assessed in trot, in‐hand, on a level concrete surface. Difference between vertical displacement minima and maxima and range of motion (ROM) were obtained. Ranges containing 50% (median), 75, 90 and 95% of absolute daily and weekly differences were calculated and intraclass correlation coefficients (ICC) calculated for daily and weekly repeats.

Results

Median absolute daily differences ranged from 4 to 7 mm and median weekly differences from 4 to 8 mm. 90% of daily differences were between 9 and 16 mm and 90% of weekly differences between 11 and 19 mm.ICCvalues were found on average across sensors and gait parameters as 0.73 (ranging from 0.40 to 0.92 across parameters) for daily repeats and as 0.65 (0.27 to 0.91) for weekly repeats.

Main limitations

Horses were of varying training and movement asymmetry levels, and no veterinary lameness examination was conducted.

Conclusions

Daily and weekly repeat gait assessments in this group of Thoroughbreds in training show lowerICCvalues than previously reported from within‐day repeats in horses during lameness examinations. We recommend conducting repeatability studies for specific groups of horses when planning long‐term studies aiming at identifying horses at risk of injury.
The peak stress method to calculate residual notch stress intensity factors in welded joints
Authors: Colussi M. , Ferro P. , Berto F. , Meneghetti G.
Published: December 2017

According to the recent literature, the intensity of linear elastic residual stress fields near the toe region of a welded joint can be quantified by the residual notch stress intensity factors (R‐NSIFs). The computational effort required to compute the R‐NSIFs implies strong limitations of applicability in practice, owing to the very refined meshes needed and to the non‐linear transient nature of welding process simulations, especially in 3‐dimensional numerical models of large structures. The peak stress method (PSM) is a design approach that takes care of the industrial needs of rapidity and ease of use. According to the PSM, it is possible to evaluate the R‐NSIFs by using the peak stress calculated at the point of singularity with coarse finite element (FE) models. While the PSM was originally calibrated by using the Ansys FE code, in the present contribution, the PSM has been calibrated to rapidly estimate the R‐NSIFs in the Sysweld FE environment.
Australian wheat production expected to decrease by the late 21st century
Authors: Wang Bin , Liu De L. , O'Leary Garry J. , Asseng Senthold , Macadam Ian , Lines‐Kelly Rebecca , Yang Xihua , Clark Anthony , Crean Jason , Sides Timothy , Xing Hongtao , Mi Chunrong , Yu Qiang
Published: December 2017

Climate change threatens global wheat production and food security, including the wheat industry in Australia. Many studies have examined the impacts of changes in local climate on wheat yield per hectare, but there has been no assessment of changes in land area available for production due to changing climate. It is also unclear how total wheat production would change under future climate when autonomous adaptation options are adopted. We applied species distribution models to investigate future changes in areas climatically suitable for growing wheat in Australia. A crop model was used to assess wheat yield per hectare in these areas. Our results show that there is an overall tendency for a decrease in the areas suitable for growing wheat and a decline in the yield of the northeast Australian wheat belt. This results in reduced national wheat production although future climate change may benefit South Australia and Victoria. These projected outcomes infer that similar wheat‐growing regions of the globe might also experience decreases in wheat production. Some cropping adaptation measures increase wheat yield per hectare and provide significant mitigation of the negative effects of climate change on national wheat production by 2041–2060. However, any positive effects will be insufficient to prevent a likely decline in production under a high CO2 emission scenario by 2081–2100 due to increasing losses in suitable wheat‐growing areas. Therefore, additional adaptation strategies along with investment in wheat production are needed to maintain Australian agricultural production and enhance global food security. This scenario analysis provides a foundation towards understanding changes in Australia's wheat cropping systems, which will assist in developing adaptation strategies to mitigate climate change impacts on global wheat production.
Signals from the south; humpback whales carry messages of Antarctic sea‐ice ecosystem variability
Authors: Bengtson Nash Susan M. , Castrillon Juliana , Eisenmann Pascale , Fry Brian , Shuker Jon D. , Cropp Roger A. , Dawson Amanda , Bignert Anders , Bohlin‐Nizzetto Pernilla , Waugh Courtney A. , Polkinghorne Bradley J. , Dalle Luche Greta , McLagan David
Published: December 2017

Southern hemisphere humpback whales (Megaptera novaeangliae) rely on summer prey abundance of Antarctic krill (Euphausia superba) to fuel one of the longest‐known mammalian migrations on the planet. It is hypothesized that this species, already adapted to endure metabolic extremes, will be one of the first Antarctic consumers to show measurable physiological change in response to fluctuating prey availability in a changing climate; and as such, a powerful sentinel candidate for the Antarctic sea‐ice ecosystem. Here, we targeted the sentinel parameters of humpback whale adiposity and diet, using novel, as well as established, chemical and biochemical markers, and assembled a time trend spanning 8 years. We show the synchronous, inter‐annual oscillation of two measures of humpback whale adiposity with Southern Ocean environmental variables and climate indices. Furthermore, bulk stable isotope signatures provide clear indication of dietary compensation strategies, or a lower trophic level isotopic change, following years indicated as leaner years for the whales. The observed synchronicity of humpback whale adiposity and dietary markers, with climate patterns in the Southern Ocean, lends strength to the role of humpback whales as powerful Antarctic sea‐ice ecosystem sentinels. The work carries significant potential to reform current ecosystem surveillance in the Antarctic region.