bluuebunny/crossref_metadata_2025 huggingface dataset:
Theory and Evidence of Arbitrage Trading of Equity Futures
Authors: Yoo Jin , Kim Geun Beom
Published: September 2020

The equity futures market was opened in May 6th, 2008 for the first time in Korea but nonetheless it has rarely been researched since. In this paper, we examine whether the market, combined with the stock market, its underlying market, has been offering any arbitrage opportunities to market participants for the period of May 6th, 2008 to March 11, 2010, focusing on the two futures contracts of Samsung Electronics and Hyundai Motors, the two most actively traded ones. Our findings are as follows. First, there have been arbitrage opportunities for the two futures in either direction. Second, the average time period for an arbitrage opportunity was two seconds so arbitrage transactions were feasible indeed. Third, nevertheless, some arbitrage transactions ended up with a loss because the estimated spot price at maturity to carry out an arbitrage trading turned out to be significantly different from the realized one. The discrepancy in these two prices causes a seemingly very safe arbitrage trading a risky one. This risky feature of an arbitrage trading has never been addressed in depth in a paper or a book before, and is a major contribution of this paper.
Office Price Index for Derivative Using S&P/Case-Shiller Estimator
Authors: Ryu Kang Min , Park Soo Hoon , Lee Chang Moo
Published: September 2020

People are starting to doubt business recovery in office market after global financial crisis in 2008. And most institutional and individual portfolios are undiversified in real estate : incurring enormous transaction costs than other financial products. Especially office market has more risks than other real estate market for high transaction costs and many related industries. Although this stuff can lead to increase the risk of investment in office market, nor are there markets that would allow individuals and institutions to hedge their risks. The establishment of office price index future and option markets is likely to hedge away large risk in office market, and provides lowering transaction costs for trading in real estate. We estimate Office Price Index using S&P/Case-Shiller repeat sale estimator which is proposed by Robert. J. Shiller in 1991. The estimator is a sort of Feasible Generalized Two Stage Least Squares, which compute Value weighted Arithmetic Price Index.
Over-and Under-Reaction in Option MarKets: Evidences from USD/KRW OTC Currency Options
Authors: Kang Byung Jin
Published: September 2020

This study investigates the over- and under-reacting behavior of USD/KRW OTC currency option investors from the year of 2006 to 2011. Using the empirical testing models suggested by Poteshman (2001), we first find that USD/KRW OTC option investors tend to under-react to the unexpected changes in instantaneous variances, which means ‘short horizon under-reaction’. Second, we find that USD/KRW OTC option market tends to slightly over-react to a long period of mostly positive (or negative) unexpected changes in instantaneous variances during the period of before global financial crisis in 2008, We find, however, that this ‘long horizon over-reaction’ in the aforementioned period is not statistically significant. Third, we find that the market tends to significantly under-react, rather than over-react, to a long period of mostly positive (or negative) unexpected changes in instantaneous variances during the period of after global financial crisis in 2008. Finally, using the different empirical testing model (i.e., model-free approach), suggested by Jiang and Tian (2010), we also obtained the same empirical results, which strengthen the robustness of them.
The Variance Swaps based on KOSPI200 Index and the Term Structure of Variance Risk Premium
Authors: Eom Young Ho , Jang Woon Wook
Published: September 2020

This study examines whether the variance risk is a priced risk factor in Korea using the over-the-counter variance swap quotes and realized variance data. We also study the term structure of variance risk premium. The empirical results show that the model with 2 stochastic variance risk factors with jumps in return is required to fit the variance swap and realized variance data. The analyses with the estimated models suggest that the variance risk premium in Korea are highly negative and the size of the premium increase with the maturities, meaning that risk averse investors in Korea are willing to pay a premium to hedge variance risk.
Information Contents of Order Flow Toxicity in the Options Market : The Case of KOSPI200 Index Options
Authors: Lee Jaeram
Published: September 2020

This study estimates the VPIN (volume-synchronized probability of informed trading) of the KOSPI200 index options, the measure of order flow toxicity suggested by Easley et al. (2012), for the first time. To apply the VPIN approach, options are categorized by their real-time moneyness. I examine the predictive power of VPIN for the future stock market volatility using time-series regression analysis. The empirical result shows that the toxic order flow measure estimated by price changes has more information than that estimated by the actual order imbalance. In general, put options contain more information than call options, and the toxic order flow measure of OTM (out-of-the-money) put options contains the most significant information about the future stock market volatility. In addition, the predictive power of toxic order flow measure is much significant in the highly volatile than in the stable market. The volatility predictability of toxic order flow measure declined significantly after the option multiplier increase, whereas it has gradually recovered over time.
Challenges and enablers of the embedded researcher model
Authors: Coates Dominiek , Mickan Sharon
Published: September 2020

Purpose

The embedded researcher is a healthcare-academic partnership model in which the researcher is engaged as a core member of the healthcare organisation. While this model has potential to support evidence translation, there is a paucity of evidence in relation to the specific challenges and strengths of the model. The aim of this study was to map the barriers and enablers of the model from the perspective of embedded researchers in Australian healthcare settings, and compare the responses of embedded researchers with a primary healthcare versus a primary academic affiliation.

Design/methodology/approach

104 embedded researchers from Australian healthcare organisations completed an online survey. Both purposive and snowball sampling strategies were used to identify current and former embedded researchers. This paper reports on responses to the open-ended questions in relation to barriers and enablers of the role, the available support, and recommendations for change. Thematic analysis was used to describe and interpret the breadth and depth of responses and common themes.

Findings

Key barriers to being an embedded researcher in a public hospital included a lack of research infrastructure and funding in the healthcare organisation, a culture that does not value research, a lack of leadership and support to undertake research, limited access to mentoring and career progression and issues associated with having a dual affiliation. Key enablers included supportive colleagues and executive leaders, personal commitment to research and research collaboration including formal health-academic partnerships.

Research limitations/implications

To support the embedded researcher model, broader system changes are required, including greater investment in research infrastructure and healthcare-academic partnerships with formal agreements. Significant changes are required, so that healthcare organisations appreciate the value of research and support both clinicians and researchers to engage in research that is important to their local population.

Originality/value

This is the first study to systematically investigate the enablers and challenges of the embedded researcher model.
Exploring predictive maintenance applications in industry
Authors: Tiddens Wieger , Braaksma Jan , Tinga Tiedo
Published: September 2020

Purpose

Asset owners and maintainers need to make timely and well-informed maintenance decisions based on the actual or predicted condition of their physical assets. However, only few companies have succeeded to implement predictive maintenance (PdM) effectively. Therefore, this paper aims to identify why only few companies were able to successfully implement PdM.

Design/methodology/approach

A multiple-case study including 13 cases in various industries in The Netherlands was conducted. This paper examined the choices made in practice to achieve PdM and possible dependencies between and motivations for these choices.

Findings

An implementation process for PdM appeared to comprise four elements: a trigger, data collection, maintenance technique (MT) selection and decision-making. For each of these elements, several options were available. By identifying the choices made by companies in practice and mapping them on the proposed elements, logical combinations appeared. These combinations can provide insight into the PdM implementation process and may also lead to guidance on this topic. Further, while successful companies typically combined various techniques, the mostly applied techniques were still those based on previous experiences.

Research limitations/implications

This research calls for better methods or procedures to guide the selection and use of suitable types of PdM, directed by the firm's ambition level and the available data.

Originality/value

While it is important for firms to make suitable choices during implementation, the literature often focusses only on developing additional techniques for PdM. This paper provides new insights into the application and selection of techniques for PdM in practice and helps practitioners reduce the often applied trial-and-error process.
Towards a holistic view of corporate social responsibility. The antecedent role of information asymmetry and cognitive distance
Authors: Caputo Francesco
Published: September 2020

Purpose

This paper aims to enlarge ongoing debate about corporate social responsibility (CSR) proposing reflections about the role of cognitive and information flows in influencing companies’ approaches and market expectations related to CSR.

Design/methodology/approach

The paper builds upon the research streams related to the information asymmetry and cognitive distance, for identifying through the interpretative lens provided by systems studies, possible key drivers on which policymakers, researchers and practitioners should act for building a suitable, shared and long-term oriented path for CSR.

Findings

The paper defines a scenario map about CSR in the light of information asymmetry and cognitive distance. Such a map supports both researchers and practitioners in better understanding actions and paths required for building a shared approach to CSR.

Research limitations/implications

Recognizing the multidimensionality of CSR and the multiple managerial and organizational contributions provided for underling its advantages for companies, the paper focuses the attention on the elements and conditions able to promote, stimulate and encourage companies’ CSR strategies.

Originality/value

The paper provides a fresh conceptual framework for explaining conditions and elements required for ensuring the success of strategies for CSR. Adopting a systems view, the paper overcomes the limitations related to a reductionist view about advantages and results of CSR to call the attention on the conditions that should be met for ensuring the emergence of a shared approach to CSR.
How the coronavirus crisis affects citizen trust in institutions and in unknown others: Evidence from ‘the Swedish experiment’
Authors: ESAIASSON PETER , SOHLBERG JACOB , GHERSETTI MARINA , JOHANSSON BENGT
Published: September 2020

We study how Swedish citizens updated their institutional and interpersonal trust as the corona crisis evolved from an initial phase to an acute phase in the spring of 2020. The study is based on a large web‐survey panel with adult Swedes (n = 11,406) in which the same individuals were asked the same set of questions at two different time points during the coronavirus pandemic (t0 and t1). The sample was self‐selected but diverse (a smaller subsample, n = 1,464, was pre‐stratified to be representative of the Swedish population on key demographics). We find support for the view that the corona crisis led to higher levels of institutional and interpersonal trust. Moreover, reactions were largely homogeneous across those groups that could potentially relate distantly to government authorities.
Systematic review with meta‐analysis: comparative risk of lymphoma with anti‐tumour necrosis factor agents and/or thiopurines in patients with inflammatory bowel disease
Authors: Chupin Antoine , Perduca Vittorio , Meyer Antoine , Bellanger Christophe , Carbonnel Franck , Dong Catherine
Published: September 2020

Background

The risk of lymphoma in patients with inflammatory bowel disease (IBD) treated with anti‐TNF agents remains unclear.

Aim

To assess the comparative risk of lymphoma with anti‐TNF agents and/or thiopurines in IBD

Methods

We searched PubMed, EMBASE and Cochrane Library to identify studies that evaluated lymphoproliferative disorders associated with anti‐TNF agents with or without thiopurines. The risk of lymphoma was assessed through four comparator groups: combination therapy (anti‐TNF plus thiopurine), anti‐TNF monotherapy, thiopurine monotherapy and control group. Pooled incidence rate ratios (IRR) were estimated through Poisson‐normal models.

Results

Four observational studies comprising 261 689 patients were included. As compared with patients unexposed to anti‐TNF and thiopurines, those exposed to anti‐TNF monotherapy, thiopurine monotherapy or combination therapy had pooled IRR (per 1000 patient‐years) of lymphoma of 1.52 (95% CI: 1.06‐2.19; P = 0.023), 2.23 (95% CI: 1.79‐2.79; P < 0.001) and 3.71 (95% CI: 2.30‐6.00; P ≤ 0.01), respectively. The risk of lymphoma associated with combination therapy was higher than with thiopurines or anti‐TNF alone with pooled IRR of 1.70 (95% CI: 1.03‐2.81; P = 0.039) and 2.49 (95% CI: 1.39‐4.47; P = 0.002), respectively. The risk did not differ between anti‐TNF monotherapy and thiopurine monotherapy with pooled IRR of 0.72 (95% CI: 0.48‐1.07; P = 0.107). All observational studies were of high quality according to the Newcastle‐Ottawa scale.

Conclusions

There is an increased risk of lymphoma in IBD patients treated with anti‐TNF agents, either alone or when combined with thiopurines.
Comparative effectiveness of ustekinumab or vedolizumab after one year in 130 patients with anti‐TNF‐refractory Crohn’s disease
Authors: Townsend Tristan , Razanskaite Violeta , Dodd Susanna , Storey Daniel , Michail Stephanie , Morgan James , Davies Michael , Penman Douglas , Watters Christopher , Swaminathan Mira , Sabine Joseph , Chapman Adam , Smith Philip J , Flanagan Paul K. , Reilly Ian , Bodger Keith , Subramanian Sreedhar
Published: September 2020

Background

Anti‐tumour necrosis factor (TNF) agents are effective in Crohn's disease but some patients lose response and require alternative biologic therapy. There are few data on comparative effectiveness of vedolizumab and ustekinumab in this setting.

Aim

To compare the effectiveness of ustekinumab and vedolizumab in anti‐TNF‐refractory Crohn's disease over 12 months.

Methods

Patients commencing ustekinumab or vedolizumab for anti‐TNF‐refractory Crohn's disease with minimum follow‐up of 12 months were included. The primary outcome measure was the difference in steroid‐free remission rates at end of induction (2 months) and at 12 months. We also assessed rates of clinical response and remission, treatment persistence, surgery and adverse events in both groups. We performed logistic regression analysis to assess factors associated with steroid‐free remission and clinical response and remission.

Results

We included 85 patients commencing vedolizumab and 45 commencing ustekinumab. In an unadjusted model, rates of steroid‐free and clinical remission were significantly higher among ustekinumab‐treated patients. After adjusting for confounders, steroid‐free remission was higher among ustekinumab‐treated patients at 2 months (odds ratio, OR 2.79, 95% confidence interval, CI 1.06‐7.39, P = 0.038) and 12 months (OR 2.01, 95% CI 0.89‐4.56, P = 0.095). More patients treated with ustekinumab remained on therapy at the end of 12 months (84.4% vs 61.5%, P = 0.007).

Conclusions

Ustekinumab appeared more effective in treating anti‐TNF‐refractory Crohn's disease and more patients persisted with therapy.
Socioeconomic Status Gradients in Young Children’s Well‐Being at School
Authors: Loft Lisbeth , Waldfogel Jane
Published: September 2020

This study examines the socioeconomic status gradients in children’s well‐being at school using data on the total population of Danish public school children age 6–11 (N = 147,994). Children completed the national well‐being at school survey, an environment‐specific self‐report of satisfaction with school, social well‐being at school, and psychological well‐being at school. Data were linked with administrative register data on family characteristics. Regression analysis was used to estimate gradients by parental education and income for each of the three dimensions of well‐being at school. Findings indicated that even in the relatively equal Danish context, children from more educated and higher‐income families experienced greater satisfaction with school and higher social and psychological well‐being at school than their less advantaged peers.
Proof‐of‐concept calculations to determine the health‐adjusted life‐year trade‐off between intravitreal anti‐VEGF injections and transmission of COVID‐19
Authors: Boyd Matt J. , Scott Daniel A. R. , Squirrell David M. , Wilson Graham A.
Published: September 2020

Background

Clinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID‐19 pandemic, in order to minimize the risk of disease transmission.

Method

We performed probability calculations to estimate COVID‐19 infection status and likelihood of disease transmission among neovascular age‐related macular degeneration patients and health‐care workers during anti‐VEGF procedures, at various community prevalence levels of COVID‐19. We then applied the expected burden of COVID‐19 illness and death expressed through health‐adjusted life‐years (HALYs) lost. We compared these results to the expected disease burden of severe visual impairment if sight protecting anti‐VEGF injections were not performed.

Results

Our calculations suggest a wide range of contexts where the benefits of treatment to prevent progression to severe visual impairment or blindness are greater than the expected harms to the patient and immediate health care team due to COVID‐19. For example, with appropriate protective equipment the benefits of treatment outweigh harms when the chance of progression to severe visual impairment is >0.044% for all scenarios where COVID‐19 prevalence was 1/1000, even when the attack rate in the clinical setting is very high (5‐43%).

Conclusion

Unless COVID‐19 prevalence is very high, the reduced disease burden from avoiding visual impairment outweighs the expected HALYs lost from COVID‐19 transmission. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment for 5 years are equivalent to nearly 400 moderate cases of infectious disease lasting 2 weeks each.
Potential unrealized mortality benefit of glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transport‐2 inhibitors: A report from the Veterans Health Administration Clinical Assessment, Reporting and Tracking program
Authors: Salahuddin Taufiq , Richardson Vanessa , McNeal Demetria M. , Henderson Kamal , Hess Paul L. , Raghavan Sridharan , Saxon David R. , Valle Javier A. , Waldo Stephen W. , Ho P. Michael , Schwartz Gregory G.
Published: September 2020

Aim

To assess the unrealized potential of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) or sodium‐glucose co‐transport‐2 inhibitor (SGLT2i) use to reduce mortality in veterans with type 2 diabetes (T2D), coronary artery disease (CAD), and other characteristics congruent with clinical trial cohorts that established the efficacy of these agents.

Methods

Veterans with T2D and CAD on angiography in 2014 who were untreated with either a GLP‐1RA or a SGLT2i were assessed for key eligibility criteria of the LEADER (GLP‐1RA) and EMPA‐REG OUTCOME (SGLT2i) trials. Trial hazard ratios and 95% confidence intervals for all‐cause death were applied to deaths observed in veterans through 2018 to estimate the potential benefit of GLP‐1RA or SGLT2i use.

Results

Median observation was 4.3 years. Of 15 987 veterans with T2D and CAD, 1186 (7.4%) were excluded for GLP‐1RA or SGLT2i treatment, and 1386 lacked glycated haemoglobin measurement. Of the remaining 13 415 patients, 4103 (30.1%) and 5313 (39.6%) fulfilled the key criteria for the LEADER and EMPA‐REG OUTCOME trials, respectively. Death occurred in 1009 (24.6%) of LEADER‐eligible patients and 1335 (25.1%) of EMPA‐REG OUTCOME‐eligible patients. Under treatment with liraglutide in LEADER‐eligible veterans, a 3.5% (0.7%‐6.2%) potential absolute mortality reduction, corresponding to 144 (28‐253) fewer deaths (0.88 [0.17‐1.56] per 100 person‐years), might have been expected. Similarly, under treatment with empagliflozin in EMPA‐REG OUTCOME‐eligible veterans, a 7.9% (4.5%‐10.8%) potential absolute mortality reduction, corresponding to 418 (230‐573) fewer deaths (1.98 [1.14‐2.72] per 100 person‐years), might have been expected.

Conclusions

This analysis indicates unrealized opportunities to reduce mortality in selected veterans with T2D and CAD via increased GLP‐1RA and SGLT2i use.
Direct oral anticoagulants and advanced liver disease: A systematic review and meta‐analysis
Authors: Menichelli Danilo , Ronca Vincenzo , Di Rocco Arianna , Pignatelli Pasquale , Marco Podda Gian ,   CAR
Published: September 2020

Background

Direct oral anticoagulants (DOACs) are recommended for stroke prevention in patients with atrial fibrillation (AF) or for treatment of deep vein thrombosis, although some concerns about safety and efficacy were raised on the use of these drugs in patients with advanced liver disease (ALD). We want to investigate the association of DOACs use with the bleeding and ischaemic risk.

Material and Methods

We performed a systematic review and metanalysis of clinical studies retrieved from PubMed (via MEDLINE) and Cochrane (CENTRAL) databases addressing the impact of DOACs therapy on bleeding events including intracranial haemorrhage (ICH), gastrointestinal and major bleeding. Secondary end points were all‐cause death, ischaemic stroke/systemic embolism (IS/SE) and recurrence/progression of vein thrombosis (rDVT).

Results

12 studies were included in the meta‐analysis: a total of 43 532 patients with ALD or cirrhosis, of whom 27 574 (63.3%) were on treatment with DOACs and 15 958 were in warfarin/low molecular weight heparin. DOACs reduced the incidence of major bleeding by 61% (pooled Hazard Ratio [HR] 0.39, 95% Confidence Interval [CI] 0.21‐0.70), ICH by 52% (HR 0.48, 95% CI 0.40‐0.59), while no difference in the reduction of any and gastrointestinal bleeding were observed. DOACs reduced also rDVT by 82% (HR 0.18, 95%CI 0.06‐0.57), but did not reduce death and IS/SE. No difference was shown according to oesophageal varices and Child Pugh score in the meta‐regression analysis between warfarin/heparin and DOACs performed on each outcome.

Conclusions

DOACs are associated with a lower incidence of bleeding and may be an attractive therapeutic option in patients with cirrhosis.
Inherited neuropathies with predominant upper limb involvement: genetic heterogeneity and overlapping pathologies
Authors: McMacken G. , Whittaker R. G. , Charlton R. , Barresi R. , Lochmüller H. , Horvath R.
Published: September 2020

Background and purpose

In a subset of patients with inherited peripheral neuropathies the first symptom is atrophy and weakness of the intrinsic muscles of the hands, without involvement of lower limbs until later in the disease course. The exact pathomechanisms of this phenotype are currently unknown. The aim of this study was to characterize the clinical, neurophysiological and genetic features of a group of patients with a clinical diagnosis of upper limb predominant Charcot‐Marie‐Tooth disease (CMT).

Methods

The clinical, electrophysiology and genetic data of 11 patients with upper limb predominant peripheral neuropathy selected from a single‐centre cohort of 461 patients diagnosed with inherited neuropathy were analysed and the clinical, electrophysiological and genetic characteristics of these patients reported.

Results

An overlapping phenotype of neuropathy and myopathy was detected in two patients. Four patients carry autosomal dominant mutations in GARS and a single patient had a homozygous mutation in SH3TC2. However, the underlying genetic diagnosis could not be confirmed in six patients by gene panel sequencing.

Conclusions

Upper limb‐onset inherited neuropathies are genetically heterogeneous and, in some cases, there is an overlapping myopathy. Autosomal dominant GARS mutations are the most common genetic cause; however, mutations in other CMT genes may also result in this phenotype in individual patients. The majority of these patients cannot be genetically diagnosed by gene panel testing of known CMT and myopathy genes, suggesting further genetic heterogeneity and highlighting the importance of further genetic investigations in these patients and families.
Blockchain speculation or value creation? Evidence from corporate investments
Authors: Autore Don M. , Clarke Nicholas , Jiang Danling
Published: September 2020

Many corporate executives believe blockchain technology is broadly scalable and will achieve mainstream adoption, yet there is little evidence of significant shareholder value creation associated with corporate adoption of blockchain technology. We collect a broad sample of firms that invest in blockchain technology and examine the stock price reaction to the “first” public revelation of this news. Initial reactions average close to +13% and are followed by reversals over the next 3 months. However, we report a striking difference based on the credibility of the investment. Blockchain investments that are at an advanced stage or are confirmed in subsequent financial statements are associated with higher initial reactions and little or no reversal. The results suggest that credible corporate strategies involving blockchain technology are viewed favorably by investors.
Construction and identification of influenza plasmid pool imparting high yields to candidate vaccine viruses in Vero cell at low temperature
Authors: Liu Ze , Geng Xingliang , Cui Zhaohai , Li Weidong , Ou Xia , Liao Guoyang
Published: September 2020

We generated plasmid pools for the rapid preparation of candidate vaccine strains, which could grow in the Vero cells at low temperature. Firstly, we cloned in the pHW2000 plasmid each of the eight gene segments (PB2, PB1, PA, hemagglutinin [HA], neuraminidase [NA], NS, NP, M) of two master donor strains (MDS), respectively, A/Yunnan/1/2005Vca(H3N2) and B/Yunnan/2/2005Vca(By), which had Vca phenotype (cold‐adapted phenotype in Vero cells). Secondly, the similar operation was implemented with each of the HA, NA and NP segments of circulating strains with epidemic potential (parental strains). The virus rescue techniques were employed in this study, according to the homology rate of HA segments between MDS and parental strains. Then, we harvested amount of new Vca virus strains. By transmission electron microscope, it could observe new viruses' diameter and length were from 100 to 120 nm. Importantly, these reassortant viruses could get high‐yield production in Vero cells at 25℃ from the beginning to the fourth generation, which was significantly differ from their original parental viruses. Additional, these production 16 new Vca strains could maintain enough antibody binding capacity and attenuation phenotype, which consisted with their MDS. So these plasmid pools constructed by mount of different influenza A and B virus gene fragments could present desired working performance and provide convenience and realization for more Vca reassortant virus as candidate vaccine strain if needing.
A simple novel approach for detecting blood–brain barrier permeability using GPCR internalization
Authors: Csaba Z. , Vitalis T. , Charriaut‐Marlangue C. , Margaill I. , Coqueran B. , Leger P.‐L. , Parente I. , Jacquens A. , Titomanlio L. , Constans C. , Demene C. , Santin M. D. , Lehericy S. , Perrière N. , Glacial F. , Auvin S. , Tanter M. , Ghersi‐Egea J.‐F. , Adle‐Biassette H. , Aubry J.‐F. , Gressens P. , Dournaud P.
Published: September 2020

Aims

Impairment of blood–brain barrier (BBB) is involved in numerous neurological diseases from developmental to aging stages. Reliable imaging of increased BBB permeability is therefore crucial for basic research and preclinical studies. Today, the analysis of extravasation of exogenous dyes is the principal method to study BBB leakage. However, these procedures are challenging to apply in pups and embryos and may appear difficult to interpret. Here we introduce a novel approach based on agonist‐induced internalization of a neuronal G protein‐coupled receptor widely distributed in the mammalian brain, the somatostatin receptor type 2 (SST2).

Methods

The clinically approved SST2 agonist octreotide (1 kDa), when injected intraperitoneally does not cross an intact BBB. At sites of BBB permeability, however, OCT extravasates and induces SST2 internalization from the neuronal membrane into perinuclear compartments. This allows an unambiguous localization of increased BBB permeability by classical immunohistochemical procedures using specific antibodies against the receptor.

Results

We first validated our approach in sensory circumventricular organs which display permissive vascular permeability. Through SST2 internalization, we next monitored BBB opening induced by magnetic resonance imaging‐guided focused ultrasound in murine cerebral cortex. Finally, we proved that after intraperitoneal agonist injection in pregnant mice, SST2 receptor internalization permits analysis of BBB integrity in embryos during brain development.

Conclusions

This approach provides an alternative and simple manner to assess BBB dysfunction and development in different physiological and pathological conditions.
E‐portfolios and Entrustable Professional Activities to support competency‐based education in dietetics
Authors: Bramley Andrea Louise , Thomas Colleen J , Mc Kenna Lisa , Itsiopoulos Catherine
Published: September 2020

The concept of Entrustable Professional Activities, recently pioneered in medical education, has emerged to support the implementation of competency‐based education. Although competency‐based frameworks are widely used in healthcare professional education to develop outcomes‐based curricula, assessment of student competency in professional placement settings remains challenging. The novel concept of Entrustable Professional Activities together with established methods of competency assessment, namely e‐portfolios and self‐assessment, was implemented in the “[La Trobe University Dietetic program in 2015–2016. This study aimed to appraise the e‐portfolio and evaluate the use of Entrustable Professional Activities to assess competence. A mixed‐methods evaluation, using qualitative and quantitative surveys with follow‐up structured consultations, was conducted with final year dietetics students and their supervisors. Dietetics students were comfortable with Entrustable Professional Activities and competency‐based assessment, whereas supervisors preferred Entrustable Professional Activity based assessment. All stakeholders valued student self‐assessment and the ongoing use of structured e‐portfolios to develop and document competency. The use of structured e‐portfolios, student self‐assessment, and the emerging concept of Entrustable Professional Activities are useful tools to support dietetics student education in professional placement settings.
The ABI4‐RbohD/VTC2 regulatory module promotes reactive oxygen species (ROS) accumulation to decrease seed germination under salinity stress
Authors: Luo Xiaofeng , Dai Yujia , Zheng Chuan , Yang Yingzeng , Chen Wei , Wang Qichao , Chandrasekaran Umashankar , Du Junbo , Liu Weiguo , Shu Kai
Published: September 2020

Salinity stress enhances reactive oxygen species (ROS) accumulation by activating the transcription of NADPH oxidase genes such as RbohD, thus mediating plant developmental processes, including seed germination. However, how salinity triggers the expression of ROS‐metabolism‐related genes and represses seed germination has not yet been fully addressed.

In this study, we show that Abscisic Acid‐Insensitive 4 (ABI4), a key component in abscisic acid (ABA) signaling, directly combines with RbohD and Vitamin C Defective 2 (VTC2), the key genes involved in ROS production and scavenging, to modulate ROS metabolism during seed germination under salinity stress.

Salinity‐induced ABI4 enhances RbohD expression by physically interacting with its promoter, and subsequently promotes ROS accumulation, thus resulting in cell membrane damage and a decrease in seed vigor. Additional genetic evidence indicated that the rbohd mutant largely rescues the salt‐hypersensitive phenotype of ABI4 overexpression seeds. Consistently, the abi4/vtc2 double mutant showed the salt‐sensitive phenotype, similar to the vtc2 mutant, suggesting that both RbohD and VTC2 are epistatic to ABI4 genetically.

Altogether, these results suggest that the salt‐induced RbohD transcription and ROS accumulation is dependent on ABI4, and that the ABI4‐RbohD/VTC2 regulatory module integrates both ROS metabolism and cell membrane integrity, ultimately repressing seed germination under salinity stress.
The potential threat of multisystem inflammatory syndrome in children during the COVID‐19 pandemic
Authors: Rothan Hussin A. , Byrareddy Siddappa N.
Published: September 2020

Multisystem inflammatory syndrome in children (MIS‐C) during the COVID‐19 pandemic raised a global alert from the Centers for Disease Control and Prevention's Health Alert Network. The main manifestations of MIS‐C (also known as pediatric MIS (PMIS)) in the setting of a severe inflammatory state include fever, diarrhea, shock, and variable presence of rash, conjunctivitis, extremity edema, and mucous membrane changes. In some cases, these symptoms progressed to multi‐organ failure. The low percentage of children with asymptomatic cases compared with mild illness and moderate illness could be correlated with the rare cases of MIS‐C. One potential explanation for the progression to severe MIS‐C disease despite the presence of readily detectable anti‐SARS‐CoV‐2 antibodies could be due to the potential role of antibody‐dependent enhancement (ADE). We reason that the incidence of the ADE phenomenon whereby the pathogen‐specific antibodies can promote pathology should be considered in vaccine development against SARS‐CoV‐2.
Towards doubling fibre yield for cotton in the semiarid agricultural area by increasing tolerance to drought, heat and salinity simultaneously
Authors: Esmaeili Nardana , Cai Yifan , Tang Feiyu , Zhu Xunlu , Smith Jennifer , Mishra Neelam , Hequet Eric , Ritchie Glen , Jones Don , Shen Guoxin , Payton Paxton , Zhang Hong
Published: September 2020

Abiotic stresses such as extreme temperatures, water‐deficit and salinity negatively affect plant growth and development, and cause significant yield losses. It was previously shown that co‐overexpression of the Arabidopsis vacuolar pyrophosphatase gene AVP1 and the rice SUMO E3 ligase gene OsSIZ1 in Arabidopsis significantly increased tolerance to multiple abiotic stresses and led to increased seed yield for plants grown under single or multiple abiotic stress conditions. It was hypothesized that there might be synergistic effects between AVP1 overexpression and OsSIZ1 overexpression, which could lead to substantially increased yields if these two genes are co‐overexpressed in real crops. To test this hypothesis, AVP1 and OsSIZ1 were co‐overexpressed in cotton, and the impact of OsSIZ1/AVP1 co‐overexpression on cotton's performance under normal growth and multiple stress conditions were analysed. It was found that OsSIZ1/AVP1 co‐overexpressing plants performed significantly better than AVP1‐overexpressing, OsSIZ1‐overexpressing and wild‐type cotton plants under single, as well as under multiple stress conditions in laboratory and field conditions. Two field studies showed that OsSIZ1/AVP1 co‐overexpressing plants produced 133% and 81% more fibre than wild‐type cotton in the dryland conditions of West Texas. This research illustrates that co‐overexpression of AVP1 and OsSIZ1 is a viable strategy for engineering abiotic stress‐tolerant crops and could substantially improve crop yields in low input or marginal environments, providing a solution for food security for countries in arid and semiarid regions of the world.
Total hip replacement in dogs with contralateral pelvic limb amputation: A retrospective evaluation of 13 cases
Authors: Gifford Amy B. , Lotsikas Peter J. , Liska William D. , Israel Sarah K. , Rochat Mark C. , Saunders W. Brian , Guiot Laurent P. , Marcellin‐Little Denis J. , Benjamino Kevin P. , Dyce Jonathan
Published: September 2020

Objective

To report the clinical characteristics, surgical management, and medium‐term outcomes of total hip replacement (THR) performed in dogs with previous contralateral pelvic limb amputation.

Animals

Thirteen client‐owned dogs.

Study design

Multi‐institutional retrospective clinical study.

Methods

Data recorded from medical records included signalment, indication for amputation and THR, and surgical complications. Implant positioning and complications were assessed on radiographs. Clinical outcomes were evaluated during follow‐up examinations by one of the authors and through a mobility‐ and lifestyle‐based questionnaire completed by owners.

Results

All 13 dogs had satisfactory clinical results at follow‐up a median of 3 months (range, 2‐36) after THR. No postoperative luxation was recorded. Four dogs had minor complications that did not require additional treatment. The only major complication was one failure of osseointegration of a cementless acetabular cup, and it was successfully revised.

Conclusion

Total hip replacement resulted in satisfactory clinical results and acceptable morbidity in this population.

Clinical significance

Total hip replacement should be considered in dogs with severe coxofemoral joint disease and contralateral pelvic limb amputation.
Antibody reactivity with new antigens revealed in multi‐transgenic triple knockout pigs may cause early loss of pig kidneys in baboons
Authors: Ariyoshi Yuichi , Takeuchi Kazuhiro , Pomposelli Thomas , Ekanayake‐Alper Dilrukshi K. , Shimizu Akira , Boyd Lennan , Estime Ermance , Ohta Mayu , Asfour Arsenoi , Scott Arn J. , Ayares David , Lorber Marc , Sykes Megan , Sachs David , Yamada Kazuhiko
Published: September 2020

Background

Recent advances in gene editing technology have enabled the production of multi‐knockout (KO) and transgenic pigs in order to overcome immunologic barriers in xenotransplantation (XTx). However, the genetic manipulations required to produce these changes may have the unintended consequence of producing or revealing neoantigens reactive with natural antibodies present in baboons. In this study, we examined whether the neoantigens that develop in multi‐transgenic (mTg) GalT, Cytidine monophospho‐N‐acetylneuraminic acid hydroxylase (CMAH), β‐1,4‐N‐acetyl‐galactosaminyl transferase 2 (B4) KO pigs can cause rejection of xenografts in baboons.

Methods

Five baboons that had <35% cytotoxicity against GalT‐KO peripheral blood mononuclear cells (PBMCs) in a pre‐screening assay received pig kidneys and vascularized thymic grafts (VT + K) from multi‐transgenic hCD47, human thrombomodulin (hTBM), human endothelial protein C receptor (EPCR) with/without hCD46 and hCD55 with GalT‐KO/NeuGC‐KO/B4‐KO (mTg Tri‐KO) swine. In order to further examine the effects of anti‐donor non‐Gal natural antibody (nAb), anti‐pig preformed IgM and IgG nAb binding against the GalT‐KO PBMCs was compared with the donor‐type PBMCs using donor pretransplant sera as well as 5 additional naïve baboon sera by flow cytometric analysis.

Results

Five baboons that received VT + K grafts had stable renal function in the first 11 days (serum creatinine < 1.5 mg/dL). Two of the five baboons had higher binding of preformed IgG to mTg Tri‐KO PBMCs than to GalT‐KO PBMCs (mTg Tri‐KO > GalT‐KO), and they rejected their grafts at POD 20. In contrast, the other three baboons demonstrated either mTg Tri‐KO = GalT‐KO or mTg Tri‐KO < GalT‐KO, and they maintained renal function 43, 52, and 154 days without rejection. Among 10 baboon sera, two had less antibody binding against PBMCs that were syngeneic to the mTg Tri‐KO than against GalT‐KO PBMCs (mTg Tri‐KO < GalT‐KO); three had similar binding to mTg Tri‐KO and GalT‐KO PBMCs (mTg Tri‐KO = GalT‐KO); and five had higher binding to m Tg Tri‐KO than to GalT‐KO PBMCs (mTg Tri‐KO > GalT‐KO).

Conclusions

These data suggest that neoantigens associated with mTg Tri‐KO promote acute xenograft rejection in a pig‐to‐baboon VT + K XTx model. The screening assays may be useful to select “safe” recipients to receive mTg Tri‐KO kidneys.
Changes in phenolic compounds and antioxidant capacity of Andean raspberries in response to Peronospora sparsa
Authors: Cardona-Hurtado Nathalia , Guerrero-Alvarez Gloria E , López-Gutiérrez Ana M
Published: September 2020

In Colombia, the Andean raspberry (Rubus glaucus Benth) is of large economic significance because of its use in industry and widespread consumption as a fresh fruit. However, this crop is highly susceptible to disease by Peronospora sparsa, a fungus that causes between 50 % and 70 % production loss. Plants respond to pathogen-induced damage by increasing the production of specific secondary metabolites, such as phenolic compounds, which have broad industrial applications. This work estimated the antioxidant capacity and phenolic content of healthy and Peronospora sparsa-infected Andean raspberry fruits. Antioxidant capacity was analyzed by DPPH and FRAP methods, while phenolic compounds were analyzed by high performance liquid chromatography coupled to diode array detection (HPLC-DAD). According to the DPPH method, antioxidant capacity increased from 45.9 ± 1.61 µmol TE g−1 fresh sample in healthy fruits to 67.02 ± 0.58 µmol TE g−1 fresh sample in affected fruits. The FRAP method revealed an antioxidant response difference from 5.19 ± 0.8 mmol TE 100 g−1 fresh sample in healthy fruits vs. 10.97 ± 0.27 mmol TE 100 g−1 fresh sample in affected fruits. The phenolic compound content was observed in a range of 4.14 ± 1.16 to 72.03 ± 26.68 mg GAE L−1 for healthy fruits and from 4.48 ± 1.76 to 221.89 ± 1.18 mg GAE L−1 for affected fruits. Phenolic acids were the main phenols detected, encompassing derivatives of gallic acid, chlorogenic acid, ferulic acid, ellagic acid, and p-coumaric acid. This work confirmed that the Peronospora sparsa-infected berries contained relatively more antioxidants and phenolic acid compounds than their healthy counterparts, and that this difference was likely due to a defense mechanism to cope with pathogen-induced damage.
Host preference, population dynamics, distribution, and injuries of Oligonychus punicae (Acari: Tetranychidae) in an eucalyptus clonal minigarden

Authors: Barros Ferraz José Cláudio , Da Silva Silvestre Moreira , De França Solange Maria , Ramalho Silva Paulo Roberto , Da Silva Melo José Wagner , De Lima Debora Barbosa
Published: September 2020

Oligonychus punicae has potential for development in several species of eucalyptus. In this study was evaluated the preference for permanence and oviposition of O. punicae in different eucalyptus species. Additionally, we evaluated its dynamics and population distribution, as well as injuries in strains of Eucalyptus urophylla in a clonal minigarden. The preference for permanence and oviposition of O. punicae was evaluated using a test with and without choice in six species of Eucalyptus. We also analyzed the dynamics, population distribution and injury levels by O. punicae on E. urophylla in a clonal minigarden. We collected samples for 24 months and counted the number of eggs, immature and adult individuals. We calculated the Morisita dispersion index. We estimated injuries on leaves of E. urophylla using visual notes. In the test with choice, Eucalyptus urophylla was the preferred host of O. punicae for permanence and oviposition. In the test without choice, the oviposition of O. punicae in eucalyptus species did not differ statistically until 24 hours of evaluation. However, there was a significant difference after 48 hours, with greater oviposition on Eucalyptus brassiana, Eucalyptus tereticornis and Eucalyptus grandis. In the population survey, we collected 3,293 mites. The population peak of O. punicae occurred in March and April 2018 and April 2019. Oligonychus punicae presented an aggregate distribution and caused injuries of 20% on average in leaves. These results are important to guide management strategies in specific infestation foci and optimizing the use of phytosanitary products.
Chemical passivation of the perovskite layer and its real-time effect on the device performance in back-contact perovskite solar cells
Authors: Jumabekov Askhat N.
Published: September 2020

The back-contact architecture for perovskite solar cells (PSCs) offers the possibility of positioning both electrodes on one side of the absorber layer and shining light directly on the perovskite photoactive layer. This helps us to avoid the occurrence of transmission losses caused by the charge collecting transparent conductive oxide electrode in the conventional sandwich structure for PSCs. The back-contact device architecture is also useful for conducting fundamental studies as it has an exposed photoactive area, permitting in situ measurements on the effects of chemical treatment, passivation, and annealing. A successful application of back-contact PSCs in studying the effect of chemical passivation of the perovskite photo-absorber layer trap states with pyridine and its influence on the device performance have been studied. The real-time effect of pyridine vapor treatment on the device performance is visualized by monitoring the maximum power output of the devices under operation conditions. The device performance enhancement by ∼12% owing to the surface passivating effect of pyridine is demonstrated.
Mining and Statistical Modeling of Natural and Variant Class IIa Bacteriocins Elucidate Activity and Selectivity Profiles across Species
Authors: Tresnak Daniel T. , Hackel Benjamin J.
Published: September 2020

Class IIa bacteriocin antimicrobial peptides (AMPs), an alternative to traditional small-molecule antibiotics, are capable of selective activity toward various Gram-positive bacteria, limiting negative side effects associated with broad-spectrum activity. This selective activity is achieved through targeting of the mannose phosphotransferase system (manPTS) of a subset of Gram-positive bacteria, although factors affecting this mechanism are not entirely understood. Peptides identified from genomic data, as well as variants of previously characterized AMPs, can offer insight into how peptide sequence affects activity and selectivity. The experimental methods presented here identify promising potent and selective bacteriocins for further evaluation, highlight the potential of simple computational modeling for prediction of AMP performance, and demonstrate that factors beyond manPTS sequence affect bacterial susceptibility to class IIa bacteriocins.