bluuebunny/crossref_metadata_2025 huggingface dataset:
Interval and tender offer closed-end funds: investment company alternatives to traditional funds
Authors: Audette James , Draney Walter , Koff Jonathan , Warren Morrison
Published: October 2019

Purpose

To introduce the concepts of interval funds and tender offer funds and compare them to other pooled investment vehicles.

Design/methodology/approach

This article provides an overview of the interval fund and tender offer fund structures, including the law, regulations and market practices regarding redemptions, liquidity, fees and expenses and other key terms.

Findings

Interval funds and tender offer funds should be considered by alternative investment managers seeking to expand into public markets or traditional fund managers that seek additional portfolio flexibility.

Originality/value

In addition to a plain English analysis of the rules and regulations applicable to interval funds and tender offer funds, the article analyzes market practices regarding redemption frequency and amount.
Effects of CEO duality and tenure on innovation
Authors: Li Mengge , Yang Jinxin
Published: October 2019

Purpose

As the primary decision makers, chief executive officers (CEOs) play pivotal roles in firm innovation. However, little is known regarding how CEOs influence the exploitation and exploration paradox. To advance theory and research, the purpose of this paper is to investigate the joint effects of CEO tenure and CEO–chair duality on a firm’s shifting emphasis between exploitative and exploratory innovation.

Design/methodology/approach

This paper takes the approach of a longitudinal sample of 81 US pharmaceutical firms.

Findings

As CEOs’ tenure advance, their firms’ percentage of exploitative innovation increases. Furthermore, non-duality (separation of board chair and CEO) further strengthens the positive relationship between CEO tenure and the percentage of exploitative innovation.

Research limitations/implications

This study integrates upper echelons theory and behavioral agency theory to juxtapose the effects of CEOs on technological innovation. This study extends knowledge of strategic leadership and innovation by showing that CEOs influence the balance between exploitative and exploratory innovation. Furthermore, this study also contributes to the corporate governance literature by demonstrating that monitoring vigilance could inhibit capable CEOs from pursuing more exploratory innovation.

Practical implications

Boards of directors should allow CEOs to have greater discretion over innovation, and vigilant monitoring and control may force CEOs to focus less on exploration.

Originality/value

This is one of the few studies that explicitly investigate how CEO influences a firm’s emphasis on exploitative innovation and exploratory innovation.
Taking risks to improve safety? Workplace learning in anesthesia
Authors: Cuvelier Lucie
Published: October 2019

Purpose

Previous results show that the anesthetists’ activity during the planning phase is aimed at neither identifying risks nor pinpointing the adverse events likely to occur; rather, it is to devise “manageable situations” that are adapted to their own competences. The present paper focuses on the issue of understanding how, in practice, these “manageable situations” are constructed. In particular it wonders if a link between the seniority of anesthetists and the way they design these “manageable situations” may be established.

Design/methodology/approach

The paper sought to answer these questions through a qualitative study conducted in partnership with anesthetists. The method, combining interviews and case-based simulation, required that 20 anesthetists “thought aloud”.

Findings

Results show that the anesthetists sometimes selected a solution that they themselves and experts viewed as riskier. Why? And who selects a riskier solution? The answer is about workplace learning and the continuous development of experience-based competences. “Manageable situations” appear to be planned situations so as to propose solutions adapted not only to present competences but also for future competences to be developed. In that sense, they are part of a developmental process at work.

Originality/value

These findings have implications for practice and they open pathways for further research studies. They call for rethinking the link between experience and workplace learning.
Stock market data modelling using fitness-oriented JAYA algorithm-based deep belief network
Authors: Swamy A. Kullaya , B. Sarojamma
Published: October 2019

Purpose

Data mining plays a major role in forecasting the open price details of the stock market. However, it fails to address the dimensionality and expectancy of a naive investor. Hence, this paper aims to study a future prediction model named time series model is implemented.

Design/methodology/approach

In this model, the stock market data are fed to the proposed deep neural networks (DBN), and the number of hidden neurons is optimized by the modified JAYA Algorithm (JA), based on the fitness function. Hence, the algorithm is termed as fitness-oriented JA (FJA), and the proposed model is termed as FJA-DBN. The primary objective of this open price forecasting model is the minimization of the error function between the modeled and actual output.

Findings

The performance analysis demonstrates that the deviation of FJA–DBN in predicting the open price details of the Tata Motors, Reliance Power and Infosys data shows better performance in terms of mean error percentage, symmetric mean absolute percentage error, mean absolute scaled error, mean absolute error, root mean square error, L1-norm, L2-Norm and Infinity-Norm (least infinity error).

Research limitations/implications

The proposed model can be used to forecast the open price details.

Practical implications

The investors are constantly reviewing past pricing history and using it to influence their future investment decisions. There are some basic assumptions used in this analysis, first being that everything significant about a company is already priced into the stock, other being that the price moves in trends

Originality/value

This paper presents a technique for time series modeling using JA. This is the first work that uses FJA-based optimization for stock market open price prediction.
Environmental pollution, economic growth and institutional quality: exploring the nexus in Nigeria
Authors: Egbetokun Samuel , Osabuohien Evans , Akinbobola Temidayo , Onanuga Olaronke Toyin , Gershon Obindah , Okafor Victoria
Published: October 2019

Purpose

Interaction between environmental pollution and economic growth determines the achievement of the green growth objective of developing economies. An economy turns around the inverted U-shaped environmental Kuznets curve (EKC) when pollution is effectively dampened by social, political and economic factors as such economy grows. Thus, the purpose of this paper is to examine the EKC considering the impact of institutional quality on six variables of environmental pollution (carbon dioxide (CO2), nitrous oxide (N2O), suspended particulate matters (SPM), rainfall, temperature and total greenhouse emission (TGH)) using the case of Nigeria.

Design/methodology/approach

The EKC model includes population density, education expenditure, foreign direct investment and gross domestic investment as control variables, and it was analysed using the autoregressive distribution lag (ARDL) econometric technique, which has not been applied in the literature on Nigeria.

Findings

The results, inter alia, indicate that there is EKC for CO2and SPM. This implies that the green growth objective can be pursued in Nigeria with concerted efforts. Other environmental pollution indicators did not exert significant influence on economic growth.

Practical implications

Therefore, it is recommended that Nigeria’s institutional quality be strengthened to limit environmental pollution in light of economic growth.

Originality/value

Previous studies are yet to apply a more developed econometric method, like the ARDL, to estimate the EKC model for Nigeria. This study fills this observed knowledge gap.
Amelioration of colitis in mice by Leuconostoc lactis EJ‐1 by M1 to M2 macrophage polarization
Authors: Jang Se‐Eun , Min Sung‐Won
Published: October 2019

Dysregulation of immune responses to environmental antigens by the intestine leads to the chronic inflammatory disease, inflammatory bowel disease (IBD). Recent studies have thus sought to identify a dietary component that can inhibit lipopolysaccharide (LPS)‐induced nuclear factor‐kappa beta (NF‐κB) signaling to ameliorate IBD. This study assessed if the lactic acid bacteria (LAB) from kimchi, suppresses the expression of tumor necrosis factor‐alpha (TNF‐α) in peritoneal macrophages induced by LPS. Leuconostoc lactis EJ‐1, an isolate from LAB, reduced the expression of interleukin‐6 (IL‐6) and IL‐1β in peritoneal macrophages induced by LPS. The study further tested whether EJ‐1 alleviates colitis induced by 2,4,6‐trinitrobenzene sulfonic acid (TNBS) in mice. TNBS significantly increased myeloperoxidase (MPO) expression, macroscopic colitis scores, and colon shortening. Oral administration of L. lactis EJ‐1 resulted in an inhibited in TNBS‐induced loss in body weight, colon shortening, MPO activity, and NF‐κB and inducible nitric oxide synthase expression; it also led to a marked reduction in cyclooxygenase‐2 expression. L. lactis EJ‐1 also inhibited the TNBS‐induced expression of TNF‐α, IL‐1β, and IL‐6; however, it induced the expression of IL‐10. The M2 macrophage markers arginase I, IL‐10, and CD206 were elevated by EJ‐1. Collectively, these results suggest that EJ‐1 inhibits the NF‐κB signaling and polarizes M1‐ to M2‐macrophage transition, which help in ameliorating colitis.
The European lavender vote: Sexuality, ideology and vote choice in Western Europe
Authors: TURNBULL‐DUGARTE STUART J.
Published: October 2019

In many European democracies, political punditry has highlighted the attempts of political parties on the left to court the ‘lavender vote’ of lesbian, gay and bisexual individuals. This article examines the presence of a gay vote in Western Europe with a focus on assessing the role of sexuality in shaping individuals’ political preferences and voting behaviour. Empirically, the effect of sexuality on both ideological identification as well as party vote choice is analysed. Using a cumulative dataset of eight rounds of the European Social Survey between 2002 and 2017, this article demonstrates that partnered lesbians and gay men are more likely than comparable heterosexuals to identify with the left, support leftist policy objectives and vote for left‐of‐centre political parties. The analysis represents the first empirical cross‐national European study of the voting behaviour of homosexual individuals and sheds new light on the importance of sexuality as a predictor of political ideology and voting behaviour within the Western European context.
Plant‐based Milks: A Review of the Science Underpinning Their Design, Fabrication, and Performance
Authors: McClements David Julian , Newman Emily , McClements Isobelle Farrell
Published: October 2019

Many consumers are interested in decreasing their consumption of animal products, such as bovine milk, because of health, environmental, and ethical reasons. The food industry is therefore developing a range of plant‐based milk alternatives. These milk substitutes should be affordable, convenient, desirable, nutritional, and sustainable. This article reviews our current understanding of the development of plant‐based milks. Initially, an overview of the composition, structure, properties, and nutritional profile of conventional bovine milk is given, because the development of successful alternatives depends on understanding the characteristics of real milk. The two main production routes for fabricating plant‐based milks are then highlighted: (i) disruption of plant materials (such as nuts, seeds, or legumes) to form aqueous suspensions of oil bodies; (ii) formation of oil‐in‐water emulsions by homogenization of oil, water, and emulsifiers. The roles of the different functional ingredients in plant‐based milks are highlighted, including oils, emulsifiers, thickeners, antioxidants, minerals, and other additives. The physicochemical basis of the appearance, texture, and stability of plant‐based milks is covered. The importance of the sensory attributes and gastrointestinal fate of bovine milk and plant‐based alternatives is also highlighted. Finally, potential areas for future work are discussed.
Hemodialysis as a Risk Factor for Ceftriaxone‐Associated Pseudolithiasis in Adults
Authors: Ubukata Masamitsu , Ohsawa Isao , Suzuki Hiroki , Asao Rin , Nakamura Yuya , Nishida Hirofumi , Nakamura Masayuki , Nitta Kosaku , Goto Yoshikazu , Gotoh Hiromichi
Published: October 2019

Ceftriaxone‐associated biliary pseudolithiasis is common among children; however, there are only a few reports of pseudolithiasis in adult patients on HD. This retrospective cohort study included 278 adult patients on ceftriaxone therapy from 1 February 2016 to 1 September 2018. Pseudolithiasis was defined as a new development of sludge or stones in the gallbladder within 60 days of ceftriaxone therapy. After excluding patients with preexisting gallstones and a history of cholecystectomy, 113 patients on maintenance HD, and another 98 patients were enrolled as the HD and control group, respectively. Thirteen patients developed pseudolithiasis. Its incidence was significantly higher in the HD group than that in the control group. Multivariate logistic regression analyses showed that development of pseudolithiasis was significantly associated with HD and ceftriaxone dose. Therefore, HD in patients receiving ceftriaxone therapy appears to be associated with a risk of pseudolithiasis. These findings highlight the need for careful follow‐up.
Production of Pork Sausages Using Pleaurotus eryngii with Different Treatments as Replacements for Pork Back Fat
Authors: Wang Liyan , Li Cheng , Ren Lili , Guo Hongyue , Li Yu
Published: October 2019

The effects of four treatments of Pleurotus eryngii (king oyster mushroom) as replacements for pork back fat were evaluated for the physicochemical, technological, and sensory properties; nitrite content; and amino acid profile in pork sausages. Five batches were manufactured: one control (formulated with pork back fat) and four treatments with raw, boiled, deep‐fried, and fried P. eryngii to replace the pork back fat in sausages. The results indicated that the fat content and energy value decreased, while the protein, moisture, total dietary fiber content, cooking loss, and water‐holding capacity of the modified sausages increased. All samples were judged acceptable for their sensory characteristics, with the best one being the sausage containing deep‐fried P. eryngii. The raw and fried P. eryngii decreased the residual nitrite content in the sausages. Boiled P. eryngii enhanced the essential amino acids content in the sausages, while the other P. eryngii treatments improved the nonessential amino acid content. In summary, P. eryngii may potentially replace fat in sausages.

Practical Application

In manufacturing pork sausages, the mushroom P. eryngii can substitute pork back fat to improve the nutritional quality by reducing fat and energy value, while enhancing the protein and total dietary fiber content in the sausages. Raw and fried P. eryngii decreased the residual nitrite content in the sausages. This study provides a basis for preparing healthier alternatives to traditional sausages by substituting pork fat with mushrooms.
Colonic mucosa‐associated candida assessed by biopsy culture is associated with disease severity in ulcerative colitis: A prospective study
Authors: Shah Jimil , Dutta Usha , Rudramurthy Shivaprakash , Chakrabarti Arunaloke , Sinha Saroj K. , Sharma Vishal , Mandavdhare Harshal , Sharma Pankaj , Kalsi Dimple , Popli Priyanka , Radhika Srinivasan , Das Ashim , Kochhar Rakesh
Published: October 2019

Objective

To evaluate the relationship of mucosa‐associated candida (MAC) and disease severity in patients with ulcerative colitis (UC).

Methods

We prospectively investigated the presence, nature, and quantification of MAC in patients with UC and its relationship with disease severity. Consecutive patients with UC were assessed for clinical, endoscopic, histological features and serum markers of disease severity. All patients underwent mucosal brushing cytology, brushing culture, and biopsy culture for candida growth. MAC was considered present if mucosal biopsy culture grew candida. Candida spp. identification was performed by matrix‐assisted laser desorption/ionization. Serum β‐D‐glucan was measured with a Fungitell assay. Patients with irritable bowel syndrome who had undergone similar investigations were included as controls.

Results

Ninety‐six patients with UC showed evidence of MAC more often than the controls (n = 20) based on biopsy culture (33.3% vs 5.0%, P = 0.011), brush cytology (30.2% vs 5.0%, P = 0.019), and brush culture (36.5% vs 10.0%, P = 0.021). Patients with UC had higher candida colony counts (≥103 CFU/mL) than controls (34.4% vs 5.0%, P = 0.007). Median β‐D‐glucan values were higher in patients with UC than in controls (103.26 pg/mL vs 66.51 pg/mL, P = 0.011). The UC group with MAC had a higher median total Mayo score, C‐reactive protein, fecal calprotectin, β‐D‐glucan, and histological activity than those without MAC.

Conclusions

Patients with UC more often show evidence of MAC and a higher candida colony count than controls. The presence of MAC is associated with high disease severity in patients with UC.
Tocilizumab monotherapy for polymyalgia rheumatica: A prospective, single‐center, open‐label study
Authors: Chino Kentaro , Kondo Tsuneo , Sakai Ryota , Saito Shuntaro , Okada Yusuke , Shibata Akiko , Kurasawa Takahiko , Okuyama Ayumi , Takei Hirofumi , Amano Koichi
Published: October 2019

Objectives

Polymyalgia rheumatica (PMR) is a systemic inflammatory disease in the elderly of unknown etiology. While glucocorticoids are the mainstay of treatment for PMR, various glucocorticoid‐related adverse events are common. Recently, several studies have reported the efficacy of tocilizumab (TCZ), an anti‐interleukin‐6 receptor antibody, for PMR treatment in addition to an accompanying reduction, or even tapering‐off, of glucocorticoids in some cases. The objective of this study was to elucidate the efficacy of TCZ monotherapy in the absence of glucocorticoids for PMR.

Method

We conducted a 2‐year, prospective, single‐center, open‐label pilot study of TCZ monotherapy in patients with PMR. TCZ (8 mg/kg) was administered at fortnightly intervals for the first 2 months and monthly over the next 10 months. Subsequently, patients were observed for another year without any treatment. The primary endpoints were the remission rates at weeks 12 and 52, and the secondary endpoints were the relapse rate and safety over the total 104 weeks.

Results

Thirteen patients were included in this study. Four of these patients achieved remission at week 12 (remission rate 31%). Four patients withdrew from the study due to adverse events (n = 2) and inefficacy (n = 2). At week 52, all 9 patients who had completed the first year achieved remission. Eight patients completed the drug‐free second year, with 7 maintaining remission.

Conclusions

TCZ monotherapy is well tolerated and can lead to remission in most patients with PMR in the absence of glucocorticoids.
NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice
Authors: Marín‐Aguilar Fabiola , Lechuga‐Vieco Ana V. , Alcocer‐Gómez Elísabet , Castejón‐Vega Beatriz , Lucas Javier , Garrido Carlos , Peralta‐Garcia Alejandro , Pérez‐Pulido Antonio J. , Varela‐López Alfonso , Quiles José L. , Ryffel Bernhard , Flores Ignacio , Bullón Pedro , Ruiz‐Cabello Jesús , Cordero Mario D.
Published: October 2019

While NLRP3‐inflammasome has been implicated in cardiovascular diseases, its role in physiological cardiac aging is largely unknown. During aging, many alterations occur in the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated the molecular mechanisms through which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3‐inflammasome protected mice from age‐related increased insulin sensitivity, reduced IGF‐1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of the age‐dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging and reduced telomere shortening. Furthermore, old NLRP3 KO mice showed an inhibition of the PI3K/AKT/mTOR pathway and autophagy improvement, compared with old wild mice and preserved Nampt‐mediated NAD+ levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age‐associated changes in the heart, preserved cardiac function of aged mice and increased lifespan.
Analysis of Partial Thromboplastin Times in Patients With Pulmonary Embolism During the First 48 Hours of Anticoagulation With Unfractionated Heparin
Authors: Prucnal Christiana K. , Jansson Paul S. , Deadmon Erin , Rosovsky Rachel P. , Zheng Hui , Kabrhel Christopher
Published: October 2019

Objective

The objective was to determine the proportion of patients with pulmonary embolism (PE) treated with unfractionated heparin (UFH) who achieved therapeutic activated partial thromboplastin time (aPTT) values within 48 hours of treatment.

Methods

Retrospective analysis of a PE response team (PERT) database was performed at a large, urban, academic teaching hospital. Inclusion criteria were adult patients with acute PE for whom the PERT was consulted and who received anticoagulation (AC) with UFH according to guideline standard dosing. aPTT values during 6‐hour time periods during the first 48 hours of AC were collected and analyzed.

Results

A total of 505 patients met inclusion criteria. For patients receiving a bolus and infusion of UFH, the proportions (95% confidence interval [CI]) of patients in the therapeutic range were 19.0% (14.2% to 25.0%) at 12 hours, 26.3% (26.3% to 33.1%) at 24 hours, 28.3% (22.0% to 35.4%) at 36 hours, and 28.4% (20.8% to 37.5%) at 48 hours. For titrated infusion only, the proportions (95% CIs) of patients were 23.3% (16.2% to 32.3%) at 12 hours, 41.4% (31.6% to 51.9%) at 24 hours, 37.0% (26.8% to 48.5%) at 36 hours, and 42.1% (30.2% to 55.0%) at 48 hours. No patient had all therapeutic aPTT values.

Conclusions

The majority of patients with acute PE spend most of their first 48 hours outside of the therapeutic range of AC when treated with guideline standard dosing of UFH. Over half of the patients fail to achieve any therapeutic PTT level within 24 hours of UFH initiation, and no patient had all therapeutic aPTTs. Future research should focus on identifying factors associated with achieving therapeutic AC with UFH.
What do HIV‐positive drug users’ experiences tell us about their antiretroviral medication‐taking? An international integrated literature review
Authors: Ho Iris Szu‐Szu , Holloway Aisha , Stenhouse Rosie
Published: October 2019

Background and aims

HIV‐positive drug users’ poor adherence to antiretroviral regimens can pose a significant and negative impact on individual and global health. This review aims to identify knowledge gaps and inconsistencies within the current evidence base and to measure HIV‐positive drug users’ adherence rates and the factors that influence their adherence.

Methods

A search of quantitative and qualitative studies in relation to HIV‐positive drug users’ adherence to antiretroviral treatment was performed using five databases: Applied Social Sciences Index and Abstract (ASSIA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline, Embase and PsycINFO (Ovid interface). Relevant studies were retrieved based on the inclusion and exclusion criteria stated in the review. Findings were compared, contrasted and synthesized to provide a coherent account of HIV‐positive drug users’ adherence rates and the factors that influence their adherence.

Results

The proportion of HIV‐positive drug users who achieved ≥ 95% adherence across the studies varied widely, from 19.3 to 83.9%. Adherence rates changed over the course of HIV treatment. The factors that influenced adherence were reported as follows: stigmatization, motivation, active drug use, accessibility and conditionality of HIV and addiction care, side effects and complexity of treatment regimens, forgetfulness and non‐incorporation of dosing times into daily schedules.

Conclusions

HIV‐positive drug users’ medication‐taking is a dynamic social process that requires health professionals to assess adherence to HIV treatment on a regular basis.
Assessment of sexual behaviour and fertility indices in male rabbits following chronic codeine use
Authors: Ajayi A. F. , Akhigbe R. E.
Published: October 2019

Background

Codeine is the latest trend of drug abuse, particularly in Nigeria and regarded as the gateway to the abuse of other substances.

Objectives

The present study examined the effects of graded doses of codeine on sexual behaviour and fertility profile.

Materials and methods

Rabbits were either administered normal saline (0.2 mL), 4mg/kg b.w of codeine (low dose), or 10mg/kg b.w of codeine (high dose) p.o for 6 weeks.

Results and discussion

Findings of the study showed that codeine administration significantly increased libido as witnessed by significantly short mount latency (ML), intromission latency (IL), post‐ejaculatory interval (PEI) and significantly increased mount frequency (MF), intromission frequency (IF) and ejaculation latency (EL). Furthermore, codeine caused a marked rise in penile reflexes evident by a significant increase in erections, quick flips, long flips and total penile reflexes. However, copulatory efficiency and fertility index were significantly lower in codeine‐treated groups when compared with the control. Serum levels of testosterone were also significantly lower in the treated groups.

Conclusions

The present study demonstrates that codeine‐induced enhancement of sexual performance is via a testosterone‐independent mechanism. It also reveals that although codeine enhances copulatory locomotor activity, it is a potential risk factor for infertility.
Editorial: accelerated infliximab induction—it’s time to settle the debate!
Authors: Chedid Victor G. , Kane Sunanda V.
Published: October 2019

LINKED CONTENT

This article is linked to Sebastian et al papers. To view these articles, visit https://doi.org/10.1111/apt.15456 and https://doi.org/10.1111/apt.15498.
Editorial: accelerated infliximab induction—it's time to settle the debate! Authors' reply
Authors: Sebastian Shaji , Kennedy Nicholas A. , Subramanian Sreedhar , Raine Tim
Published: October 2019

LINKED CONTENT

This article is linked to Sebastian et al and Chedid and Kane papers. To view these articles, visit https://doi.org/10.1111/apt.15456 and https://doi.org/10.1111/apt.15483.
Gene‐based association analysis for bivariate time‐to‐event data through functional regression with copula models
Authors: Wei Yue , Liu Yi , Sun Tao , Chen Wei , Ding Ying
Published: October 2019

Several gene‐based association tests for time‐to‐event traits have been proposed recently to detect whether a gene region (containing multiple variants), as a set, is associated with the survival outcome. However, for bivariate survival outcomes, to the best of our knowledge, there is no statistical method that can be directly applied for gene‐based association analysis. Motivated by a genetic study to discover the gene regions associated with the progression of a bilateral eye disease, age‐related macular degeneration (AMD), we implement a novel functional regression (FR) method under the copula framework. Specifically, the effects of variants within a gene region are modeled through a functional linear model, which then contributes to the marginal survival functions within the copula. Generalized score test statistics are derived to test for the association between bivariate survival traits and the genetic region. Extensive simulation studies are conducted to evaluate the type I error control and power performance of the proposed approach, with comparisons to several existing methods for a single survival trait, as well as the marginal Cox FR model using the robust sandwich estimator for bivariate survival traits. Finally, we apply our method to a large AMD study, the Age‐related Eye Disease Study, and to identify the gene regions that are associated with AMD progression.
Vaccines for emerging pathogens: from research to the clinic. Part two
Authors: Williamson E D
Published: October 2019

For this two-part Clinical & Experimental Immunology Review Series, Guest Editor E. Diane Williamson invited experts in their fields to contribute articles on the status of vaccine research and development for emerging pathogens. Part One addressed our progress in developing vaccines for emerging and re-emerging viruses and considered current work on effective vaccines for bacterial pathogens. In this edition of the journal, we are pleased to present Part Two, in which our authors emphasise the importance of vaccine formulation and of the use of effective delivery vehicles, as well as the prospects for licensure for current candidate vaccines.
Identification of pigments related to allergic tattoo reactions in 104 human skin biopsies
Authors: Serup Jørgen , Hutton Carlsen Katrina , Dommershausen Nils , Sepehri Mitra , Hesse Bernhard , Seim Christian , Luch Andreas , Schreiver Ines
Published: October 2019

Background

Red tattoos are prone to allergic reactions. The identity of the allergen(s) is mostly unknown.

Objectives

Chemical analysis of human skin biopsies from chronic allergic reactions in red tattoos to identify culprit pigment(s) and metals.

Material and methods

One hundred four dermatome biopsies were analyzed by matrix‐assisted laser desorption/ionization tandem mass spectrometry (MALDI‐MS/MS) for identification of commonly used organic pigments. Metal concentrations were assessed by inductively coupled plasma (ICP)‐MS and x‐ray fluorescence (XRF). Fourteen patients had cross‐reactions in other red tattoos.

Results

In total, the identified pigments were mainly azo Pigment Red (P.R.) 22 (35%), P.R. 210 (24%), P.R. 170 (12%), P.R. 5 (0.9%), P.R. 112 (0.9%), and Pigment Orange (P.O.) 13 (11%). P.R. 122 (0.9%) and Pigment Violet (P.V.) 23 (8%) were also common. P.R. 22, P.R. 170, and P.R. 210 also dominated in patients with cross‐reactions. In 22% of the biopsies, no red pigment was detected. Element analysis indicated the presence of the sensitizers nickel and chromium.

Conclusions

P.R. 22, P.R. 170, and P.R. 210 were identified as the prevailing pigments behind chronic allergic reactions in red tattoos. The epitope causing the reaction might be a pigment‐degradation product. Metal contamination may derive from different sources, and its role in red tattoo allergy cannot be ascertained.
Making Territory and Negotiating Citizenship in a Climate Mitigation Initiative in Indonesia
Authors: Setyowati Abidah B.
Published: October 2019

For almost two decades, the concept of Payments for Ecosystem Services (PES) has been widely adopted in Indonesia, in policy initiatives ranging from pilot projects to more established PES schemes and Reducing Emissions from Deforestation and Forest Degradation (REDD+) programmes. Drawing on a case study of a REDD+ initiative in Aceh, Indonesia, this article analyses how the initiative became an avenue to renegotiate political authority, territory and citizenship. Analysis of relevant documents, combined with focus group discussions and interviews at local and national levels, reveals the complex processes by which the authority to govern forest is claimed and legitimized through the revision of provincial land‐use plans, and shows how citizenship is rearticulated through participatory mapping processes. The article demonstrates that the initiative has been negotiated and reshaped to conform to local aspirations for greater control over forests and to achieve broader development goals. The discourses of green economy and REDD+ have provided the Aceh government and communities with a new ‘surface of engagement’ to express Acehnese struggles over territory and citizenship by aligning with global climate change issues.
Online engineering education for manufacturing technology: Is a remote experiment a suitable tool to teach competences for “Working 4.0”?
Authors: Terkowsky Claudius , Frye Silke , May Dominik
Published: October 2019

The demands of modern industry contexts (so‐called Industry 4.0) are going to reshape the working world of future engineers. It seems obvious that these technological developments will affect higher education institutions with increasing intensity. For years, there has been a vivid discussion on the IT competences, which need to be developed by students in order to face emerging technology changes. To tackle the question regarding industry expectations towards future engineers, in this article a remote laboratory at a German university is analysed to identify potentials for future‐oriented teaching and learning in the light of the required competences for “Working 4.0”. Current scientific studies and industry agendas about Working 4.0 competences are identified, connected learning objectives are derived and the focused remote laboratory is linked to these objectives. As a result, it can be shown that this educational setting has the potential to reflect the complexity of Working 4.0. However, the results also show that the examined laboratory addresses only some of the competences in the context of Industry 4.0. Furthermore, it is argued in how far industry demands serve as the only basis for educational development efforts. The scientific studies and the industry agenda offer a limited and more political perspective on educational development. Nevertheless, based on the research in this article, it can be argued that remote labs (and online labs in general) have the potential to lift traditional laboratory‐based engineering education to a modern engineering education 4.0.
Dorsal hippocampus cholinergic and nitrergic neurotransmission modulates the cardiac baroreflex function in rats
Authors: Ferreira‐Junior Nilson Carlos , Lagatta Davi Campos , Kuntze Luciana Bärg , Fujiwara Eduardo Akira , Firmino Egidi Mayara Silva , Borges‐Assis Anna Bárbara , Resstel Leonardo Barbosa Moraes , Sampaio Karla Nívea
Published: October 2019

Hippocampus is a limbic structure involved in the baroreflex and chemoreflex control that receives extensive cholinergic input from basal forebrain. Hippocampal muscarinic receptors activation by acetylcholine might evoke nitric oxide synthesis, which is an important neuromodulator of cardiovascular responses. Thus, we hypothesize that cholinergic and nitrergic neurotransmission within the DH modulates the baroreflex and chemoreflex function. We have used vasoactive drugs (phenylephrine and sodium nitroprusside), and potassium cyanide infused peripherally to induce, respectively, baroreflex or chemoreflex responses in awake animals. Bilateral injection into the DH of the acetylcholinesterase inhibitor (neostigmine) reduced baroreflex responses. Meanwhile, the non‐selective muscarinic receptor antagonist (atropine) or the M1‐selective muscarinic receptor antagonist increased baroreflex responses (pirenzepine). Furthermore, the neuronal nitric oxide synthase inhibitor (N‐propyl) or the intracellular NO scavenger (carboxy‐PTIO) increased baroreflex responses, as well as the selective inhibitor of NO‐sensitive guanylyl cyclase (ODQ), increased the baroreflex responses. Besides, bilateral administration of an ineffective dose of a neuronal nitric oxide synthase inhibitor abolished the reduction in the baroreflex responses evoked by an acetylcholinesterase inhibitor. On the other hand, we have demonstrated that hippocampal cholinergic neurotransmission did not influence the chemoreflex function. Taken together, our findings suggest that nNOS‐derived nitric oxide in the DH participates in acetylcholine‐evoked baroreflex responses.
Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions
Authors: Anderson Lyndsey L. , Absalom Nathan L. , Abelev Sarah V. , Low Ivan K. , Doohan Peter T. , Martin Lewis J. , Chebib Mary , McGregor Iain S. , Arnold Jonathon C.
Published: October 2019

Objective

Cannabidiol (CBD) has been approved by the US Food and Drug Administration (FDA) to treat intractable childhood epilepsies, such as Dravet syndrome and Lennox‐Gastaut syndrome. However, the intrinsic anticonvulsant activity of CBD has been questioned due to a pharmacokinetic interaction between CBD and a first‐line medication, clobazam. This recognized interaction has led to speculation that the anticonvulsant efficacy of CBD may simply reflect CBD augmenting clobazam exposure. The present study aimed to address the nature of the interaction between CBD and clobazam.

Methods

We examined whether CBD inhibits human CYP3A4 and CYP2C19 mediated metabolism of clobazam and N‐desmethylclobazam (N‐CLB), respectively, and performed studies assessing the effects of CBD on brain and plasma pharmacokinetics of clobazam in mice. We then used the Scn1a+/− mouse model of Dravet syndrome to examine how CBD and clobazam interact. We compared anticonvulsant effects of CBD‐clobazam combination therapy to monotherapy against thermally‐induced seizures, spontaneous seizures and mortality in Scn1a+/− mice. In addition, we used Xenopus oocytes expressing γ‐aminobutyric acid (GABA)A receptors to investigate the activity of GABAA receptors when treated with CBD and clobazam together.

Results

CBD potently inhibited CYP3A4 mediated metabolism of clobazam and CYP2C19 mediated metabolism of N‐CLB. Combination CBD‐clobazam treatment resulted in greater anticonvulsant efficacy in Scn1a+/− mice, but only when an anticonvulsant dose of CBD was used. It is important to note that a sub‐anticonvulsant dose of CBD did not promote greater anticonvulsant effects despite increasing plasma clobazam concentrations. In addition, we delineated a novel pharmacodynamic mechanism where CBD and clobazam together enhanced inhibitory GABAA receptor activation.

Significance

Our study highlights the involvement of both pharmacodynamic and pharmacokinetic interactions between CBD and clobazam that may contribute to its efficacy in Dravet syndrome.
GATORopathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations
Authors: Iffland Philip H. , Carson Vincent , Bordey Angelique , Crino Peter B.
Published: October 2019

The mechanistic target of rapamycin (mTOR) pathway has been implicated in a growing number of malformations of cortical development (MCD) associated with intractable epilepsy. Mutations in single genes encoding mTOR pathway regulatory proteins have been linked to MCD such as focal cortical dysplasia (FCD) types IIa and IIb, hemimegalencephaly (HME), and megalencephaly. Recent studies have demonstrated that the GATOR1 protein complex, comprised of DEPDC5, NPRL3, and NPRL2, plays a pivotal role in regulating mTOR signaling in response to cellular amino acid levels and that mutations in DEPDC5, NPRL3, or NPRL2 are linked to FCD, HME, and seizures. Histopathological analysis of FCD and HME tissue specimens resected from individuals harboring DEPDC5, NPRL3, or NPRL2 gene mutations reveals hyperactivation of mTOR pathway signaling. Family pedigrees carrying mutations in either DEPDC5 or NPRL3 share clinical phenotypes of epilepsy and MCD, as well as intellectual and neuropsychiatric disabilities. Interestingly, some individuals with seizures associated with DEPDC5, NPRL3, or NPRL2 variants exhibit normal brain imaging suggesting either occult MCD or a role for these genes in non‐lesional neocortical epilepsy. Mouse models resulting from knockdown or knockout of either Depdc5 or Nprl3 exhibit altered cortical lamination, neuronal dysmorphogenesis, and enhanced neuronal excitability as reported in models resulting from direct mTOR activation through expression of its canonical activator RHEB. The role of the GATOR1 proteins in regulating mTOR signaling suggest plausible options for mTOR inhibition in the treatment of epilepsy associated with mutations in DEPDC5, NPRL3, or NPRL2.
Stifle radiography in Thoroughbreds from 6 to 18 months of age
Authors: Santschi E. M. , Prichard M. A. , Whitman J. L. , Batten C. A. , Strathman T. A. , Canada N. C. , Morehead J. P.
Published: October 2019

The radiographic appearance of the stifle of young horse changes during the first 18 months of life but is not well described in Thoroughbreds. Our objective was to describe the radiographic appearance of the Thoroughbred stifle from 5 to 18 months of age and determine whether limiting exercise impacts the prevalence of radiographic abnormalities (RA). Bilateral stifle radiographs were obtained at a mean of 161 days of age in 141 subjects (set 1) and 347 days (set 2), and in 114 available subjects at 534 days (set 3), and graded for RA of the trochlear ridges (TR) and medial femoral condyle (MFC). The impact of exercise limits on RA was determined from a subgroup of subjects with set 1 RA that had 30–90 days limited exercise. Stifle RA were present in 50 subjects (35%) at set 1: 39 TR and 11 MFC. At set 2, 24 subjects (15.6%) had RA: 13 TR and 11 MFC. Set 1 RA had resolved in 36 (72%) subjects, persisted in 11 (22%) and changed location in 3. Ten of 91 (11%) subjects developed new RA at set 2. Twenty‐seven subjects were unavailable for set 3 imaging, 6 with LTR RA at set 2. At set 3, 12/114 (11%) subjects had RA: 5 TR and 7 MFC. Set 2 RA resolved in 9 (50%) subjects, persisted in 8 (44%), and changed location in one. Three of 96 subjects developed new RA at set 3. Radiographic abnormality prevalence at set 3 was not different after limiting exercise. It was concluded that RA in the TR and MFC are common in 6‐month‐old Thoroughbreds and often resolve by 18 months. Radiographic abnormalities that develop later (~12 months of age) are less likely to resolve.
Unfolding Relations among Mindful Parenting, Recurrent Conflict, and Adolescents’ Externalizing and Internalizing Problems
Authors: Park Ye Rang , Nix Robert L. , Duncan Larissa G. , Coatsworth J. Douglas , Greenberg Mark T.
Published: October 2019

The current study examined unfolding relations among mothers’ mindful parenting, parent–adolescent recurrent conflict, and adolescents’ externalizing and internalizing problems. In a community sample of 117 families (31% black, Asian, American Indian, or Latino), parents and adolescents (52% female; average age = 12.13 years) were followed over 15 months. Parents answered questions about mindful parenting and recurrent conflict, and adolescents reported on their own externalizing and internalizing problems. Path analyses indicated that higher levels of mindful parenting were significantly related to lower levels of recurrent conflict 2–3 months later, controlling for previous levels of recurrent conflict. Moreover, lower levels of recurrent conflict were significantly related to lower levels of externalizing problems and internalizing problems 1 year later, controlling for previous levels of those problems. Subgroup analyses indicated that relations were comparable across subgroups defined by adolescent gender, race, parent marital status, and family financial strain. The effects of mindful parenting were robust even after accounting for other indicators of positive and supportive parenting, namely inductive reasoning and warmth in the parent–adolescent relationship. These findings highlight the potential of mindful parenting to improve family interactions and adolescent adjustment.
Phylogenetic placement of environmental sequences using taxonomically reliable databases helps to rigorously assess dinophyte biodiversity in Bavarian lakes (Germany)
Authors: Gottschling Marc , Chacón Juliana , Žerdoner Čalasan Anže , Neuhaus Stefan , Kretschmann Juliane , Stibor Herwig , John Uwe
Published: October 2019

Reliable determination of organisms is a prerequisite to explore their spatial and temporal occurrence and to study their evolution, ecology, and dispersal. In Europe, Bavaria (Germany) provides an excellent study system for research on the origin and diversification of freshwater organisms including dinophytes, due to the presence of extensive lake districts and ice age river valleys. Bavarian freshwater environments are ecologically diverse and range from deep nutrient‐poor mountain lakes to shallow nutrient‐rich lakes and ponds.

We obtained amplicon sequence data (V4 region of small subunit‐rRNA, c. 410 bp long) from environmental samples collected at 11 sites in Upper Bavaria. We found 186 operational taxonomic units (OTUs) associated with Dinophyceae that were further classified by means of a phylogenetic placement approach.

The maximum likelihood tree inferred from a well‐curated reference alignment comprised a systematically representative set of 251 dinophytes, covering the currently known molecular diversity and OTUs linked to type material if possible. Environmental OTUs were scattered across the reference tree, but accumulated mostly in freshwater lineages, with 79% of OTUs placed in either Apocalathium, Ceratium, or Peridinium, the most frequently encountered taxa in Bavaria based on morphology.

Twenty‐one Bavarian OTUs showed identical sequences to already known and vouchered accessions, two of which are linked to type material, namely Palatinus apiculatus and Theleodinium calcisporum. Particularly within Peridiniaceae, delimitation of Peridinium species was based on the intraspecific sequence variation.

Our approach indicates that high‐throughput sequencing of environmental samples is effective for reliable determination of dinophyte species in Bavarian lakes. We further discuss the importance of well‐curated reference databases that remain to be developed in the future.
Beyond translation: Engaging with culturally and linguistically diverse consumers
Authors: Harrison Reema , Walton Merrilyn , Chitkara Upma , Manias Elizabeth , Chauhan Ashfaq , Latanik Monika , Leone Desiree
Published: October 2019

Background

In the context of an effective consumer engagement framework, there is potential for health‐care delivery to be safer. Consumers from culturally and linguistically diverse (CALD) backgrounds may experience several barriers when trying to engage about their health care, and they are not acknowledged sufficiently in contemporary strategies to facilitate patient engagement.

Methods

Four focus group discussions were facilitated by bilingual fieldworkers in Arabic, Mandarin, Turkish and Dari in a district of Sydney, Australia that has a high proportion of CALD consumers. Each group included 5‐7 health‐care consumers who, using a topic guide, discussed their experiences of barriers and facilitators when engaging with health‐care services in Australia. Thematic analysis was undertaken to identify, analyse and report patterns in the data.

Results

In all, 24 consumers participated. Six inter‐related themes emerged: navigating the health system; seeking meaningful interpretation; understanding and managing expectations; respectful professional care; accessing services; and feeling unsafe.

Conclusions

The incorporation of strategies such as professional interpreters and migrant health workers may go some way to addressing the needs of culturally or linguistically diverse consumers and facilitate communication, but do not sufficiently address the range of barriers to consumer engagement identified in this work. Understanding consumer experience in the context of the complex factors that may be associated with poor engagement and poor outcomes such as health literacy, cultural, educational and linguistic background, and health‐care setting or condition, may contribute to better understanding about how to deliver quality health care to these patients.