bluuebunny/crossref_metadata_2025 huggingface dataset:
Engineering multiple levels of specificity in an RNA viral vector
Authors: Gao Xiaojing J. , Chong Lucy S. , Ince Michaela H. , Kim Matthew S. , Elowitz Michael B.
Published: May 2020

Synthetic molecular circuits could provide powerful therapeutic capabilities, but delivering them to specific cell types and controlling them remains challenging. An ideal “smart” viral delivery system would enable controlled release of viral vectors from “sender” cells, conditional entry into target cells based on cell-surface proteins, conditional replication specifically in target cells based on their intracellular protein content, and an evolutionarily robust system that allows viral elimination with drugs. Here, combining diverse technologies and components, including pseudotyping, engineered bridge proteins, degrons, and proteases, we demonstrate each of these control modes in a model system based on the rabies virus. This work shows how viral and protein engineering can enable delivery systems with multiple levels of control to maximize therapeutic specificity.
Quantitative live-cell imaging and computational modelling yield novel insight into endogenous WNT/CTNNB1 signaling dynamics
Authors: de Man S.M.A. , Zwanenburg G. , van der Wal T. , Hink M.A. , van Amerongen R.
Published: May 2020

WNT/CTNNB1 signaling regulates tissue development and homeostasis in all multicellular animals. Multiple aspects of the underlying molecular mechanism remain poorly understood and critical information on endogenous WNT/CTNNB1 signaling dynamics is missing. Here we combine CRISPR/Cas9-mediated genome editing and quantitative live-cell microscopy to measure diffusion characteristics of fluorescently tagged, endogenous CTNNB1 in human cells with high spatiotemporal resolution under both physiological and oncogenic conditions. State-of-the-art functional imaging reveals that a substantial fraction of CTNNB1 resides in slow-diffusing complexes in the cytoplasm, irrespective of the activation status of the pathway. The identity of this cytoplasmic CTNNB1 complex changes according to the phosphorylation status of CTNNB1 as it undergoes a major reduction in size when WNT/CTNNB1 is (hyper)activated. We also measure the concentration of complexed and free CTNNB1 in both the cytoplasm and the nucleus before and after WNT stimulation, and use these parameters to build a minimal computational model of WNT/CTNNB1 signaling. Using this integrated experimental and computational approach, our work reveals that WNT pathway activation regulates the dynamic distribution of CTNNB1 across different functional pools by modulating three regulatory nodes: the cytoplasmic destruction complex, nucleocytoplasmic shuttling and nuclear retention.
Developing key performance indicators for hospital facilities management services: a developing country perspective
Authors: Amos Daniel , Au-Yong Cheong Peng , Musa Zairul Nisham
Published: May 2020

Purpose

Key performance indicators (KPIs) help to monitor performance, thereby revealing the gap between planned and executed results relative to organizational objectives. The purpose of this paper is to develop KPIs for performance measurement of facilities management (FM) services in public hospitals.

Design/methodology/approach

Following a comprehensive literature review of KPIs in FM, a set of KPIs were first selected. This was then subjected to content validation by experts. Thereafter a questionnaire survey was conducted to identify participants perception on the level of importance of the proposed KPIs. The main analytical tool used was SPSS factor analysis/principal component extraction.

Findings

Adapting an expanded balanced scorecard typology, the paper identifies 17 KPIs, which are useful for performance improvement of FM. The study also introduces new financial dimensions beyond the traditional cost and profit-centered metrics.

Research limitations/implications

The study was limited to three FM services. Although the results of the Kruskal–Wallis test shows no significant difference in the level of importance on more than 80% of the indicators, larger sample is required in future studies to examine indicator preference for the respective services. An empirical study to test the proposed indicators to measure FM performance could also be a next step.

Originality/value

The paper presents the first step to develop performance indicators, which are of relevance to FM performance measurement and could be utilized to improve performance. The indicators are largely generic and can easily be adapted by other FM service sectors for performance measurement.
The role of product innovation and customer centricity in transforming tacit and explicit knowledge into profitability
Authors: López-Cabarcos M. Ángeles , Srinivasan Suresh , Vázquez-Rodríguez Paula
Published: May 2020

Purpose

By fusing knowledge-based theory, organizational learning theory and dynamics capability theory, this study aims to explore, on the one hand, the linkage between exploration, sensing and tacit knowledge, and on the other hand, exploitation, seizing and explicit knowledge. Thereby, it argues that not only tacit knowledge but also explicit knowledge contributes to competitive advantage for firms. This study also investigates how knowledge transforms into profitability.

Design/methodology/approach

The conceptual model is tested with a study sample of 153 industrial organizations using structural equation modelling.

Findings

Results confirm the importance of both tacit and explicit knowledge for achieving sustainable competitive advantages. Furthermore, both tacit and explicit knowledge transform into profitability, both directly and through product innovation and customer centricity which play partial mediating roles.

Practical implications

Explicit knowledge strategies can be easier to manage, implement and institutionalize than tacit knowledge strategies, which require human component and intervention to succeed. Managers should hence first implement explicit knowledge strategies to gain expeditious results. Further, with the advent of digital technologies and algorithms that can extract deep customer insights and organizational experiences which are highly tacit in nature and codifying the same into explicit knowledge, the importance of explicit knowledge is further enlarged.

Originality/value

By fusing three adjacent theories to establish a robust model specification, this study is able to demonstrate the contribution of explicit knowledge in the firm’s competitive advantages.
An artificial intelligence approach to support knowledge management on the selection of creativity and innovation techniques
Authors: Botega Luiz Fernando de Carvalho , da Silva Jonny Carlos
Published: May 2020

Purpose

Creativity is an important skill for design teams to reach new and useful solutions. Designers often use one or more of creativity and innovation techniques (CITs) to achieve the desired creative potential during new product development (NPD). The selection of adequate CITs requires considerable expertise, given the multiple application contexts and the extensive number of techniques available. The purpose of this study is to present a creativity support system able to manage this amount of information and provide valuable knowledge to improve NPD.

Design/methodology/approach

This study presents a knowledge-based system prototype using artificial intelligence (AI) to support knowledge management on the selection of CITs for design. CITs assertion is modelled through a double inference process using five categories, correlating over 500 different entry scenarios to 24 implemented CITs. The techniques are classified according to: design stage, innovation focus, team relationship, execution method and difficult of use. Prototype outputs explanations on the inference process and chosen techniques information.

Findings

To demonstrate the system scope, two opposite design cases are presented. The system was validated by experts in knowledge management and mechanical engineering design. The validation process demonstrates relevance of the approach and improvement directions for future developments.

Originality/value

Though literature contains toolkits and taxonomy for CITs, no work applies AI to identify design scenarios, select best CITs and instruct about their use. Validators reported to know less than half of the available techniques, showing a clear knowledge gap among design experts.
Co-creative place innovation in an arctic town
Authors: Lindberg Malin , Wikberg Nilsson Åsa , Segerstedt Eugenia , Hidman Erik , Nilsson Kristina L. , Karlberg Helena , Balogh Johanna
Published: May 2020

Purpose

The purpose of this paper is to shed light on co-creative approaches for place innovation in an Arctic town, based on the relocation of Kiruna’s city center in northern Sweden. Three cases of co-creative innovation processes in Kiruna are investigated and compared: an R&D project about local perceptions and visions of attractive urban environments; an R&D project about norm-creative design principles for inclusive and attractive urban design; and an R&D project about cross-industrial synergies for city center attractiveness.

Design/methodology/approach

The study’s research design encompasses a comparative and participatory approach. The comparative approach implies investigation and comparison of three cases of co-creative innovation processes in Kiruna. The participatory approach implies joint development of new knowledge by researchers and local actors. The data consists of participatory observations of workshops and qualitative interviews with local actors.

Findings

The study reveals that the studied processes have harnessed the city center relocation as an opportunity to make Kiruna more attractive to residents and visitors, by using the co-creative approaches of Living Lab, Now-Wow-How and Norm-creative design. These approaches have enabled experts and local actors to jointly identify excluding patterns and norms in the relocation process and to envision inclusive and attractive (re-)configurations and (re-)conceptualizations of the future Kiruna.

Research limitations/implications

The results add to the academic strand of inclusive urban transformation, by providing insights into co-creative approaches for re-imagining an Arctic town in times of industrial and social change. New insights are provided regarding how the geographical, industrial and cultural identity of an Arctic town can be harnessed to envision new configuration, content and communication that is attractive and accessible for a diversity of residents and visitors.

Practical implications

The results highlight the potential to harness Arctic and rural characteristics in the promotion of urban attractiveness and public well-being, especially when combined with co-creative identification and transformation of excluding norms and patterns.

Originality/value

The results provide new insights into how co-creative approaches may facilitate innovative and inclusive renewal of towns and cities in the Arctic and beyond.
Service encounter microblog word of mouth and its impact on firm reputation
Authors: Barhorst Jennifer Brannon , Wilson Alan , McLean Graeme James , Brooks Joshua
Published: May 2020

Purpose

It has now become a normal part of the consumption journey for consumers to share their positive and negative service encounters with firms on microblogs such as Twitter. There is, however, a limited amount of research on service encounter microblog word of mouth (SEMWOM) and its impact on firm reputation from a receiver’s perspective. This study aims to understand the comparative effects of positive and negative valence SEMWOM on receivers’ perceptions of firms’ reputations and the factors that are particularly salient to receivers’ perceptions of firm reputation upon exposure to SEMWOM.

Design/methodology/approach

An experiment exposed 372 Twitter users to positive and negative valence SEMWOM. To determine whether changes in perception of firm reputation occurred on exposure to both positive and negative valence SEMWOM, participants’ perceptions of a range of US airlines were measured before and after exposure to the SEMWOM. To confirm the factors that influence the perception of reputation on such exposure, six structural equation models were created to determine the comparative effects of positive and negative valence SEMWOM among three electronic WOM media as follows: video, photo and text.

Findings

Both positive and negative valence SEMWOM affect receivers’ perceptions of airlines’ reputations on exposure. Furthermore, the factors that influence perceptions of reputation on exposure to SEMWOM vary depending on valence and type of media contained in a tweet.

Originality/value

Although consumers now routinely share their positive and negative service encounters with brands on microblogs, scant research has examined receivers of positive and negative valence SEMWOM, important actors in the microblog domain. This study addresses this research gap by empirically investigating the impact of both positive and negative valence SEMWOM on receivers’ perceptions of firm reputation upon exposure to it.
Cláusulas abusivas en contratos de transporte aéreo de personas: doctrina jurisprudencial sobre el cargo por remisión de tarjeta de embarque
Authors: Cano Ortega Cristina
Published: May 2020

Purpose

Este artículo tiene por objeto analizar uno de los casos más importantes en los últimos años en los que se han declarado nulas ciertas cláusulas abusivas incluidas por las aerolíneas en los contratos de transporte aéreo con los consumidores, en concreto, se trata de la Sentencia de la Audiencia Provincial de Madrid, sección 28, de 26 de julio de 2017 y, especialmente, se estudiará la cláusula de cargo por remisión de la tarjeta de embarque.

Design/methodology/approach

A través del estudio de la mencionada sentencia, este trabajo mostrará cómo el contrato de transporte aéreo de personas siendo uno de los contratos más importantes actualmente, presenta una situación de especial desequilibrio y desprotección de los consumidores frente a las aerolíneas.

Findings

La falta de poder de negociación de los consumidores, las escasas alternativas que tienen en muchos casos y los precios generalmente altos de este contrato de transporte, hacen imprescindibles dispensar una protección adecuada a los consumidores en este contexto. Esto se puede lograr a través de leyes tuitivas que protejan sus intereses económicos y, especialmente como se analiza en el artículo, mediante la prohibición de cláusulas abusivas en los contratos de transporte aéreo.

Originality/value

El artículo hace un recorrido por algunas de las cláusulas abusivas incluidas en los contratos de transporte aéreo de pasajeros en los últimos años y muestra cómo debe evitarse que las aerolíneas impongan estas cláusulas que perjudican a la parte más débil del contrato y advierte que estamos aún lejos de conseguir una efectiva protección del consumidor en este ámbito como se explica con algún ejemplo final.
Bioactive compounds, associated health benefits and safety considerations of Moringa oleifera L.: an updated review
Authors: Chhikara Navnidhi , Kaur Amolakdeep , Mann Sandeep , Garg M.K. , Sofi Sajad Ahmad , Panghal Anil
Published: May 2020

Purpose

The purpose of this paper is to review the nutritional and phytochemical value of Moringa oleifera L., along with health benefits. Moringa oleifera, a highly valued plant grown throughout the world and all parts of tree used in different food formulations, possess industrial and therapeutic uses. This plant is gaining popularity because of its nutrient-rich root, leaves, flowers and fruits, having immense traditional medicinal uses and proved pharmacological properties.

Design/methodology/approach

Major well-known bibliometric information sources such as Web of Science, Scopus, Mendeley and Google Scholar were searched with keywords such as nutrition value of Moringa oleifera, bioactive compounds, health benefits, processing and safety were chosen to obtain a database of 1,386 papers. A final database of 70 scientific sources was made after sorting and classifying them according to different criteria based on topic relevance, country of origin and year of publication.

Findings

The literature reflects that Moringa contains all necessary macro, micro-nutrients and bioactive compounds (terpenoids, polyphenols, flavonoids, glucosinolates, alkaloids, glycosides and carotenoids). Scientific studies illustrate that M. oleifera and its bioactive constituents could play a vital role in the prevention of several chronic and degenerative diseases associated with oxidation stress. The recent upsurge in consumer interest for health foods has opened up new vistas for plant products containing bioactive compounds in different food formulations.

Originality/value

This paper highlights phytochemicals, pharmacological properties, bio-accessibility, food and industrial applications of Moringa. Moringa pods are traditionally preferred for enlarged liver and spleen, intestinal worms, weakness, neurological disorders and skin disease. A seed is natural and an inexpensive coagulant used to remove organic particles from water.
The association of food insecurity with sociodemographic factors and depression in the elderly population of Qarchak city – Iran
Authors: Rafat Rana , Rezazadeh Arezoo , Arzhang Pishva , Alipourr Abbas
Published: May 2020

Purpose

Elderly people are at higher risk of food insecurity because of limited or uncertain inaccessibility to adequate food supply. This is not only as a result of economic limitation but also as the outcome of the inability to intake food because of cognitive or functional impairment and health problems. Because of the lack of data about food insecurity and depression among the elderly population in Iran, this study was conducted to examine the relationship between socioeconomic factors and depression with food insecurity among the elderly population.

Design/methodology/approach

This cross-sectional study was performed in 2016 on 720 elderly people of Qarchak city that were selected by the proportional stratified sampling method. Food insecurity was evaluated using the FaCPS-FSSM food security questionnaire; Geriatric Depression Scale questionnaire to measure the score of depression and the socioeconomic questionnaire filled out during interviews. All statistical analyses were performed using the SPSS version 22 software.

Findings

Food insecurity was found in 396 (56.1%) of the elderly population. Food insecure elderly population had lower education (P < 0.001). While the percentage of educated individuals who were in food security was 53.2%, the percentage for not educated participants was 28.7%. Household economic status (P < 0.001). Data showed 64.6% of individuals with the normal economic condition were in food security, and the percent for the poor economic condition was 37.2%. Food insecurity was highly associated with depression in the elderly population (odds ratio: 4.76, 8.92 and 3.32 for mild, moderate and severe hunger, respectively, P < 0.001).

Originality/value

Food insecurity is related to low economic status and education. The results of this study indicated that food help from governmental organizations, charities and having health insurance may be associated with reduced risk of food insecurity in the elderly population and consequently lower depression prevalence among them.
The role of sustainability reporting in shareholder perception of tax avoidance
Authors: Rudyanto Astrid , Pirzada Kashan
Published: May 2020

Purpose

The purpose of this study is to examine the moderating effect of sustainability reporting on the relationship between tax avoidance and firm value. This study also examines the moderating effect of sustainability reporting in both environmentally sensitive firms and non-environmentally sensitive firms.

Design/methodology/approach

This research uses moderated panel regression with 596 observations and 734 observations for cash effective tax rate (ETR) and generally accepted accounting principles effective tax rate (GAAP ETR) of firms listed on the Indonesian Stock Exchange between 2014 and 2016. Tax avoidance is measured by both cash ETR and GAAP ETR.

Findings

This paper shows that sustainability reporting moderates the relationship between tax avoidance (GAAP ETR) and firm value. The results show that GAAP ETR has a negative association with firm value in non-environmentally sensitive firms and a positive association with firm value in environmentally sensitive firms. Consequently, the sustainability report alters only the effect of GAAP ETR on firm value in non-environmentally sensitive firms. The results imply that, unlike environmentally sensitive firms, non-environmentally sensitive firms need sustainability reporting to reduce the reputational costs of tax avoidance.

Originality/value

How shareholders view tax avoidance remains unclear; research on this topic often fails to produce a uniform result. The present research fills this gap by using the existence of sustainability reporting as proof of companies’ ethical motivations to moderate the association of tax avoidance and firm value, which has not been discussed in previous research.
The Covid-19 Pandemic
Authors: Tarran Brian
Published: May 2020

Statistics, statistical concepts and perspectives
Pandemics and Exponential Growth
Authors: Cochran James J.
Published: May 2020

James J. Cochran explains why a misunderstanding or disregard of exponential growth may have extremely grave consequences
nosoi: A stochastic agent‐based transmission chain simulation framework in r
Authors: Lequime Sebastian , Bastide Paul , Dellicour Simon , Lemey Philippe , Baele Guy
Published: May 2020

The transmission process of an infectious agent creates a connected chain of hosts linked by transmission events, known as a transmission chain. Reconstructing transmission chains remains a challenging endeavour, except in rare cases characterized by intense surveillance and epidemiological inquiry. Inference frameworks attempt to estimate or approximate these transmission chains but the accuracy and validity of such methods generally lack formal assessment on datasets for which the actual transmission chain was observed.

We here introduce nosoi, an open‐source r package that offers a complete, tunable and expandable agent‐based framework to simulate transmission chains under a wide range of epidemiological scenarios for single‐host and dual‐host epidemics. nosoi is accessible through GitHub and CRAN, and is accompanied by extensive documentation, providing help and practical examples to assist users in setting up their own simulations.

Once infected, each host or agent can undergo a series of events during each time step, such as moving (between locations) or transmitting the infection, all of these being driven by user‐specified rules or data, such as travel patterns between locations.

nosoi is able to generate a multitude of epidemic scenarios, that can—for example—be used to validate a wide range of reconstruction methods, including epidemic modelling and phylodynamic analyses. nosoi also offers a comprehensive framework to leverage empirically acquired data, allowing the user to explore how variations in parameters can affect epidemic potential. Aside from research questions, nosoi can provide lecturers with a complete teaching tool to offer students a hands‐on exploration of the dynamics of epidemiological processes and the factors that impact it. Because the package does not rely on mathematical formalism but uses a more intuitive algorithmic approach, even extensive changes of the entire model can be easily and quickly implemented.
Onset time and duration of action of rocuronium 0.6 mg/kg in patients above 80 years of age: A comparison with young adults
Authors: Bjerring Cecilie , Vested Matias , Arleth Tobias , Eriksen Kirsten , Albrechtsen Charlotte , Rasmussen Lars S.
Published: May 2020

Background

The number of elderly is increasing, and a large proportion of these people will require surgery and anaesthesia. However, little data exist regarding rocuronium in patients above 80 years of age. The aim of this study was to determine the onset time and duration of action for rocuronium 0.6 mg/kg in patients above 80 years compared with young adults.

Methods

This prospective observational study included 16 young (18‐40 years) and 16 elderly (>80 years) patients scheduled for total intravenous anaesthesia. Neuromuscular block following rocuronium 0.6 mg/kg was monitored with acceleromyography using train‐of‐four (TOF) stimulation. The primary outcome was onset time (from administration of rocuronium until TOF count = 0). Secondary outcomes were duration of action (from administration to TOF ratio >0.9) and intubating conditions according to Intubation Difficulty Score.

Results

Elderly patients, median age of 84 years, had significantly prolonged onset time compared to younger patients; median 135 seconds (135‐158) vs 90 seconds (90‐105), respectively, a mean difference of 82 seconds (40‐124) and Wilcoxon Mann‐Whitney odds (WMW) of 19.48 (7.48‐X). Duration of action in elderly patients was significantly longer, with a median time of 81 minute (71‐97) vs 53 minute (42‐73), respectively, a mean difference of 31 minute (14‐48), and WMW odds of 6.35 (2.59‐X). There was no significant difference in intubating conditions.

Conclusions

Patients above 80 years had significantly prolonged onset time and duration of action after rocuronium 0.6 mg/kg compared with patients aged 18‐40 years.
Zonisamide as an Adjunctive Treatment to Cognitive Processing Therapy for Veterans With Posttraumatic Stress Disorder and Comorbid Alcohol Use Disorder: A Pilot Study
Authors: Petrakis Ismene , Ralevski Elizabeth , Arias Albert J. , DeNegre Diana , Newcomb Jenelle , Gianoli Mayumi , McCarthy Elissa , Meshberg‐Cohen Sarah , Yoon Gihyun
Published: May 2020

Background and Objectives

There are high rates of comorbid alcohol use disorder (AUD) among those who have posttraumatic stress disorder (PTSD). Ideally, treatment for comorbidity should address both disorders simultaneously. Zonisamide, an anticonvulsant, may be effective in decreasing alcohol use and may attenuate symptoms of PTSD. Treatment strategies can include medication in combination with a proven evidence‐based psychotherapy designed to treat PTSD, such as cognitive processing therapy (CPT).

Methods

This 12‐week pilot study was designed to test feasibility, acceptability, and preliminary efficacy of zonisamide (400 mg) as an adjunct to CPT for veterans with PTSD and comorbid AUD. Veterans (n = 24) with PTSD and current alcohol dependence were randomized in a 3:1 ratio to receive zonisamide or placebo in a double‐blind fashion. All subjects received CPT enhanced to include sessions addressing drinking behavior.

Results

Subjects overall reported a significant decrease in drinking outcomes, craving, and symptoms of PTSD. Zonisamide was well‐tolerated and easily administered with CPT, which was also well‐tolerated. Exploratory analysis of comparison of groups suggests there was no advantage of zonisamide vs placebo in drinking or PTSD outcomes. There was a numeric but nonsignificant higher rate of abstinence with zonisamide (50%) vs placebo (33%).

Conclusion and Scientific Significance

The interpretation of the results is limited by the pilot nature of this study. The combination of psychosocial treatment with medication management mimics real‐world treatment. In order to isolate the individual contributions of medication vs psychotherapy a much larger study would need to be conducted. (Am J Addict 2020;29:515–524)
Pleasing the Principal: U.S. Influence in World Bank Policymaking
Authors: Clark Richard , Dolan Lindsay R.
Published: May 2020

How do policies in international organizations reflect the preferences of powerful institutional stakeholders? Using an underutilized data set on the conditions associated with World Bank loans, we find that borrower countries that vote with the United States at the United Nations are required to enact fewer domestic policy reforms, and on fewer and softer issue areas. Though U.S. preferences permeate World Bank decision making, we do not find evidence that borrower countries trade favors in exchange for active U.S. intervention on their behalf. Instead, we propose that U.S. influence operates indirectly when World Bank staff—consciously or unconsciously—design programs that are compatible with U.S. preferences. Our study provides novel evidence of World Bank conditionality and shows that politicized policies can result even from autonomous bureaucracies.
Increasing interest of students from under‐represented groups in medicine—A systematised review
Authors: Reeves Nicole S. , Cheek Colleen , Hays Richard , Sargent Aryelle , McComiskie Alice , Santini Carlos , Nguyen Jamie , Chalwe Khezia , Mubarak Adil
Published: May 2020

Objective

Community engagement activities are the entry point to a “pipeline” of activity aimed at supporting under‐represented students and nurturing their interest in medical careers following graduation. This review aimed to describe the range of activities medical schools undertake to encourage and support rural students or other targeted under‐represented populations to apply to medical school, and the reported outcomes. The overarching aim was to identify which programs prior to application into medicine are most effective.

Design

A systematised review.

Setting

Medical Education articles published January 2000 to May 2018.

Participants

Population groups under‐represented in medicine, including rural students.

Interventions

Programs delivered to participants prior to application to medical school.

Main outcome measures

Reach, format and duration of programs, number of participants applying and completing medical school.

Results

A search of several databases identified 2688 articles. After filtering for relevance, 1271 articles were considered for the final review. Of the 155 full‐text articles assessed, 133 were excluded as they did not meet the eligibility criteria. A further three articles were added on review of references. Nine reviewers conducted data abstraction from 25 articles.

Conclusion

There is a need for improved evidence to define the best ways to support under‐represented groups in medicine. Important features appear to be targeting interested students and supporting their attainment of entry requirements. Successful programs might be those which enhance a student intake representative of the population.
Impact of smoking on gestational diabetes mellitus and offspring birthweight in primiparous women
Authors: Masalin Senja , Kautiainen Hannu , Gissler Mika , Pennanen Pirjo , Eriksson Johan G. , Laine Merja K.
Published: May 2020

Introduction

Smoking has been shown to affect glucose homeostasis and increase the risk for type 2 diabetes mellitus. Further, gestational diabetes mellitus (GDM) and smoking are known to influence offspring birthweight. The effect of smoking on glucose homeostasis in pregnancy is less studied and the findings are inconsistent. The aim of this study was to evaluate the effect of smoking on risk for GDM and to evaluate the impact of smoking and GDM on offspring birthweight.

Material and methods

This is an observational cohort study encompassing 4111 Finnish primiparous women from the city of Vantaa, Finland, who delivered a singleton child between 2009 and 2015. Data were obtained from Finnish national registers. Study participants had complete oral glucose tolerance test results and were divided into three groups according to smoking status: non‐smokers (I), smokers who quit during first trimester (II), and smokers who continued after first trimester (III).

Results

Prevalence of GDM was 19.8%, 24.3%, and 26.6% in non‐smokers, those who quit, and those who continued after the first trimester, respectively (P = .004 for differences between groups). The odds ratio for GDM in smokers who continued after the first trimester compared with non‐smokers was 1.65 (95% CI 1.09‐2.57) after adjustments for age, prepregnancy body mass index, education, and cohabitation. In women without GDM, offspring birthweight was lowest in those who continued smoking after the first trimester (P = .010 for differences between groups). In women with GDM, smoking status did not influence offspring birthweight.

Conclusions

Smoking during pregnancy is associated with an increased risk for GDM. Offspring birthweight is lowest in women who continue smoking after the first trimester. If pregnancy is complicated by GDM, offspring birthweight is not influenced by smoking.
Animal models of mechanisms of SARS‐CoV‐2 infection and COVID‐19 pathology
Authors: Cleary Simon J. , Pitchford Simon C. , Amison Richard T. , Carrington Robert , Robaina Cabrera C. Lorena , Magnen Mélia , Looney Mark R. , Gray Elaine , Page Clive P.
Published: May 2020

The coronavirus disease 2019 (COVID‐19) pandemic caused by SARS‐CoV‐2 infections has led to a substantial unmet need for treatments, many of which will require testing in appropriate animal models of this disease. Vaccine trials are already underway, but there remains an urgent need to find other therapeutic approaches to either target SARS‐CoV‐2 or the complications arising from viral infection, particularly the dysregulated immune response and systemic complications which have been associated with progression to severe COVID‐19. At the time of writing, in vivo studies of SARS‐CoV‐2 infection have been described using macaques, cats, ferrets, hamsters, and transgenic mice expressing human angiotensin I converting enzyme 2 (ACE2). These infection models have already been useful for studies of transmission and immunity, but to date only partly model the mechanisms involved in human severe COVID‐19. There is therefore an urgent need for development of animal models for improved evaluation of efficacy of drugs identified as having potential in the treatment of severe COVID‐19. These models need to reproduce the key mechanisms of COVID‐19 severe acute respiratory distress syndrome and the immunopathology and systemic sequelae associated with this disease. Here, we review the current models of SARS‐CoV‐2 infection and COVID‐19‐related disease mechanisms and suggest ways in which animal models can be adapted to increase their usefulness in research into COVID‐19 pathogenesis and for assessing potential treatments.

Linked Articles

This article is part of a themed issue on The Pharmacology of COVID‐19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc
Is grandparents' social class associated with adult grandchildren's oral health? Analysis of two British cohorts
Authors: Delgado‐Angulo Elsa K. , Alshehri Reem , Scambler Sasha , Bernabé Eduardo
Published: May 2020

Objectives

No studies have taken a multigenerational approach to the study of oral health inequalities. This study investigated whether grandparents' social class was associated with adult grandchildren's oral health.

Methods

Data from the 1958 National Child and Development Study (NCDS) and the 1970 British Cohort Study (BCS) were analysed. Cohort members' occupational social class and persistent trouble with mouth, teeth or gums in the past 12 months were reported at ages 33 years in the NCDS and 26 years in the BCS. Information on grandparents' and parents' social class was reported by the cohort members' mothers during childhood. The association between grandparents' social class and cohort members' report of persistent trouble with mouth, teeth or gums was tested in marginal structural models (MSMs).

Results

Data from 9853 NCDS and 6487 BCS participants were analysed. Grandparents' social class was not associated with cohort members' report of persistent trouble with teeth, gums or mouth in the NCDS sample (odds ratios of 1.25 [95% Confidence Interval: 0.95‐1.65] for social class IV/V and 1.12 [95% CI: 0.76‐1.64] for social class IIINM‐M relative to social class I/II) or the BCS sample (odds ratios of 0.98 [95% CI: 0.68‐1.43] for social class IV/V and 0.88 [95% CI: 0.67‐1.16] for social class IIINM‐M relative to social class I/II).

Conclusion

This study provided no support for an independent association between grandparents' social class and adult grandchildren's oral health.
Pastoral leadership lessons from Bonhoeffer: The alt‐right, the twitter mob, and ressentiment
Authors: Root Andrew
Published: May 2020

Dietrich Bonhoeffer's radio address “The Younger Generation's Altered Conception of the Führer,” has much to teach us about what kind of pastoral leadership is needed in our present social and political contexts. Personal antipathies have blossomed into generational antinomies, and the resentments of one side versus another threaten to take over our perceptions of reality and perhaps even reality itself. In looking at Bonhoeffer's diagnosis of why the “younger generation” was seeking a strong‐man leader to help them demolish the adversaries who had aggrieved them, we can see ourselves. In listening to Bonhoeffer's cure, we may find our own medicine.
GSK‐3β regulates the synaptic expression of NMDA receptors via phosphorylation of phosphatidylinositol 4 kinase type IIα
Authors: Amici Mascia , Lee Yeseul , Pope Robert J. P. , Bradley Clarrisa A. , Cole Adam , Collingridge Graham L.
Published: May 2020

Deregulation of GSK‐3β is strongly implicated in a variety of serious brain conditions, such as Alzheimer disease, bipolar disorder and schizophrenia. To understand how GSK‐3β becomes dysregulated in these conditions, it is important to understand its physiological functions in the central nervous system. In this context, GSK‐3β plays a role in the induction of NMDA receptor‐dependent long‐term depression (LTD) and several substrates for GSK‐3β have been identified in this form of synaptic plasticity, including KLC‐2, PSD‐95 and tau. Stabilization of NMDA receptors at synapses has also been shown to involve GSK‐3β, but the substrates involved are currently unknown. Recent work has identified phosphatidylinositol 4 kinase type IIα (PI4KIIα) as a neuronal GSK‐3β substrate that can potentially regulate the surface expression of AMPA receptors. In the present study, we investigated the synaptic role of PI4KIIα in organotypic rat hippocampal slices. We found that knockdown of PI4KIIα has no effect on synaptic AMPA receptor‐mediated synaptic transmission but substantially reduces NMDA receptor‐mediated synaptic transmission. Furthermore, the ability of the selective GSK‐3 inhibitor, CT99021, to reduce the amplitude of NMDA receptor‐mediated currents was occluded in shRNA‐PI4KIIα transfected neurons. The effects of knocking down PI4KIIα were fully rescued by a shRNA‐resistant wild‐type construct, but not by a mutant construct that cannot be phosphorylated by GSK‐3β. These data suggest that GSK‐3β phosphorylates PI4KIIα to stabilize NMDA receptors at the synapse.
Adaptive genetic potential and plasticity of trait variation in the foundation prairie grass Andropogon gerardii across the US Great Plains’ climate gradient: Implications for climate change and restoration
Authors: Galliart Matthew , Sabates Sofia , Tetreault Hannah , DeLaCruz Angel , Bryant Johnny , Alsdurf Jake , Knapp Mary , Bello Nora M. , Baer Sara G. , Maricle Brian R. , Gibson David J. , Poland Jesse , St Amand Paul , Unruh Natalie , Parrish Olivia , Johnson Loretta
Published: May 2020

Plant response to climate depends on a species’ adaptive potential. To address this, we used reciprocal gardens to detect genetic and environmental plasticity effects on phenotypic variation and combined with genetic analyses. Four reciprocal garden sites were planted with three regional ecotypes of Andropogon gerardii, a dominant Great Plains prairie grass, using dry, mesic, and wet ecotypes originating from western KS to Illinois that span 500–1,200 mm rainfall/year. We aimed to answer: (a) What is the relative role of genetic constraints and phenotypic plasticity in controlling phenotypes? (b) When planted in the homesite, is there a trait syndrome for each ecotype? (c) How are genotypes and phenotypes structured by climate? and (d) What are implications of these results for response to climate change and use of ecotypes for restoration? Surprisingly, we did not detect consistent local adaptation. Rather, we detected co‐gradient variation primarily for most vegetative responses. All ecotypes were stunted in western KS. Eastward, the wet ecotype was increasingly robust relative to other ecotypes. In contrast, fitness showed evidence for local adaptation in wet and dry ecotypes with wet and mesic ecotypes producing little seed in western KS. Earlier flowering time in the dry ecotype suggests adaptation to end of season drought. Considering ecotype traits in homesite, the dry ecotype was characterized by reduced canopy area and diameter, short plants, and low vegetative biomass and putatively adapted to water limitation. The wet ecotype was robust, tall with high biomass, and wide leaves putatively adapted for the highly competitive, light‐limited Eastern Great Plains. Ecotype differentiation was supported by random forest classification and PCA. We detected genetic differentiation and outlier genes associated with primarily precipitation. We identified candidate gene GA1 for which allele frequency associated with plant height. Sourcing of climate adapted ecotypes should be considered for restoration.
Spherulitic microbialites from modern hypersaline lakes, Rottnest Island, Western Australia
Authors: Bischoff Karl , Sirantoine Eva , Wilson Moyra E. J. , George Annette D. , Mendes Monteiro Juliana , Saunders Martin
Published: May 2020

Fibrous‐radiating carbonate spherulites spatially associated with poorly crystalline Mg‐Si substances have formed within conical microbialites in modern hypersaline lakes on Rottnest Island, Western Australia. Two spherulitic fabrics can be distinguished based on compositional and textural differences. The oldest (lowermost) fabric comprises variably intergrown aragonitic spherulites 100–500 μm wide, containing micritic nuclei with coccoid cell molds in various stages of cell division. Spherulite matrices contain aggregates of individual nanospheres 150–200 nm wide, composed of a poorly crystalline Mg‐Si phase, locally containing cell molds with similar dimensions to those within spherulite nuclei. The younger (upper) fabric comprises sub‐polyhedral networks of mineralized EPS composed of an Mg‐Si substance. The polyhedrons contain aragonite‐replaced coccoid cells, voids, and polyhedral spherulites 8–12 μm wide with a morphology determined by fossil EPS, interpreted to have been produced by coccoid cyanobacteria. These spherulites are composed of high‐Mg calcite, inferred to have formed in association with heterotrophic bacteria. Stable isotope data, textural relationships, and geochemical modeling are consistent with cyanobacterial oxygenic photosynthesis influencing the precipitation of Mg‐Si substances and aragonitic spherulites by locally increasing the pH. The morphology of the polyhedral spherulites suggests the former presence of EPS and that faceted spherulites with similar dimensions in the geological record may represent biosignatures. The Rottnest Island conical microbialites demonstrate an intimate association between microbial features and processes and spherulitic fabrics, potentially providing insights into texturally and compositionally similar features in the geological record.
Salty, mild, and low plant biomass grasslands increase top‐heaviness of invertebrate trophic pyramids
Authors: Welti Ellen A. R. , Kuczynski Lucie , Marske Katharine A. , Sanders Nathan J. , de Beurs Kirsten M. , Kaspari Michael
Published: May 2020

Aim

Multiple hypotheses predict how gradients of nutrient availability, plant biomass, and temperature shape trophic pyramids. We aim to disentangle the simultaneous influence of those factors and their indirect effects on trophic structure and individual trophic levels.

Location

United States.

Time period

2017.

Major taxa studied

Invertebrates.

Methods

To examine differences in trophic pyramid shape and abundance within trophic levels and across ecological gradients, we conducted 54 standardized surveys of invertebrate communities in North American grasslands. We tested for the direct and indirect effects of plant biomass, temperature, sodium (Na), other essential elements (e.g. N, P, and K), and toxic heavy metals, (e.g. Ar and Pb) in plant tissue on both individual trophic levels, and trophic pyramid shape, estimated as the community trophic mean (CTM).

Results

Plant sodium increased CTM, indicating that high plant sodium concentrations are associated with top‐heavy invertebrate trophic pyramids. Sites with higher plant biomass had higher proportions of herbivores compared to higher trophic levels. Finally, increasing temperature resulted in more top‐heavy trophic pyramids. Overall, plant biomass, temperature, and plant chemistry directly and indirectly affected the abundances within different trophic levels, highlighting the complexity of factors regulating trophic structure.

Main conclusions

Trophic structure of grassland invertebrate communities is strongly influenced by plant sodium, plant biomass, and to a lesser extent, temperature. Grasslands occupy 30% of the Earth’s terrestrial surface and are an imperiled ecosystem due to conversion to row crop agriculture. As biogeochemistry and temperature in the Anthropocene are increasingly modified, our results have considerable implications for the trophic structure of future grassland communities.
A decision support system for fraud detection in public procurement
Authors: Velasco Rafael B. , Carpanese Igor , Interian Ruben , Paulo Neto Octávio C. G. , Ribeiro Celso C.
Published: May 2020

Over the past few years, investigators in Brazil have been uncovering numerous corruption and money laundering schemes at all levels of government and in the country's largest corporations. It is estimated that between 2% and 5% of the global GDP is lost annually because of such practices, not only directly impacting public services and private sector development but also strengthening organized crime. However, most law enforcement agencies do not have the capability to carry out systematic corruption risk assessment leveraging on the availability of data related to public procurement. The currently prevailing approach employed by Brazilian law enforcement agencies to detect companies involved in potential cases of fraud consists in receiving circumstantial evidence or complaints from whistleblowers. As a result, a large number of companies involved in fraud remain undetected and unprosecuted. The decision support system (DSS) described in this work addresses these existing limitations by providing a tool for systematic analysis of public procurement. It allows the law enforcement agencies to establish priorities concerning the companies to be investigated. This DSS incorporates data mining algorithms for quantifying dozens of corruption risk patterns for all public contractors inside a specific jurisdiction, leading to improvements in the quality of public spending and to the identification of more cases of fraud. These algorithms combine operations research tools such as graph theory, clusterization, and regression analysis with advanced data science methods to allow the identification of the main risk patterns, such as collusion between bidders, conflicts of interest (e.g., a politician who owns a company contracted by the same government body where he or she was elected), and companies owned by a potentially straw person used for disguising its real owner (e.g., beneficiaries of cash conditional transfer programs). The DSS has already led to a detailed analysis of large public procurement datasets, which add up to more than 50 billion dollars. Moreover, the DSS provided strategic inputs to investigations conducted by federal and state agencies.