bluuebunny/crossref_metadata_2025 huggingface dataset:
Tourism spatial distribution in Brazil: a recent assessment using thematic cartography
Authors: Ragagnin Pimentel Maurício , Pereira Melise de Lima
Published: February 2020

Purpose

This study aims to: (1) describe the spatial distribution of tourism in Brazil; (2) assess Brazilian tourism growth and its location between 2007 and 2016; (3) discuss the implications of the findings to the understanding of tourism in Brazil and (4) debate about the methodological specifics of this work.

Design/methodology/approach

Thematic cartography is used to explore and analyze tourism spatial distribution in Brazil. The proxy used was the number of jobs in the lodging industry in the years of 2007 and 2016, available at the Ministry of Labor RAIS data set. Descriptive statistics, Spearman's rank correlation and Ward's method for cluster analysis were applied in the construction procedures of this three-step process method.

Findings

The uneven distribution of tourism across the country and its concentration in specific areas of the Brazilian territory are presented in three thematic maps. Between 2007 and 2016 most of the growth in accommodation jobs has been in already established tourist destinations. There is a softening of accommodation Jobs concentration in large metropolises, and a trend that this growth takes place in more tourism specialized cities. Nevertheless, it is in small cities where tourism plays a significant role in changing local economies.

Originality/value

It presents and discusses Brazilian tourism spatial distribution. It assesses the whole national territory, with data broken at the country's smallest administrative level. It uses a data set that is still original in tourism literature. It considers previous research on spatial distribution and proposes a new method.
Developing 21st century leaders, a complete new process
Authors: Knights John , Grant Danielle , Young Greg
Published: February 2020

Purpose

It is becoming more generally accepted that there is a need to develop a new kind of leader to meet the needs of our 21st century VUCA world. The bookcases are full of volumes that describe “what” great leaders should do, but “how” to develop such leaders is usually limited to a macro or systemic solution rather than focusing on granular behavioural change of the individual. This paper describes the qualities and characteristics of Transpersonal Leaders, then focuses on developing these leaders through a new coaching process and finally explains how experienced coaches can be trained to coach these leaders.

Design/methodology/approach

Our research over the last 20 years of working with leaders individually and in teams has focused on this issue. We have been developing “21st century ready” leaders, referred to as Transpersonal Leaders, for over 10 years in teams, but only recently have we been developing such leaders through a new coaching process. We have also developed a methodology that codifies the development of Transpersonal Leaders which, in turn, allows us to replicate the programme by training other professionals, potentially in large numbers.

Findings

Graduates of the Transpersonal Coach Training Programme say that it has been a transformational personal experience, enabling them to take their leader clients to a new level. Leaders who have been coached say the programme has equipped them to learn a practical approach to becoming an authentic, ethical, caring and more effective leader.

Originality/value

This is a unique approach to coaching leaders but based on proven learning principles.
Do tournament incentives motivate chief executive officers to be socially responsible?
Authors: Ali Shahid , Zhang Junrui , Usman Muhammad , Khan Muhammad Kaleem , Khan Farman Ullah , Siddique Muhammad Abubakkar
Published: February 2020

Purpose

This study aims to investigate the question concerning whether tournament incentives motivate chief executive officers (CEOs) to be socially responsible.

Design/methodology/approach

Data from all A-share Chinese companies listed on the Shanghai and Shenzhen stock exchanges for the period from 2010 to 2015 are used. To draw inferences from the data, ordinary least squares (OLS) regression and cluster OLS are used as a baseline methodology. To control for the possible issue of endogeneity, firm-fixed-effects regression, two-stage least squares regression and propensity score matching are used.

Findings

A reliable evidence is found that tournament incentives motivate CEOs to be more socially responsible. Additional analysis reveals that the positive effect of CEO tournament incentives on corporate social responsibility performance (CSRP) is more pronounced in state-owned firms than it is in non-state-owned firms. The study’s findings are consistent with tournament theory and the conventional wisdom hypothesis, which proposes that better incentives lead to competitiveness, which improves financial and social performance.

Practical implications

The study’s findings have implications for companies and regulators who wish to enhance CSRP by giving tournament incentives to top managers. Investment in social responsibility may reduce the conflict between executives and employees and improve the corporate culture.

Originality/value

This study contributes to the existing literature by providing the first evidence that CEOs’ tournament incentives play a vital role in CSRP. The study’s findings contribute to tournament theory.
Spatial biomonitoring of airborne heavy metals emitted from a steel recycling plant
Authors: Adeleke Abayomi Isaac , Fakinle Bamidele Sunday , Odunlami Olayemi Abosede , Sonibare Jacob Ademola
Published: February 2020

Purpose

The study investigated the heavy metal flux around the vicinity of a steel recycling factory using passive biomonitoring technique with several pollution indices to assess the quality of the ambient environment.

Design/methodology/approach

The vegetation around the facility was identified, and the most abundant species were selected for analysis. The collected samples were dried, milled, sieved and analyzed for elemental composition using energy dispersive X-ray fluorescence (ED-XRF). Pollution indices were used to quantitatively assess the data.

Findings

Results show that maximum contamination occurs at the vicinity of factory. Generally, the deterioration of the ambient air around the vicinity of the steel recycling plant decreases with increasing distance from the steel recycling plant. However, for the radius considered in this study – 1 km, the ambient air at 1 km of the steel recycling facility is quickly deteriorating, and there is an urgent need for measures to mitigate the air quality impact of the steel recycling facility.

Originality/value

The study shows that the metal recycling process emits high levels of heavy metals to the environment, and there is an urgent need for personal protective equipment for the human population working in and around the close proximity of the recycling plant.
Inhibitors in the recycling of organs and implications to the environment
Authors: Dhakate Nikhil , Joshi Rohit
Published: February 2020

Purpose

Environmental sustainability in health care is an important issue due to the limited available healthcare resources and increase in demand. For instance, organ recycling and transplantation may reduce the increasing pressure on healthcare resources. The purpose of this paper is to set out to identify and interrelate the inhibitors that significantly influence the recycling of human organs and their implications to the environment in developing economies such as India.

Design/methodology/approach

The study uses Delphi–ISM–regression, a three-step method, to investigate the possible reasons for the poor supply chain efficiency of organ recycling and to explore the consequence of excessive use of healthcare resources on the environment. The Delphi technique facilitates the identification, synthesis, and prioritization of the inhibitors. Then, using focused group discussion, the interpretive structure modeling (ISM) presents the interaction among the inhibitors into a hierarchy. Further, on the basis of 257 valid responses received on the structured survey instrument, the regression model examines the influence of identified constructs on one of the identified root causes.

Findings

The ISM presents the hierarchy-based model that depicts high driving power and low dependence inhibitors leading to reduced organ recycling rate. “Negative Intentions of family members” toward organ donationt“Willingness to discuss with family” and “Perceived Behavioral Control” emerged as the significant factors influencing organ recycling rate, which adversely impact the environment sustainability.

Originality/value

The patients on the organ waiting list put pressure on the availability of medical resources and, ultimately, on the environment through the consumption of different drugs and disposable of medical wastes. The study suggests policymakers and hospitals improve on the existing policies for an efficient supply chain of human organ recycling. The Indian situation echoes the situation in most of the emerging economies, and similar solutions can apply there too.
The role of customers and employees in the buffer effect of corporate social responsibility in times of crisis
Authors: Ellouze Dorra
Published: February 2020

Purpose

The purpose of the paper is to investigate the role of customers and employees in the buffer effect of CSR around the 2008 financial crisis in the European context.

Design/methodology/approach

Using a sample of 323 European firms listed in STOXX Europe 600 Index, different models are estimated to test whether the effect of CSR ratings on firms' relationships with their customers and employees could be different during the 2008 financial crisis relative to the pre-crisis and post-crisis periods.

Findings

The paper shows that CSR rating has a significantly negative impact on firms' accounts receivable and a significantly positive effect on employee productivity during the crisis period (from 2007 to 2009). However, there is no significant effect of CSR rating during the non-crisis periods. These results suggest that during negative events, customers are willing to continue supporting high-CSR firms by paying their invoices faster. Furthermore, these firms benefit from higher productivity of their employees who are willing to work harder in periods of uncertainty.

Research limitations/implications

Firms should invest in CSR practices to maintain strong and cooperative relationships with their customers and employees. Also, investors should choose firms engaging in more social capital. Moreover, policymakers should encourage implementing CSR practices which act as an insurance-like protection in times of negative events.

Originality/value

This paper adds to the previous studies by investigating whether the cooperative role of customers and employees can explain the buffer role of CSR around the crisis. Furthermore, it considers companies located in several European countries for a long period (from 2004 to 2012) to compare periods of crisis and non-crisis.
How does interactive use of budgets affect creativity?
Authors: Sitepu Eddy Mayor Putra , Appuhami Ranjith , Su Sophia
Published: February 2020

Purpose

The purpose of this paper is to examine the relationship between the interactive use of budgets, role clarity and individual creativity.

Design/methodology/approach

Survey data was collected from mid-level managers in publicly listed Indonesian companies. The data was analysed using partial least squares.

Findings

The findings indicate that while there is no direct association between an interactive use of budgets and individual creativity, an interactive use of budgets can affect individual creativity via role clarity.

Originality/value

This study is one of only a few studies that provide empirical evidence on the relationships between individual creativity, role clarity and the interactive use of budgets. While previous studies have been undertaken in Western countries such as the USA and the UK, this study focuses on an emerging economy – Indonesia in which firms have been trying to improve individual creativity.
Synthesis and characterization of nano-ceramic pigment Co0.5Zn0.5Al2O4 via polyacrylamide gel method
Authors: Rahimian Masoud , Saebnoori Ehsan , Hassanzadeh-Tabrizi S.A.
Published: February 2020

Purpose

The purpose of this paper is to synthesize and characterize nano-ceramic blue pigment Co0.5Zn0.5Al2O4 via polyacrylamide gel method. Generally, the high cost and the environmental toxicity of cobalt aluminate pigments lead them to become less common and cause problems in production process. To significantly reduce this problem, it is required to reduce the cobalt in the pigment and replace the cobalt with some amounts of zinc in the structure.

Design/methodology/approach

In this paper, calcination temperature and its effects on phase specification and color properties of final product were investigated. The powders were studied by using XRD, FESEM, TG/DTA, FTIR, UV-Vis and colorimetric in CIELab space, in which the calcination temperatures were set to 600°C, 800°C and 1,000 °C, and the inert atmosphere was air.

Findings

According to the XRD patterns, single-phase spinel structure with a good crystallinity was formed even in the low temperature. The infrared spectra displayed vibrations at about 500, 560 and 680 cm−1, which were ascribed to the spinel structure. FESEM images showed nanoscale particles with an average size of 32 nm. Regarding the Co2+ spin transitions in tetrahedral sites, the UV-Vis spectra presented three bands at 552, 598 and 628 nm.

Practical implications

The colorimetric data indicated the formation of blue pigments corresponding to negative values of b*. The color of pigments was affected by calcination temperature.

Originality/value

The characterization analysis shows that a blue pigment has been obtained in this research. Different degrees of blue color were obtained at different calcination temperatures.
Managing omni-customer brand experience via augmented reality
Authors: Cuomo Maria Teresa , Tortora Debora , Festa Giuseppe , Ceruti Francesca , Metallo Gerardino
Published: February 2020

Purpose

The adoption of augmented reality (AR) settings represents an extraordinary opportunity to enrich the value of the omni-customer brand experience, especially in fashion retail. AR enhances the brand of extra-contents, both informational and sensorial, amplifies its significance toward consumers and inflects its commercial and emotional charm through new dimensions in the store. In this light, the purpose of this paper is to verify whether AR affects customer behavior toward brands in the retailing system.

Design/methodology/approach

By means of a qualitative approach, a preliminary research question linking technological settings of the store/brand and customer informational eagerness has been analyzed in a fashion retailing chain store. To frame the research question, the omni-customer segment perspective has been assumed, taking into consideration two main dimensions as follows: implementation of in-store AR settings; and affective/cognitive/functional structure of the experiential brand value.

Findings

Preliminary findings suggest that AR can create extra brand value by simplifying the decision-making process and engaging customers. In the sum four “realms” in terms of augmented brand experience can emerge and be managed by retailers.

Originality/value

Even though the contribution of AR is easily understood in selling activities from a marketing perspective, very few retail applied studies can be found to-date. The present analysis aims to narrow this gap. It also contributes to brand management, stimulating the integration of the AR dimension as an additional facet of a brand tool kit in the “project” for value co-creation.
A novel respiration pattern biometric prediction system based on artificial neural network
Authors: Raji Rafiu King , Adjeisah Michael , Miao Xuhong , Wan Ailan
Published: February 2020

Purpose

The purpose of this paper is to introduce a novel respiration pattern-based biometric prediction system (BPS) by using artificial neural network (ANN).

Design/methodology/approach

Respiration patterns were obtained using a knitted piezoresistive smart chest band. The ANN model was implemented by using four hidden layers to help achieve the best complexity to produce an adequate fit for the data. Not only did this study give a detailed distribution of an ANN model construction including the scheme of parameters and network layers, ablation of the architecture and the derivation of back-propagation during the iterations but also engaged a step-based decay to systematically drop the learning rate after specific epochs during training to minimize the loss and increase the model’s accuracy as well as to limit the risk of overfitting.

Findings

Findings establish the feasibility of using respiratory patterns for biometric identification. Experimental results show that, with a learning rate drop factor = 0.5, the network is able to continue to learn past epoch 40 until stagnation occurs which yielded a classification accuracy of 98 per cent. Out of 51,338 test set, the model achieved 51,557 correctly classified instances and 169 misclassified instances.

Practical implications

The findings provide an impetus for possible studies into the application of chest breathing sensors for human machine interfaces in the area of entertainment.

Originality/value

This is the first time respiratory patterns have been applied in biometric prediction system design.
Improving barrier and operational risk analysis (BORA) using criticality importance analysis case study: oil and gas separator
Authors: Bourareche Mouloud , Nait Said Rachid , Zidani Fatiha , Ouazraoui Nouara
Published: February 2020

Purpose

The purpose of this paper is to show the impact of operational and environmental conditions (risk influencing factors) on the component criticality of safety barriers, safety barrier performance and accidents frequency and therefore on risk levels.

Design/methodology/approach

The methodology focuses on the integration of criticality importance analysis in barrier and operational risk analysis method, abbreviated as BORA-CIA. First, the impact of risk influencing factors (RIFs) associated with basic events on safety barrier performance and accident frequency is studied, and then, a risk evaluation is performed. Finally, how unacceptable risks can be mitigated regarding risk criteria is analyzed.

Findings

In the proposed approach (BORA-CIA), the authors show how specific installation conditions influence risk levels and analyze the prioritization of components to improve safety barrier performance in oil and gas process.

Practical implications

The proposed methodology seems to be a powerful tool in risk decision. Ordering components of safety barriers taking into account RIFs allow maintenance strategies to be undertaken according to the real environment far from average data. Also, maintenance costs would be estimated adequately.

Originality/value

In this paper, an improved BORA method is developed by incorporating CIA. More precisely, the variability of criticality importance factors of components is used to analyze the prioritization of maintenance actions in an operational environment.
Combined immunosuppressive therapy provides favorable prognosis and increased risk of cytomegalovirus reactivation in anti‐melanoma differentiation‐associated gene 5 antibody‐positive dermatomyositis
Authors: Matsuda Kazuki M. , Yoshizaki Ayumi , Kuzumi Ai , Fukasawa Takemichi , Ebata Satoshi , Yoshizaki‐Ogawa Asako , Sato Shinichi
Published: February 2020

Anti‐melanoma differentiation‐associated gene 5 (MDA5) antibody (Ab) is myositis‐specific autoantibody associated with rapidly progressive interstitial lung disease (ILD) and poor prognosis. In this retrospective observational study, we aimed to verify the efficacy and safety of introducing combined immunosuppressive therapy for anti‐MDA5 Ab‐positive dermatomyositis (DM) from their early stage. We recruited all Japanese patients diagnosed with DM in our clinic between January 2011 and October 2018, who had anti‐MDA5 Ab, anti‐aminoacyl transfer RNA synthetase Ab or anti‐transcriptional intermediary factor 1‐γ Ab. Combined immunosuppressive therapy was defined as combination of systemic corticosteroids, i.v. cyclophosphamide and tacrolimus. The difference of clinical features among the three groups was analyzed by multiple comparison analysis. The longitudinal change of the measurements from baseline was examined by Wilcoxon signed‐rank test. Association between therapeutic regimens and adverse events was examined by logistic regression analysis. As a result, combined immunosuppressive therapy was most frequently used in the anti‐MDA5 Ab‐positive group, which significantly improved their forced vital capacity of the lung. Interval time since initial visit until starting treatment was the shortest in the anti‐MDA5 Ab‐positive group. There was no significant difference in the incidence of death and recurrence among the three groups. Cytomegalovirus reactivation was most common in the anti‐MDA5 Ab‐positive group, associated with combined immunosuppressive therapy. Collectively, early introduction of combined immunosuppressive therapy was effective for DM patients with anti‐MDA5 Ab. At the same time, clinicians should be aware of the risk of cytomegalovirus reactivation during the treatment.
Angiomatoid Spitz nevus with surrounding pagetoid melanocytic proliferation on the sole of the foot: An unusual case report with immunohistochemical studies for angiogenic factors
Authors: Anju Keisuke , Nakamura Yoshiyuki , Okiyama Naoko , Ishitsuka Yosuke , Saito Akimasa , Watanabe Rei , Fujisawa Yasuhiro
Published: February 2020

Angiomatoid Spitz nevus (ASN) is a rare histological variant of Spitz nevus (SN) that is characterized by prominent blood vessel proliferation around the intradermal melanocytes of SN. In contrast, SN may have pagetoid components, which are characterized by epidermal proliferation of single melanocytes. However, cases of ASN with predominant pagetoid melanocytic proliferation in the epidermis have not been reported. Here, we report a case of ASN with surrounding pagetoid melanocytic proliferation without formation of tumor nests in the epidermis in the plantar region. A 12‐year‐old girl presented with a bright red nodule surrounded by a brown macule on the sole of her right foot. Histologically, the nodule showed tumor nests in the dermis, composed of spindle or epithelioid melanocytes containing abundant cytoplasm and large nuclei. Around the nests, numerous blood vessels were seen. In the overlying epidermis of the nodule, numerous eosinophilic Kamino bodies were found along the dermal–epidermal interface. In the macule, proliferation of oval melanocytes was present as single‐cell units in the epidermis. Theses melanocytes had abundant cytoplasm with large nuclei, which were larger than those of the surrounding keratinocytes. From these findings, a diagnosis of ASN with surrounding pagetoid melanocytic proliferation was made. Vascular endothelial growth factor and fibroblast growth factor 2 were strongly expressed in the melanocytes as well as in the endothelial cells in our case. Therefore, angiogenic factors produced by the melanocytes of SN might have played important roles in the surrounding angiogenesis of this case.
Plasmodium infection cure cycles induce modulation of conventional dendritic cells
Authors: Adachi Ryosuke , Tamura Takahiko
Published: February 2020

Malaria is one of the most widespread human infectious diseases worldwide and a cause of mortality. It is difficult to induce immunological memory against the malarial parasite Plasmodium. The immunity to clinical malaria disease is acquired with multiple infection and treatment cycles, along with substantial reduction in parasite burden. However, the mechanism of the acquired immunity remains largely unclear. Conventional DCs (cDCs) play a pivotal role in orchestration of immune responses. The purpose of this study is to analyze the characterization of cDCs after the infection and cure treatment cycles. Mice were infected with the lethal rodent malarial parasite Plasmodium berghei ANKA, which was followed by cure treatment with the antimalarial drug pyrimethamine. This was then followed by a challenge with live parasites. The mice that went through infection cure cycles showed significant immune response, demonstrating robust immunological memory against malaria parasites. We investigated the cytokine production capacity of splenic cDCs in both naive and infection cure mice by stimulating purified splenic cDCs with LPS (TLR4 agonist) or CpG (TLR9 agonist). The capacity of cytokine production was found to be significantly decreased in infection cure mice. The suppression of cytokine production was sustained for a long term (6 months). Moreover, the surface expression of MHC Class II molecules was significantly lower in infection cure mice than in naive mice. These results suggest that Plasmodium infection and cure treatment resulted in strong immunological memory and modulation of full functionality of cDCs.
Detection of prey odours underpins dietary specialization in a Neotropical top‐predator: How army ants find their ant prey
Authors: Manubay John Aidan , Powell Scott
Published: February 2020

Deciphering the mechanisms that underpin dietary specialization and niche partitioning is crucial to understanding the maintenance of biodiversity. New world army ants live in species‐rich assemblages throughout the Neotropics and are voracious predators of other arthropods. They are therefore an important and potentially informative group for addressing how diverse predator assemblages partition available prey resources.

New World army ants are largely specialist predators of other ants, with each species specializing on different ant genera. However, the mechanisms of prey choice are unknown. In this study, we addressed whether the army antEciton hamatum:(a) can detect potential prey odours, (b) can distinguish between odours of prey and non‐prey and (c) can differentiate between different types of odours associated with its prey.

Using field experiments, we tested the response of army ants to the following four odour treatments: alarm odours, dead ants, live ants and nest material. Each treatment had a unique combination of odour sources and included some movement in two of the treatments (alarm and live ants). Odour treatments were tested for both prey and non‐prey ants. These data were used to determine the degree to whichE. hamatumare using specific prey stimuli to detect potential prey and direct their foraging.

Army ants responded strongly to odours derived from prey ants, which triggered both increased localized recruitment and slowed advancement of the raid as they targeted the odour source. Odours from non‐prey ants were largely ignored. Additionally, the army ants had the strongest response to the nest material of their preferred prey, with progressively weaker responses across the live ant, dead ant and alarm odours treatments respectively.

This study reveals that the detection of prey odours, and especially the most persistent odours related to the prey's nest, provides a mechanism for dietary specialization in army ants. If ubiquitous across the Neotropical army ants, then this olfaction‐based ecological specialization may facilitate patterns of resource partitioning and coexistence in these diverse predator communities.
Living With Stigma: Spatial and Social Divisions in a Danish City
Authors: Jensen Sune Qvotrup , Prieur Annick , Skjott‐Larsen Jakob
Published: February 2020

Inspired by Bourdieu's theory of homology between social, mental and spatial structures, this essay dissects the relationship between spatial and social divisions in the Danish city of Aalborg using varied data from official statistics, surveys, qualitative interviews and field observations. Spatial divisions reflect differences in the objective distribution of economic and cultural capital, and are accompanied by symbolic divisions in residents’ minds. Some nuances are, however, added to Bourdieu's homology argument, as there are discrepancies between objective distributions and mental schemes, such that the latter exaggerate and dramatize the former. The neighbourhood of Aalborg East is subjected to this symbolic exaggeration in the form of spatial stigma or territorial stigmatization. An analysis of residents’ strategies for coping with spatial stigma furthermore provides an illustration of Wacquant's claim that this stigmatization can be met with a range of socially patterned responses ranging from acceptance or indifference to recalcitrance.
Diversity of lacewing assemblages (Neuropterida:Neuroptera) in different forest habitats and agricultural areas in the East Mediterranean area of Turkey
Authors: Bozdoğan Hakan
Published: February 2020

The objectives of this study were to understand lacewing diversity patterns and the role of environmental factors in determining lacewing diversity in four habitat types: agricultural area (crops and orchards), pine forest (Pinus nigra Arnold and, Pinus brutia Ten), natural forest (cedar and willow‐oak), and mixed forest (beech and oak).

Several diversity patterns were evaluated, including evenness and dominance, in the East Mediterranean area of Turkey by analyzing the abundance and species composition of lacewing assemblages using the Simpson and Shannon Diversity Indices. It was questioned whether these communities are structured according to environmental conditions such as altitude, temperature, rainfall, wind and humidity. This question was explored using generalized linear models (GLMs) and principal component analysis (PCA) to detect the effect of ecological parameters on the species composition of the lacewing assemblages. The data suggest that the species abundance, composition, and diversity of lacewings are affected by different forest and agricultural habitat types. Based on the results of the present study, it is recommended that the area of farmland under cultivation is decreased and the area of sustainably managed forest and agricultural land is increased in order to better protect lacewing diversity in the East Mediterranean area of Turkey.
Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer
Authors: Sugano Teppei , Seike Masahiro , Saito Yoshinobu , Kashiwada Takeru , Terasaki Yasuhiro , Takano Natsuki , Hisakane Kakeru , Takahashi Satoshi , Tanaka Toru , Takeuchi Susumu , Miyanaga Akihiko , Minegishi Yuji , Noro Rintaro , Kubota Kaoru , Gemma Akihiko
Published: February 2020

Background

Interstitial lung disease (ILD) induced by immune checkpoint inhibitors (ICIs) is a potentially life‐threatening adverse event. The purpose of this study was to evaluate whether the development of immune‐related adverse events (irAEs), especially ILD, was associated with treatment efficacy and to research the features and risk factors of ILD in advanced non‐small cell lung cancer (NSCLC).

Methods

Between December 2015 and November 2018, 130 advanced NSCLC patients were treated with nivolumab, pembrolizumab or atezolizumab. The patients were categorized into two groups (irAEs group or non‐irAEs group). Subsequently, we divided the irAEs group into two groups based on the incidence of ILD (ILD group and irAEs‐non‐ILD group). Treatment efficacy and the characteristics of ILD were evaluated.

Results

A total of 39 (30%) patients developed irAEs. ILD was observed in 16 (12%) patients. Patients with ILD had a higher objective response rate (ORR) compared with irAEs‐non‐ILD patients and non‐irAEs patients (63%, 43% and 22%, respectively). Median progression‐free survival (mPFS) was 15.9 months in ILD patients, 5.4 months in irAEs‐non‐ILD patients and 3.3 months in non‐irAEs patients (log‐rank test, P = 0.033). Pre‐existing interstitial pneumonia (IP) was an independent risk factor for ILD‐induced ICIs (odds ratio [OR] 14.7; 95% confidence interval [CI]: 2.16–99.6, P = 0.006).

Conclusions

ORR and PFS were significantly better in ILD patients than in irAEs‐non‐ILD and non‐irAEs patients. Pre‐existing history of IP was an independent risk factor for ILD‐induced ICIs.
Age‐related changes to macrophages are detrimental to fracture healing in mice
Authors: Clark Daniel , Brazina Sloane , Yang Frank , Hu Diane , Hsieh Christine L. , Niemi Erene C. , Miclau Theodore , Nakamura Mary C. , Marcucio Ralph
Published: February 2020

The elderly population suffers from higher rates of complications during fracture healing that result in increased morbidity and mortality. Inflammatory dysregulation is associated with increased age and is a contributing factor to the myriad of age‐related diseases. Therefore, we investigated age‐related changes to an important cellular regulator of inflammation, the macrophage, and the impact on fracture healing outcomes. We demonstrated that old mice (24 months) have delayed fracture healing with significantly less bone and more cartilage compared to young mice (3 months). The quantity of infiltrating macrophages into the fracture callus was similar in old and young mice. However, RNA‐seq analysis demonstrated distinct differences in the transcriptomes of macrophages derived from the fracture callus of old and young mice, with an up‐regulation of M1/pro‐inflammatory genes in macrophages from old mice as well as dysregulation of other immune‐related genes. Preventing infiltration of the fracture site by macrophages in old mice improved healing outcomes, with significantly more bone in the calluses of treated mice compared to age‐matched controls. After preventing infiltration by macrophages, the macrophages remaining within the fracture callus were collected and examined via RNA‐seq analysis, and their transcriptome resembled macrophages from young calluses. Taken together, infiltrating macrophages from old mice demonstrate detrimental age‐related changes, and depleting infiltrating macrophages can improve fracture healing in old mice.
Increased miR‐34c mediates synaptic deficits by targeting synaptotagmin 1 through ROS‐JNK‐p53 pathway in Alzheimer’s Disease
Authors: Shi Zhongli , Zhang Kaixia , Zhou Huimin , Jiang Lei , Xie Bing , Wang Ruiyuan , Xia Wenzhen , Yin Yajuan , Gao Zhaoyu , Cui Dongsheng , Zhang Rui , Xu Shunjiang
Published: February 2020

Alzheimer's disease (AD) and cancer have inverse relationship in many aspects. Some tumor suppressors, including miR‐34c, are decreased in cancer but increased in AD. The upstream regulatory pathways and the downstream mechanisms of miR‐34c in AD remain to be investigated. The expression of miR‐34c was detected by RT–qPCR in oxidative stressed neurons, hippocampus of SAMP8 mice, or serum of patients with amnestic mild cognitive impairment (aMCI). Dual luciferase assay was performed to confirm the binding sites of miR‐34c in its target mRNA. The Morris water maze (MWM) was used to evaluate learning and memory in SAMP8 mice administrated with miR‐34c antagomir (AM34c). Golgi staining was used to evaluate the synaptic function and structure. The dramatically increased miR‐34c was mediated by ROS‐JNK‐p53 pathway and negatively regulated synaptotagmin 1 (SYT1) expression by targeting the 3′‐untranslated region (3′‐UTR) of syt1 in AD. The expression of SYT1 protein was reduced by over expression of miR‐34c in the HT‐22 cells and vice versa. Administration of AM34c by the third ventricle injection or intranasal delivery markedly increased the brain levels of SYT1 and ameliorated the cognitive function in SAMP8 mice. The serum miR‐34c was significantly increased in patients with aMCI and might be a predictive biomarker for diagnosis of aMCI. These results indicated that increased miR‐34c mediated synaptic and memory deficits by targeting SYT1 through ROS‐JNK‐p53 pathway and the miR‐34c/SYT1 pathway could be considered as a promising novel therapeutic target for patients with AD.
Opioid agonist treatment and fatal overdose risk in a state‐wide US population receiving opioid use disorder services
Authors: Krawczyk Noa , Mojtabai Ramin , Stuart Elizabeth A. , Fingerhood Michael , Agus Deborah , Lyons B. Casey , Weiner Jonathan P. , Saloner Brendan
Published: February 2020

Background and aims

Evidence from randomized controlled trials establishes that medication treatment with methadone and buprenorphine reduces opioid use and improves treatment retention. However, little is known about the role of such medications compared with non‐medication treatments in mitigating overdose risk among US patient populations receiving treatment in usual care settings. This study compared overdose mortality among those in medication versus non‐medication treatments in specialty care settings.

Design

Retrospective cohort study using state‐wide treatment data linked to death records. Survival analysis was used to analyze data in a time‐to‐event framework.

Setting

Services delivered by 757 providers in publicly funded out‐patient specialty treatment programs in Maryland, USA between 1 January 2015 and 31 December 2016.

Participants

A total of 48 274 adults admitted to out‐patient specialty treatment programs in 2015–16 for primary diagnosis of opioid use disorder.

Measurements

Main exposure was time in medication treatment (methadone/buprenorphine), time following medication treatment, time exposed to non‐medication treatments and time following non‐medication treatment. Main outcome was opioid overdose death during and after treatment. Hazard ratios were calculated using Cox proportional hazard regression. Propensity score weights were adjusted for patient information on sex, age, race, region of residence, marital and veteran status, employment, homelessness, primary opioid, mental health treatment, arrests and criminal justice referral.

Findings

The study population experienced 371 opioid overdose deaths. Periods in medication treatment were associated with substantially reduced hazard of opioid overdose death compared with periods in non‐medication treatment [adjusted hazard ratio (aHR) = 0.18, 95% confidence interval (CI) = 0.08–0.40]. Periods after discharge from non‐medication treatment (aHR = 5.45, 95% CI = 2.80–9.53) and medication treatment (aHR = 5.85, 95% CI = 3.10–11.02) had similar and substantially elevated risks compared with periods in non‐medication treatments.

Conclusions

Among Maryland patients in specialty opioid treatment, periods in treatment are protective against overdose compared with periods out of care. Methadone and buprenorphine are associated with significantly lower overdose death compared with non‐medication treatments during care but not after treatment is discontinued.
Cost‐effectiveness of grass pollen allergen immunotherapy in adults
Authors: Di Bona Danilo , Bilancia Massimo , Albanesi Marcello , Caiaffa Maria Filomena , Macchia Luigi
Published: February 2020

Background

Major scientific societies, such as the EAACI or the AAAAI, do not express any suggestion on which form of allergen immunotherapy (AIT) is to be preferred (subcutaneous immunotherapy, SCIT, vs sublingual immunotherapy, SLIT). This choice could depend on their relative pharmacoeconomic value.

Objective

To assess the cost‐effectiveness of AIT for grass pollen, administered as SCIT or SLIT.

Methods

We created a Markovian Model, to evaluate, in a hypothetical cohort of adult patients suffering from moderate‐to‐severe rhino‐conjunctivitis with or without allergic asthma, the cost‐effectiveness of SLIT (tablets, Grazax® and Oralair®) or SCIT (various currently available products, plus indirect nonmedical costs, such as travel and productivity costs) in addition to pharmacological therapy, assuming a 9‐year horizon to capture AIT long‐term effects. The incremental cost‐effectiveness ratio (ICER) was calculated assuming pharmacological therapy as the reference comparator.

Results

In the base case, SCIT was slightly more expensive, but more effective than SLIT, being the most cost‐effective option (ICER for SCIT, €11 418; ICER for SLIT, €15 212). ICERs greater than €120 000 for both SCIT and SLIT were demonstrated in a scenario assuming that low treatment persistence rates, which are common in real‐life, lead to absence of long‐term AIT clinical benefit. Considering indirect nonmedical costs SLIT resulted more cost‐effective than SCIT (ICER for SCIT, €17 318; ICER for SLIT, €15 212).

Conclusion

In daily practice, AIT for grass pollens may be a cost‐effective option only in patients with low discontinuation rates. SCIT, which is less affected by this limitation than SLIT, seems the most cost‐effective AIT form.
Factors associated with rapid improvement in visual acuity in patients with Leber's hereditary optic neuropathy after gene therapy
Authors: Liu Hong‐li , Yuan Jia‐jia , Zhang Yong , Tian Zhen , Li Xin , Wang Dan , Du Yang‐yang , Song Lin , Li Bin
Published: February 2020

Purpose

To analyse the factors associated with rapid and significant improvement in visual acuity in patients with Leber's hereditary optic neuropathy (LHON) after gene therapy and explain the theory of this improvement.

Methods

We recruited 149 patients with LHON, who underwent gene therapy, and divided them into two groups according to the absence or presence of rapid and significant visual acuity improvements within 3 days of treatment. A bivariate logistic regression model was used to analyse relevant factors including age, the period between onset and treatment, baseline values of best corrected visual acuity (BCVA), visual field index (VFI) and pretreatment average retinal nerve fibre‐layer thickness (GRNFL). The corresponding parameters for the injected and non‐injected eyes were analysed separately.

Results

The period between onset and treatment, and pretreatment baseline BCVA was significantly associated with rapid and significant improvement in visual acuity for both, the injected and non‐injected eyes. Moreover, pretreatment baseline VFI and GRNFL were not significantly associated with rapid and significant improvement in visual acuity. Age was significantly associated with rapid and significant improvement in visual acuity of the injected eyes.

Conclusion

The period between onset and treatment, and pretreatment baseline BCVA may be important predictors of rapid and significant improvement in visual acuity in patients with LHON after gene therapy.
Development and validation of the DIGIGLO, a tool for assessing the digital competence of educators
Authors: Alarcón Rafael , del Pilar Jiménez Elena , de Vicente‐Yagüe María Isabel
Published: February 2020

Educators must be able to adapt to the opportunities provided by information and communication technologies, making use of those which are best suited to meeting their students' needs and identifying areas of practice in which they themselves need to develop their skills. The European Framework for the Digital Competence of Educators (DigCompEdu) proposes 22 basic competences, organised into six areas, which educators should ideally acquire. The present study seeks to build on this Framework by developing and validating an assessment tool that considers a total of eight areas: the six areas covered by DigCompEdu and two new areas corresponding to extrinsic factors in the digital competence of educators. The latter refers specifically to the digital resources and support services that are available to educators in their working environment. A total of 509 teacher educators from across Spain and Latin America completed the 29‐item DIGIGLO questionnaire. Analysis of the Spanish language instrument's construct validity and psychometric properties showed it to be a valid and reliable tool for assessing the digital competence of educators across the eight areas considered.

Practitioner Notes

What is already known about this topic

Educators must be able to adapt (habituate) to the opportunities provided by information and communication technologies.

The European Framework for the Digital Competence of Educators (DigCompEdu) proposes 22 basic competences, organised into six areas, which educators should ideally acquire.

The speed with which digital technology is developing means that educators need to keep track of their own digital skills.

What this paper adds

We develop and validate an instrument for assessing educators' digital competence (the DIGIGLO) that considers external factors not included within the DigCompEdu.

These external factors refer to the digital resources and support services that are available to educators in their working environment.

The total score on the 29‐item questionnaire provides a measure of educators' overall digital competence across eight different areas.

Implications for practice and/or policy

The DIGIGLO is a brief and easy‐to‐use tool for assessing the digital competence of educators, a key issue in the educational field today.

It extends the scope of the DigCompEdu Framework by including two further areas of digital competence (digital environment and extrinsic digital engagement).

Application of the instrument can provide individual educators and their institutions with useful feedback about both strengths and areas in need of improvement with regard to the use of digital technology in teaching.
Mixed company: a framework for understanding the composition and organization of mixed‐species animal groups
Authors: Goodale Eben , Sridhar Hari , Sieving Kathryn E. , Bangal Priti , Colorado Z. Gabriel J. , Farine Damien R. , Heymann Eckhard W. , Jones Harrison H. , Krams Indrikis , Martínez Ari E. , Montaño‐Centellas Flavia , Muñoz Jenny , Srinivasan Umesh , Theo Anne , Shanker Kartik
Published: February 2020

Mixed‐species animal groups (MSGs) are widely acknowledged to increase predator avoidance and foraging efficiency, among other benefits, and thereby increase participants' fitness. Diversity in MSG composition ranges from two to 70 species of very similar or completely different phenotypes. Yet consistency in organization is also observable in that one or a few species usually have disproportionate importance for MSG formation and/or maintenance. We propose a two‐dimensional framework for understanding this diversity and consistency, concentrating on the types of interactions possible between two individuals, usually of different species. One axis represents the similarity of benefit types traded between the individuals, while the second axis expresses asymmetry in the relative amount of benefits/costs accrued. Considering benefit types, one extreme represents the case of single‐species groups wherein all individuals obtain the same supplementary, group‐size‐related benefits, and the other extreme comprises associations of very different, but complementary species (e.g. one partner creates access to food while the other provides vigilance). The relevance of social information and the matching of activities (e.g. speed of movement) are highest for relationships on the supplementary side of this axis, but so is competition; relationships between species will occur at points along this gradient where the benefits outweigh the costs. Considering benefit amounts given or received, extreme asymmetry occurs when one species is exclusively a benefit provider and the other a benefit user. Within this parameter space, some MSG systems are constrained to one kind of interaction, such as shoals of fish of similar species or leader–follower interactions in fish and other taxa. Other MSGs, such as terrestrial bird flocks, can simultaneously include a variety of supplementary and complementary interactions. We review the benefits that species obtain across the diversity of MSG types, and argue that the degree and nature of asymmetry between benefit providers and users should be measured and not just assumed. We then discuss evolutionary shifts in MSG types, focusing on drivers towards similarity in group composition, and selection on benefit providers to enhance the benefits they can receive from other species. Finally, we conclude by considering how individual and collective behaviour in MSGs may influence both the structure and processes of communities.