bluuebunny/crossref_metadata_2025 huggingface dataset:
Weather and labor productivity in construction: a literature review and taxonomy of studies
Authors: Al Refaie Anas Moussa , Alashwal Ali M. , Abdul-Samad Zulkiflee , Salleh Hafez
Published: June 2020

Purpose

Climate change and global warming have increased concerns over the influence of weather on workers' health and productivity in construction projects. A significant number of studies can be found in the weather and productivity interplay area. The purpose of this paper is to review the recently published papers in this area to explore the trends of research and topics discussed and to determine knowledge gaps and directions for future research.

Design/methodology/approach

Recent papers published between 2014 and 2019 were synthesized, reviewed and analyzed using bibliometric and text mining analysis.

Findings

The results revealed the trends of publications, the main authors contributed to this area and countries that attracted most of the research papers. Based on the review, this study presented a taxonomy of studies consisting of seven clusters, namely productivity management, seasons, weather factors, participants' conditions, uniform and clothing, work time and health and safety.

Originality/value

This review paper sheds a light into the topics discussed in this area, the interrelationship between the topics and the significant topics that should be continued in the future. Global warming concerns necessitate the need for more studies in tropical countries and countries that are expected to expose to high temperatures and heat stress, which greatly impact labor productivity. The paper highlighted the need to understand how weather influences workers' psychological conditions and subsequently their productivity.
Curriculum integration of sustainability in engineering education – a national study of programme director perspectives
Authors: Leifler Ola , Dahlin Jon-Erik
Published: June 2020

Purpose

This study aims to report on how programme directors address sustainability within engineering education at Swedish universities and engineering colleges.

Design/methodology/approach

The study was performed as a survey with follow-up interviews around the following core questions: to what extent do programme directors possess a deep understanding of the subject of sustainable development? Which are the core competencies in sustainable development that programme directors identify as important for their engineering students to acquire during their basic training? To what extent are those competencies integrated into engineering education today and what kind of support do programme directors receive from their department to integrate these competencies into the curriculum?

Findings

Programme directors believe that learning for sustainable development is important mainly based on their personal convictions. However, out of 10 potential learning objectives extracted from the literature, only four-six are implemented in degree programmes. Learning objectives and activities are not always aligned, as students are required to learn about interdisciplinary collaboration without working with students from other faculties. The programme directors receive some support from the department, but they express a need for additional support. Examples of support that they suggest are faculty training, efficient teaching material and incorporation of sustainability in the quality assessment instruments for degree programmes.

Originality/value

This study is the first comprehensive, national survey of what programme directors think about sustainability in higher education. Their views are important in the attempt to accelerate the integration of sustainability in higher education curricula.
How does primary, secondary and tertiary education affect global terrorism? Fresh evidence with international panel data
Authors: Rajput Sheraz Mustafa
Published: June 2020

Purpose

This paper aims to assess the effects of different levels of education, namely, primary, secondary and tertiary, on global terrorism, measured by incidence of global terrorism.

Design/methodology/approach

Based on annual panel data covering 120 countries from 1990 to 2017, zero-inflated negative binomial regression (NBR) model is applied to estimate relationship between education and terrorism.

Findings

The findings reveal that higher attainment of education at primary and secondary level lowers terrorism worldwide. The findings strongly hold across the most affected regions of the world including Middle East and North Africa, South Asia, Sub-Saharan Africa and Europe. Drawing a comparison between the OECD and non-OECD countries, the results are substantially supported throughout.

Research limitations/implications

This study highlights the significance of education, at least up to secondary level, as an effective measure to reduce the extent of terrorist activities worldwide. Apart from this, more focus on education is recommended across the most affected regions (Middle East and North Africa, South Asia and Sub-Saharan Africa), specifically and the world, generally. Furthermore, as this study focuses at macro level, the future research may focus on factors enforcing individuals to resort to terrorism at individual and group level.

Originality/value

Unlike previous studies, this study contributes to existing literature through investigating the impact of terrorism at different levels of education.
Re-examining the government expenditure–growth nexus in ECOWAS countries
Authors: Olaoye Olumide Olusegun , Orisadare Monica , Okorie Ukafor Ukafor , Abanikanda Ezekiel
Published: June 2020

Purpose

The purpose of this study is to investigate the effect of government expenditure on economic growth in 15 Economic Community of West African States (ECOWAS) countries over the period of 2005–2017. More precisely, this paper investigates whether institutional environment influences the effect of government spending on economic growth.

Design/methodology/approach

This study adopts the generalized method of moments-system method of estimation to address the problem of dynamic endogeneity inherent in the relationship. Similarly, unlike previous studies which assume that the disturbances of a panel model are cross-sectionally independent, we account for cross-section dependency and cross-country heterogeneity inherent in empirical modeling using Driscoll and Kraay's nonparametric covariance matrix estimator, adjusted for use with both balanced and unbalanced panels along with Monte Carlo simulations.

Findings

The authors find that though, government spending has a positive impact on economic growth but the level of institutional quality adversely affect that positive impact. This suggests that the institutional environment in ECOWAS countries is a drag and not a push factor for government fiscal operations and/policies. Thus, the results provide empirical evidence that there is a conditional relationship between government spending and economic growth in African countries. That is, the effect of government spending on economic growth is dependent on the quality of institutions. Lastly, these findings suggest that in order for government spending to contribute to economic growth, African countries must develop a strong institutional environment.

Originality/value

Unlike previous time series studies for African countries which concentrated on the two variable case, we include institutional quality as a third variable to underline the potential importance of institutional quality for economic growth in ECOWAS countries.
Testing the influence of real-time performance feedback on employees in digital services
Authors: Lechermeier Jonas , Fassnacht Martin , Wagner Tillmann
Published: June 2020

Purpose

While digital media changed the nature of communication in service contexts, often allowing customers to interact instantly with service providers, the implications and opportunities for managing service employees are widely unknown. This is surprising, given that service employees are an important determinant of service firms’ success. This article examines the effects of real-time performance feedback on employees’ service performance and investigates both how and under what conditions timely feedback encourages employees’ engagement.

Design/methodology/approach

Two experiments test the conceptual model and the proposed hypotheses. A field experiment uses real customer feedback gathered after interaction with the app-chat of a large telecommunications provider. It tests the effect of feedback timing on service employees’ performance and also examines the effect of feedback timing on their engagement. A subsequent scenario-based experiment then investigates the influence of selected moderators on the feedback timing–engagement relationship.

Findings

This article finds that real-time feedback leads to greater service performance than subsequent feedback. Furthermore, real-time feedback positively affects service employee engagement through the perceived controllability of the feedback and the service situation. Finally, feedback valence, task goals, individuals’ need for closure (NCL), and gender interact with feedback timing to influence employee engagement.

Originality/value

This research investigates the potential of real-time performance feedback for service firms, combines and extends a variety of literature streams, and provides recommendations for the future management of service employees.
Crowdfunded and then? The role of intellectual capital in the growth of equity-crowdfunded companies
Authors: Troise Ciro , Matricano Diego , Candelo Elena , Sorrentino Mario
Published: June 2020

Purpose

This paper aims to investigate whether and to what extent equity crowdfunding (ECF) is able to build enduring businesses. This research explores the post-campaign growth of equity-crowdfunded companies and analyses the impact of intellectual capital (IC) on their growth. To achieve the above aim, we provide a theoretical framework that includes the three well-known dimensions of IC – i.e. human, structural and relational capital – as independent variables and company growth, meant as sales and employment growth, as dependent variable.

Design/methodology/approach

This research uses a quantitative methodology based on two regression analyses. The authors use hand-collected data on 51 successful equity-crowdfunded projects listed on seven Italian platforms.

Findings

The authors find that three variables, namely prior industry experience (human-capital), product innovation (structural-capital) and equity offered (relational-capital) are significant and positively related to the growth of equity-crowdfunded companies. In particular, prior industry experience positively influences sales growth; product innovation positively influences employment growth. Equity offered, instead, has a strong positive impact on both sales and employment growth. Companies that offer a larger percentage of equity during the campaign disclose higher probabilities of growth.

Practical implications

The study has useful implications for several stakeholders, in particular, founders, platform managers, crowdfunders, policy makers and authorities.

Originality/value

The results shed some light on the nascent research field related to post-campaign scenarios of equity-crowdfunded companies. This paper is the first to explore the impact of IC on the growth of companies funded through ECF.
Immunodepression induced by influenza A virus (H1N1) in lymphoid organs functions as a pathogenic mechanism
Authors: Xiang Li , Hu Xiaoyan , Zhang Jinping , She Junping , Li Mingyuan , Zhou Tiejun
Published: June 2020

In recent years, the frequency of influenza epidemics around the world has posed a great threat to the lives of people, especially those in developing countries. However, it is unclear which organs are the targets of influenza A viruses (IAVs) and what histopathology is caused by IAVs. In this study, BALB/c female mice were infected with H1N1 by nasal inoculation for 5 days. After euthanasia, the brain, heart, lungs, thymus, liver, spleen, hilar lymph nodes, pancreas, kidneys, and adrenal glands were collected. Among these organs, only the lungs, thymus, spleen, and hilar lymph nodes showed lesions. Lung histopathology was characterized by widening of the septum, lymphocyte infiltration, alveolar effusion, and alveolar hyaline membrane formation. The thymus and spleen exhibited atrophy due to the apoptosis of numerous lymphocytes. Although the hilar lymph nodes were enlarged, lymphocyte apoptosis still occurred. The nucleocapsid protein (NP) of IAVs was present not only in the lungs but also in the thymus, spleen, and hilar lymph nodes. In peripheral blood, CD19+B lymphocyte levels clearly decreased whileCD3+CD8+T and CD3+CD4+T lymphocyte levels temporarily decreased but subsequently increased. These results demonstrate that H1N1 in the lungs could reach lymphoid organs, induce the depletion of B and T lymphocytes in peripheral blood and lymphoid organs, and suppress adaptive immunity.
Synthesis, characterization, biological activity and electrochemistry studies of iron(III) complex with curcumin‐oxime ligand
Authors: Özbolat Gülüzar , Alizadeh Yegani Arash
Published: June 2020

Iron overload is a key target in drug development. This study aimed to investigate the coordination of Fe(III) ions with a curcumin‐oxime ligand that may be used in the treatment of iron overload. The synthesis of the curcumin‐oxime ligand and curcumin‐oxime‐Fe(III) complex was successfully made and characterized in its solid‐state and solution‐state using FT‐IR, UV‐Vis, elemental analysis, and 1H‐NMR. However, in this study, we investigated the apoptotic effects of the curcumin‐oxime Fe (III) complex on SW480. SW480 cells were exposed to 99.2% medium for 48 hours. After 48 hours, the incubation period, cells were harvested by centrifugation and washed in phosphate‐buffered saline (PBS) and lysed in radio‐immunoprecipitation assay (RIPA) buffer for 20 minutes and supernatants were taken and pellets were discarded. ELISA test was used to examine the expression, and activity of cleaved caspase‐3, Bax, and Bcl‐2 proteins in SW480 cells. ELISA test results indicated that the activities of apoptotic proteins Bax, caspase 3 and Bcl‐2 in human SW480 cell lines significantly increased in 48 hours treatment. Also, the activity of Bcl‐2 was observed to decrease significantly. Catalase activities of the complex were investigated. The findings showed that the complex has a catalase activity. The findings suggest that this type of complex may constitute a new and interesting basis for the future search of new and more potent drugs. The SOD activity of the result showed that the complexes possessed a considerable SOD activity with an IC50 value of 7.685 µM. Also, when compared with the control, a complex increased the SOD levels (P < .05). Electrochemistry studies in the literature have shown that the Fe3+/Fe2+couple redox process occurs in low potential. This value is within the range of compounds that are expected to show superoxide dismutase activity. The Ipc/Ipashows that one electron transport takes place in the complex. Our results suggest that curcumin‐oxime may represent a new approach in the treatment of iron overload.
Rethinking vulnerability through Covid‐19
Authors: Napier A. David
Published: June 2020

In times of crisis, inequalities are more commonly exaggerated than ameliorated – meaning both that vulnerable populations are often forced to make do with what resources are at hand and that many of those who barely manage in ‘normal’ times are pushed beyond capability and opportunity thresholds. Indeed, new case definitions of vulnerability that emerge in a crisis may push previously unrecognized groups (e.g. service employees, ‘care’ facility residents) into extreme vulnerability, as borderline coping quickly becomes calamity coping. To understand emerging vulnerability, it is therefore critical for social scientists to have a seat at the table where scarce resources are being allocated – before, during and after a crisis.
Struggling for food in a time of crisis: Responsibility and paradox
Authors: CAPLAN PAT
Published: June 2020

Struggling for food in a time of crisis: responsibility and paradox. Responsibility is a useful lens through which to examine the current state of food poverty in the UK in the context of the Covid‐19 crisis, noting that this concept contains several paradoxes. Currently, responsibility involves the voluntary sector, the food industry and the state, a situation which the author has been exploring for the last five years in an ethnographic study of food poverty and food aid in the UK. Food aid organizations, especially food banks, have mushroomed during the period of austerity. This reveals the first paradox: namely, that the existence of food banks conveys the message that ‘something is being done’, but in actuality this is very far from being sufficient to meet the needs of either the ‘old’ or ‘new’ food insecure. The second paradox is that at the onset of the crisis, a government which had been responsible for inflicting austerity on the country for 10 years, dramatically reversed some of its policies. However, predictably, this did not change the situation vis‐à‐vis food insecurity. The third paradox is that the frequent rhetoric invoking the two world wars has not resulted in lessons being learned – notably, the creation of a ministry to deal with food and rationing, as in the Second World War. The final paradox relates to Brexit and its likely deleterious effects on food security, particularly if no ‘deal’ is achieved with the European Union, as seems likely. The voluntary food aid sector, try as it may, cannot possibly assume responsibility for the long‐standing and now hugely increased problems of food insecurity. That belongs to the state.
Characterization and target gene analysis of microRNAs in the antennae of the parasitoid wasp Microplitis mediator
Authors: Shan Shuang , Wang Shan‐Ning , Song Xuan , Khashaveh Adel , Lu Zi‐Yun , Dhiloo Khalid Hussain , Li Rui‐Jun , Gao Xi‐Wu , Zhang Yong‐Jun
Published: June 2020

MicroRNAs (miRNAs), a class of non‐coding single‐strand RNA molecules encoded by endogenous genes, are about 21–24 nucleotides long and are involved in the post‐transcriptional regulation of gene expression in plants and animals. Generally, the types and quantities of miRNAs in the different tissues of an organism are diverse, and these divergences may be related to their specific functions. Here we have identified 296 known miRNAs and 46 novel miRNAs in the antennae of the parasitoid wasp Microplitis mediator by high‐throughput sequencing. Thirty‐three miRNAs were predicted to target olfactory‐associated genes, including odorant binding proteins (OBPs), chemosensory proteins, odorant receptors (ORs), ionotropic receptors (IRs) and gustatory receptors. Among these, 17 miRNAs were significantly highly expressed in the antennae, four miRNAs were highly expressed both in the antennae and head or wings, while the remaining 12 miRNAs were mainly expressed in the head, thorax, abdomen, legs and wings. Notably, miR‐9a‐5p and miR‐2525‐3p were highly expressed in male antennae, whereas miR‐1000‐5p and novel‐miR‐13 were enriched in female antennae. The 17 miRNAs highly expressed in antennae are likely to be associated with olfaction, and were predicted to target one OBP (targeted by miR‐3751‐3p), one IR (targeted by miR‐7‐5p) and 14 ORs (targeted by 15 miRNAs including miR‐6‐3p, miR‐9a‐5p, miR‐9b‐5p, miR‐29‐5p, miR‐71‐5p, miR‐275‐3p, miR‐1000‐5p, miR‐1000‐3p, miR‐2525‐3p, miR‐6012‐3p, miR‐9719‐3p, novel‐miR‐10, novel‐miR‐13, novel‐miR‐14 and novel‐miR‐28). These candidate olfactory‐associated miRNAs are all likely to be involved in chemoreception through the regulation of chemosensory gene expression in the antennae of M. mediator.
Correlation among PME activity, viscoelastic, and structural parameters for Carica papaya edible tissue along ripening
Authors: Sanchez Nestor , Gutiérrez‐López Gustavo F. , Cáez‐Ramírez Gabriela
Published: June 2020

Papaya fruit, widely consumed around the world, is mechanically and structurally affected by several enzymatic processes during ripening, where pectin methylesterase plays a key role. Hence, the aim of this work was to evaluate possible correlations among physicochemical changes, mechanical parameters, viscoelastic behavior, and enzyme activity of pectin methylesterase to provide information about the softening phenomenon by applying the Maxwell and Peleg models. Mechanical parameters were estimated by texture profile analysis, enzyme activity by Michaelis–Menten parameters, and viscoelastic behavior by relaxation test responses fitted to these models. The Maxwell model described properly mechanical changes during ripening, displaying a better adjustment (R2 > 0.97) than the Peleg model (0.80 < R2 < 0.84). Pearson correlation analysis (P ≤ 0.01) indicated an inversely proportional relation among firmness, total soluble solids, and the first elastic element of the Maxwell model. Besides, the PME Michaelis–Menten affinity constant showed a correlation between the first elastic element and the first viscoelastic element of the Maxwell model. Findings of this work pointed out that the first Maxwell elastic element could explain structural changes as papaya ripening advance, associated with pectin methylesterase activity, cell wall disruption, and cell assembling into the tissue.

Practical Application

Mechanical and viscoelastic behavior of papaya fruit tissue were described by the Maxwell model associating both viscous and elastic elements to the softening process. The results provide background and practical knowledge to describe structural changes during the ripening process of papaya depending on its enzymatic activity. Outcomes could be further applied to understand changes in other fruits or food matrixes that soften during postharvest, storage, and food chain supply processes.
Overall and chemotherapy‐free survival following stereotactic body radiation therapy for abdominopelvic oligometastases
Authors: Shahi Jeevin , Peng Jonathan , Donovan Elysia , Vansantvoort Jasmin , Wong Raimond , Tsakiridis Theodoros , Quan Kimmen , Parpia Sameer , Swaminath Anand
Published: June 2020

Introduction

Limited data establish the efficacy and safety of SBRT in the abdominopelvic (AP) space, where SBRT delivery is challenging due to the proximity of radiosensitive luminal gastrointestinal (GI) organs. The aim of this study was to assess clinical outcomes in patients with AP OM treated with SBRT.

Methods

Eligible patients were those with OM (defined as metastases in ≤3 total sites) in the AP space (excluding liver) treated with SBRT. Descriptive statistics and Kaplan–Meier estimates of (LC), progression‐free survival (PFS), overall survival (OS) and chemotherapy‐free survival (CFS) were performed.

Results

Fifty‐one patients with 58 AP OM received SBRT between 2011 and 2015. Median follow‐up was 21.9 months. All SBRT treatments were delivered in 5 fractions with a median dose of 35 Gy (25–40 Gy). Progression post‐SBRT occurred in 38/51 patients (75%), with a median PFS of 4.9 months (95% CI: 2.5–7.5), and 2‐year PFS of 29%. Rates of 2‐and 4‐year LC were 74% and 69%, respectively. Median OS was 42.6 months (95% CI: 31–55). Oligometastatic progression occurred in 21/38 patients, and of those, 48% (10/21) received further SBRT. Resulting 2‐ and 4‐year CFS were 47% and 37%, respectively (median 15.1 months). Nineteen patients (37%) experienced a grade 1 or 2 acute toxicity. One grade 3 (acute) toxicity was observed. No grade 4 or 5 toxicities were detected.

Conclusions

SBRT to AP OM was associated with sustained LC, excellent OS and minimal toxicity. The use of SBRT allowed for prolonged CFS and the salvage of limited‐burden distant failures.
Contracting with private rewards
Authors: Kirkegaard René
Published: June 2020

The canonical moral hazard model is extended to allow the agent to face endogenous and noncontractible uncertainty. The agent works for the principal and simultaneously pursues outside rewards. The contract offered by the principal thus manipulates the agent's work–life balance. The participation constraint is slack whenever it is optimal to distort the agent's work–life balance away from life compared to a symmetric‐information benchmark. Then, the agent's expected utility is high and he faces flatter incentives. Such contracts may be optimal when the two activities are strong substitutes in the agent's cost function or when reservation utility is low.
Influences of seasons and dietary composition on diurnal raptor habitat use in Chembe Bird Sanctuary, Zambia: Implications for conservation
Authors: Nyirenda Vincent R. , Yambayamba Arthur M. , Chisha‐Kasumu Exildah
Published: June 2020

Diurnal raptor habitat use has conservation implications due to environmental and anthropogenic interactions. Three tree‐nesting diurnal raptors, black kites (Milvus milvus), steppe buzzards (Buteo vulpinus) and African fish eagles (Haliaeetus vocifer), were studied from December 2016 to October 2017. The objective was to determine factors influencing diurnal raptor habitat selection and use in and around Chembe Bird Sanctuary of Kalulushi district, Zambia. We surveyed for birds in ten randomly selected 200 × 200 m sample plots in each of the five stratified sampling units (miombo woodland, grasslands, human settlements, Lake Chembe and marsh). Seasons and dietary composition variably influenced the distribution, habitat selection and use by raptors. The three raptors devised a suit of behaviours to curtail challenges associated with seasonal food and water availability, and anthropogenic disturbances. There is a need to promote multi‐stakeholder engagement and involvement in raptor conservation.
Implementation of advanced radiotherapy technology to improve clinical outcomes in rural NSW
Authors: Banjade Dilli , Allan Julaine , Thuraisingam Kandeepan , Mishra Ajeet , Newham Ben , Tan Shiaw Juen (Eugene) , Renshaw Amy , Hammond Rodney , Stevens Graham , Warr George
Published: June 2020

Problem

Availability of advanced radiotherapy technology to treat cancer is limited in regional Australia. At Central West Cancer Care Centre, the utilisation rate of intensity‐modulated radiotherapy and volumetric modulated arc therapy was significantly lower compared to other NSW public health services. Stereotactic ablative body radiotherapy treatment was not available at Central West Cancer Care Centre.

Design

To increase the intensity‐modulated radiotherapy/volumetric modulated arc therapy utilisation rate and to make stereotactic ablative body radiotherapy treatment available through quality improvement projects with multi‐disciplinary collaboration.

Setting

Central West Cancer Care Centre is part of Western NSW Local health District. Central West Cancer Care Centre has two linear accelerators for delivering intensity‐modulated radiotherapy, volumetric modulated arc therapy and stereotactic ablative body radiotherapy treatments, and a computed tomography simulator with 4D computed tomography capability.

Key measures for improvement

Intensity‐modulated radiotherapy/volumetric modulated arc therapy utilisation rate increases to > 65%

Stereotactic ablative body radiotherapy available to Central West Cancer Care Centre patients

Strategy for change

A multi‐disciplinary active of team radiation oncologists, medical physics specialists and radiation therapists developed an implementation plan for each treatment technique.

Effect of change

There was a significant increase in use of advanced techniques. The impact on patients included the following:

Fewer side effects and improved control of disease as the advanced techniques directed the dose to the tumour and reduced the radiation dose to organ at risk.

Treatment completed sooner than conventional radiotherapy, as the required dose required fewer trips to the hospital.

Rural and remote patients were not required to travel to a metropolitan centre to have stereotactic ablative body radiotherapy treatment.

Lessons learnt

Strong commitment from a trained team and a collaborative approach is important for the implementation of advanced technology in regional centres.
Smalt production in the Ore Mountains: Characterization of samples related to the production of blue pigment in Bohemia
Authors: Zlámalová Cílová Z. , Gelnar M. , Randáková S.
Published: June 2020

The study deals with the chemical composition of samples related to the production of a blue pigment/smalt. The samples examined come from the regions of Soví huť and Horní Blatná (north‐west Bohemia) dating to the 16th and 17th centuries. These locations are often mentioned in relation to the discoverer of smalt production technology: Christopher Schürer. The aim of the study is to evaluate the chemical composition of samples from both localities as well as with respect to the ores occurring in the given regions. The samples can be divided into two basic groups. The first clearly represents smalt (potassium glass coloured with cobalt), while the second apparently constitutes the samples of the so‐called ‘speiss’ (an aluminosilicate mass with metallic compounds). The analysis of the smalt confirmed the representation of minor elements bismuth and nickel (always) and uranium and molybdenum (rarely), which are found in Co ores from the Ore Mountains. The paper is the first to present the composition of actual blue pigment finds originating directly from the production sites, while the available literature has so far only reported the results of analyses of the pigments already used when referring to the Ore Mountains.
Video‐assisted thoracoscopic right upper lobectomy in a patient with a displaced bronchus and vascular abnormalities
Authors: Momose Naoya , Takahashi Tsuyoshi , Sugimura Aya , Sekihara Keigo , Nagasaka Satoshi
Published: June 2020

Bronchial abnormalities are rare, and they are infrequently associated with pulmonary vascular abnormalities. It is important to identify such abnormal anatomical structures before lobectomy of the lung under thoracoscopy. There have been only three reports on video‐assisted thoracoscopic lobectomy in patients with anomalous bronchi and vascular abnormalities to date. Here, we present a report of video‐assisted thoracoscopic right upper lobectomy performed in a patient with bronchial and vascular abnormalities. Both preoperative imaging and intraoperative findings revealed a displaced anomalous B2 bronchus arising from the bronchus intermedius, as well as abnormal distribution of the aberrant vein V2 draining into vein V6. It is critical to understand the precise anatomical structures preoperatively to perform video‐assisted thoracoscopic pulmonary lobectomy safely.
Managing access to advanced therapy medicinal products: Challenges for NHS Wales
Authors: Champion Andrew R. , Lewis Sian , Davies Stuart , Hughes Dyfrig A.
Published: June 2020

Advanced Therapy Medicinal Products (ATMPs), which include gene, somatic cell therapies and tissue‐engineered medicines, have the potential to transform current care pathways by offering durable and potentially curative outcomes. However, they are exceptionally expensive, with prices exceeding £1m per patient in some cases. With an expectation that a large number of ATMPs will soon gain marketing authorisation (global market is estimated to reach £9bn to £14bn by 2025), healthcare payers and providers face a number of challenges to facilitate patient access to this new category of medicines.

This viewpoint reflects on the experience of introducing ATMPs into the National Health Service in Wales where £1 in every £200 spent on medicines (2019/2020) is expected to be on ATMPs for just 20 patients. Evidence to date makes it apparent that decisions regarding clinical and cost‐effectiveness and the scale of the budget impact of implementing ATMPs create both financial and health service risks. Consequently, there are significant policy implications. A critical examination is made of the approaches taken for the health technology assessment and appraisal of ATMPs, the methods of payment and service impacts of these medicines, and the approach taken to horizon scanning and subsequent modelling of the financial impact over the next 10 years.
Plasma and cerebrospinal fluid pharmacokinetics of ondansetron in humans
Authors: Chiang Manting D. , Frey Karen , Lee Chris , Kharasch Evan D. , Tallchief Dani , Sawyer Christopher , Blood Jane , Back Hyunmoon , Kagan Leonid , Haroutounian Simon
Published: June 2020

Aims

Changes in serotonergic sensory modulation associated with overexpression of 5‐HT3 receptors in the central nervous system (CNS) have been implicated in the pathophysiology of neuropathic pain after peripheral nerve damage. 5‐HT3 receptor antagonists such as ondansetron can potentially alleviate neuropathic pain, but have limited effectiveness, due potentially to limited CNS access. However, there is currently limited information on CNS disposition of systemically‐administered 5‐HT3 receptor antagonists. This study evaluated the cerebrospinal fluid (CSF) disposition of ondansetron, as a surrogate of CNS penetration.

Methods

Fifteen patients were given a single 16 mg intravenous 15 minute infusion of ondansetron, followed by serial blood and a single CSF sampling. Population pharmacokinetic (PK) modelling was implemented to describe the average and individual plasma and CSF profiles of ondansetron. A two‐compartmental model was used to capture ondansetron plasma PK with a single CSF compartment to describe distribution to the CNS.

Results

The individual model‐estimated CSF to plasma partition coefficients of ondansetron were between 0.09 and 0.20. These values were mirrored in the calculated CSF penetration ratios, ranging from 0.08 to 0.26.

Conclusions

After intravenous administration, CSF concentrations of ondansetron were approximately 7‐fold lower than those observed in the plasma. A model could be developed to describe individual CSF concentration–time profiles of ondansetron based on a single CSF data point. The low CSF penetration of ondansetron may explain its limited analgesic effectiveness, and affords an opportunity to explore enhancing its CNS penetration for targeting conditions such as neuropathic pain.
Population pharmacokinetics of olanzapine in children
Authors: Maharaj Anil R. , Wu Huali , Zimmerman Kanecia O. , Autmizguine Julie , Kalra Rohit , Al‐Uzri Amira , Sherwin Catherine M.T. , Goldstein Stuart L. , Watt Kevin , Erinjeri Jinson , Payne Elizabeth H. , Cohen‐Wolkowiez Michael , Hornik Christoph P.
Published: June 2020

Aims

The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model‐informed paediatric dosing scheme.

Methods

The PopPK of olanzapine was characterized using opportunistically collected plasma samples from children receiving olanzapine per standard of care for any indication. A nonlinear mixed effect modelling approach was employed for model development using the software NONMEM (v7.4). Simulations from the developed PopPK model were used to devise a paediatric dosing scheme that targeted comparable plasma exposures to adolescents and adults.

Results

Forty‐five participants contributed 83 plasma samples towards the analysis. The median (range) postnatal age and body weight of participants were 3.8 years (0.2–19.2) and 14.1 kg (4.2–111.7), respectively. The analysis was restricted to pharmacokinetic (PK) samples collected following enteral administration (oral and feeding tube). A one‐compartment model with linear elimination provided an appropriate fit to the data. The final model included the covariates body weight and postmenstrual age (PMA) on apparent olanzapine clearance (CL/F). Typical CL/F and apparent volume of distribution (scaled to 70 kg) were 16.8 L/h (21% RSE) and 663 L (13% RSE), respectively. Developed dosing schemes used weight‐normalized doses for children ≤6 months postnatal age or <15 kg and fixed doses for children ≥15 kg.

Conclusion

We developed a paediatric PopPK model for enterally‐administered olanzapine. To our knowledge, this analysis is the first study to characterize the PK of olanzapine in participants ranging from infants to adolescents. Body weight and PMA were identified as influential covariates for characterizing developmental changes in olanzapine apparent clearance.
Early phase II study of mixed 19‐peptide vaccine monotherapy for refractory triple‐negative breast cancer
Authors: Toh Uhi , Sakurai Sayaka , Saku Shuko , Takao Yuko , Okabe Mina , Iwakuma Nobutaka , Shichijo Shigeki , Yamada Akira , Itoh Kyogo , Akagi Yoshito
Published: June 2020

We undertook an early phase II study of mixed 19‐peptide cancer vaccine monotherapy for 14 advanced metastatic triple‐negative breast cancer (mTNBC) patients refractory to systemic chemotherapy to develop a new type of cancer vaccine. The treatment protocol consisted of a weekly vaccination for 6 weeks, and there were no severe adverse events related to the vaccination throughout the trial. Increase of peptide‐specific IgG against the vaccinated human leukocyte antigen‐matched peptides, but not against the nonmatched peptides, was positively correlated with overall survival (OS) (P < .01). The median OS was 11.5 or 24.4 months in all 14 patients or the 10 patients who completed the vaccination. The patients with lower C‐reactive protein levels or 3 or fewer systemic chemotherapies were favorable candidates for this treatment. Advancement of this therapy to the next stage of study could be warranted based on the safety and immune boosting determined herein (clinical trial registration number: UMIN000014616).
Expression of classical human leukocyte antigen class I antigens, HLA‐E and HLA‐G, is adversely prognostic in pancreatic cancer patients
Authors: Hiraoka Nobuyoshi , Ino Yoshinori , Hori Shutaro , Yamazaki‐Itoh Rie , Naito Chie , Shimasaki Mari , Esaki Minoru , Nara Satoshi , Kishi Yoji , Shimada Kazuaki , Nakamura Naoya , Torigoe Toshihiko , Heike Yuji
Published: June 2020

The expression of classical human leukocyte antigen class I antigens (HLA‐I) on the surfaces of cancer cells allows cytotoxic T cells to recognize and eliminate these cells. Reduction or loss of HLA‐I is a mechanism of escape from antitumor immunity. The present study aimed to investigate the clinicopathological impacts of HLA‐I and non–classical HLA‐I antigens expressed on pancreatic ductal adenocarcinoma (PDAC) cells. We performed immunohistochemistry to detect expression of HLA‐I antigens in PDAC using 243 PDAC cases and examined their clinicopathological influences. We also investigated the expression of immune‐related genes to characterize PDAC tumor microenvironments. Lower expression of HLA‐I, found in 33% of PDAC cases, was significantly associated with longer overall survival. Higher expression of both HLA‐E and HLA‐G was significantly associated with shorter survival. Multivariate analyses revealed that higher expression of these three HLA‐I antigens was significantly correlated with shorter survival. Higher HLA‐I expression on PDAC cells was significantly correlated with higher expression of IFNG, which also correlated with PD1, PD‐L1 and PD‐L2 expression. In vitro assay revealed that interferon gamma (IFNγ) stimulation increased surface expression of HLA‐I in three PDAC cell lines. It also upregulated surface expression of HLA‐E, HLA‐G and immune checkpoint molecules, including PD‐L1 and PD‐L2. These results suggest that the higher expression of HLA‐I, HLA‐E and HLA‐G on PDAC cells is an unfavorable prognosticator. It is possible that IFNγ promotes a tolerant microenvironment by inducing immune checkpoint molecules in PDAC tissues with higher HLA‐I expression on PDAC cells.
Clinical and radiographic assessment of circular versus triangular cross‐section neck Implants in the posterior maxilla: A 1‐year randomized controlled trial
Authors: Li Manni Lou , Lecloux Geoffrey , Rompen Eric , Aouini Walid , Shapira Lior , Lambert France
Published: June 2020

Objectives

Implants with a triangular neck were recently introduced to limit peri‐implant bone loss. The primary objective of this randomized controlled trial was to compare peri‐implant bone changes of circular versus triangular cross‐section neck implants 1 year after loading. The secondary objectives were to assess buccal hard tissue thickness changes, Pink Esthetic Score (PES), and patient satisfaction.

Material and methods

Thirty four patients requiring replacement of the single, intercalated missing tooth of healed site for at least 4 months in the posterior maxilla were randomized into 2 groups according to the type of implant. Immediately after surgery and 1 year after final restoration, a cone beam CT (CBCT) was performed to assess proximal bone remodeling and buccal bone thickness. Peri‐implant soft tissue health, PES, and patient‐reported outcome measures (PROMs) were recorded.

Results

No implant loss occurred within the follow‐up period. The mean ± SD peri‐implant proximal bone loss 1 year after loading was 0.22 ± 0.30 mm for triangular and 0.42 ± 0.67 mm for circular implants necks (p = .25). Peri‐implant bone loss exceeding 2 mm was observed in a single implant in the circular neck group. Buccal bone thickness remained stable and did not differ different between the 2 groups. The peri‐implant soft tissue health, PES, and patient satisfaction were also comparable.

Conclusions

Within the limitations of the present study, patient clinical and radiographic outcomes did not differ between triangular and circular cross‐section neck implants in the posterior maxilla.
A multispecies assessment of wildlife impacts on local community livelihoods
Authors: Pozo Rocío A. , LeFlore Eric G. , Duthie A. Bradley , Bunnefeld Nils , Jones Isabel L. , Minderman Jeroen , Rakotonarivo O. Sarobidy , Cusack Jeremy J.
Published: June 2020

Conflicts between the interests of agriculture and wildlife conservation are a major threat to biodiversity and human well‐being globally. Addressing such conflicts requires a thorough understanding of the impacts associated with living alongside protected wildlife. Despite this, most studies reporting on human–wildlife impacts and the strategies used to mitigate them focus on a single species, thus oversimplifying often complex systems of human–wildlife interactions. We sought to characterize the spatiotemporal patterns of impacts by multiple co‐occurring species on agricultural livelihoods in the eastern Okavango Delta Panhandle in northern Botswana through the use of a database of 3264 wildlife‐incident reports recorded from 2009 to 2015 by the Department of Wildlife and National Parks. Eight species (African elephants [Loxodonta africana], hippopotamuses [Hippopotamus amphibious], lions [Panthera leo], cheetah [Acinonyx jubatus], African wild dogs [Lycaon pictus], hyenas [Crocuta crocuta], leopards [Panthera pardus], and crocodiles [Crocodylus niloticus]) appeared on incident reports, of which 56.5% were attributed to elephants. Most species were associated with only 1 type of damage (i.e., either crop damage or livestock loss). Carnivores were primarily implicated in incident reports related to livestock loss, particularly toward the end of the dry season (May–October). In contrast, herbivores were associated with crop‐loss incidents during the wet season (November–April). Our results illustrate how local communities can face distinct livelihood challenges from different species at different times of the year. Such a multispecies assessment has important implications for the design of conservation interventions aimed at addressing the costs of living with wildlife and thereby mitigation of the underlying conservation conflict. Our spatiotemporal, multispecies approach is widely applicable to other regions where sustainable and long‐term solutions to conservation conflicts are needed for local communities and biodiversity.
Intertwined effects of defaunation, increased tree mortality and density compensation on seed dispersal
Authors: Fedriani J. M. , Ayllón D. , Wiegand T. , Grimm V.
Published: June 2020

Contemporary defaunation has profound ecological consequences ranging from local or even global co‐extinctions of interacting species to the loss of ecosystem functions and services critical for humanity. Other components of global change (climate change, introduced pests, land use changes) are also harming ecosystem functioning by augmenting tree mortality worldwide. Defaunation and increased tree mortality often coincide in many human‐altered ecosystems but whether they interact, leading to non‐additive effects on ecosystem functioning, remains largely unknown. However, under some ecological circumstances, the decline or extirpation of one species due to defaunation can be neutralized by increases in the abundance of some functionally similar species (i.e. ‘density compensation’). We combined long‐term field data with individual‐based modelling to investigate the potential interactive effects of seed disperser loss, increased tree mortality and density compensation on seed dispersal in a heterogeneous landscape. Our simulation experiments showed that both stressors markedly limit not only the quantity of seed dispersal but also its quality since the impact on seed dispersal strongly varied among habitat types that differ strikingly in suitability for tree establishment. Density compensation had a marked positive effect on seed dispersal which, however, was largely limited under increased tree mortality. The combined negative effects of defaunation and increased tree mortality on seed dispersal were lower than the expected additive effect. This highlights the need to account for the joint operation of multiple stressors to accurately predict the impacts of global change on the link between biodiversity and ecosystem functioning.
Anagrelide influences thrombotic risk, and prolongs progression‐free and overall survival in essential thrombocythaemia vs hydroxyurea plus aspirin
Authors: Kellner Adam , Dombi Peter , Illes Arpad , Demeter Judit , Homor Lajos , Ercsei Ibolya , Simon Zsofia , Karadi Eva , Herczeg Jozsef , Gy Korom Viktoria , Gasztonyi Zoltan , Szerafin Laszlo , Udvardy Miklos , Egyed Miklos
Published: June 2020

Objective

We report an extension study of patients with essential thrombocythaemia (ET) in the Hungarian Myeloproliferative Neoplasm (HUMYPRON) Registry, which demonstrated that over 6 years anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous thrombotic events (TEs) vs hydroxyurea+aspirin.

Methods

Data on patients with ET were collected through completion of a questionnaire developed according to 2008 WHO diagnostic criteria and with regard to Landolfi, Tefferi and IPSET criteria for thrombotic risk. Data were entered into the registry from 14 haematological centres. TEs, secondary malignancies, disease progression and survival were compared between patients with ET treated with anagrelide (n = 116) and with hydroxyurea+aspirin (n = 121).

Results

Patients were followed for (median) 10 years. A between‐group difference in the number of patients with TEs was observed (25.9% anagrelide vs 38.0% hydroxyurea+aspirin; P = .052). Minor arterial events were more frequently reported in the hydroxyurea+aspirin group (P < .001); there were marginally more reports of major arterial events in the anagrelide group (P = .049). TE prior to diagnosis was found to significantly influence TE incidence (P > .001). Progression‐free survival (P = .004) and survival (P = .001) were significantly increased for the anagrelide group vs hydroxyurea+aspirin.

Conclusions

Anagrelide reduced TEs, and increased progression‐free and overall survival vs hydroxyurea+aspirin over (median) 10 years.