bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Organisation and the Dynamics of Tubules in the Endoplasmic Reticulum
Authors: Perkins H. , Ducluzaux P. , Woodman P. , Allan V. , Waigh T.
Published: March 2020

The endoplasmic reticulum (ER) is a eukaryotic subcellular organelle composed of tubules and sheet-like areas of membrane connected at junctions. The tubule network is highly dynamic and undergoes rapid and continual rearrangement. There are currently few tools to evaluate network organisation and dynamics. We quantified ER network organisation in Vero and MRC5 cells, and developed a classification system for ER dynamics in live cells. The persistence length, tubule length, junction coordination number and angles of the network were quantified. Hallmarks of imbalances in ER tension, indications of interactions with microtubules and other subcellular organelles, and active reorganisation and dynamics were observed. Live cell ER tubule dynamics were classified using a Gaussian mixture model, defining tubule motion asactiveorthermaland conformational phase space analysis allowed this classification to be refined by tubule curvature states.

STATEMENT OF SIGNIFICANCE

The endoplasmic reticulum (ER), a subcellular organelle, is an underexplored real-world example of active matter. Many processes essential to cell survival are performed by the ER, the efficacy of which may depend on its organisation and dynamics. Abnormal ER morphology is linked to diseases such as hereditary spastic paraplegias and it is possible that the dynamics are also implicated. Therefore, analysing the ER network in normal cells is important for the understanding of disease-related alterations. In this work, we outline the first thorough quantification methods for determining ER organisation and dynamics, deducing that tubule motion has a binary classification as active or thermal. Active reorganisation and dynamics along with indications of tension imbalances and membrane contact sites were observed.
The use and benefit of management accounting practices in Libyan oil companies
Authors: Kalifa Abdarahman M. , Triyuwono Iwan , Irianto Gugus , Prihatiningtias Yeney Widya
Published: March 2020

Purpose

The purpose of this study is to describe the use and benefit of TMAPs and CMAPs in Libyan oil companies.

Design/methodology/approach

The data were collected by distributing 210 mailed questionnaires to senior financial staff, such as financial managers, heads of cost department, financial accountants, department of management accounting employees, managerial accountants and Auditors. IFAC-based model was used in analyzing evolution stages in Libyan management accounting practices.

Findings

This study finds that Libyan oil companies use CMAPs more than TMAPs, the latter being commonly used in Libyan manufacturing companies. This study also finds that CMAPs are more beneficial than TMAPs.

Practical implications

This study provides more understanding of the use and the benefit of TMAPs and CMAPs and fills research gap regarding the matter, as well as provides new findings that can be used for further research regarding the use and benefit of TMAPs and CMAPs for Libyan oil companies.

Originality/value

The results contribute to a better understanding concerning the use and benefit of TMAPs and CMAPs in Libyan oil companies.
Diversity management as navigation through organizational paradoxes
Authors: Nadiv Ronit , Kuna Shani
Published: March 2020

Purpose

Accumulated evidence suggests that efforts at diversity management (DM) yield mixed results or even fail in terms of promoting workforce diversity. Previous scholarly attempts to explain the mixed results of DM initiatives provided only partial understanding. This study applies a paradox perspective to better understand the challenges of DM from the vantage point of diversity managers, who play a central role in the promotion and implementation of diversity initiatives.

Design/methodology/approach

In-depth interviews with diversity managers in large business organizations in Israel explored practitioners' conceptions of the challenges underlying the implementation of diversity initiatives. A grounded theory approach was utilized.

Findings

The findings reveal the emergence of paradox: diversity initiatives generate organizational tensions that undermine their success and hence amplify the need for further diversity interventions. Three distinct paradoxes are identified: necessary change vs desire for stability; bureaucratic control vs flexible procedures; and long-term business gains vs short-term losses. Diversity managers utilize two opposing strategies to contend with these paradoxes.

Research limitations/implications

This study does not represent voices of diverse employees or of top executives. The data focused on mid-level practitioners' descriptions of DM challenges and their methods of contending with them.

Practical implications

The findings shed light on an effective strategy of contending with paradox. Recognizing paradox and navigating it properly may greatly advance the success of costly DM change interventions. Implications are suggested regarding the academic education and training of DM practitioners.

Originality/value

Based on the paradox framework, which offers a novel vantage point for understanding the challenges of implementing DM, the findings contribute to the scholarly understanding of the limited success of DM interventions.
How do teaching quality and pedagogical practice enhance vocational student engagement? A mixed-method classroom observation approach
Authors: Zhao Yanmin , Ko James
Published: March 2020

Purpose

The purpose of this paper is to investigate vocational teaching behaviours in facilitating pedagogical practice concerning students' classroom engagement.

Design/methodology/approach

A mixed-method approach with quantitative classroom observations and qualitative field notes was conducted at two higher vocational institutions in Guangdong province, south of China. Sixty lesson observations were rated combining with supplementary field notes from 20 teacher participants analysed through a comparative coding process.

Findings

Means of dimensions of teaching behaviours and student engagement were calculated based on taking the averages of the means of items theoretically associated with each dimension. Through thematic analysis of observational notes, vocational instructions and students' engagement in vocational learning environment were more diversified in terms of vocational teaching practice, which manifested that vocational teaching behaviours focused more on adjusting students' practical learning.

Research limitations

The limitation is shown that the quantitative sample is small, yet affords greater depth of data for further discussion.

Originality/value

This study develops its setting and orientation by applying the classroom observation instrument into the Chinese high vocational context and offers more in-depth insights and exploration of the characteristics of teaching practice in vocational classrooms.
Preventing skin staining: an effective iron infusion protocol
Authors: Crowley Clare Margaret , McMahon Gabriela , Desmond Joanna , Imcha Mendinaro
Published: March 2020

Purpose

To implement a safe and effective intravenous iron infusion protocol to prevent skin staining.

Design/methodology/approach

Mixed methods approach was utilised including education, auditing, self-reported survey, patient information leaflet and patient feedback. In total 25 healthcare professionals completed the survey and 15 patients provided feedback.

Findings

No skin staining or severe adverse reactions were observed over eight weeks. Audit results found 53 per cent of staff were compliant with the recommended IV iron infusion protocol and 46 per cent informed patients of skin staining risk. Self-report surveys indicated 92 per cent flushed the cannula with sodium chloride before starting the infusion, 88 per cent flushed the cannula after the infusion and 76 per cent informed patients of skin staining risk. Patient feedback was largely positive and constructive.

Research limitations

Limitations include self-reported bias, short audit time interval, missing data and discrepancy between audit and survey results.

Originality/value

This quality improvement project was developed following two skin staining incidences at our maternity hospital. Although rare, skin staining after intravenous iron infusion is potentially permanent and may be distressing for some patients. Intravenous iron is considered safe and effective to treat anaemia during pregnancy and is often prescribed for this patient cohort. To avoid medicolegal action and patient dissatisfaction, it is essential that patients are informed of potential skin staining and an evidence-based administration protocol is utilised.
The impact of individual differences on multitasking ability
Authors: Crews Derek E. , Russ Molly J.
Published: March 2020

Purpose

The study's purpose was to explore the impact of multitasking on efficiency and accuracy and the relationship between individual differences and multitasking ability.

Design/methodology/approach

An experimental study was conducted with individuals that completed an in-box exercise and a personality assessment. Three groups were established as follows: those that completed the in-box exercise without interruption (control group), those that were given a portion of the same initial task but were then interrupted and given an additional task (low multitask group) and those that were given the same initial tasks, then interrupted three times (high multitask group).

Findings

The results show that there were significant effects of gender and age on multitasking efficiency. Females made fewer errors than males. Younger and older participants took more time to complete the experiment, which indicates an inverted U relationship and may mean that people become more effective at multitasking with experience and practice, but then less effective as they get older. The study also found that personality had no significant effect on multitasking efficiency.

Research limitations/implications

The study was limited in that the sample was 91 percent female, did not include anyone over the age of 51 and did not measure intelligence or experience.

Practical implications

The findings may have implications for employee training, evaluation and formulation of workplace standards and regulations.

Orginality/value

This study provides empirical research extending the understanding of the nature and impact of multitasking and individual differences based on gender, age and personality.
Does PhD qualification improve pedagogical competence? A study on teaching and training in higher education
Authors: Okolie Ugochukwu Chinonso , Igwe Paul Agu , Nwajiuba Chinyere Augusta , Mlanga Sunday , Binuomote Michael Olayinka , Nwosu Hyginus Emeka , Ogbaekirigwe Charles O.
Published: March 2020

Purpose

There has been much debate in recent times about the factors that improve the quality of teaching in higher education (HE) institutions. This has been especially fueled by the increasing importance attached to Doctor of Philosophy (PhD) qualification. To fill the existing gap in the current literature in this regard, this study aims to investigate whether HE teachers (lecturers) who undergo pedagogical training (PT) in addition to obtaining PhD qualification possess higher knowledge and pedagogical competencies (PCs) than those that relied only on having PhD qualification without further teaching qualifications.

Design/methodology/approach

Drawing upon data collected through a structured questionnaire administered to 1,174 Nigerian HE teachers in various disciplines from 39 HE institutions, in addition to two focus groups, the study adopts a mixed-methods research. The quantitative data were analyzed descriptively while qualitatively data were coded, transcribed verbatim, and analyzed thematically.

Findings

This article proposes that teachers who undergo PT in addition to obtaining PhD tend to have more PCs and perform better than those that have not undergone any form of PT. Also, it found a statistically significant difference between PCs of HE teachers who have undergone PT in addition to PhD qualification from those without PT. The implication is that teachers who have undergone PT are more effective in facilitating teaching and learning than those who have not completed PT.

Research limitations/implications

Despite the merits of the mixed-methods research, a major limitation of this study is the failure to compare students' achievements or successes based on the two distinct samples. However, the limitations create opportunities for further studies into the subject matter.

Originality/value

This study is timely, given that Nigeria (like many African countries) has a low quality HE system and low graduate outcomes (related to knowledge, employability, and skills). More so, research into pedagogical content knowledge (PCK) and practices are rare or nonexistent in the literature related to Nigeria and other African countries' HE system.
Gamechanger: harnessing football for social change
Authors: Irvine Fitzpatrick Linda , Maciver Donald , Dempster Leeann , Forsyth Kirsty
Published: March 2020

Purpose

The purpose of this paper is to present a case study of an intersectoral partnership that has taken place in Scotland (United Kingdom) entitled Gamechanger. The main idea of Gamechanger was for statutory, commercial and voluntary organisations to work in partnership to harness the power of football (soccer), to tackle health inequalities and social exclusion. The paper will detail how Gamechanger has been developed, with reference to the newly developed “Incite” model for effective intersectoral partnership working.

Design/methodology/approach

This paper draws on the authors’ experiences of leading and evaluating intersectoral partnerships from 2015 to 2019. The report draws on the work which took place during that period, and the achievements in relation to Gamechanger.

Findings

Gamechanger has led to significant innovations. It has encouraged sectors to work together, and develop new ways of responding to difficult societal problems.

Originality/value

Gamechanger is believed to be the first initiative of its kind developed with a football club in Scotland.

Conclusions

This work has been developed through robust community-informed efforts. The scope and scale of the projects to deliver community benefits is significant. Gamechanger has provided a means for football to take a different approach to how it works to benefit communities.
The capability of organizations to manage delayed retirement
Authors: Kadefors Roland , Wikström Ewa , Arman Rebecka
Published: March 2020

Purpose

This work was undertaken in order to develop a conceptual model for identification of the capability of an organization to implement age management measures.

Design/methodology/approach

Barriers to delayed retirement were reviewed; observations retrieved from a research consortium study were used to identify main attributes that needed to be taken into consideration in the development of the model.

Findings

The capability of organizations to react to the demographic challenge by introduction of age management measures can be classified operatively as “proactive”, “reactive”, “passive” or “chained”, depending on their resources and preferences.

Practical implications

The model may be useful to HR as a point of departure in the development of a business case for age management and a didactic tool to be used in internal marketing.

Originality/value

The concept “organizational capability” was developed as a corollary to the individual aspects of capability; recognizing preference and resource as main drivers made it possible to develop a typology that is new and is easy to understand and apply.
Politics and institution of corporate governance in Vietnamese state-owned enterprises
Authors: Cong Phuong Nguyen , Dinh Khoi Nguyen Tran , Phuoc Vu Ha
Published: March 2020

Purpose

The paper aims to examine how the change in political ideology and institutions affects corporate governance (CG) of the state-owned enterprise (SOE) in Vietnam, as well as its consequences.

Design/methodology/approach

To link macro-level institutional change to micro level of the reform process of the Vietnamese SOE governance, we draw from the “Varieties of Capitalism” (VoC) framework adopt a triangulation approach for data collection.

Findings

The paper shows the CG of SOEs is a variant of capitalist CG. Changes in the function, state control and structure of governance in the Vietnamese SOEs have been shaped by the political ideology and institution. It also shows that the political and bureaucratic interferences of the state in SOEs are for political interests rather than for firms’ effectiveness.

Research limitations/implications

The political ideology has existed in major aspects of the governance structure of the SOEs as a part of the party’s effort to maintain its economic legitimacy and a government of “control and domination”.

Practical implications

The findings of this study can be seen as a reference for the Vietnamese Government and governments of other developing countries in making incremental improvements in existing institutions rather than choosing the “best” model of CG.

Originality/value

The paper contributes to the literature by applying the VoC framework to analyse the change in SOE governance in a transition country while preserving the communist ideology. It can deepen our understanding of the SOE governance in Vietnam and enrich comparative studies of CG in the transition countries.
Effect of chia (Salvia hispanica L.) seeds incorporation on nutritional quality of muffin mix
Authors: Sharma Vishakha , Mogra Renu , Mordia Azad
Published: March 2020

Purpose

Study on chia seeds is receiving increasing interest because of their nutritional and health-promoting properties that have been recognized by their high content of antioxidants, proteins, minerals and dietary fibers. Hence, the purpose of this study is to develop a value-added food product using chia seeds and to assess the nutritional properties, shelf life and consumer acceptability of the developed product.

Design/methodology/approach

Six different formulations of muffin mix were prepared by incorporating chia seeds with wheat flour in various ratios and evaluated for sensory characteristics. The nutritional components and shelf lives of the developed products were also evaluated. The developed product was stored for three months to assess the shelf life.

Findings

Results indicated that muffins made with chia seeds can be added up to 20% in wheat flour without affecting the sensory scores (p= 0.0014). Regarding nutritional evaluation, the results revealed that 20% incorporation of chia seeds significantly increased the total antioxidant activity (p= 0.001), increased the crude protein (p= 0.0001), fat (p= 0.0001) and crude fiber (p= 0.001) contents and lowered the carbohydrate (p= 0.0001) content when compared to the control sample. Muffin mix made with chia seeds had significantly higher mineral content (calcium, phosphorus, zinc and iron) than did the control. The developed product had a shelf-life stability of three months in terms of moisture content, peroxide value and total bacterial count and was well accepted by consumers.

Originality/value

Intrinsic characteristics of chia seeds can improve the quality of muffins and bring health benefits to the consumers.
In spite of technology: a failure in student project ownership
Authors: Stamp Pauline , Peters Theodore , Gorycki Andrew
Published: March 2020

Purpose

Students often complain about doing group work, which may lead them to be less engaged as a group and to seek shortcuts in developing their presentations. The purpose of his essay is identify and preferentially rectify student behavioral errors arising from placing too much trust in technology that can lead to too little personal interaction and engagement. The authors present their viewpoint on the classroom presentation outcome of a student group that used Google Docs to “prepare” for their presentation.

Design/methodology/approach

In a recent organizational behavior course, the authors had one such group arrive for their in-class presentation, only to discover that one group member was absent. The group had used Google Docs to share their research, yet no member read what the others had submitted. As a result, none of the group members could present the missing student’s material, with the obvious negative grading and finger-pointing outcomes.

Findings

The authors recognized that students needed more management direction than simply being proficient with technology. They lacked engagement behaviors leading to project responsibility. Engagement behaviors would include voice/face-to-face communication and content-related discussions questioning assumptions while strategically planning and operationalizing their topic of presentation.

Originality/value

The educational implications suggest an expanded role for the instructor to emphasize the role of student engagement behavior and the over-reliance on technology. Practical implications suggest making stronger connections to workplace expectations, making the student experience more transferable to their incipient workplaces and promoting the concept of team over group in terms of responsibility and conscientiousness and ultimately justifying their participation in providing value for their employer.
In search of the frugal innovation strategy
Authors: Santos Leandro Lima , Borini Felipe Mendes , Oliveira Júnior Moacir de Miranda
Published: March 2020

Purpose

In the past years, many contributions have been published addressing frugal innovation and other types of resource-constrained innovations in the management field. Throughout this paper frugal innovation is reported as a phenomenon, concept, research field and strategy, showing the different ways the literature refers to it and how scattered the concept is. However, based on the understanding, the authors decided to address frugal innovation as a kind of innovation strategy that helps companies to innovate in resource-constrained environments. Therefore, considering the increasing interest in the frugal innovation topic and adding the perspective of business strategy for resource-constrained conditions, the research question addressed in this paper is: what are the main features of the frugal innovation literature that unfold its current perspectives for business strategy? In this sense, the purpose of this study is to analyze the scientific production in frugal innovation through a literature mapping and review to better understand it, delimiting different perspectives and creating boundaries to other business strategies or approaches.

Design/methodology/approach

The authors performed a co-citation analysis using the Vosviewer software to notice how authors are arranged in clusters based on their understanding of the topic. Furthermore, the authors also performed a systematic literature review (SLR) analyzing the extant literature on frugal innovation based on the clusters found through the co-citation method. The final sample used in the study included 42 papers published between 2011 and 2019, using the Web of Science platform as a data source.

Findings

By means of SLR, the findings of this study provided a more organized view of frugal innovation through the co-citation analysis and the qualitative analysis of the clusters, which were the basis for the parameters established. After the conceptualization of frugal innovation strategy (FIS) and the delimitation of boundaries of FIS, the authors bring the reflections about the contribution to the literature and the practice (managers and society) by showing three assumptions to be tested and confirmed in future studies and a framework to guide companies in search of a FIS.

Originality/value

This study contributes to the discussion on frugal innovation moving a step forward to clarify the research field on this subject providing the main characteristics for researchers and practitioners. The paper has delimited the boundaries of FIS. The assumptions established in the discussion can become hypotheses for empirical studies. In addition, the authors explain why, what is, where and to whom the FIS can be developed and applied. Furthermore, the authors contribute by developing the FIS framework, with four strategic positions based on the boundaries of FIS organized by the complexity technological level. The strategic positions are frugal innovation orientation (FIO), FIO to value shared, FIO to market and FIS.
Downregulation of lysyl oxidase in venous malformations: Association with vascular destabilization and sclerotherapy
Authors: Zhu Junyi , Shao Ming , Guo Fengyuan , Ren Jiangang , Tang Zirong , Geng Jinhuan , Xu Zhi , Jia Jun , Chen Lili , Jia Yulin
Published: March 2020

Venous malformations (VM) are localized defects in vascular morphogenesis manifested by dilated venous channels with reduced perivascular cell coverage. As a vital enzyme for extracellular matrix (ECM) deposition, lysyl oxidase (LOX) plays important roles in vascular development and diseases. However, the expression and significance of LOX are unknown in VM. Herein, 22 VM specimens and eight samples of normal skin tissues were evaluated immunohistochemically for the expression of LOX, α‐smooth muscle cell actin (α‐SMA) and transforming growth factor‐β (TGF‐β). In vitro studies on human umbilical vein endothelial cells (HUVEC) were employed for determining potential mechanisms. Our results showed that LOX expression was significantly reduced in VM compared with normal skin tissues, in parallel with attenuated perivascular α‐SMA+ cell coverage and TGF‐β downregulation in VM. Further correlation analysis indicated that LOX expression was positively correlated with perivascular α‐SMA+ cell coverage and TGF‐β expression in VM. Moreover, marked elevation of LOX, TGF‐β and α‐SMA was observed in bleomycin‐treated VM samples. Furthermore, our in vitro data demonstrated that both recombinant TGF‐β and bleomycin induced obvious increase of LOX expression and activity and a concomitant increase in ECM components in HUVEC, which could be reversed by LOX inhibition. To our best knowledge, this study revealed for the first time the downregulation of LOX in VM and its correlation with vascular destabilization and TGF‐β‐induced endothelial ECM deposition. Moreover, our results highlighted that LOX may be implicated in the sclerotherapy of VM and holds promise as a therapeutic target.
SSRI use during pregnancy and risk for postpartum haemorrhage: a national register‐based cohort study in Sweden
Authors: Skalkidou A , Sundström‐Poromaa I , Wikman A , Hesselman S , Wikström AK , Elenis E
Published: March 2020

Objective

Evaluate whether selective serotonin reuptake inhibitor (SSRI) use during pregnancy, as well as prior or current untreated psychiatric illness is associated with postpartum haemorrhage (PPH).

Design

National register‐based cohort study based on data from the Swedish Pregnancy Register.

Setting

Sweden, nationwide coverage.

Population

A total of 31 159 pregnant women with singleton deliveries after gestational week 22+0 between January 2013 and July 2017.

Methods

Pregnant women with self‐reported SSRI use at any time point during pregnancy were compared with non‐SSRI‐treated women with prior or current psychiatric illness, as well as wiith healthy women with no psychiatric illness or reporting SSRI use.

Main outcome measures

Postpartum haemorrhage defined as blood loss >1000 ml during the first 2 hours postpartum reported by the delivering midwife or obstetrician.

Results

Postpartum haemorrhage prevalence was 7.0% among healthy women, 7.6% among women with prior or current psychiatric illness and 9.1% among women treated with SSRI. The unadjusted odds for PPH among women with prior or current psychiatric illness and women on SSRI treatment were increased by 9 and 34%, respectively, compared with healthy unmedicated women without a history of psychiatric illness (odds ratio [OR] 1.09, 95% CI 1.04–1.14 and OR 1.34, 95% CI 1.24–1.44, respectively). The estimates remained unchanged after adjustment for several confounders (such as maternal age, body mass index [BMI], parity, prior caesarean section, smoking, occupation and country of birth) and potential covariates (such as delivery mode, polyhydramnion, preterm delivery, labour dystocia and infant birthweight >4000 g).

Conclusions

Higher risk for PPH was observed both among women treated with SSRI during pregnancy and among women with prior or current psychiatric illness.

Tweetable abstract

SSRI use at any point during pregnancy and prior or current history of psychiatric illness was associated with an increased likelihood for PPH.
Can reintroductions to degraded habitat succeed? A test using the common brushtail possum
Authors: Moseby Katherine E. , Brandle Robert , Hodgens Patrick , Bannister Hannah L.
Published: March 2020

Habitat degradation contributes to species decline, and habitat quality is an important factor influencing reintroduction success globally. Habitat quality can include a range of physical resources such as nest sites and food resources but also anything that can restrict the use of these resources such as predation risk or competition. In arid Australia, introduced predators are thought to be the primary cause of mammal extinction and reintroduction failure although habitat clearance and alteration are also major causes of population decline. Common brushtail possums are one arid Australian marsupial close to regional extinction. To understand whether habitat quality was limiting their recovery, we reintroduced 148 possums into an area where introduced red foxes were controlled but historic overgrazing had degraded the habitat. We measured both direct (hollow availability, midstorey cover and high‐quality plant foods) and indirect (survival, condition, reproduction, movement) measures of habitat quality. Sixty‐seven released possums and 26 post‐release recruits were radiocollared for up to 2 years after release. Post‐release survival of radiocollared possums was high after 12 months (0.70), and there were no deaths from starvation. Predation by feral cats was the most common cause of mortality, and the open, degraded habitat may have exacerbated predation risk. Continuous breeding, good body condition and comparative home ranges with other sites suggested that food resources were not limiting. Possums used natural tree hollows in Eucalyptus spp. with no use of artificial nest boxes. Results suggest that historically degraded habitat was not a barrier to short‐term reintroduction success when foxes were controlled and natural tree hollows were plentiful. However, demographic data on hollow‐bearing tree species suggest a possible future decline in availability of hollows. These factors, combined with the unknown effects of drought, and synergistic effects of predation and poor quality habitat, suggest long‐term reintroduction success may require improved habitat and cat control.
Exposure–response characterisation of tildrakizumab in chronic plaque psoriasis: Pooled analysis of 3 randomised controlled trials
Authors: Kerbusch Thomas , Li Hanbin , Wada Russell , Jauslin Petra M. , Wenning Larissa
Published: March 2020

Aims

In this exposure–response analysis, the dosing regimen for tildrakizumab, an antibody for treating moderate‐to‐severe chronic plaque psoriasis, was determined using data from 3 randomised controlled trials (P05495/NCT01225731: phase 2b, n = 355; reSURFACE 1/NCT01722331: phase 3, n = 772; reSURFACE 2/NCT01729754: phase 3, n = 1090).

Methods

A maximum drug effect (Emax) logistic‐regression exposure–efficacy model was used to describe the week 12 Psoriasis Area and Severity Index (PASI) responses with average concentration of tildrakizumab during weeks 1–12 (Cavg12) as exposure metric. The impact of covariates (e.g., body weight, region) was tested. Exposure–safety, longitudinal pharmacokinetic–pharmacodynamic and risk–benefit analyses were also conducted.

Results

At week 12, Emax was estimated at 62.2, 37.9 and 14.6% of responders for PASI75/90/100, respectively. Exposure–response curves plateaued at exposures >5 μg mL−1. Heavier subjects had a lower response rate to placebo as measured by PASI75/90/100 than lighter subjects. PASI100 placebo response was less in subjects with higher baseline PASI score and older age. Simulated week 12 PASI75 increased by ≤4% on increasing the dose from 100 to 200 mg every 12 weeks (Q12W). The pharmacokinetic–pharmacodynamic model adequately described the time course of PASI change after treatment in the entire population and in each subject. Risk–benefit profiles were favourable for the 100‐ and 200‐mg doses in different weight subgroups.

Conclusions

Patients with moderate‐to‐severe psoriasis should receive 100‐mg subcutaneous tildrakizumab Q12W. Patients with high body weight (>90 kg) may benefit from a higher dose (200‐mg Q12W).
Implicating endothelial cell senescence to dysfunction in the ageing and diseased brain
Authors: Graves Sara I. , Baker Darren J.
Published: March 2020

Cerebrovascular endothelial cells (CECs) are integral components of both the blood‐brain barrier (BBB) and the neurovascular unit (NVU). As the primary cell type of the BBB, CECs are responsible for the tight regulation of molecular transport between the brain parenchyma and the periphery. Additionally, CECs are essential in neurovascular coupling where they help regulate cerebral blood flow in response to regional increases in cellular demand in the NVU. CEC dysfunction occurs during both normative ageing and in cerebrovascular disease, which leads to increased BBB permeability and neurovascular uncoupling. This MiniReview compiles what is known about the molecular changes underlying CEC dysfunction, many of which are reminiscent of cells that have become senescent. In general, cellular senescence is defined as an irreversible growth arrest characterized by the acquisition of a pro‐inflammatory secretory phenotype in response to DNA damage or other cellular stresses. We discuss evidence for endothelial cell senescence in ageing and cardiovascular disease, and how CEC senescence may contribute to age‐related cerebrovascular dysfunction.
Bayesian latent multi‐state modeling for nonequidistant longitudinal electronic health records
Authors: Luo Yu , Stephens David A. , Verma Aman , Buckeridge David L.
Published: March 2020

Large amounts of longitudinal health records are now available for dynamic monitoring of the underlying processes governing the observations. However, the health status progression across time is not typically observed directly: records are observed only when a subject interacts with the system, yielding irregular and often sparse observations. This suggests that the observed trajectories should be modeled via a latent continuous‐time process potentially as a function of time‐varying covariates. We develop a continuous‐time hidden Markov model to analyze longitudinal data accounting for irregular visits and different types of observations. By employing a specific missing data likelihood formulation, we can construct an efficient computational algorithm. We focus on Bayesian inference for the model: this is facilitated by an expectation‐maximization algorithm and Markov chain Monte Carlo methods. Simulation studies demonstrate that these approaches can be implemented efficiently for large data sets in a fully Bayesian setting. We apply this model to a real cohort where patients suffer from chronic obstructive pulmonary disease with the outcome being the number of drugs taken, using health care utilization indicators and patient characteristics as covariates.
CD14+CD16+ monocytes are involved in daratumumab‐mediated myeloma cells killing and in anti‐CD47 therapeutic strategy
Authors: Storti Paola , Vescovini Rosanna , Costa Federica , Marchica Valentina , Toscani Denise , Dalla Palma Benedetta , Craviotto Luisa , Malavasi Fabio , Giuliani Nicola
Published: March 2020

A deep elucidation of the mechanisms of action of anti‐CD38 monoclonal antibodies (mAbs), such as daratumumab (DARA), is required to identify patients with multiple myeloma (MM) who are more responsive to this treatment. In the present study, an autologous ex vivo approach was established, focussing on the role of the monocytes in the anti CD38‐mediated killing of MM cells. In bone marrow (BM) samples from 29 patients with MM, we found that the ratio between monocytes (CD14+) and MM cells (CD138+) influences the response to DARA. Further, the exposure of the BM samples to DARA is followed by the formation of a CD138+CD14+ double‐positive (DP) population, that quantitatively correlates with the anti‐MM cells killing. These effects were dependent on the presence of a CD14+CD16+ monocyte subset and on high CD16 expression levels. Lastly, the addition of a mAb neutralising the CD47/signal‐regulatory protein α (SIRPα) axis was able to increase the killing mediated by DARA. The effects were observed only in coincidence with high CD14+:CD138+ ratio, with a significant presence of the DP population and were correlated with CD16 expression. In conclusion, the present study underlines the critical role of the CD16+ monocytes in DARA anti‐MM killing effects and gives a rationale to test the combination of an anti‐CD47 mAb with anti‐CD38 mAbs.
Prediction of the haemostatic effects of bypassing therapy using comprehensive coagulation assays in emicizumab prophylaxis‐treated haemophilia A patients with inhibitors
Authors: Furukawa Shoko , Nogami Keiji , Shimonishi Naruto , Nakajima Yuto , Matsumoto Taisei , Shima Midori
Published: March 2020

In emicizumab prophylaxis, the concomitant therapy using bypassing agents (BPAs) is required for breakthrough bleeding and invasive procedures with attention to thrombotic complications. To predict coagulant effects of BPAs in emicizumab‐treated patients with haemophilia A (PwHA) with inhibitor (PwHAwI), blood samples from emicizumab‐treated PwHAwI (n = 8) and PwHA without inhibitor (n = 2) in phase 1/2 and HAVEN 1 study, spiked with activated prothrombin complex concentrates (aPCC) or recombinant factor VIIa (rFVIIa) ex vivo, and blood samples from emicizumab‐treated PwHAwI‐receiving BPAs were analysed by Ca2+‐triggered rotational thromboelastometry (ROTEM) and ellagic acid/tissue factor‐triggered clot waveform analysis (CWA). Spiked aPCC, corresponded to 10–100 U/kg, markedly shortened ROTEM parameters beyond the normal range, while spiked rFVIIa, corresponded to 90–270 μg/kg, shortened them within near‐normal range. Each of the spiked BPA‐improved adjusted maximum coagulation velocity of CWA to within or near the normal range. In blood samples at post‐infusion of aPCC (44–73 U/kg) or rFVIIa (79–93 μg/kg), the parameters of both assays improved to approximately the normal range. Taken together, ex vivo results of spiking tests in ROTEM and CWA, except aPCC spiking test in ROTEM, were relatively consistent with in vivo ones, and could usefully predict the coagulant effects of concomitant bypassing therapy for emicizumab‐treated PwHAwI.
Metagenomic characterization of lysine acetyltransferases in human cancer and their association with clinicopathologic features
Authors: Jiang Yuanyuan , Guo Xuhui , Liu Lanxin , Rode Shomita , Wang Rui , Liu Hui , Yang Zeng‐Quan
Published: March 2020

Lysine acetyltransferases (KATs) are a highly diverse group of epigenetic enzymes that play important roles in various cellular processes including transcription, signal transduction, and cellular metabolism. However, our knowledge of the genomic and transcriptomic alterations of KAT genes and their clinical significance in human cancer remains incomplete. We undertook a metagenomic analysis of 37 KATs in more than 10 000 cancer samples across 33 tumor types, focusing on breast cancer. We identified associations among recurrent genetic alteration, gene expression, clinicopathologic features, and patient survival. Loss‐of‐function analysis was carried out to examine which KAT has important roles in growth and viability of breast cancer cells. We identified that a subset of KAT genes, including NAA10, KAT6A, and CREBBP, have high frequencies of genomic amplification or mutation in a spectrum of human cancers. Importantly, we found that 3 KATs, NAA10, ACAT2, and BRD4, were highly expressed in the aggressive basal‐like subtype, and their expression was significantly associated with disease‐free survival. Furthermore, we showed that depletion of NAA10 inhibits basal‐like breast cancer growth in vitro. Our findings provide a strong foundation for further mechanistic research and for developing therapies that target NAA10 or other KATs in human cancer.
DOES BIG GOVERNMENT HURT GROWTH LESS IN HIGH‐TRUST COUNTRIES?
Authors: Bergh Andreas , Bjørnskov Christian
Published: March 2020

Social trust is linked to both public sector size and to economic growth, thereby helping to explain how some countries combine high taxes with high levels of economic growth. This paper examines if social trust insulates countries against the negative effects of public sector size on growth, documented in several studies. We note that the effect is theoretically ambiguous. In panel data from 66 countries across 40 years, we find no robust evidence of insulation effects: when excluding countries with uncertain trust scores, our results suggest that big government hurts growth also in high‐trust countries, and that the mechanism is by lowering private investments. (JEL H10, O11, P16, Z10)
The potential effects of autonomous vehicles on alcohol consumption and drink‐driving behaviours
Authors: Booth Leon , Norman Richard , Pettigrew Simone
Published: March 2020

Introduction

By removing the need for a driver, autonomous vehicles (AV) are expected to substantially reduce rates of drink‐driving. However, this benefit may be accompanied by an unintended negative consequence in the form of greater overall alcohol consumption due to increased availability of affordable and convenient transport.

Aims

To assess: (i) the extent to which drinkers may choose to use AVs after consuming alcohol; (ii) the extent to which drinkers may consume more alcohol if they are using an AV afterwards; and (iii) whether demographic, alcohol‐related and AV‐related factors are associated with the likelihood of engaging in these behaviours.

Design and Methods

A total of 1334 Australians of legal driving age who consume alcohol completed an online survey. Two regression models were used to calculate whether the analysed respondent characteristics were associated with intentions to use AVs after drinking and to consume more alcohol if using an AV afterwards.

Results

Around half of the respondents (49%) reported being likely to use an AV after consuming alcohol, and over one‐third (37%) reported being likely to consume more alcohol if using an AV afterwards. Younger age, more frequent alcohol consumption, a positive attitude to AVs and a preference for using 'ride‐share' AVs were associated with a greater likelihood of engaging in these behaviours.

Discussion and Conclusions

The results suggest that the introduction of AVs is likely to reduce drink‐driving rates while facilitating greater participation in heavy episodic drinking. This will constitute a challenge to policymakers in their efforts to minimise alcohol‐related harms.
Soil health cluster analysis based on national monitoring of soil indicators
Authors: Seaton Fiona M. , Barrett Gaynor , Burden Annette , Creer Simon , Fitos Eleonora , Garbutt Angus , Griffiths Rob I. , Henrys Pete , Jones Davey L. , Keenan Patrick , Keith Aidan , Lebron Inma , Maskell Lindsay , Pereira M. Gloria , Reinsch Sabine , Smart Simon M. , Williams Bronwen , Emmett Bridget A. , Robinson David A.
Published: March 2020

A major challenge in soil science is to monitor and understand the state and change of soils at a national scale to inform decision making and policy. To address this, there is a need to identify key parameters for soil health and function and determine how they relate to other parameters, including traditional soil surveys. Here we present a national‐scale dataset of topsoil sampled as part of a wider agri‐environment monitoring scheme in Wales, UK. Over 1,350 topsoils (0–15 cm) were sampled across a very wide range of habitats and a range of physical, chemical and biological soil quality indicators were measured. We show consistent differences in soil physicochemical properties across habitat types, with carbon decreasing and pH increasing across the habitat productivity gradient from bogs through woodlands and grasslands to arable systems. The soils within our dataset are largely within the limits identified as important for supporting habitat function, with the exception of excessive phosphate levels in mesotrophic grassland. Cluster detection methods identified four soil functional classes based on measured topsoil properties, which were more related to habitat type than the genesis‐based soil classification from soil maps. These soil functional classes can be interpreted as phenoforms within the soil genoforms found by traditional soil classification. This shows the importance of land‐use management in determining the soil health and functional capacity of soils. Our work provides an account of the current state of soil health in Wales, its relationship to soil function and a baseline for future monitoring to track changes against agri‐environment and other policy targets.

Highlights

We measured soil physicochemical properties in ~1,350 sites in a variety of temperate habitats

There was a strong gradient in soil carbon and pH, with other variables being correlated with these

Mesotrophic grassland sites had phosphate levels above the identified limit for good functioning

Soil classes from topsoil properties were more related to land use than soil map classifications
On the Superior Statistical Properties of Frequency Scales in Job Analyses
Authors: Babcock Ben , Risk Nicole M. , Wyse Adam E.
Published: March 2020

This study compared the statistical properties of four job analysis task survey response scale types: criticality, difficulty in learning, importance, and frequency. We used nine job analysis studies spanning two fields, medical imaging and allied health professionals, to compare the job analysis scales in terms of variability and interrater agreement. Results showed that frequency scales using absolute anchors had greater between‐task variability and higher interrater agreement for all nine studies. This may have occurred due to what has been described by past research as self‐presentation bias. In this case, an aggregate base percentage of respondents always responded that tasks in their domain are highly critical, highly important, and easy to learn. These results showed that frequency scales with absolute anchors yielded data with better statistical performance than other more subjective scales. These properties do not answer the question of whether a scale matches an exam's purpose, which is the most important consideration for job analyses. They do, however, suggest that, if statistics are a primary deciding factor, strong consideration should be given to using frequency scales with absolute anchors.