bluuebunny/crossref_metadata_2025 huggingface dataset:
ARHGEF18/p114RhoGEF coordinates PKA/CREB signaling and actomyosin remodeling to drive trophoblast cell-cell fusion during placenta morphogenesis
Authors: Beal Robert , Fernandez Ana Alonso-Carriazo , Grammatopoulos Dimitris K. , Matter Karl , Balda Maria S.
Published: July 2020

Coordination of cell-cell adhesion, actomyosin dynamics and gene expression is crucial for morphogenetic processes underlying tissue and organ development. Rho GTPases are main regulators of the cytoskeleton and adhesion. They are activated by guanine nucleotide exchange factors in a spatially and temporally controlled manner. However, the roles of these Rho GTPase activators during complex developmental processes are still poorly understood. ARHGEF18/p114RhoGEF is a tight junction-associated RhoA activator that forms complexes with myosin II, and regulates actomyosin contractility. Here we show that p114RhoGEF/ ARHGEF18 is required for mouse syncytiotrophoblast differentiation and placenta development.In vitroandin vivoexperiments identify that p114RhoGEF controls expression of AKAP12, a protein regulating PKA signalling, and is required for PKA-induced actomyosin remodelling, CREB-driven gene expression of proteins required for trophoblast differentiation, and, hence, trophoblast cell-cell fusion. Our data thus indicate that p114RhoGEF links actomyosin dynamics and cell-cell junctions to PKA/CREB signalling, gene expression and cell-cell fusion.
Micro-biogeography greatly matters for competition: Continuous chaotic bioprinting of spatially-controlled bacterial microcosms
Authors: Ceballos-González Carlos Fernando , Bolívar-Monsalve Edna Johana , Quevedo-Moreno Diego Alonso , Lam-Aguilar Li Lu , Borrayo-Montaño Karen Ixchel , Yee-de León Juan Felipe , Zhang Yu Shrike , Moisés Alvarez Mario , Santiago Grissel Trujillo-de
Published: July 2020

Cells do not work alone but instead function as collaborative micro-societies. The spatial distribution of different bacterial strains (micro-biogeography) in a shared volumetric space, and their degree of intimacy, greatly influences their societal behavior. Current microbiological techniques are commonly focused on the culture of well-mixed bacterial communities and fail to reproduce the micro-biogeography of polybacterial societies.

Here, fine-scale bacterial microcosms are bioprinted using chaotic flows induced by a printhead containing a static mixer. This straightforward approach (i.e., continuous chaotic bioprinting) enables the fabrication of hydrogel constructs with intercalated layers of bacterial strains. These multi-layered constructs are used to analyze how the spatial distributions of bacteria affect their social behavior. Bacteria within these biological microsystems engage in either cooperation or competition, depending on the degree of shared interface. Remarkably, the extent of inhibition in predator-prey scenarios increases when bacteria are in greater intimacy. Furthermore, twoEscherichia colistrains exhibit competitive behavior in well-mixed microenvironments, whereas stable coexistence prevails for longer times in spatially structured communities. Finally, the simultaneous extrusion of four inks is demonstrated, enabling the creation of higher complexity scenarios.

Thus, chaotic bioprinting will contribute to the development of a greater complexity of polybacterial microsystems, tissue-microbiota models, and biomanufactured materials.
Flexibility and mobility of SARS-CoV-2-related protein structures
Authors: Römer Rudolf A. , Römer Navodya S. , Wallis A. Katrine
Published: July 2020

The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of SARS-CoV-2 drug targets, i.e. SARS-CoV-2 protein structures as deposited on the Protein Databank (PDB). We study their flexibility, rigidity and mobility, an important first step in trying to ascertain their dynamics for further drug-related docking studies. We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. For example, for the SARS-CoV-2 spike protein in the open configuration, our method identifies a possible further opening and closing of the S1 subunit through movement of SBdomain. With full structural information of this process available, docking studies with possible drug structures are then possible in silico. In our study, we present full results for the more than 200 thus far published SARS-CoV-2-related protein structures in the PDB.
A PP2A-Integrator complex fine-tunes transcription by opposing CDK9
Authors: Vervoort Stephin J. , Welsh Sarah A. , Devlin Jennifer R. , Barbieri Elisa , Knight Deborah A. , Costacurta Matteo , Todorovski Izabela , Kearney Conor J. , Sandow Jarrod J. , Bjelosevic Stefan , Fan Zheng , Vissers Joep H. A. , Pavic Karolina , Martin Ben P. , Gregory Gareth , Kong Isabella Y. , Hawkins Edwin D. , Hogg Simon J. , Kelly Madison J. , Newbold Andrea , Simpson Kaylene J. , Kauko Otto , Harvey Kieran F. , Ohlmeyer Michael , Westermarck Jukka , Gray Nathanael , Gardini Alessandro , Johnstone Ricky W.
Published: July 2020

Gene expression is tightly controlled by Cyclin-dependent kinases (CDKs) which regulate the RNA Polymerase II (RNAPII) transcription cycle at discrete checkpoints. RNAPII pausing is a CDK9-controlled rate-limiting process that occurs shortly after initiation and is required for spatio-temporal control of transcription in multicellular organisms. We discovered that CDK9-mediated RNAPII pause-release is functionally opposed by a protein phosphatase 2A (PP2A) complex. PP2A dynamically competes for key CDK9 substrates, DSIF and RNAPII, and is recruited to transcription pausing sites by INTS6, a subunit of the Integrator complex. INTS6 depletion disrupts the Integrator-PP2A association and confers resistance to CDK9 inhibition. This results in unrestrained activity of CDK9 and dysregulation of acute transcriptional responses. Pharmacological PP2A activation amplifies RNAPII pausing mediated by CDK9 inhibitors and synergizes therapeutically in a model of MLL-rearranged leukemia. These data demonstrate that finely-tuned gene expression relies on the delicate balance of kinase and phosphatase activity throughout the transcription cycle.

HIGHLIGHTS

Loss of INTS6 confers resistance to CDK9 inhibition

INTS6 recruits PP2A to Integrator and chromatin

PP2A/INTS6 complexes functionally oppose CDK9

PP2A/INTS6 fine-tune acute transcriptional responses

Synergistic anti-cancer activity between PP2A activators and CDK9 inhibitors
Sub-3 Å resolution structure of 110 kDa nitrite reductase determined by 200 kV cryogenic electron microscopy
Authors: Adachi Naruhiko , Yamaguchi Takahide , Moriya Toshio , Kawasaki Masato , Koiwai Kotaro , Shinoda Akira , Yamada Yusuke , Yumoto Fumiaki , Kohzuma Takamitsu , Senda Toshiya
Published: July 2020

Cu-containing nitrite reductases (NiRs), a well-studied family of 110 kDa enzymes, play central roles in denitrification and have over 100 Protein Data Bank entries. However, such issues as crystal packing, photoreduction, and lack of high pH cases have impeded structural analysis of the catalytic mechanism. Here we show the cryogenic electron microscopy (cryo-EM) structures ofAchromobacter cycloclastesNiR (AcNiR) at 2.99 and 2.85 Å resolution with pH 6.2 and 8.1, respectively. Comprehensive comparisons with cryo-EM and 56AcNiR crystal structures suggested crystallographic artifacts in residues 185–215 and His255 due to packing and photoreduction, respectively. With electron paramagnetic resonance spectroscopy, a newly developed map comparison method supported local structural changes at pH 8.1 around the type-2 Cu site, including His255 deprotonation. While the theoretical coordination error estimation of cryo-EM structures remains difficult, combined analysis using X-ray and cryo-EM structures will allow deeper insight into the local structural changes of proteins.
Encoding and control of airflow orientation by a set ofDrosophilafan-shaped body neurons
Authors: Currier Timothy A. , Matheson Andrew M. M. , Nagel Katherine I.
Published: July 2020

How brain circuits convert sensory signals into goal-oriented movement is a central question in neuroscience. In insects, a region known as the Central Complex (CX) is believed to support navigation, but how its compartments process diverse sensory cues to guide navigation is not fully clear. To address this question, we recorded from genetically-identified CX cell types inDrosophilaand presented directional visual, olfactory, and airflow cues known to elicit orienting behavior. We found that a group of columnar neurons targeting the ventral fan-shaped body (ventral P-FNs) are robustly tuned for airflow direction. Unlike compass neurons (E-PGs), ventral P-FNs do not generate a “map” of airflow direction; rather they are tuned to two directions – approximately 45° to the right or left of the midline – depending on the hemisphere of the cell body. Ventral P-FNs with both direction preferences innervate each CX column, potentially forming a basis for constructing representations of airflow in various directions. We explored two possible sources for ventral P-FN airflow tuning, and found that they mostly likely inherit these responses via a pathway from the lateral accessory lobe (LAL) to the noduli (NO). Silencing ventral P-FNs prevented flies from adopting stable orientations relative to airflow in closed-loop flight. Specifically, silenced flies selected improper corrective turns following changes in airflow direction, but not after airflow pauses, suggesting a specific deficit in sensory-motor action selection. Our results identify a group of central complex neurons that robustly encode airflow direction and are required for proper orientation to this stimulus.
A novel and accurate analytical-numerical method for inrush current modeling of three-limb power transformers
Authors: Taghikhani Mohammad Ali , Taghikhani Zahra
Published: July 2020

Purpose

Using appropriate solution techniques for transformer inrush current transient study is of great prominence owing to the inevitable inclusion of differential equations leading to complicated analysis procedures. This study aims to propose an analytical-numerical method to accurately analyze the three-phase three-limb core-type transformer inrush current in different cases considering the nonlinear behavior of the iron core.

Design/methodology/approach

The proposed method focuses on acquiring equations for inrush current and also the magnetic core flux by the application of a simulation-based iterative approach. In this regard, multiple integral equations are solved taking the time intervals into account. Then several derivations and integrations of matrix terms are substituted into the obtained results so as to simplify the solution process.

Findings

The method provides notable enhancements in computation time and also excellent qualities of accuracy compared with conventional numerical methods.

Practical implications

The proposed method is simulated for two three-phase transformers via MATLAB software. The obtained simulation results have been also compared with experimental tests.

Originality/value

Actually, the analytical-numerical method is capable of computing higher number of iterations in a shorter time efficiently, while making use of the conventional numerical procedures may not result in expected convergences. The simulation results of the proposed analytical-numerical technique illustrate a close agreement with the experimental test, and hence, verify the method preciousness.
EXOS: does the retention of salesforce matter in entrepreneurial start-ups?
Authors: Kumar Jitender , Gupta Ashish , Tapar Archit Vinod , Khan Md Chand Rashid
Published: July 2020

Learning outcomes

The cases highlight the challenges in running a new start-up especially by women in a developing nation such as India in a high growth industry. The success of a business depends on employee motivation, sales, marketing, functional coordination and coordinated efforts from all the executives. Experten Office Supplies Pvt. Ltd. (EXOS) was women empowered entrepreneurial startup (printing) in Mumbai established themselves as a trustable brand among their clientele for their office stationeries need. At Initial stages, they started with a good pace and growth in revenue. Directors of EXOS, Komal and Upasana Sanjay Kumar, were facing a downturn, their declining sales and were stressed regarding the resignation of their core member Pravin. The reasons for the situation were many, including unplanned motivational factors, non-risk-taking ability, no proper sales management (organization structure), planning process issues, lack of reward system and dependency on a person, less marketing initiative. These issues must be resolved to come back in the business, increase its sales, better sales organization structure. After the case analysis, students should be able to: know the key role of marketing and sales as a management function. Develop motivation policies for the salesforce and key team members in the organization. Understand the salesforce retention strategies of the organization.

Case overview/synopsis

In September 2019, directors of EXOS, Komal and Upasana Sanjay Kumar were discussing the downturn of EXOS and were stressed regarding their declining sales and profit margin. Both were disappointed at the resignation of their Business Manager. They were in worry as the new deal that they were about to get which could have made them earn, but Pravin resigned from the job in short notice. The case has short- and long-term aspects. The short-term aspect is about the decision related to EXOS’s top performer, Pravin, how to retain him, which motivational factor will help him to rethink his resignation. The long-term aspect deals with framing a motivation model that will prevent the organization from a similar situation in the future. The case outlines the human resource management issues and particularly the importance of motivation to retain the talent of a small startup firm. Directors recognize the importance of Pravin and they have a realization that the deal on which Pravin is working is critical. Under this situation, Upasana has to stop Pravin.

Complexity academic level

Undergraduate, Master of Business Administration (MBA) or in the Management Development Programs.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS: 8 Marketing.
Financial characteristics of takeover targets: a French empirical evidence
Authors: Meghouar Hicham , Ibrahimi Mohammed
Published: July 2020

Purpose

The purpose of this research is to highlight the financial characteristics of large French targets which were subject to takeovers during the period 2001–2007 and thereafter deduct the implicit motivations of acquirers.

Design/methodology/approach

Using a global sample of 128 French listed companies (64 targets and 64 non-targets), the authors carried out Wilcoxon–Mann–Whitney testing and logistic regression in order to test nine hypotheses likely to discriminate between the two categories of companies (targets and non-targets).

Findings

According to the results, target firms are more unbalanced in terms of growth resources and less rich in liquidity than their peers. They have unused debt capacity, offer greater opportunities for growth than firms in the control group and present low levels of value creation.

Research limitations/implications

The main limitation of this study is regarding the sample size, limited by the exclusive use of large firms (deals of over $100m). The scope of this research could be broadened in future by including medium-sized companies.

Practical implications

The authors believe that their results have two major implications. First, they enable market investors to achieve abnormal returns by investing in predicted targets through a portfolio of high takeover probability firms. Second, CEO of companies that are potentially targeted can assess their takeover likelihood in order to act and to manage such a situation for the benefit of their shareholders.

Originality/value

This research concerns the last wave of takeover prior to the subprime-mortgage financial crisis (2001–2007), a period that has not been sufficiently covered in empirical studies. This research contributes to the existing literature in two main respects. First, the results of this study improve our understanding of motivations for takeovers, particularly in the French context. Second, the introduction of new accounting and financial variables, not previously tested in the literature, enriches the available information concerning the profile of takeover targets.
Exploring interdisciplinary teamwork to support effective ward rounds
Authors: Walton Victoria , Hogden Anne , Long Janet C. , Johnson Julie , Greenfield David
Published: July 2020

Purpose

This paper aims to explore if health professionals share understanding of teamwork that supports collaborative ward rounds.

Design/methodology/approach

A purpose-designed survey was conducted in two acute medical and two rehabilitation wards from a metropolitan teaching hospital. Medical officers, nurses and allied health professionals participated. To understand characteristics that support collaborative ward rounds, questions developed from literature and industry experience asked: what are the enablers and challenges to teamwork; and what are clinicians’ experiences of positive teamwork? Descriptive and thematic analyses were applied to the dimensions of effective teamwork as a framework for deductive coding.

Findings

Seventy-seven clinicians participated (93% response rate). Findings aligned with dimensions of teamwork framework. There was no meaningful difference between clinicians or specialty. Enablers to teamwork were: effective communication, shared understanding of patient goals, and colleague’s roles. Challenges were ineffective communication, individual personalities, lack of understanding about roles and responsibilities, and organisational structure. Additional challenges included: time; uncoordinated treatment planning; and leadership. Positive teamwork was influenced by leadership and team dynamics.

Practical implications

Ward rounds benefit from a foundation of collaborative teamwork. Different dimensions of teamwork present during ward rounds support clinicians’ shared understanding of roles, expectations and communication.

Originality/value

Rounds such as structured rounding, aim to improve teamwork. Inverting this concept to first develop effective collaboration will support team adaptability and resilience. This enables teams to transition between the multiple rounding processes undertaken in a single ward. The emphasis becomes high-quality teamwork rather than a single rounding process.
Incorporating sustainability into software projects: a conceptual framework
Authors: Khalifeh Amin , Farrell Peter , Alrousan Mohammad , Alwardat Shaima , Faisal Masar
Published: July 2020

Purpose

The paper aims to present a conceptual framework that helps in incorporating sustainability into software projects, highlights the importance of project sustainability and provides an extensive review of recent relevant contributions across various fields.

Design/methodology/approach

The authors carried out a systematic bibliographic search on relevant published materials to analyse links between the two disciplines (sustainability and software projects). Furthermore, content analysis was applied to the final selected publications to identify and classify relevant triple bottom line (TBL) aspects to develop the framework.

Findings

The inclusion of TBL-related aspects is the most efficient and effective method used to incorporate sustainability into projects. Most of the relevant contributions in the software literature have focussed on either project product or project process or on one or two dimensions of sustainability rather than the three dimensions of the TBL theory. This study contributes by proposing a conceptual framework that encompasses TBL-related aspects for incorporating sustainability into processes and products of software projects.

Research limitations/implications

Validating the proposed framework empirically could be an interesting research issue. In addition, future works may focus on different types of industries, such as information systems, telecommunications and service sectors, which have seldom been studied in the literature.

Practical implications

Software companies – or other relevant organisations – may use the proposed framework as a measurement tool to evaluate the environmental and social impacts of their current products and project management practices. Consequently, these organisations may pay more attention to incorporating sustainability into their project management practices.

Originality/value

The proposed framework may contribute towards a more sustainable orientation by providing a unique combination of TBL-related aspects that gives academics and practitioners a better understanding of how software projects can be managed sustainably.
Sustainable resource management in a supply chain: a methodological proposal combining zero-inflated fuzzy time series and clustering techniques
Authors: Ewbank Henrique , Frutuoso Roveda José Arnaldo , Monteiro Masalskiene Roveda Sandra Regina , Ribeiro Admilson ĺrio , Bressane Adriano , Hadi-Vencheh Abdollah , Wanke Peter
Published: July 2020

Purpose

The purpose of this paper is to analyze demand forecast strategies to support a more sustainable management in a pallet supply chain, and thus avoid environmental impacts, such as reducing the consumption of forest resources.

Design/methodology/approach

Since the producer presents several uncertainties regarding its demand logs, a methodology that embed zero-inflated intelligence is proposed combining fuzzy time series with clustering techniques, in order to deal with an excessive count of zeros.

Findings

A comparison with other models from literature is performed. As a result, the strategy that considered at the same time the excess of zeros and low demands provided the best performance, and thus it can be considered a promising approach, particularly for sustainable supply chains where resources consumption is significant and exist a huge variation in demand over time.

Originality/value

The findings of the study contribute to the knowledge of the managers and policymakers in achieving sustainable supply chain management. The results provide the important concepts regarding the sustainability of supply chain using fuzzy time series and clustering techniques.
MHD boundary layer heat and mass transfer flow of nanofluid through porous media over inclined plate with chemical reaction
Authors: Reddy P. Sudarsana , Sreedevi P.
Published: July 2020

Purpose

Steady-state mixed convection boundary layer flow, heat and mass transfer characteristics of Buongiorno's model nanofluid over an inclined porous vertical plate with thermal radiation and chemical reaction are presented in this analysis.

Design/methodology/approach

The governing nonlinear partial differential equations represent the flow model that can be converted into system of nonlinear ordinary differential equations using the similarity variables and are solved numerically using finite element method.

Findings

The rates of nondimensional temperature and concentration are both decelerate with the higher values of thermophoresis parameter (Nt).

Originality/value

The work carried out in this paper is original.
Glycemic response of Emblica officinalis powder-incorporated Indian recipes
Authors: Venugopal Shonima , Iyer Uma , Sanghvi Richa
Published: July 2020

Purpose

Glycemic index (GI) is a physiological basis for ranking carbohydrate foods based on the blood glucose responses they produce after ingestion. Emblica officinalis (E. officinalis) is a medicinal plant that purportedly has hypoglycaemic and hypolipidemic properties. This study aims to determine the glycemic and lipemic responses of freeze-dried E. officinalis powder-incorporated recipes.

Design/methodology/approach

Two sets of four equicarbohydrate (50 g) recipes (vegetable cutlet, handvo, muthiya and methi thepla) were developed, one without E. officinalis powder incorporation (standard) and one with E. officinalis powder incorporation at the 2 g level (test). After overnight fasting, 50 g glucose, standard and test recipes were administered to healthy adult volunteers at different instances (each 3–4 days apart) and blood glucose levels were measured using capillary sampling every 15 min for 2 h. The glycemic response and GI values were then calculated.

Findings

Among the standard recipes, lowest glycemic response was obtained by methi thepla (60.90 ± 15.54) and highest glycemic response by handvo (90.57 ± 33.88). Incorporation of E. officinalis powder brought about a non-significant reduction in the GI of methi thepla (p = 0.94), vegetable cutlet (p = 0.54), muthiya (p = 0.69) and handvo (p = 0.09). Maximum per cent reduction was for handvo, which shifted from the high to medium GI category. The lipemic response was lowest with muthiya, showing a fall in triacylglycerol (TG) levels (3.9%). E. officinalis powder incorporation in muthiya led to a further fall (7.8%) in TG levels.

Originality/value

Incorporation of freeze-dried E. officinalis powder in Indian recipes can bring about a reduction in the postprandial glycemic and lipemic responses.
Recovery of non-regenerable exhausted resin by hydrothermal chlorination
Authors: Al Onur , Boncukcuoğlu Recep , Güneysu Sinan
Published: July 2020

Purpose

Cationic resin is widely used in decolouring of textile wastewaters. Tonnes of resin are used in sector, and disposal of resin is being a second waste problem. The purpose of this paper is to investigate the adsorption behaviour of the methylene blue cationic dye from aqueous solution on the cation exchanger Lewatit CNP80 to understand the regenerability of cation exchanger resin from textile wastewaters.

Design/methodology/approach

Cationic resin was used as an alternative low-cost adsorbent for removing methylene blue dye from textile wastewaters. The adsorption study was carried out in the batch mode. Batch adsorption studies were carried out to examine the effect of parameters such as methylene blue concentration, temperature, pH, resin dose, shaking speed and contact time.

Findings

It was observed that dye-removal capacity of resin was reached from 17 mgg−1 to 19.4 mgg−1 at 25 °C temperature, pH 5 in 15 min. At the appropriate range of parameters, it was observed that more than 98% removal efficiency was achieved for methylene blue dye, and also, this study was focussed on whether the resin regenerates. In regeneration studies, our purpose was to recover of non-regenerable exhausted cationic resin by NaOCl. Regeneration of Lewatit CNP80 was performed in five cycles. After regeneration, the authors tried to determine whether the adsorption capacity was affected by regeneration.

Originality/value

In this study, the authors focussed on regeneration studies. The aim is to find easy, low-cost regeneration agent. In conclusion, the authors found that NaOCl is eligible for regeneration studies. The exhausted resin was recovered by NaOCl, and the authors also tested 5th regeneration cycles. Sodium hypochlorite is not a common regeneration agent for adsorption studies. Generally, resin is regenerated by HCl or other regeneration agent products. As a result of that, operational cost was reduced, and the other thing that the authors want to emphasise is textile industry wastewater based high temperature; therefore, this regeneration study can easily work with textile industries.
If they will have me, I think I will stay a while: compassion and containment illustrated by the Ingrebourne Therapeutic Community
Authors: Harrison Tom
Published: July 2020

Purpose

The purpose of this paper is to illustrate the evolution of discerning compassion and how it was used in the Ingrebourne Therapeutic Community.

Design/methodology/approach

This paper is derived from a PhD thesis which was researched through interviews and archival research. The fundamental finding was that the therapeutic community approach was almost unique in providing a structured approach to implementing discerning compassion.

Practical implication

The therapeutic community approach for discerning compassion, in which the response to distress aims to promote flourishing.

Social implications

This paper offers a model that has implications on how care is delivered in other settings.

Originality/value

There is little literature that explores the role of compassion in therapeutic communities or in care environments of any form. The approach taken here places compassion in a historical and philosophical setting and contrasts it with the kindness expressed in traditional psychiatric care that promoted “tranquility”.
Lean Six Sigma implementation and sustainability roadmap for reducing medication errors in hospitals
Authors: Trakulsunti Yaifa , Antony Jiju , Douglas Jacqueline Ann
Published: July 2020

Purpose

The purpose of this study is to propose a Lean Six Sigma (LSS) roadmap to guide healthcare practitioners in the implementation of LSS along with a customized LSS tool kit for reducing medication errors.

Design/methodology/approach

The authors initially critically reviewed several frameworks/roadmaps of Lean, Six Sigma and LSS which have been proposed in healthcare sector from the existing literature. This review has led to an understanding of key characteristics, limitations and reasons behind the development of such frameworks/roadmaps. A conceptual roadmap was developed and then validated by a number of LSS experts and a healthcare practitioner. Based on the previous studies and taking LSS experts’ opinions into account, a revised roadmap for reducing medication is presented.

Findings

The roadmap for LSS in reducing medication errors is developed. This roadmap includes three phases: Phase 1 cultural readiness for LSS employment in reducing medication errors; Phase 2 preparation, initialization and implementation; and Phase 3 sustainability.

Research limitations/implications

The roadmap has been tested with only a handful of practitioners of LSS. Moreover, only two case studies have been carried out in a Thai hospital setting which followed the roadmap. In order to improve the validity of research, more case studies need to be executed and more people should be used for testing the roadmap with varied cultures.

Originality/value

This is the first attempt in the development of a LSS roadmap that healthcare practitioners can follow to reduce medication errors using LSS methodology and sustaining LSS in their organizations.
Case of melorheostosis associated with ipsilateral verrucous epidermal nevus, linear connective tissue nevus, diffuse hyperpigmentation and hypertrichosis: A fortuitous coincidence?
Authors: Di Altobrando Ambra , Neri Iria , Gurioli Carlotta , Misciali Cosimo , Baraldi Carlotta , Pedrini Elena , Gnoli Maria , Tremosini Morena , Sangiorgi Luca , Patrizi Annalisa
Published: July 2020

Melorheostosis (MEL) is a rare benign bone disorder that can be associated with several anomalies, including vascular abnormalities, nevus sebaceus, unilateral nevoid telangiectasia, linear scleroderma and hypertrichosis. We report the case of a 6‐year‐old patient who showed an unusual co‐occurrence of bone hyperostosis and different skin lesions affecting the same side of the body: MEL, verrucous epidermal nevus, connective tissue nevus, linear scleroderma‐like disorder, hyperpigmentation and hypertrichosis. The spatial co‐occurrence of these conditions made us speculate as to whether they originated from a common genetic mechanism or if their co‐occurrence was completely accidental.
Xylomelum occidentale (Proteaceae) accesses relatively mobile soil organic phosphorus without releasing carboxylates
Authors: Zhong Hongtao , Zhou Jun , Azmi Azrul , Arruda André J. , Doolette Ashlea L. , Smernik Ronald J. , Lambers Hans
Published: July 2020

Hundreds of Proteaceae species in Australia and South Africa typically grow on phosphorus (P)‐impoverished soils, exhibiting a carboxylate‐releasing P‐mobilizing strategy. In the Southwest Australian Biodiversity Hotspot, two Xylomelum (Proteaceae) species are widely distributed, but restricted within that distribution.

We grew Xylomelum occidentale in hydroponics at 1 μM P. Leaves, seeds, rhizosheath and bulk soil were collected in natural habitats.

Xylomelum occidentale did not produce functional cluster roots and occupied soils that are somewhat less P‐impoverished than those in typical Proteaceae habitats in the region. Based on measurements of foliar manganese concentrations (a proxy for rhizosphere carboxylate concentrations) and P fractions in bulk and rhizosheath soil, we conclude that X. occidentale accesses organic P, without releasing carboxylates. Solution 31P‐NMR spectroscopy revealed which organic P forms X. occidentale accessed.

Xylomelum occidentale uses a strategy that differs fundamentally from that typical in Proteaceae, accessing soil organic P without carboxylates. We surmise that this novel strategy is likely expressed also in co‐occurring non‐Proteaceae that lack a carboxylate‐exuding strategy. These co‐occurring species are unlikely to benefit from mycorrhizal associations, because plant‐available soil P concentrations are too low.

Synthesis. Our findings show the first field evidence of effectively utilizing soil organic P by X. occidentale without carboxylate exudation and explain their relatively restricted distribution in an old P‐impoverished landscape, contributing to a better understanding of how diverse P‐acquisition strategies coexist in a megadiverse ecosystem.
The good Arab: conditional inclusion and settler colonial citizenship among Palestinian citizens of Israel in Jewish Tel Aviv
Authors: Hackl Andreas
Published: July 2020

Dominant majorities often use idealized categories to validate the ‘goodness’ and deservingness of minority citizens. For Palestinian citizens of Israel, this category is the ‘good Arab’. Since its origins in early Jewish settlement of Palestine, it has become a powerful and controversial metaphor in Israeli public discourse. As an experienced condition of limited inclusion, the ‘good Arab’ exemplifies the Palestinian dilemma of accessing socioeconomic opportunities in Jewish Israeli spaces that stigmatize and fend off their ethnonational identity. Combining a historical genealogy of the ‘good Arab’ with ethnographic research among Palestinians in Tel Aviv, this article shows how a historically evolved logic of settler colonial control and indigenous erasure continues to define liberal frameworks of conditional citizenship and inclusion. Theorized through the emerging concept ofconditional inclusion, these insights open up new avenues for analysis and comparison in anthropological debates surrounding indigenous struggles, settler colonialism, urban inclusion, and citizenship.
All in the family: Transnational families and stepwise migration strategies
Authors: Francisco‐Menchavez Valerie
Published: July 2020

Filipino transnational families often hold the histories of stepwise migration carried out by earlier generations. In this article, I argue that considering the transnational family as the unit of analysis for studying stepwise migration can help us understand onward migratory trajectories in two important ways. First, stepwise migratory choices are affected by how past generations within the transnational family have fared in particular locations. Second, transnational families' transmission of stepwise strategies among migrant and nonmigrant family at different points in the migration process offer opportunities for an alternative geographic analysis of care exchange in global households. A 5‐year multisited, longitudinal ethnography between New York City and Metro Manila using family histories of migrant and nonmigrant family members in Filipino transnational families calls attention to the transnational family unit as a repository of information that stepwise migrants use reimagining the sociospatial arrangement of care.
Unexpected favorable outcome to sintilimab plus bevacizumab in an EGFR‐mutated non‐small cell lung cancer patient: A case report
Authors: Zhang Yiruo , Zhao Mei , Cao Shuliang , Zhang Xuchao , Du Yingying
Published: July 2020

A 53‐year‐old man diagnosed with disease stage IIIB pulmonary adenocarcinoma underwent chemotherapy and radiotherapy in the first‐line setting. After disease progression, he received targeted therapy because of subsequent detection of EGFR exon 19 del mutation. Following an increase in his adrenal metastases, a combination of immunotherapy and antiangiogenic therapy (sintilimab plus bevacizumab) was commenced. After one month, imaging showed that the adrenal metastases had shrunk and a progression‐free survival (PFS) of 6.0 months was achieved. In this case, we showed that the PD1 inhibitor sintilimab plus bevacizumab was effective in a refactory advanced EGFR‐mutant NSCLC with positive PD‐L1 expression.

Key points

Our case report provides clinical evidence of the durable response of a patient with advanced EGFR‐mutant lung adenocarcinoma to a combination of immunotherapy and anti‐angiogenic agent, sintilimab and bevacizumab, as subsequent‐line therapy. Sintilimab and bevacizumab combination therapy was well‐tolerated and effective, resulting in dramatic tumor reduction and improvement in clinical symptoms.
Post‐operative alarm signs in the rapid response system and hospital mortality after non‐cardiac surgery
Authors: Song In‐Ae , Cha Jun Kwon , Oh Tak Kyu , Lee Yeon Joo , Jo You Hwan , Lee Dong‐Seon , Min Hyunju , Choi Yun Young , Lee Eun Young , Yun Mi‐Ae , Lee Da‐Yun
Published: July 2020

Background

A variety of rapid response systems (RRSs) based on the systematic assessment of vital signs and laboratory tests have been developed to reduce hospital mortality through the early detection of alarm signs, while deterioration may still be reversible. This study aimed to determine the association between alarm signs and post‐operative hospital mortality during post‐operative days (POD) 0‐3 in patients undergoing non‐cardiac surgery.

Methods

This retrospective observational study used data from the registry of a single tertiary academic hospital. The study population included patients who were ≥18 years old, admitted between 1 January 2013 and 30 June 2018 for non‐cardiac surgery, and subsequently transferred to the general ward.

Results

A total of 116 329 patients were included in the analysis. Among them, 10 099 patients (8.7%) showed positive alarm criteria and triggered the RRS in the post‐operative ward during POD 0‐3. In the multivariate logistic regression model, PaO2 <55 mm Hg, SpO2 <90%, and total CO2 <15 mmol/L were associated with a 3.57‐, 3.46‐, and 12.53‐fold increase in post‐operative hospital mortality, respectively. Moreover, when compared to the no alarm signs group, patients with 1, 2, 3, and ≥4 alarm signs showed a 2.79‐, 2.76‐, 6.54‐, and 20.02‐fold increase in hospital mortality, respectively.

Conclusion

Increased post‐operative hospital mortality was found to be associated with alarm signs detected by the RRS during POD 0‐3. The post‐operative alarm signs detected by the RRS may therefore be useful in determining high‐risk patients who require medical interventions in the surgical ward.
Gabapentin Enacarbil Extended‐Release Versus Placebo: A Likely Responder Reanalysis of a Randomized Clinical Trial
Authors: Laska Eugene M. , Siegel Carole E. , Lin Ziqiang , Bogenschutz Michael , Marmar Charles R.
Published: July 2020

Background

We reanalyzed a multisite 26‐week randomized double‐blind placebo‐controlled clinical trial of 600 mg twice‐a‐day Gabapentin Enacarbil Extended‐Release (GE‐XR), a gabapentin prodrug, designed to evaluate safety and efficacy for treating alcohol use disorder. In the original analysis (n = 338), published in 2019, GE‐XR did not differ from placebo. Our aim is to advance precision medicine by identifying likely responders to GE‐XR from the trial data and to determine for likely responders if GE‐XR is causally superior to placebo.

Methods

The primary outcome measure in the reanalysis is the reduction from baseline of the number of heavy drinking days (ΔHDD). Baseline features including measures of alcohol use, anxiety, depression, mood states, sleep, and impulsivity were used in a random forest (RF) model to predict ΔHDD to treatment with GE‐XR based on those assigned to GE‐XR. The resulting RF model was used to obtain predicted outcomes for those randomized to GE‐XR and counterfactually to those randomized to placebo. Likely responders to GE‐XR were defined as those predicted to have a reduction of 14 days or more. Tests of causal superiority of GE‐XR to placebo were obtained for likely responders and for the whole sample.

Results

For likely responders, GE‐XR was causally superior to placebo (p < 0.0033), while for the whole sample, there was no difference. Likely responders exhibited improved outcomes for the related outcomes of percent HDD and drinks per week. Compared with unlikely responders, at baseline likely responders had higher HDDs; lower levels of anxiety, depression, and general mood disturbances; and higher levels of cognitive and motor impulsivity.

Conclusions

There are substantial causal benefits of treatment with GE‐XR for a subset of patients predicted to be likely responders. The likely responder statistical paradigm is a promising approach for analyzing randomized clinical trials to advance personalized treatment.
Anthropogenic effects on the occurrence of medium‐sized mammals on the Brazilian Pampa biome
Authors: de Lima D. O. , Banks‐Leite C. , Lorini M. L. , Nicholson E. , Vieira M. V.
Published: July 2020

The Pampa biome within Brazil is one of South America’s most endangered biomes, due to conversion to croplands and use for cattle farming, with very limited coverage by protected areas. We investigated the impacts of (i) human population density, (ii) grassland and (iii) forest cover, (iv) protected areas and (v) mean size of farms on the occurrence patterns of 18 medium‐sized mammal species. We gathered information on the occurrence of these species between 2001 and 2010 from the literature and using unpublished field data from local experts. We obtained 1066 records, varying between 13 and 101 per species. Grassland cover had consistently positive effects on species richness (considering the 18 analyzed species), endangered species (considering 10 species that are endangered or data deficient) and occurrence of five individual species (considering each species separately). Human population density, forest cover and mean size of farms had diverse effects on individual species; however, both forest cover and human population density had positive effects on species richness and endangered species occurrence. For human population density this may result from areas suitable for people being similar to those suitable for many native species. The protected area network of the Pampa biome appeared ineffective at protecting the focal species, with predominantly negative effects on mammal occurrence. This inefficiency is probably related to its minor coverage; only 2.9% of the biome area is under any level of protection and only 0.4% under strict protection. To guarantee the conservation of mammal species in this threatened biome, it is important to protect the last remnants of native vegetation, mainly grasslands, avoiding their conversion into croplands.
Estimating the amount of collagen and elastic fibres in bovine teats
Authors: Koskenniemi Heidi , Laakkonen Juha
Published: July 2020

The amount of collagen and elastic fibres near the Fürstenberg's rosette in histological sections of bovine teats was estimated using the ImageJ image processing software. This method holds promise for comparing tissue types within and between sections but it was not a reliable way to quantify the absolute amount of tissue types in a sample. The amount of elastic fibres and collagen was similar in cow teats with a history or acute case of mastitis infection and in non‐infected cows, but this could not be statistically tested due to limitations in the study material.
Economic considerations on the usage of biologics in the allergy clinic
Authors: Azzano Pauline , Dufresne Élise , Poder Thomas , Bégin Philippe
Published: July 2020

The advent of biologic therapies has transformed care for severe atopic disorders but their high cost poses new challenges with regard to long‐term sustainability and fair allocation of resources. This article covers the basic concepts of cost‐utility analyses and reviews the available literature on cost utility of biologic drugs in atopic disorders. When used within their limits as part of a multi‐dimensional assessment, economic analyses can be extremely useful to guide decision‐making and prioritization of care. Despite the good quality of most cost‐utility analyses conducted for the use of biologics in asthma and other atopic diseases, their conclusions regarding cost‐effectiveness are extremely variable. This is mainly due to the use of inconsistent estimates of health utility benefit with therapy. Development of reliable and validated instruments to measure disutility in atopic disorders and measure of indirect costs in atopic disease are identified as a priority for future research.
Different alteration patterns of sub‐macular choroidal thicknesses in aquaporin‐4 immunoglobulin G antibodies sero‐positive neuromyelitis optica spectrum diseases and isolated optic neuritis
Authors: Peng Chunxia , Li Li , Yang Mo , Teng Da , Wang Junqing , Lai Mengying , Qian Haiyan , Li Hongyang , Zhou Huanfen , Xu Quangang , Wei Shihui
Published: July 2020

Purpose

The ocular choroid is a sensitive biomarker of vascular perfusion in optic neuritis (ON) patients due to its vascular structures. The purpose of this study was to evaluate alterations in sub‐macular choroidal thicknesses (sub‐MCT) in aquaporin‐4 immunoglobulin G antibodies (AQP4‐IgG) sero‐positive neuromyelitis optica spectrum disease (AQP4‐IgG+/NMOSD) and isolated ON (ION) patients using optical coherence tomography (OCT).

Methods

A total of 208 ON patients (275 eyes) and healthy controls (HCs) who underwent sub‐MCT and retinal microstructure detection with OCT were enrolled in this study.

Results

Among all the ON patients, 102 (49.0%) cases were identified as serum AQP4‐IgG‐positive, with 106 (51.0%) cases being negative, excluding multiple sclerosis as the ION cohort. The sub‐MCT in the AQP4‐IgG+/NMOSD patients decreased in 0–6 months after ON attacks. However, for the ION cohort, the sub‐MCT decreased in 0–2 months and then stayed normal or slightly increased in 2–4 months after the first ON attack, finally sharply decreasing after 6 months. For unilateral AQP4‐IgG+/NMOSD patients, eyes without ON also presented retinal layer thinning and sub‐MCT slight reduction independent of ON attacks.

Conclusions

The sub‐MCT in AQP4‐IgG+/NMOSD patients were reduced at all stages of ON, which distinguished the ION patients as decreasing only at chronic stage of ON. It implied that ocular vascular hypoperfusion plays a potential role in ON pathogenesis and the different patterns could be caused by the distinct pathogenesis of AQP4‐IgG+/NMOSD and ION.