bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial immune evasion proteins: The therapeutic potential of CHIPS
Authors: Tromp Angelino T. , Zhao Yuxi , Jongerius Ilse , Heezius Erik C.J.M , Abrial Pauline , Ruyken Maartje , van Strijp Jos A. G. , de Haas Carla.J.C. , Spaan András N. , van Kessel Kok P.M. , Henry Thomas , Haas Pieter-Jan A.
Published: February 2020

Bacterial pathogens have evolved to secrete strong anti-inflammatory proteins that target the immune system. It was long speculated whether these virulence factors could serve as therapeutics in diseases in which abnormal immune activation plays a role. We adopted the secreted Chemotaxis Inhibitory Protein of Staphylococcus aureus (CHIPS) as a model virulence factor-based therapeutic agent for diseases in which C5aR1 stimulation plays an important role. We show that administration of CHIPS in human C5aR1 knock-in mice successfully dampens C5a mediated neutrophil migration during immune complex-initiated inflammation. Subsequent CHIPS toxicology studies in animal models were promising. However, during a small phase-I trial, healthy human volunteers showed adverse effects directly after CHIPS administration. Subjects showed clinical signs of anaphylaxis with mild leukocytopenia and increased C-reactive protein concentrations, suggesting an inflammatory response, which are believed to be related to the presence of relatively high circulating anti-CHIPS antibodies. Even though our data in mice shows CHIPS as a potential anti-inflammatory agent, safety issues in human subjects temper the use of CHIPS in its current form as a therapeutic candidate. The use of staphylococcal proteins, or other bacterial proteins, as therapeutics or immune-modulators in humans is severely hampered by pre-existing circulating antibodies.
Foxm1 regulates neuronal progenitor fate during spinal cord regeneration
Authors: Pelzer Diane , Phipps Lauren S. , Thuret Raphael , Baker Syed Murtuza , Dorey Karel
Published: February 2020

Mammals have limited tissue regeneration capabilities, particularly in the case of the central nervous system. Spinal cord injuries are often irreversible and lead to the loss of motor and sensory function below the site of the damage [1]. In contrast, amphibians such asXenopustadpoles can regenerate a fully functional tail, including their spinal cord, following amputation [2,3]. A hallmark of spinal cord regeneration is the re-activation of Sox2/3+ progenitor cells to promote regrowth of the spinal cord and the generation of new neurons [4,5]. In axolotls, this increase in proliferation is tightly regulated as progenitors switch from a neurogenic to a proliferative division via the planar polarity pathway (PCP) [6–8]. How the balance between self-renewal and differentiation is controlled during regeneration is not well understood. Here, we took an unbiased approach to identify regulators of the cell cycle expressed specifically inX.tropicalisspinal cord after tail amputation by RNAseq. This led to the identification of Foxm1 as a potential key transcription factor for spinal cord regeneration.Foxm1-/-X.tropicalistadpoles develop normally but cannot regenerate their spinal cords. Using single cell RNAseq and immunolabelling, we show thatfoxm1+ cells in the regenerating spinal cord undergo a transient but dramatic change in the relative length of the different phases of the cell cycle, suggesting a change in their ability to differentiate. Indeed, we show that Foxm1 does not regulate the rate of progenitor proliferation but is required for neuronal differentiation leading to successful spinal cord regeneration.
Recreation of an antigen-driven germinal center in vitro by providing B cells with phagocytic antigen
Authors: Martínez-Riaño Ana , Delgado Pilar , Mendoza Pilar , Oeste Clara L. , Abia David , Rodríguez-Bovolenta Elena , Turner Martin , Alarcón Balbino
Published: February 2020

Successful vaccines rely on activating a functional humoral response that results from generating class-switched high affinity immunoglobulins (Igs) with a superior capacity to neutralize infection. Key to this process is the germinal center (GC) reaction, in which B cells are selected in their search for antigen and T cell help. A major hurdle to understanding the mechanisms of B cell:T cell cooperation has been the lack of anin vitrosystem to recreate GCs in an antigen-specific manner. Here we report the generation of functional antigen-specific high affinity Igs of different isotypes in simple 2-cell type cultures of naïve B and T cells. It is crucial for this process for B cells to take up antigen by a phagocytic mechanism, which results in stronger and more sustained BCR signals compared to stimulation with a soluble antigen. We also show the applicability of the system to generate antibodies of potential clinical interest.
Continuum theory of active phase separation in cellular aggregates
Authors: Kuan Hui-Shun , Pönisch Wolfram , Jülicher Frank , Zaburdaev Vasily
Published: February 2020

Dense cellular aggregates are common in many biological settings, ranging from bacterial biofilms to organoids, cell spheroids and tumors. Motivated byNeisseria gonorrhoeaebiofilms as a model system, we present a hydrodynamic theory to study dense, active, viscoelastic cellular aggregates. The dynamics of these aggregates, driven by forces generated by individual cells, is intrinsically out-of-equilibrium. Starting from the force balance at the level of individual cells, we arrive at the dynamic equations for the macroscopic cell number density via a systematic coarse-graining procedure taking into account a nematic tensor of intracellular force dipoles. We describe the basic process of aggregate formation as an active phase separation phenomenon. Our theory furthermore captures how two cellular aggregates coalesce. Merging of aggregates is a complex process exhibiting several time scales and heterogeneous cell behaviors as observed in experiments. In our theory, it emerges as a coalescence of active viscoelastic droplets where the key timescales are linked to the turnover of the active force generation. Our theory provides a general framework to study the rheology and dynamics of dense cellular aggregates out of thermal equilibrium.
Drug GRADE: an integrated analysis of population growth and cell death reveals drug-specific and cancer subtype-specific response profiles
Authors: Schwartz Hannah R. , Richards Ryan , Fontana Rachel E. , Joyce Anna J. , Honeywell Megan E. , Lee Michael J.
Published: February 2020

In the pre-clinical evaluation of anti-cancer drugs, two different measurement approaches are used: relative viability, which scores an amalgam of growth arrest and cell death, and fractional viability, which more specifically scores the degree of cell killing. In this study, we directly quantify relationships between drug-induced growth inhibition and drug-induced cell death by counting live and dead cells over time using quantitative microscopy. We find that most drugs affect both growth and death, but with different proportions and with different relative timing. These features lead to a non-uniform and unpredictable relationship between the canonical relative and fractional drug response measurements. To unify these disparate measurements, we create a new data visualization and data analysis platform, called drug GRADE, which characterizes the degree to which cell death contributes to an observed reduction in population size for any given drug. Our new method reveals both drug- and genotype-specific drug responses, which are not captured using traditional pharmaco-metrics. Taken together, this study highlights the extremely idiosyncratic nature of drug-induced growth and cell death and provides a new analysis tool for quantitatively evaluating these behaviors.
Myocardial damage induced by a single high dose of isoproterenol in C57BL/6J mice triggers a persistent adaptive immune response against the heart
Authors: Forte Elvira , Panahi Mona , Ng Fu Siong , Boyle Joseph J. , Branca Jane , Bedard Olivia , Hasham Muneer G. , Benson Lindsay , Harding Sian E. , Rosenthal Nadia , Sattler Susanne
Published: February 2020

Heart failure is the common final pathway of a range of conditions resulting in myocardial damage and a major cause of morbidity and mortality worldwide. Strategies to improve tissue repair and prevent heart failure thus remain an urgent clinical need. Recent studies have documented activation of the adaptive immune system in response to myocardial damage and have implicated anti-heart autoimmunity in the development of heart failure. In an attempt to target anti-heart autoimmune responses as new therapeutic avenue, the number of experimental studies usingin vivomodels of myocardial damage to study the ensuing immune response has surged.

The beta-adrenergic agonist isoproterenol-hydrochloride has been used for its cardiac effects in a variety of different dosing and administration regimes. Most prominently, low doses (<10mg/kg sc) over an extended time period induce cardiac hypertrophy and fibrosis. In addition, single injections of high doses (>100mg/kg) induce cardiomyocyte necrosis and have been used to mimic acute myocardial necrotic lesions as seen in myocardial infarction (MI). However, despite significant resource and animal welfare advantages, concerns about off-target effects and clinical relevance have so far limited uptake in the cardiovascular research community.

To assess suitability of the isoproterenol model for the analysis of chronic post-MI immunological readouts, we treated C57BL/6J mice with a single intra-peritoneal bolus injection of 160mg/kg isoproterenol. Our results confirm the presence of necrotic lesions in the myocardium with significant resemblance of the histopathology of Type 2 MI. Kidneys develop mild fibrosis secondary to early cardiac damage, while other organs remain unaffected. Most importantly, we showed that isoproterenol treatment causes myocardial inflammation and fibrosis, activation of T cells in the heart-draining mediastinal lymph nodes, deposition of mature antibodies in the myocardium and the presence of auto-antibodies against the heart in the serum 12 weeks after the initial injury.

In summary, this simple and cost-effective experimental model with significant animal welfare benefits induces myocardial damage reminiscent of human Type 2 MI, which is followed by a persistent adaptive immune response against the heart. This makes it a suitable and high-throughput model to study pathological mechanisms of anti-heart autoimmunity as well as to test potential immunomodulatory therapeutic approaches.
Widefield light sheet microscopy using an Airy beam combined with deep-learning super-resolution
Authors: Corsetti Stella , Wijesinghe Philip , Poulton Persephone B. , Sakata Shuzo , Vyas Khushi , Herrington C. Simon , Nylk Jonathan , Gasparoli Federico , Dholakia Kishan
Published: February 2020

Imaging across length scales and in depth has been an important pursuit of widefield optical imaging. This promises to reveal fine cellular detail within a widefield snapshot of a tissue sample. Current advances often sacrifice resolution through selective sub-sampling to provide a wide field of view in a reasonable time scale. We demonstrate a new avenue for recovering high-resolution images from sub-sampled data in light-sheet microscopy using deep-learning super-resolution. We combine this with the use of a widefield Airy beam to achieve high-resolution imaging over extended fields of view and depths. We characterise our method on fluorescent beads as test targets. We then demonstrate improvements in imaging amyloid plaques in a cleared brain from a mouse model of Alzheimer’s disease, and in excised healthy and cancerous colon and breast tissues. This development can be widely applied in all forms of light sheet microscopy to provide a two-fold increase in the dynamic range of the imaged length scale. It has the potential to provide further insight into neuroscience, developmental biology and histopathology.
Sequence-based Prediction of Metamorphic Behavior in Proteins
Authors: Chen N. , Das M. , LiWang A. , Wang L.-P.
Published: February 2020

An increasing number of proteins have been demonstrated in recent years to adopt multiple three-dimensional folds with different functions. These metamorphic proteins are characterized by having two or more folds with significant differences in their secondary structure, where each fold is stabilized by a distinct local environment. So far, about 90 metamorphic proteins have been identified in the Protein Databank (PDB), but we and others hypothesize that a far greater number of metamorphic proteins remain undiscovered. In this work, we introduce a computational model to predict metamorphic behavior in proteins using only knowledge of the sequence. In this model, secondary structure prediction programs are used to calculatediversity indices, which are measures of uncertainty in predicted secondary structure at each position in the sequence; these are then used to assign protein sequences as likely to be metamorphic vs. monomorphic (i.e. having just one-fold). We constructed a reference dataset to train our classification method, which includes a novel compilation of 140 likely-monomorphic proteins, and a set of 201 metamorphic proteins taken from the literature. Our model is able to classify proteins as metamorphic vs. monomorphic with a Matthews correlation coefficient of ∼0.4 and true positive / true negative rates of ∼65% / 80%, suggesting that it is possible to predict metamorphic behavior in proteins using only sequence information.

Statement of Significance

This paper introduces the diversity index as a descriptor to distinguish metamorphic proteins, which possess multiple stable folds, from monomorphic proteins that possess only one fold. The diversity index is designed to measure uncertainty in computationally predicted secondary structure, which we hypothesize is elevated for metamorphic proteins. We tested our hypothesis by training a binary classifier using the diversity index and an annotated dataset of metamorphic and monomorphic proteins, and found an optimal Matthews correlation coefficient of 0.4, supporting the hypothesis and demonstrating for the first time that it is possible to predict metamorphic behavior in proteins using only sequence information. The sequence-based classifier has broader applicability compared to methods that rely on making comparison to experimentally measured structures.
SkewIT: Skew Index Test for detecting mis-assembled bacterial genomes
Authors: Lu Jennifer , Salzberg Steven L
Published: February 2020

GC skew is a phenomenon observed in many bacterial genomes, wherein the two replication strands of the same chromosome contain different proportions of guanine and cytosine nucleotides. Here we demonstrate that this phenomenon, which was first discovered in the mid-1990s, can be used today as an analysis tool for the 15,000+ complete bacterial genomes in NCBI’s Refseq library. In order to analyze all 15,000+ genomes, we introduce a new method, SkewIT (Skew Index Test), which calculates a single metric representing the degree of GC skew for a genome. Using this metric, we demonstrate how GC skew patterns are conserved within certain bacterial phyla, e.g. Firmicutes, but show different patterns in other phylogenetic groups such as Actinobacteria. We also discovered that outlier values of SkewIT highlight potential bacterial mis-assemblies. Using our newly defined metric, we identify multiple mis-assembled chromosomal sequences in NCBI’s Refseq library of complete bacterial genomes.

Software Availability

SkewIT scripts for analysis of bacterial genomes are provided in the following repository: https://github.com/jenniferlu717/SkewIT.
Instrumented immobilizing boot quantifies reduced Achilles tendon loading during gait
Authors: Hullfish Todd J , O’Connor Kathryn M. , Baxter Josh R.
Published: February 2020

Achilles tendon ruptures are common injuries that lead to functional deficits in two-thirds of patients. Progressively loading the healing tendon has been associated with superior outcomes, but the loading profiles that patients experience throughout rehabilitation have not yet been established. In this study, we developed and calibrated an instrumented immobilizing boot paradigm that is aimed at longitudinally quantifying patient loading biomechanics to develop personalized rehabilitation protocols. We used a 3-part instrumented insole to quantify the ankle loads generated by the Achilles tendon and secured a load cell in-line with the posterior strut of the immobilizing boot to quantify boot loading. We then collected gait data from five healthy young adults to demonstrate the validity of this instrumented immobilizing boot paradigm to assess Achilles tendon loading during ambulation. We developed a simple calibration procedure to improve the measurement fidelity of the instrumented insole needed to quantify Achilles tendon loading while ambulating with an immobilizing boot. By assessing Achilles tendon loading with the ankle constrained to 0 degrees and 30 degrees plantar flexion, we confirmed that walking with the foot supported in plantar flexion decreased Achilles tendon loading by 60% (P< 0.001). This instrumented immobilizing boot paradigm leverages commercially available sensors and logs data using a small microcontroller secured to the boot and a handheld device, making our paradigm capable of continuously monitoring biomechanical loading outside of the lab or clinic.
Dispersion of functional gradients across the lifespan
Authors: Bethlehem Richard A.I. , Paquola Casey , Seidlitz Jakob , Ronan Lisa , Bernhardt Boris ,   Cam-CAN Consortium, Tsvetanov Kamen A.
Published: February 2020

Ageing is commonly associated with changes to segregation and integration of functional brain networks, but, in isolation, current network-based approaches struggle to elucidate changes across the many axes of functional organisation. However, the advent of gradient mapping techniques to neuroimaging provides a new means of studying functional organisation in a multi-dimensional connectivity space. Here, we studied ageing and behaviourally-relevant differences in a three-dimensional connectivity space using the Cambridge Centre for Ageing Neuroscience cohort (n=643). Building on gradient mapping techniques, we developed a set of measures to quantify the dispersion within and between functional communities. We detected a strong shift of the visual network across the lifespan from an extreme to a more central position in the 3D gradient space. In contrast, the dispersion distance of transmodal communities (dorsal attention, ventral attention, frontoparietal and default mode) did not change. However, these communities were increasingly dispersed with increasing age, reflecting more dissimilar functional connectivity profiles within each community. Increasing dispersion of frontoparietal and ventral attention networks, in particular, was associated negatively with cognition, measured by fluid intelligence. By using a technique that explicitly captures the ordering of functional systems in a multi-dimensional hierarchical framework, we identified behaviorally-relevant age-related differences of within and between network organisation. We propose that the study of functional gradients across the lifespan could provide insights that may facilitate the development of new strategies to maintain cognitive ability across the lifespan in health and disease.
A benchmark of protein solubility prediction methods on UDP-dependent glycosyltransferases
Authors: Ghomi Fatemeh Ashari , Kittilä Tiia , Welner Ditte Hededam
Published: February 2020

UDP-dependent glycosyltransferases (UGTs) are enzymes that glycosylate a wide variety of natural products, thereby modifying their physico-chemical properties, i.e. solubility, stability, reactivity, and function. To successfully leverage the UGTs in biocatalytic processes, we need to be able to screen and characterise themin vitro, which requires efficient heterologous expression in amenable hosts, preferablyEscherichia coli. However, many UGTs are insoluble when expressed in standard and attempted optimisedE. coliconditions, resulting in many unproductive and costly experiments. To overcome this limitation, we have investigated the performance of 11 existing solubility predictors on a dataset of 57 UGTs expressed inE. coli. We show that SoluProt outperforms other methods in terms of both threshold-independent and threshold-dependent measures. Among the benchmarked methods, only SoluProt is significantly better than random predictors using both measures. Moreover, we show that SoluProt uses a threshold for separating soluble and insoluble proteins that is optimal for our dataset. Hence, we conclude that using SoluProt to select UGT sequences forin vitroinvestigation will significantly increase the success rate of soluble expression, thereby minimising cost and enabling efficient characterisation efforts for biocatalysis research.
Being different matters! A closer look into product differentiation in specialty coffee family farms in Central America
Authors: Discua Cruz Allan , Centeno Caffarena Leonardo , Vega Solano Marcos
Published: February 2020

Purpose

There is a growing interest in understanding the strategic behaviour of family firms producing international commodities such as coffee, particularly in contexts where decisions about what products to sell, where to commercialise them and how to promote them appear to be highly based on both business and family aspects. The purpose of this paper is to explore product differentiation strategies in family firms in the specialty coffee industry across Latin American countries. Whilst the socioeconomic relevance of coffee production in Central America is unequivocal, the approach and rationale of families that engage in specialty coffee production remain underexplored.

Design/methodology/approach

This study examines product differentiation in specialty coffee family farms across countries in Central America: Guatemala, Honduras and Nicaragua. The study relies on in-depth interviews, case studies and an interpretative approach to unpick the dynamics of product differentiation by families in business dedicated to producing specialty coffee.

Findings

The findings show that product differentiation in specialty coffee family farms is influenced by both business and family aspects and driven by entrepreneurial stewards. Coffee-farming families can engage in product differentiation through a shared vision, a combination of traditional and specialised knowledge, and through the continuous development of an exchange network. The findings reveal a connection between families in business balancing family and business interests, and the strategic intention to build up their assets entrepreneurially over time.

Originality/value

This study contributes to the literature on stewardship and strategic behaviour in family firms when families in business engage in differentiating their products in a highly competitive industry. More specifically, this study focuses on companies across countries where coffee is of crucial socioeconomic importance, and where the said companies are owned and managed by families. The study expands understanding of product differentiation in family-enterprise-first businesses and suggests that the family elements in differentiation can be explained through an entrepreneurial stewardship perspective.
Impact of instantaneous curvature on force and heat generation in manufacturing processes – a mathematical modelling
Authors: C. Sreerag , R. Gokul , J. Vinaykumar , G. Rajyalakshmi
Published: February 2020

Purpose

In any machining process, the surface profile of the workpiece is continuously changing with respect to time and input parameters. In a conventional machining process, input parameters are feed and depth of cut whilst other parameters are considered to be constant throughout the process.

Design/methodology/approach

The direct and indirect participation of this instantaneous curvature can be used to optimize the strategy of cutting operation in terms of different parameters like heat generation-induced stresses, etc. The concepts of the metric tensor and Riemannian curvature tensor are made use in this study as a representation of curvature itself. The objective of this study is to create a mathematical methodology that can be implemented on a highly flexible machining process to find an optimum cutting strategy for a particular output parameter.

Findings

The study also includes different case studies for the validation of this newly introduced mathematical methodology.

Originality/value

The study will also find its position in other mechanical processes like forging and casting where instantaneous curvature affects various mechanical properties.
Supply chain data analytics and supply chain agility: a fuzzy sets (fsQCA) approach
Authors: Shamout Mohamed Dawood
Published: February 2020

Purpose

Practitioners and researchers have reached a consensus that supply chain analytics is a strong determinant for desirable organizational outcomes such as supply chain performance and agility. The purpose of this paper is to examine a configural combination (i.e. causal recipes) subsuming supply chain data analytics, firmsize, age and annual sales to predict supply chain agility based on knowledge-based theory.

Design/methodology/approach

Survey data (n = 215) were obtained from firms operating in the United Arab Emirates. Consequently, fuzzy sets qualitative comparative analysis (fsQCA) technique was applied to the data to establish causal recipes that are necessary and sufficient to achieve high scores of supply chain agility.

Findings

Results from fsQCA support the major tenets of complexity theory that several configural combinations (i.e. supply chain data analytics, firm size, firm age and annual sales) are sufficient and necessary conditions for achieving higher scores of supply chain agility.

Originality/value

This study is first of its kind in understanding the association between supply chain data analytics and agility with fsQCA technique. This research also offers a headway for supply chain managers in identifying configural combinations of antecedents manifesting high scores for supply chain agility. Implications for theory and practice are illustrated as well as future research course.
Expanding higher education and wage inequality in Chile
Authors: Murakami Yoshimichi , Nomura Tomokazu
Published: February 2020

Purpose

This study aims to analyse the contribution of the expansion and diversification of higher education to Chile's increase in wage inequality from 1992 to 2000 and its subsequent decrease from 2000 to 2013.

Design/methodology/approach

The wage equation for each year is estimated using data from the national household survey, Encuesta de Caracterización Socioeconómica Nacional (CASEN). Using the method proposed by Firpo et al. (2009), the evolution of wage changes is decomposed into composition and wage structure effects of each explanatory variable at different points of the wage distribution.

Findings

The results show that the positive composition effect of higher education, derived from the increasing share of both workers with university degrees and those with vocational degrees, is substantially larger at the upper quantiles and exceeds the negative wage structure effect, thereby contributing to increasing wage inequality from 1992 to 2000. By contrast, the negative wage structure effect of higher education, primarily derived from the decreasing return to university degrees, is substantially larger at the upper quantiles and exceeds the positive composition effect, thereby contributing to decreasing wage inequality from 2000 to 2013.

Originality/value

This study contributes to the literature by showing that the expansion of higher education increased inequality in the 1990s and decreased it in the 2000s while the increasing supply of workers with vocational degrees decreased wage premiums for university degrees in the latter period.
Exploring the success of Thai advertising: historical perspective
Authors: Chantamas Marissa , Chaisuwan Bu-nga
Published: February 2020

Purpose

This paper aims to provide a comprehensive record of the development of Thai advertising, which started as being heavily influenced by the West and subsequently evolved with a unique style that fits well with the global advertising trends.

Design/methodology/approach

The analysis was done based on literature review and content analysis of Thai advertising. In addition, ten in-depth interviews were conducted with executives of the Advertising Association of Thailand and academics.

Findings

Thai advertising progressed from being influenced by the growth of transnational advertising agencies. This resulted in strong creative foundations that blended well with the unique Thai emotional flair. In addition, consumer protection has grown in importance, leading to a strong commitment in pushing for self-regulation.

Research limitations/implications

Examination of Thai advertising shows that the strength of Thai advertising lies in its human resources. This exploration of challenges and success of Thai advertising has shed light on how the advertising industry can be developed for creativity leadership in the global arena. The limitation is that the paper misses interviews with digital agencies.

Practical implications

This paper provides a comprehensive presentation of Thai advertising history in terms of agency development, creativity, and self-regulation.

Originality/value

This paper aims to provide a better understanding of the Thai advertising industry based on agency ownership and growth, creativity development leading to the unique Thai emotional advertising and self-regulation.
Evidence on the impacts of business coaching
Authors: Wiginton James G. , Cartwright Phillip A.
Published: February 2020

Purpose

Based upon a survey of 87 companies having used the services of business coaches, this paper considers the extent to which coaching is likely to be beneficial to a leader's business success as well as that of the respective company.

Design/methodology/approach

The research methodology is mixed methods and survey-based combining quantitative Likert scaling with open-ended questions.

Findings

At the 99 percent confidence level, surveyed respondents believe that, on average, the coaching process has provided results above the investment required and has led to progress for them and their organizations. Of the six targeted areas, five showed a very positive relationship between the coaching experience and the results from its clients.

Research limitations/implications

As the research is based on a convenience sample it has shortcomings relative to probability sampling. However, it is widely recognized that such samples can be attained more easily, more rapidly, and at less cost than probability-based samples. On the other hand, it is understood that inferences to broader populations of interest are limited.

Practical implications

The results confirm findings from past research such as that reported by the Institute of Coaching (2018), that managers should not undervalue potential contributions to individual and company attributes from coaching.

Originality/value

The motivation for this paper is to bring together both academic and practitioner experience to provide more evidence and understanding related to the coaching definition, its implementation, and effectiveness. While not conclusive in the absolute sense, the original data original collected and analyzed for this research is based on known client contacts in close time proximity to the coaching engagement and delivers added insight to current research.
The quality movement's three operational paradigms: a text mining venture
Authors: Carnerud Daniel
Published: February 2020

Purpose

This study aims to analyze four text-mining studies of quality management (QM) to illustrate and problematize how the research on quality has informed the quality paradigm since the 1980s. By understanding history, one can better manage current developments.

Design/methodology/approach

The findings are based on a meta-analysis of four text-mining studies that explore and describe 11,579 research entries on quality between 1980 and 2017.

Findings

The findings show that the research on quality during the past 30 years form a research paradigm consisting of three operational paradigms: an operative paradigm of backend quality orbiting around QM, total QM (TQM) and service quality; an operative paradigm of middle-way quality, circling around the International Organization for Standardization (ISO), business excellence frameworks (BEFs) and quality awards; and an operative paradigm of frontend quality, revolving around reliability, costs and processes. The operative paradigms are interconnected and complementary; they also show a divide between a general management view of quality and a hands-on engineering view of quality. The findings indicate that the research on quality is a long-lived standalone paradigm, supporting the notion of quality being a genuine academic entity, not a fashion or fad.

Research limitations/implications

The empirical basis of the study is four text-mining studies. Consequently, the results and findings are based on a limited number of findings.

Originality

Text-mining studies targeting research on quality are scarce, and there seem to be no prior models that depict the quality paradigm based on such studies. The perspectives presented here will advance the existing paradigmatic discourse. The new viewpoints aim to facilitate and deepen the discussion on current and future directions of the paradigm.
When does weather synchronize life‐history traits? Spatiotemporal patterns in juvenile body mass of two ungulates
Authors: Herfindal Ivar , Tveraa Torkild , Stien Audun , Solberg Erling J. , Grøtan Vidar
Published: February 2020

Theory predicts that animal populations will be synchronized over large distances by weather and climatic conditions with high spatial synchrony. However, local variation in population responses to weather, and low synchrony in key weather variables or in other ecological processes may reduce the population synchrony.

We investigated to what extent temperature and precipitation during different periods of the year synchronized juvenile body mass of moose and reindeer in Norway. We expected high synchronizing effect of weather variables with a high and consistent explanatory power on body mass dynamics across populations, and a weaker synchronizing effect of weather variables whose effect on body mass varied among populations.

Juvenile body mass in both species was related to temperature and precipitation during several periods of the year. Temperature had the strongest explanatory power in both species, with a similar effect across all populations.

There was higher spatial synchrony in temperature compared to precipitation, and accordingly temperature had the strongest synchronizing effect on juvenile body mass. Moreover, periods with strong explanatory power had stronger synchronizing effect on juvenile body mass in both species. However, weather variables with large variation in the effects on body mass among populations had weak synchronizing effect.

The results confirm that weather has a large impact on the spatial structure of population properties but also that spatial heterogeneity, for instance, in environmental change or population density may affect how and to what extent populations are synchronized.
Does Cultural Difference Affect Investment–Cash Flow Sensitivity? Evidence from OECD Countries
Authors: Kashefi‐Pour Eilnaz , Amini Shima , Uddin Moshfique , Duxbury Darren
Published: February 2020

We investigate the influence of national culture on corporate investment–cash flow sensitivity. We conjecture that national culture shapes managerial perceptions of information asymmetry and agency problems, thus impacting the investment–cash flow relationship. We document empirical evidence in support of our claim. By linking the investment–cash flow sensitivity to cultural differences, our findings show that, while collectivism has an attenuating influence, uncertainty avoidance, power distance and masculinity have a reinforcing effect on the relationship between cash flow and investment. Our results hold for a sample of 205,268 firm‐years across 24 OECD countries between 1990 and 2017, and are robust after accounting for alternative statistical approaches, sample compositions and measures of cultural dimensions, along with controls for institutional and governmental factors. In addition, by decomposing cash flow into uses and sources of funds in a dynamic multi‐equation model, where firms make financing and investment decisions jointly subject to the constraint that sources must equal uses of cash, we find that national culture shapes how firms react to changes in cash flow.
Phospholipase C gamma (PLCγ) regulates soluble trehalase in the 20E‐induced fecundity of Apolygus lucorum
Authors: Tan Yong‐An , Zhao Xu‐Dong , Sun Hou‐Jun , Zhao Jing , Xiao Liu‐Bin , Hao De‐Jun , Jiang Yi‐Pin
Published: February 2020

Apolygus lucorum is the dominant pathogenic insect attacking Bacillus thuringiensis (Bt) cotton in China. Additionally, 20‐hydroxyecdysone (20E) has important functions in many biological processes, including insect reproduction. Phospholipase C (PLC), which is an essential enzyme for phosphoinositide metabolism, is involved in 20E signal transduction, but its function in 20E‐mediated reproduction in A. lucorum remains unclear. In this study, 20E increased AlPLCγ transcription as well as the abundance and activity of the encoded protein during molting and metamorphosis. The 20E treatment also induced the considerable accumulation of two second messengers, inositol triphosphate and diacylglycerol. The expression levels of genes encoding vitellogenin (AlVg) and soluble trehalase (AlTre‐1) were similar to those of AlPLCγ, and were upregulated in response to 20E. The silencing of AlPLCγ resulted in downregulated expression of AlTre‐1 and AlVg. However, the silencing of AlTre‐1 and AlVg did not affect AlPLCγ expression. Moreover, the silencing of AlVg did not alter AlTre‐1 expression. Furthermore, an examination of the insect specimens indicated that AlPLCγ is required for female adult reproduction, and that downregulated expression of this gene is associated with decreases in fecundity, adult longevity, and egg hatching rate as well as delayed oocyte maturation. We propose that 20E regulates AlTre‐1 expression via AlPLCγ and affects Vg expression as well as ovary development to facilitate the reproductive activities of A. lucorum females.
Escalation in Failed Military Interventions: Saudi and Emirati Quagmires in Yemen
Authors: Darwich May
Published: February 2020

External interventions are an enduring feature of international relationships. While the causes for interventions have been at the heart of studies on interventions, the dynamics of termination versus escalation have received little attention. This article poses the question: why do intervenors persist in failed military interventions despite diminishing prospects of victory? Whereas some scholars adhered to rational choice approaches, others focused on cognitive and emotional psychology to explain seemingly puzzling decisions at the origin of war continuation. This article builds on the emerging literature on status in IR to unravel the escalation of commitment to a failed war. It argues that when leaders engage their own status and that of their countries to an eventual success in a military intervention, persistence in the war becomes the only solution to salvage their status. Through this lens, this article presents an explanation for Saudi and Emirati escalations in what was planned as a brief operation in Yemen since 2015. Understanding the dynamics of persisting in failed wars has clear implications for the development of international relations theory, the conduct of regional powers in military interventions, and the practice of conflict resolution in the Middle East and beyond.
A practical method for evaluating spatial biodiversity offset scenarios based on spatial conservation prioritization outputs
Authors: Moilanen Atte , Kujala Heini , Mikkonen Ninni
Published: February 2020

Biodiversity offsetting is a tool to balance ecological damage caused by human activity with new benefits created elsewhere. Offsetting is implemented by protecting, restoring or managing sufficiently large areas of habitat. While there are concerns about the true feasibility of offsetting, they are becoming a common policy tool world‐wide. Operationally uncomplicated, quantitative approaches to spatial analysis of offsets are rare and their use is often restricted by the availability of suitable spatial data.

We describe a practical method for offsets that builds upon two layers of relatively easily sourced spatial data, a balanced spatial priority ranking and a weighted range size rarity map. Together with (a) spatial information about impact and offset areas, and (b) extra parameters for the effectiveness of avoided loss and the amount of leakage expected, we can evaluate whether the proposed offset exchange represents a credible no net loss or net positive impact with an upward trade. The priority ranking and range size rarity maps can be produced in various ways, most notably using existing conservation planning tools. Here we used the standard outputs of the Zonation spatial prioritization software.

We illustrate the method and associated visualization in the context of offsetting of boreal forests in Finland, where forests experience high and increasing pressures from forestry and bioenergy sectors. The example is timely as there is political demand for the uptake of biodiversity offset policies in Finland, and boreal forests are the most common biotope.

The methods described here are applicable to biomes around the world. The described tools are made available as r scripts that utilize standard Zonation outputs, thus providing direct linkage to any past or future Zonation applications. As a limitation, the present methods only apply to avoided loss offsets.
Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification
Authors: Trizuljak Jakub , Sperr Wolfgang R. , Nekvindová Lucie , Elberink Hanneke O. , Gleixner Karoline V. , Gorska Aleksandra , Lange Magdalena , Hartmann Karin , Illerhaus Anja , Bonifacio Massimiliano , Perkins Cecelia , Elena Chiara , Malcovati Luca , Fortina Anna B. , Shoumariyeh Khalid , Jawhar Mohamad , Zanotti Roberta , Bonadonna Patrizia , Caroppo Francesca , Zink Alexander , Triggiani Massimo , Parente Roberta , von Bubnoff Nikolas , Yavuz Akif S. , Hägglund Hans , Mattsson Mattias , Panse Jens , Jäkel Nadja , Kilbertus Alex , Hermine Olivier , Arock Michel , Fuchs David , Sabato Vito , Brockow Knut , Bretterklieber Agnes , Niedoszytko Marek , van Anrooij Björn , Reiter Andreas , Gotlib Jason , Kluin‐Nelemans Hanneke C. , Mayer Jiri , Doubek Michael , Valent Peter
Published: February 2020

Background

In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM.

Methods

We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM.

Results

We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event‐free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly.

Conclusion

Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.
Simultaneous (two‐surgeon) versus staged bilateral knee arthroplasty: an observational study of intraoperative and post‐operative outcomes
Authors: Gill Stephen D. , Hill‐Buxton Leaha‐Marie , Gwini Stella May , Morrison Stewart , Moreira Brett , Beattie Sally , Thomson Andrew , Page Richard S.
Published: February 2020

Background

The advantages of simultaneous bilateral total knee arthroplasty (sim‐BTKA) remain controversial. This study investigated the effects of two‐surgeon sim‐BTKA compared to separate admission staged BTKA regarding intraoperative and post‐operative outcomes and health service costs.

Methods

Patients underwent sim‐BTKA or staged BTKA between 1 November 2008 and 30 June 2016. Data were extracted from a joint replacement registry and medical records. Median regression and chi‐squared tests were used for between‐group comparisons.

Results

Median hospital total length of stay was 5 days less for sim‐BTKA (n = 122) than staged BTKA group (n = 46) (7 versus 12; 95% confidence interval (CI) 3.9, 6.1), and 9 days less for inpatient rehabilitation (17 versus 26; 95% CI 3.7, 14.3). However, 80% of sim‐BTKA patients went to inpatient rehabilitation (versus 27% following staged BTKA), so median total length of stay was 9 days less for staged BTKA (13 versus 22; 95% CI −12.8, −5.2). Total anaesthesia time was 135 min less for sim‐BTKA (P < 0.001), while staged BTKA required less blood transfusions (P = 0.001). Complication rates were similar, except for superficial infections which were observed twice as often after staged BTKA (30% versus 15%, P = 0.048). Twelve months following sim‐BTKA and the first staged total knee arthroplasty, sim‐BTKA had better WOMAC pain, stiffness and function scores (P ≤ 0.05). Average inpatient costs (hospital and rehabilitation) were $6388 less for sim‐BTKA.

Conclusion

Sim‐BTKA appears to be a comparatively safe alternative to staged BTKA. Sim‐BTKA may be superior to staged BTKA due to faster improvements in pain and function and lower healthcare costs. How these results generalize to other health services requires further investigation.
Gut microbiota in atherosclerosis: focus on trimethylamine N‐oxide
Authors: Zhu Yingqian , Li Qingqing , Jiang Hua
Published: February 2020

The increasing prevalence of cardiovascular diseases cannot adequately be explained by traditional risk factors. Recently, accumulating evidence has suggested that gut microbiota‐derived numerous metabolites are contributors to atherosclerotic events. Among them, the role of trimethylamine N‐oxide (TMAO) in promoting atherosclerosis has gained attention. TMAO is reported to exert the proatherogenic effects by impacting on the traditional risk factors of atherosclerosis and is associated with high risk of cardiovascular events. Besides that, TMAO is involved in the complex pathological processes of atherosclerotic lesion formation, such as endothelial dysfunction, platelet activation and thrombus generation. In light of these promising findings, TMAO may serve as a potential target for atherosclerosis prevention and treatment, which is conceptually novel, when compared with existing traditional treatments. It is likely that regulating TMAO production and associated gut microbiota may become a promising strategy for the anti‐atherosclerosis therapy.