bluuebunny/crossref_metadata_2025 huggingface dataset:
Single molecule analysis of effects of non-canonical guide RNAs and specificity-enhancing mutations on Cas9-induced DNA unwinding
Authors: Okafor Ikenna C. , Singh Digvijay , Wang Yanbo , Jung Minhee , Wang Haobo , Mallon John , Bailey Scott , Lee Jungjoon K. , Ha Taekjip
Published: May 2019

Cas9 has made a wide range of genome engineering applications possible. However, its specificity continues to be a challenge. Non-canonical gRNAs and new engineered variants of Cas9 have been developed to improve specificity but at the cost of the on-target activity. DNA unwinding is the primary checkpoint before cleavage by Cas9 and was shown to be made more sensitive to sequence mismatches by specificity-enhancing mutations in Cas9. Here we performed single-molecule FRET-based DNA unwinding experiments using various combinations of non-canonical gRNAs and different Cas9s. All engineered Cas9s were less promiscuous than wild type when canonical gRNA was used but HypaCas9 had much-reduced on-target unwinding. Cas9-HF1 and eCas9 showed the best balance between low promiscuity and high on-target activity with canonical gRNA. When extended gRNAs with one or two guanines added were used, Sniper1-Cas9 showed the lowest promiscuity while maintaining high on-target activity. Truncated gRNA generally reduced unwinding and adding a non-matching guanine to the 5’ end of gRNA influenced unwinding in a sequence-context dependent manner. Our results are consistent with cell-based cleavage data and provide a mechanistic understanding of how various Cas9/gRNA combinations perform in genome engineering.
Transcriptome-wide association study of attention deficit hyperactivity disorder identifies associated genes and phenotypes
Authors: Liao Calwing , Laporte Alexandre D. , Spiegelman Dan , Akçimen Fulya , Joober Ridha , Dion Patrick A. , Rouleau Guy A.
Published: May 2019

Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental psychiatric disorders. Previous studies have shown that the disorder is highly heritable and associated with several different risk-taking behaviors. Additionally, brain-imaging studies have identified various brain regions such as the cerebellum and frontal cortex to be altered in ADHD. Large genome-wide association studies (GWAS) have identified several loci associated with ADHD. However, understanding the biological relevance of these genetic loci has proven to be difficult. Here, we conducted the largest ADHD transcriptome-wide association study (TWAS) to date consisting of 19,099 cases and 34,194 controls and identified 9 transcriptome-wide significant hits. We successfully demonstrate that several previous GWAS hits can be largely explained by expression. Probabilistic causal fine-mapping of TWAS signals prioritized KAT2B with a posterior probability of 0.467 in the dorsolateral prefrontal cortex and TMEM161B with a posterior probability of 0.838 in the amygdala. Furthermore, pathway enrichments identified dopaminergic and norepinephrine pathways, which are highly relevant for ADHD. Finally, we used the top eQTLs associated with the TWAS genes to identify phenotypes relevant to ADHD and found an inverse genetic correlation with educational attainment and a positive correlation with “ever smoker”, maternal smoking at birth, BMI, and schizophrenia. Overall, our findings highlight the power of TWAS to identify novel risk loci and prioritize putatively causal genes.
Pattern similarity analyses of frontoparietal task coding: Individual variation and genetic influences
Authors: Etzel Joset A. , Courtney Ya’el , Carey Caitlin E. , Gehred Maria Z. , Agrawal Arpana , Braver Todd S.
Published: May 2019

Pattern similarity analyses are increasingly used to characterize coding properties of brain regions, but relatively few have focused on cognitive control processes in FrontoParietal regions. Here, we use the Human Connectome Project (HCP) N-back task fMRI dataset to examine individual differences and genetic influences on the coding of working memory load (0-back, 2-back) and perceptual category (Face, Place). Participants were grouped into 105 MZ (monozygotic) twin, 78 DZ (dizygotic) twin, 99 non-twin sibling, and 100 unrelated pairs. Activation pattern similarity was used to test the hypothesis that FrontoParietal regions would have higher similarity for same load conditions, while Visual regions would have higher similarity in same perceptual category conditions. Results confirmed this highly robust regional double dissociation in neural coding, which also predicted individual differences in behavioral performance. In pair-based analyses, anatomically-selective genetic relatedness effects were observed: relatedness predicted greater activation pattern similarity in FrontoParietal only for load coding, and in Visual only for perceptual coding. Further, in related pairs, the similarity of load coding in FrontoParietal regions was uniquely associated with behavioral performance. Together, these results highlight the power of task fMRI pattern similarity analyses for detecting key coding and heritability features of brain regions.
A New Minimally Invasive Technique for Repairing Achilles Tendon Rupture:A Biomechanical Study
Authors: zhao Peng , Sun Dawei , Xiong Yaru , Zhuo Ribo
Published: May 2019

Introduction

The incidence of Achilles tendon rupture shows a gradually increasing trend, which is mainly managed by minimally invasive treatment due to its advantages, such as low wound infection rate. At present, the firmness of the commonly applied minimally invasive suture method for Achilles tendon remains controversial. Our research group has developed a novel suture method for Achilles tendon, which has achieved favorable clinical outcomes. Therefore, this experiment aimed to explore the optimal approach to repair Achilles tendon rupture through comparing the biomechanical strength of the commonly used Achilles tendon suture methods currently.

Materials and methods

6 fresh frozen human cadaveric Achilles tendon specimens were sutured by three kinds of technique, and were tested through the cyclical loading after repair.

Results

Results of cyclical loading showed that, the repair using the new technique was stronger after 10 cycles, 1000 cycles, and rupture. Moreover, the new technique had displayed superior anti-deformation strength to that of the Ma-Griffith technique.

Conclusions

Our experimental results demonstrate that, the new technique proposed by our research group can attain comparable biomechanical properties to those of the Krachow technique. However, the sample size in this study is small, and further clinical trials are warranted.
The drift diffusion model as the choice rule in inter-temporal and risky choice: a case study in medial orbitofrontal cortex lesion patients and controls
Authors: Peters Jan , D’Esposito Mark
Published: May 2019

Sequential sampling models such as the drift diffusion model have a long tradition in research on perceptual decision-making, but mounting evidence suggests that these models can account for response time distributions that arise during reinforcement learning and value-based decision-making. Building on this previous work, we implemented the drift diffusion model as the choice rule in inter-temporal choice (temporal discounting) and risky choice (probability discounting) using a hierarchical Bayesian estimation scheme. We validated our approach in data from nine patients with focal lesions to the ventromedial prefrontal cortex / medial orbitofrontal cortex (vmPFC/mOFC) and nineteen age- and education-matched controls. Choice model parameters estimated via standard softmax action selection were reliably reproduced using the drift diffusion model as the choice rule, both for temporal discounting and risky choice. Model comparison revealed that, for both tasks, the data were best accounted for by a variant of the drift diffusion model including a non-linear mapping from value-differences to trial-wise drift rates. Posterior predictive checks of the winning models revealed a reasonably good fit to individual participants reaction time distributions. We then applied this modeling framework and 1) reproduced our previous results regarding temporal discounting in vmPFC/mOFC patients and 2) showed in a previously unpublished data set on risky choice that vmPFC/mOFC patients exhibit increased risk-taking relative to controls. Analyses of diffusion model parameters revealed that vmPFC/mOFC damage abolished neither value sensitivity nor asymptote of the drift rate. Rather, it substantially increased non-decision times and reduced response caution during risky choice. Our results highlight that novel insights can be gained from applying sequential sampling models in studies of inter-temporal and risky decision-making in cognitive neuroscience.
Benchmarking principal component analysis for large-scale single-cell RNA-sequencing
Authors: Tsuyuzaki Koki , Sato Hiroyuki , Sato Kenta , Nikaido Itoshi
Published: May 2019

Principal component analysis (PCA) is an essential method for analyzing single-cell RNA-seq (scRNA-seq) datasets, but large-scale scRNA-seq datasets require long computational times and a large memory capacity.

In this work, we review 21 fast and memory-efficient PCA implementations (10 algorithms) and evaluate their application using 4 real and 18 synthetic datasets. Our benchmarking showed that some PCA algorithms are faster, more memory efficient, and more accurate than others. In consideration of the differences in the computational environments of users and developers, we have also developed guidelines to assist with selection of appropriate PCA implementations.
Reconstructing wells from high density regions extracted from super-resolution single particle trajectories
Authors: Parutto P. , Heck J. , Heine M. , Holcman D.
Published: May 2019

Large amount of super-resolution single particle trajectories has revealed that the cellular environment is enriched in heterogenous regions of high density, which remain unexplained. The biophysical properties of these regions are characterized by a drift and their extension (a basin of attraction) that can be estimated from an ensemble of trajectories. We develop here two statistical methods to recover the dynamics and local potential wells (field of force and boundary) using as a model a truncated Ornstein-Ulhenbeck process. The first method uses the empirical distribution of points, which differs inside and outside the potential well, while the second focuses on recovering the drift field. Finally, we apply these two methods to voltage-gated calcium channels and phospholipids moving on the surface of neuronal cells and recover the energy and size of these high-density regions with nanometer precision.
Robinson-Foulds Reticulation Networks
Authors: Markin Alexey , Anderson Tavis K. , Vadali Venkata SKT , Eulenstein Oliver
Published: May 2019

Phylogenetic (hybridization) networks allow investigation of evolutionary species histories that involve complex phylogenetic events other than speciation, such as reassortment in virus evolution or introgressive hybridization in invertebrates and mammals. Reticulation networks can be inferred by solving thereticulation network problem, typically known as thehybridization network problem. Given a collection of phylogenetic input trees, this problem seeks aminimum reticulation networkwith the smallest number of reticulation vertices into which the input trees can be embedded exactly. Unfortunately, this problem is limited in practice, since minimum reticulation networks can be easily obfuscated by even small topological errors that typically occur in input trees inferred from biological data. We adapt the reticulation network problem to address erroneous input trees using the classic Robinson-Foulds distance. TheRF embedding costallows trees to be embedded into reticulation networksinexactly, but up to a measurable error. The adapted problem, called theRobinson-Foulds reticulation network (RF-Network) problemis, as we show and like many other problems applied in molecular biology, NP-hard. To address this, we employ local search strategies that have been successfully applied in other NP-hard phylogenetic problems. Our local search method benefits from recent theoretical advancements in this area. Further, we introduce inpractice effective algorithms for the computational challenges involved in our local search approach. Using simulations we experimentally validate the ability of our method,RF-Net, to reconstruct correct phylogenetic networks in the presence of error in input data. Finally, we demonstrate how RF-networks can help identify reassortment in influenza A viruses, and provide insight into the evolutionary history of these viruses. RF-Net was able to estimate a large and credible reassortment network with 164 taxa.
CD8+T cell immunity is compromised by anti-CD20 treatment and rescued by IL-17A
Authors: Vernengo Facundo Fiocca , Beccaria Cristian G. , Furlan Cintia L. Araujo , Boari Jimena Tosello , Almada Laura , Serrán Melisa Gorosito , Gazzoni Yamila , Montes Carolina L. , Rodríguez Eva V. Acosta , Gruppi Adriana
Published: May 2019

Treatment with anti-CD20, used in many diseases in which B cells play a pathogenic role, has been associated with susceptibility to intracellular infections. Here, we studied the effect of anti-CD20 injection on CD8+T cell immunity using an experimental model ofTrypanosoma cruziinfection, in which CD8+T cells play a pivotal role. C57BL/6 mice were treated with anti-CD20 for B cell depletion prior toT. cruziinfection. Infected anti-CD20-treated mice exhibited a CD8+T cell response with a conserved expansion phase followed by an early contraction, resulting in a strong reduction in total and parasite-specific CD8+T cells at 20 days postinfection. Anti-CD20 injection decreased the number of effector and memory CD8+T cells and reduced the frequency of proliferating and cytokine producing CD8+T cells. Accordingly, infected anti-CD20-treated mice presented a lower cytotoxicity ofT. cruzipeptide-pulsed target cellsin vivo. All of these alterations in CD8+T cell immunity were associated with increased tissue parasitism. Anti-CD20 injection also dampened an established CD8+T cell response, indicating that B cells were involved in the maintenance rather than the induction of CD8+T cell immunity. Anti-CD20 injection also resulted in a marked reduction in the frequency of IL-6- and IL-17A-producing cells, and only rIL-17A injection partially restored the CD8+T cell response in infected anti-CD20-treated mice. Thus, anti-CD20 reduced CD8+T cell immunity, and IL-17A is a candidate for rescuing deficient responses either directly or indirectly.

Importance

Monoclonal antibody targeting the CD20 antigen on B cells is used to treat the majority of Non-Hodgkin lymphoma patients and some autoimmune disorders. This therapy generates adverse effects, notably opportunistic infections and activation of viruses from latency. Here, using the infection murine model with the intracellular parasiteTrypanosoma cruzi, we report that anti-CD20 treatment not only affects B cell response but also CD8+T cells, the most important immune effectors involved in control of intracellular pathogens. Anti-CD20 treatment, directly or indirectly, affects cytotoxic T cell number and function and this deficient response was rescued by the cytokine IL-17A. The identification of IL-17A as the cytokine capable of reversing the poor response of CD8+T cells provide information about a potential therapeutic treatment aimed at enhancing defective immunity induced by B cell depletion.
Benchmarking algorithms for gene regulatory network inference from single-cell transcriptomic data
Authors: Pratapa Aditya , Jalihal Amogh P. , Law Jeffrey N. , Bharadwaj Aditya , Murali T. M.
Published: May 2019

We present a comprehensive evaluation of state-of-the-art algorithms for inferring gene regulatory networks (GRNs) from single-cell gene expression data. We develop a systematic framework called BEELINE for this purpose. We use synthetic networks with predictable cellular trajectories as well as curated Boolean models to serve as the ground truth for evaluating the accuracy of GRN inference algorithms. We develop a strategy to simulate single-cell gene expression data from these two types of networks that avoids the pitfalls of previously-used methods. We selected 12 representative GRN inference algorithms. We found that the accuracy of these methods (measured in terms of AUROC and AUPRC) was moderate, by and large, although the methods were better in recovering interactions in the synthetic networks than the Boolean models. Techniques that did not require pseudotime-ordered cells were more accurate, in general. The observation that the endpoints of many false positive edges were connected by paths of length two in the Boolean models suggested that indirect effects may be predominant in the outputs of the algorithms we tested. The predicted networks were considerably inconsistent with each other, indicating that combining GRN inference algorithms using ensembles is likely to be challenging. Based on the results, we present some recommendations to users of GRN inference algorithms, including suggestions on how to create simulated gene expression datasets for testing them. BEELINE, which is available athttp://github.com/murali-group/BEELINEunder an open-source license, will aid in the future development of GRN inference algorithms for single-cell transcriptomic data.
Unique and redundant roles of SOX2 and SOX17 in regulating the germ cell tumour fate
Authors: Jostes Sina , Fellermeyer Martin , Merges Gina , Kristiansen Glen , Nettersheim Daniel , Schorle Hubert
Published: May 2019

Embryonal carcinomas (ECs) and seminomas are testicular germ cell tumours. ECs display expression of SOX2, while seminomas display expression of SOX17. In somatic differentiation, SOX17 drives endodermal cell fate. However, seminomas lack expression of endoderm markers, but show features of pluripotency. Here, we use ChIP-sequencing to report and compare the binding pattern of SOX17 in seminoma-like TCam-2 cells to SOX2 in EC-like 2102EP cells and SOX17 in somatic cells. In seminoma-like cells, SOX17 was detected at canonical (SOX2/OCT4), compressed (SOX17/OCT4) and other SOX family member motifs. SOX17 directly regulatesTFAP2C,PRDM1andPRDM14, thereby maintaining latent pluripotency and supressing somatic differentiation. In contrast, in somatic cells canonical motifs are not bound by SOX17. In sum only 11% of SOX17 binding sites overlap in seminoma-like and somatic cells. This illustrates that binding site choice is highly dynamic and cell type specific. Deletion of SOX17 in seminoma-like cells resulted in loss of pluripotency, marked by a reduction of OCT4 protein level and loss of alkaline phosphatase activity. Further, we found that in EC-like cells SOX2 regulates pluripotency-associated genes, predominantly by partnering with OCT4. In conclusion, SOX17 (in seminomas) functionally replaces SOX2 (in ECs) to maintain expression of the pluripotency cluster.
Single-cell transcriptomics reveals expansion of cytotoxic CD4 T-cells in supercentenarians
Authors: Hashimoto Kosuke , Kouno Tsukasa , Ikawa Tomokatsu , Hayatsu Norihito , Miyajima Yurina , Yabukami Haruka , Terooatea Tommy , Sasaki Takashi , Suzuki Takahiro , Valentine Matthew , Pascarella Giovanni , Okazaki Yasushi , Suzuki Harukazu , Shin Jay W. , Minoda Aki , Taniuchi Ichiro , Okano Hideyuki , Arai Yasumichi , Hirose Nobuyoshi , Carninci Piero
Published: May 2019

Supercentenarians, people who have reached 110 years of age, are a great model of healthy aging. Their characteristics of delayed onset of age-related diseases and compression of morbidity imply that their immune system remains functional. Here we performed single-cell transcriptome analysis of 61,202 peripheral blood mononuclear cells (PBMCs), derived from seven supercentenarians and five younger controls. We identified a marked increase of cytotoxic CD4 T-cells (CD4 CTLs) coupled with a substantial reduction of B-cells as a novel signature of supercentenarians. Furthermore, single-cell T-cell receptor sequencing of two supercentenarians revealed that CD4 CTLs had accumulated through massive clonal expansion, with the most frequent clonotypes accounting for 15% to 35% of the entire CD4 T-cell population. The CD4 CTLs exhibited substantial heterogeneity in their degree of cytotoxicity as well as a nearly identical transcriptome to that of CD8 CTLs. This indicates that CD4 CTLs utilize the transcriptional program of the CD8 lineage while retaining CD4 expression. Our study reveals that supercentenarians have unique characteristics in their circulating lymphocytes, which may represent an essential adaptation to achieve exceptional longevity by sustaining immune responses to infections and diseases.

Significance

Exceptionally long-lived people such as supercentenarians tend to spend their entire lives in good health, implying that their immune system remains active to protect against infections and tumors. However, their immunological condition has been largely unexplored. We profiled thousands of circulating immune cells from supercentenarians at single-cell resolution, and identified a large number of CD4 T-cells that have cytotoxic features. This characteristic is very unique to supercentenarians, because generally CD4 T-cells have helper, but not cytotoxic, functions under physiological conditions. We further profiled their T-cell receptors, and revealed that the cytotoxic CD4 T-cells were accumulated through clonal expansion. The conversion of helper CD4 T-cells to a cytotoxic variety might be an adaptation to the late stage of aging.
Thymically-derived Foxp3+ regulatory T cells are the primary regulators of type 1 diabetes in the non-obese diabetic mouse model
Authors: Holohan Daniel R. , Van Gool Frédéric , Bluestone Jeffrey A.
Published: May 2019

Regulatory T cells (Tregs) are an immunosuppressive population that are identified based on the stable expression of the fate-determining transcription factor forkhead box P3 (Foxp3). Tregs can be divided into distinct subsets based on whether they developed in the thymus (tTregs) or in the periphery (pTregs). Whether there are unique functional roles that distinguish pTregs and tTregs remains largely unclear. To elucidate these functions, efforts have been made to specifically identify and modify individual Treg subsets. Deletion of the conserved non-coding sequence (CNS)1 in the Foxp3 locus leads to selective impairment of pTreg generation without disrupting tTreg generation in the C57BL/6J background. Using CRISPR-Cas9 genome editing technology, we removed the Foxp3 CNS1 region in the non-obese diabetic (NOD) mouse model of spontaneous type 1 diabetes mellitus (T1D) to determine if pTregs contribute to autoimmune regulation. Deletion of CNS1 impaired in vitro induction of Foxp3 in naïve NOD CD4+ T cells, but it did not alter Tregs in most lymphoid and non-lymphoid tissues analyzed except for the large intestine lamina propria, where a small but significant decrease in RORγt+ Tregs and corresponding increase in Helios+ Tregs was observed in NOD CNS1−/− mice. CNS1 deletion also did not alter the development of T1D or glucose tolerance despite increased pancreatic insulitis in pre-diabetic female NOD CNS1−/− mice. CNS1 Furthermore, the proportions of autoreactive Tregs and conventional T cells (Tconvs) within pancreatic islets were unchanged. These results suggest that pTregs dependent on the Foxp3 CNS1 region are not the dominant regulatory population controlling T1D in the NOD mouse model.
Induction of β-adrenergic metaplasticity of LTP requires intact anchoring of PKA
Authors: Hoffman Janlyn R. , Brandwein Nathan J. , Nguyen Peter V.
Published: May 2019

Beta-adrenergic receptors (β-ARs) prime hippocampal synapses to stabilize long-term potentiation (LTP). This “metaplasticity” can persist for 1–2 h after pharmacologic activation of β-ARs. It requires activation of PKA (cAMP-dependent protein kinase) during β-AR priming. A-kinase anchoring proteins (AKAPs) tether PKA to downstream signaling proteins. We hypothesized that induction of this metaplasticity requires intact functioning of AKAPs. Acute application of stearated ht31, a membrane-permeant inhibitor of AKAPs, either during β-AR activation 30 min prior to LTP induction or during LTP induction, attenuated the persistence of LTP. A control, inactive ht31 peptide did not affect β-AR-mediated metaplasticity. These findings implicate PKA anchoring in the induction of β-adrenergic metaplasticity of LTP.
How do government regulations and policies respond to the growing online-enabled transportation service (OETS) in Indonesia, the Philippines, and Taiwan?
Authors: Mutiarin Dyah , Nurmandi Achmad , Jovita Hazel , Fajar Mukti , Lien Yao-Nan
Published: May 2019

Purpose

This paper aims to explore the dynamic context of the sharing economy in the transportation sector. This paper looks into the development of government regulations on the growing business of transportation network companies in Indonesia, the Philippines (represented as middle-income countries) and Taiwan (high-income country). How do government regulations and policies respond to the growing online-enabled transportation service (OETS) in Indonesia, the Philippines and Taiwan?

Design/methodology/approach

This study is qualitative-comparative research. Data on the transportation sector of each country have been gathered from reputable online sources.

Findings

Authors found evidence that the policy responses made by the Governments of Indonesia, Philippines and Taiwan to the sharing economy in the transportation sector are incremental and trial-error based policies.

Research limitations

This paper has not addressed the policy issues’ relationship between driver and platform companies.

Practical implications

The future of the relationship between sharing firms and local governments suggests that the focus should be on stronger consumer protections, deeper economic redistribution and achievement of other policy aims (Rauch and Schleicher, 2015).

Originality/value

This is a comparative study on different levels of economy, particularly between low- or middle-income and high-income country.
Artificial intelligence and policy: quo vadis?
Authors: Lauterbach Anastassia
Published: May 2019

Purpose

This paper aims to inform policymakers about key artificial intelligence (AI) technologies, risks and trends in national AI strategies. It suggests a framework of social governance to ensure emergence of safe and beneficial AI.

Design/methodology/approach

The paper is based on approximately 100 interviews with researchers, executives of traditional companies and startups and policymakers in seven countries. The interviews were carried out in January-August 2017.

Findings

Policymakers still need to develop an informed, scientifically grounded and forward-looking view on what societies and businesses might expect from AI. There is lack of transparency on what key AI risks are and what might be regulatory approaches to handle them. There is no collaborative framework in place involving all important actors to decide on AI technology design principles and governance. Today's technology decisions will have long-term consequences on lives of billions of people and competitiveness of millions of businesses.

Research limitations/implications

The research did not include a lot of insights from the emerging markets.

Practical implications

Policymakers will understand the scope of most important AI concepts, risks and national strategies.

Social implications

AI is progressing at a very fast rate, changing industries, businesses and approaches how companies learn, generate business insights, design products and communicate with their employees and customers. It has a big societal impact, as – if not designed with care – it can scale human bias, increase cybersecurity risk and lead to negative shifts in employment. Like no other invention, it can tighten control by the few over the many, spread false information and propaganda and therewith shape the perception of people, communities and enterprises.

Originality/value

This paper is a compendium on the most important concepts of AI, bringing clarity into discussions around AI risks and the ways to mitigate them. The breadth of topics is valuable to policymakers, students, practitioners, general executives and board directors alike.
Investigation of equivalent correlation coefficient based on the Mehler’s formula
Authors: Zu Yunfei , Fan Wenliang , Zhang Jingyao , Li Zhengling , Ohsaki Makoto
Published: May 2019

Purpose

Conversion of the correlated random variables into independent variables, especially into independent standard normal variables, is the common technology for estimating the statistical moments of response and evaluating reliability of random system, in which calculating the equivalent correlation coefficient is an important component. The purpose of this paper is to investigate an accurate, efficient and easy to implement estimation method for the equivalent correlation coefficient of various incomplete probability systems.

Design/methodology/approach

First, an approach based on the Mehler’s formula for evaluating the equivalent correlation coefficient is introduced, then, by combining with polynomial normal transformations, this approach is improved to be valid for various incomplete probability systems, which is named as the direct method. Next, with the convenient linear reference variables for eight frequently used random variables and the approximation of the Rosenblatt transformation introduced, a further improved implementation without iteration process is developed, which is named as the simplified method. Finally, several examples are investigated to verify the characteristics of the proposed methods.

Findings

The results of the examples in this paper show that both the proposed two methods are of high accuracy, by comparison, the proposed simplified method is more effective and convenient.

Originality/value

Based on the Mehler’s formula, two practical implementations for evaluating the equivalent correlation coefficient are proposed, which are accurate, efficient, easy to implement and valid for various incomplete probability systems.
The Global call for action on infection prevention and control
Authors: Avortri Gertrude Sika , Nabyonga-Orem Juliet
Published: May 2019

Purpose

Healthcare-associated infections (HAIs) constitute a major threat to patient safety and affect hundreds of millions of people worldwide. The World Health Organization in 2016 published guidelines on the core components for infection prevention and control (IPC) programme. This was in response to a global call for focused action. The purpose of this paper is to examine and promote understanding of the tenets of the IPC guidelines and highlight their implications for implementation in low-income countries.

Design/methodology/approach

Drawing from personal experiences in leading the implementation of health programmes as well as a review of published and grey literature on IPC, authors discussed and proposed practical approaches to implement IPC priorities in low-income setting.

Findings

Availability of locally generated evidence is paramount to guide strengthening leadership and institutionalisation of IPC programmes. Preventing infections is everybody’s responsibility and should be viewed as such and accorded the required attention.

Originality/value

Drawing from recent experiences from disease outbreaks and given the heavy burden of HAIs especially in low-income settings, this paper highlights practical approaches to guide implementation of the major components of IPC.
Leadership styles’ influence on the quality of nursing care
Authors: Alloubani Aladeen , Akhu-Zaheya Laila , Abdelhafiz Ibrahim Mubarak , Almatari M.
Published: May 2019

Purpose

The purpose of this paper is to investigate managers’ leadership styles, from the perspective of registered nurses, and its effects on the quality of nursing care in both the private and public healthcare sectors. An additional aim is to assess the relationship between leadership styles and particular organisational outcomes.

Design/methodology/approach

The sample for this quantitative research study was comprised of 400 respondents, among which 50 were nurse managers, 150 were staff nurses and the remaining respondents were patients. Two questionnaires were used in this study: the multi-factor leadership questionnaire (MLQ) 5X short and a patient satisfaction with nursing care quality questionnaire (PSNCQQ).

Findings

A positive correlation was found between the transformational leadership style with leadership outcomes and the quality of nursing care (r=0.811**, 0.759**, 0.789** and 0.877** for extra effort, job satisfaction, leader effectiveness and quality, respectively).

Practical implications

Although the sample study was extensive, a possible limitation is that the research utilised convenient sample who are working in the private and public healthcare sectors thus limiting the generalisability of the study.

Originality/value

This study was proposed as a baseline for upcoming studies in areas of education, nursing practice, research and quality. Moreover, this study was expected to be imperative to the hospital’s management, in order to improve the current level of leadership, education models and advancement programs for the healthcare sector’s senior staff.
Quality assurance as a foundational element for an integrated system of dementia care
Authors: Heckman George A. , Crutchlow Lauren , Boscart Veronique , Hillier Loretta , Franco Bryan , Lee Linda , Molnar Frank , Seitz Dallas , Stolee Paul
Published: May 2019

Purpose

Many countries are developing primary care collaborative memory clinics (PCCMCs) to address the rising challenge of dementia. Previous research suggests that quality assurance should be a foundational element of an integrated system of dementia care. The purpose of this paper is to understand physicians’ and specialists’ perspectives on such a system and identify barriers to its implementation.

Design/methodology/approach

The authors used interviews and a constructivist framework to understand the perspectives on a quality assurance framework for dementia care and barriers to its implementation from ten primary care and ten specialist physicians affiliated with PCCMCs.

Findings

Interviewees found that the framework reflects quality dementia care, though most could not relate quality assurance to clinical practice. Quality assurance was viewed as an imposition on practitioners rather than as a measure of system integration. Disparities in resources among providers were seen as barriers to quality care. Greater integration with specialists was seen as a potential quality improvement mechanism. Standardized electronic medical records were seen as important to support both quality assurance and clinical care.

Practical implications

This work identified several challenges to the implementation of a quality assurance framework to support an integrated system of dementia care. Clinicians require education to better understand quality assurance. Additional challenges include inadequate resources, a need for closer collaboration between specialists and PCCMCs, and a need for a standardized electronic medical record.

Originality/value

Greater health system integration is necessary to provide quality dementia care, and quality assurance could be considered a foundational element driving system integration.
Survey of isolation room equipment and resources in an academic hospital
Authors: Telford Brittany , Healy Ray , Flynn Ellen , Moore Emma , Ravi Akshaya , Geary Una
Published: May 2019

Purpose

The purpose of this paper, a point prevalence study, is to quantify the incidence of isolation and identify the type of communicable diseases in isolation. The paper evaluates isolation precaution communication, availability of personal protective equipment (PPE) as well as other equipment necessary for maintaining isolation precautions.

Design/methodology/approach

A standardised audit tool was developed in accordance with the National Standards for the Prevention and Control of Healthcare Associated Infections (May 2009). Data were collected from 14 March 2017 to 16 March 2017, through observation of occupied isolation rooms in an academic hospital in Dublin, Ireland. The data were subsequently used for additional analysis and discussion.

Findings

In total, 14 per cent (125/869) of the total inpatient population was isolated at the time of the study. The most common isolation precaution was contact precautions (96.0 per cent). In all, 88 per cent of known contact precautions were due to multi-drug resistant organisms. Furthermore, 96 per cent of patients requiring isolation were isolated, 92.0 per cent of rooms had signage, 90.8 per cent had appropriate signs and 93.0 per cent of rooms had PPE available. Finally, 31 per cent of rooms had patient-dedicated and single-use equipment and 2.4 per cent had alcohol wipes available.

Practical implications

The audit tool can be used to identify key areas of noncompliance associated with isolation and inform continuous improvement and education.

Originality/value

Currently, the rate of isolation is unknown in Ireland and standard guidelines are not established for the evaluation of isolation rooms. This audit tool can be used as an assessment for isolation room compliance.
Reducing interruptions during medication preparation and administration
Authors: Mortaro Alberto , Pascu Diana , Pancheri Serena , Mazzi Mariangela , Tardivo Stefano , Bellamoli Claudio , Ferrarese Federica , Poli Albino , Romano Gabriele , Moretti Francesca
Published: May 2019

Purpose

According to literature, interruptions during drug administration lead to a significant proportion of medication errors. Evidence on the effectiveness of interventions to reduce interruption is still limited. The purpose of this paper is to explore main reasons for interruptions during drug administration rounds in a geriatric ward of an Italian secondary hospital and test the effectiveness of a combined intervention.

Design/methodology/approach

This is a pre and post-intervention observational study based on direct observation. All nurse staff (24) participated to the study that lead to observe a total of 44 drug dispensing rounds with 945 drugs administered to 491 patients in T0 and 994 drugs to 506 patients in T1.

Findings

A significant reduction of raw number of interruptions (mean per round from 17.31 in T0 to 9.09 in T1, p<0.01), interruptions/patient rate (from 0.78 in T0 to 0.40 in T1, p<0.01) and interruptions/drugs rate (from 0.44 in T0 to 0.22 in T1, p<0.01) were observed. Needs for further improvements were elicited (e.g. a greater involvement of support staff).

Practical implications

Nurse staff should be adequately trained on the risks related to interruptions during drug administration since routine activity is at high risk of distractions due to its repetitive and skill-based nature.

Originality/value

A strong involvement of both MB and leadership, together with the frontline staff, helped to raise staff motivation and guide a bottom-up approach, able to identify tailored interventions and serve concurrently as training instrument tool.
Does CSR matter in the pharmaceutical distribution industry?
Authors: Mehralian Gholamhossein , Zarei Leila , Akhgari Mehdi , Peikanpour Mohammd
Published: May 2019

Purpose

Given the important role of corporate social responsibility (CSR) in today’s business world, this study aims to investigate how it affects the performance of pharmaceutical distribution companies by using the balanced scorecard (BSC).

Design/methodology/approach

Drawing upon the existing literature, a questionnaire consisting of 32 questions was prepared and distributed to examine ongoing practices and to probe uninvestigated domains related to CSR. To confirm the efficiency of the research model and the accuracy of the measurement model – which was utilized to examine the correlation between different variables – variable scores were acquired from a national study and were entered into a structural equation model.

Findings

Analysis of 933 completed questionnaires revealed the existence of large correlation between subsets of the considered dimensions. The questionnaire contained five underlying dimensions: employee relations, corporate governance, societal concern, economic and financial concern and environmental concerns. All CSR variables can be condensed into these five dimensions, which are the main features of the CSR model proposed for the Iranian pharmaceutical distribution companies. Not only did the results support the research model but also indicated that CSR’s impact on BSC and its four components – financial perspective, customer perspective, internal process perspective and learning and growth perspective – was both positive and significant.

Practical implications

This paper identifies five dimensions through which CSR practices can effect positive changes in an organization’s performance in relation to the four BSC perspectives. Thus, in focusing on these dimensions, a company increases its likelihood of enhancing its performance and, consequently, realizing significant gains. In addition, as managers play the most significant role in CSR implementation, they should support all associated practices to achieve their strategic goals.

Originality/value

Pharmaceutical distribution companies tend to apply CSR – which is commonly described as informal and voluntary humanitarian activities – to different domains, including the workplace, marketplace, community and environment. This study contributes to the existing literature by shedding light on various domains in which CSR practices are applied to enhance organizational success in pharmaceutical distribution companies.
M&As get another assist: when CEOs add intuition to the decision mix
Authors: Kuusela Hannu , Koivumäki Siiri , Yrjölä Mika
Published: May 2019

Purpose

The purpose of this paper is to analyze the use of intuition in successful merger and acquisition (M&A) decisions. M&As are strategic decisions that can create growth, open up new markets and strengthen the company’s position and competence portfolio. Strategic decisions involve, by their very nature, considerable investments and have company-wide and long-lasting implications. At the same time, the decision-makers have access to large amounts of data from various sources, but these data are often uncertain and inaccurate and entail numerous assumptions. Therefore, M&A decisions are only rational to a degree, and emotional elements, such as intuition, likely play a significant role.

Design/methodology/approach

Acknowledging how critically important, but also how difficult, M&As are, the authors analyzed nine instances (cases) of successful acquisitions, in which the executives believed that the role of intuition was critical.

Findings

The findings show that intuition in strategic decision-making emerges on three levels: individual, collective and environmental.

Practical implications

This paper encourages top executives to proactively acknowledge and take advantage of intuition in their strategic decision-making. It proposes a framework to help with these endeavors.

Originality/value

This paper contributes by highlighting that intuition is not just a factor on an individual level; it can also surface from group interactions as well as the environment. Surprisingly, all the executives interviewed spoke of the positive effects that intuition can have on acquisition decisions. This is in contrast to the dominant view that considers intuition as nonrational and even as a form of bias.
Open coopetition: when multiple players and rivals team up
Authors: Roth Steffen , Leydesdorff Loet , Kaivo-Oja Jari , Sales Augusto
Published: May 2019

Purpose

This paper aims to extend the existing views of coopetition into the broader context of open coopetition.

Design/methodology/approach

The authors build on the literature about open innovation cooperation between competitors in the open-source software industry, which we generalize to show that open coopetition between competitors and third parties can be observed in other industries and institutional settings.

Findings

The authors outline a research program on the management challenges of open coopetition-related and argue that open coopetition can not only be observed between business rivals but also between partners from university, industry, government and further institutional backgrounds.

Originality/value

The authors introduce to so-far neglected roots of the emerging research program on open coopetition and extend the prevailing business focus of open coopetition research to also systematically include open coopetition between partners from business and other spheres of society.
When does creativity matter: the impact of consumption motive and claim set-size
Authors: Benoit Ilgım Dara , Miller Elizabeth G.
Published: May 2019

Purpose

This paper aims to identify two boundary conditions (consumption motive and claim set-size) affecting the effectiveness of an advertisement’s creativity.

Design/methodology/approach

Across two experiments, the authors find support for hypotheses using both hedonic vs utilitarian products (Study 1) and hedonic vs utilitarian decision goals within the same product category (Study 2).

Findings

Creativity is more effective for an advertisement when the consumption motive is utilitarian (vs hedonic). Further, using a larger claim set-size within an advertisement increases (decreases) the effectiveness of advertisement creativity for those with hedonic (utilitarian) consumption motives.

Research limitations/implications

This research contributes to the creativity literature by showing when creativity matters depending on the consumption motive and claim set-size. In addition, this research expands the utilitarian vs hedonic consumption literature by highlighting another way in which these two motives differ. Finally, this study expands the claim set-size literature by demonstrating that the effects of claim set-size depend on both consumption motive and features of the ad (i.e. its level of creativity).

Practical implications

These findings help marketers manage their advertising budget more effectively and efficiently knowing when advertisement creativity matters and thus when to invest in creativity.

Originality/value

The present research is the first to explicitly study boundary conditions for when ad creativity matters and shows that creativity matters more (i.e. enhances persuasiveness of the ad and attitudes toward the ad) when the consumption motive is utilitarian, especially when ads have small claim set-size. Additionally, creativity matters for hedonic consumption contexts if the advertisement has a large claim size.